{ "Contributors": [ "COVID-QA" ], "Source": [ "COVID-QA" ], "URL": [ "https://github.com/deepset-ai/COVID-QA/tree/master" ], "Categories": [ "Question Answering" ], "Definition": [ "Given a question, answer it with comprehensive details." ], "Reasoning": [], "Input_language": [ "English" ], "Output_language": [ "English" ], "Instruction_language": [ "English" ], "Domains": [ "Medical Knowledge" ], "Positive Examples": [], "Negative Examples": [], "Instances": [ { "input": "What is the main cause of HIV-1 infection in children?", "output": "Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. " }, { "input": "What plays the crucial role in the Mother to Child Transmission of HIV-1 and what increases the risk", "output": "DC-SIGNR plays a crucial role in MTCT of HIV-1 and that impaired placental DC-SIGNR expression increases risk of transmission." }, { "input": "How many children were infected by HIV-1 in 2008-2009, worldwide?", "output": "more than 400,000 children were infected worldwide, mostly through MTCT and 90% of them lived in sub-Saharan Africa. " }, { "input": "What is the role of C-C Motif Chemokine Ligand 3 Like 1 (CCL3L1) in mother to child transmission of HIV-1?", "output": "High copy numbers of CCL3L1, a potent HIV-1 suppressive ligand for CCR5, are associated with higher chemokine production and lower risk of MTCT of HIV-1 among South African infants" }, { "input": "What is DC-GENR and where is it expressed?", "output": "Dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node-specific ICAM-grabbing non-integrin (L-SIGN)) can interact with a plethora of pathogens including HIV-1 and is expressed in placental capillary endothelial cells" }, { "input": "How does the presence of DC-SIGNR affect the MTCT of HIV-1?", "output": "the presence of DC-SIGNR at the placental endothelial cell surface may protect infants from HIV-1 infection by capturing virus and promoting its degradation/presentation. " }, { "input": "Why do low levels of DC-SIGNR enhance Mother to Child Transmission of HIV-1?", "output": "in placenta containing low levels of DC-SIGNR, HIV-1 would preferentially binds CCR5 on endothelial cells resulting in a loss of placental barrier integrity and enhanced passage of maternal HIV-1-infected cells in foetal circulation leading to MTCT of HIV-1" }, { "input": "What is the percentage of Mother to Child Transmission of HIV-1, when there is no intervention?", "output": "Without specific interventions, the rate of HIV-1 mother-tochild transmission (MTCT) is approximately 15-45%" }, { "input": "Does C-C chemokine receptor type 5 (CCR5) affect the transmission of HIV-1?", "output": "Genetic variants in CCR5 have been shown to influence vertical transmission of HIV-1. CCR5 promoter variants resulting in higher expression of the receptor were associated with increased risk of MTCT of HIV-1 among sub-Saharan Africans" }, { "input": "How does Mannanose Binding Lectin (MBL) affect elimination of HIV-1 pathogen?", "output": "Mannose-binding lectin (MBL) is an innate immune receptor synthesised in the liver and secreted in the bloodstream in response to inflammation signal. MBL promotes pathogen elimination by opsonization and phagocytosis," }, { "input": "How can CCR5's effect in HIV-1 transmission be reduced?", "output": "The 32-pb deletion polymorphism in CCR5 has be shown to protect from vertical transmission of HIV-1" }, { "input": "What is IFITM?", "output": "interferon-induced transmembrane" }, { "input": "How many cysteine residues are contained in the first transmembrane domain of IFITM3?", "output": "three" }, { "input": "What inhibits S-palmitoylation?", "output": "2-bromopalmitic acid (2BP)" }, { "input": "What interaction is inhibited by the presence of 2-bromopalmitic acid (2BP)?", "output": "IFITM5 with FKBP11" }, { "input": "What is a function associated with IFITM5?", "output": "bone formation factor." }, { "input": "What regulates the antiviral activity of IFITM3?", "output": "S-palmitoylation on the protein" }, { "input": "What is another name for IFITM5?", "output": "bonerestricted IFITM-like (BRIL) protein" }, { "input": "Why is the expression of IFITM5 not promoted by interferons?", "output": "the region upstream of the ifitm5 gene lacks the interferon regulatory elements" }, { "input": "What is the amino acid similarity between IFITM5 and the other IFITM proteins?", "output": "~ 65% similarity" }, { "input": "What is the amino acid similarity between IFITM 1, IFITM 2, and IFITM 3?", "output": "~ 85% similarity" }, { "input": "What amino acid might be involved in calcium binding in the C-terminal region of a protein?", "output": "aspartate" }, { "input": "What is the size of bovine coronavirus?", "output": "31 kb" }, { "input": "What is the molecular structure of bovine coronavirus?", "output": "single-stranded, linear, and nonsegmented RNA" }, { "input": "How many nucleotides does bovine coronavirus contain?", "output": "30,847 nucleotides" }, { "input": "What is the size of the orf1ab gene in bovine coronavirus?", "output": "20kb" }, { "input": "Is the orf1ab gene at the 3' or 5' end of the bovine coronavirus genome?", "output": "5= side" }, { "input": "What is a significant cause of Influenze like illness among healthy adolescents and adults presenting for medical evaluation?", "output": "HCoV" }, { "input": "What is the most common species of Human Coronavirus among adults?\n", "output": "HCoV-OC43" }, { "input": "Which Human Coronavirus showed species specific clinical characteristics of its infection?", "output": "HCoV\u2010HKU1" }, { "input": "What causes the outbreak of SARS and MERS.", "output": "Highly virulent species of HCoV" }, { "input": "What is the case fatality rate of SARS and MERS?", "output": "ranged from 14% to 45%" }, { "input": "What were the common HCOV strains in the 5 year USA study?", "output": " HCoV-OC43 and HCoV-229E" }, { "input": "Which species are more prevalent but less severe?", "output": "HCoV-HKU1, HCoV-OC43, HCoV-NL63, and HCoV-229E" }, { "input": "What is required for a Hepatitis B infection in cells?", "output": "both intracellular and cell-surface factors" }, { "input": "What regulates the broad, but less specific, virus-cell interaction in a hepatitis B infection?", "output": "heparan sulfates in the membrane proteins" }, { "input": "Which protein domain of the Hepatitis B envelope is necessary for infection?", "output": "Nterminus of HBV preS1 (amino acids 1-47) " }, { "input": "Where is NTCP located in the body?", "output": "lateral surface (canalicular) of hepatocytes" }, { "input": "What does the NTCP protein mediate?", "output": "bile acid transport " }, { "input": "Is NTCP sufficient to allow HBV infection?", "output": "not sufficient" }, { "input": "Why is NTCP thought to not be sufficient for HBV infection?", "output": "the majority of HepaRG cells were found to express NPCT but not to be infected" }, { "input": "What kinds of viruses are Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), eastern equine encephalitis virus (EEEV), sindbis virus(SV), and dengue virus(DV)?", "output": "arboviruses" }, { "input": "What are the current clinically-available methods to detect encephalitis viral antigens?", "output": "ELISA and IFA" }, { "input": "What methods exist for detecting multiple antigens simultaneously in a one-sample, laboratory test?", "output": "two-dimensional gel electrophoresis , protein chip, mass spectrometry, and suspension array technology" }, { "input": "How many antigens could be detected by Liew's multiplex ELISA test?", "output": "9" }, { "input": "What kind of antibodies were used in the ELISA-array assay?", "output": "monoclonal" }, { "input": "How was the ELISA assay validated?", "output": "using cultured viruses and inoculated chicken eggs with patient sera" }, { "input": "What capture antibodies were used in the study?", "output": "4D5, 2B5, 1F1, 2B8, 4F9, and 4E11" }, { "input": "What was the spotting concentration range for the capture antibodies?", "output": "from 0.2 to 0.0125 mg/ml" }, { "input": "How was the proper spotting concentration determined?", "output": "combination of minimized cross reaction and higher signal intensity" }, { "input": "How was cross reaction detection determined?", "output": "by applying JEV, YF, and DV cultures" }, { "input": "How was the ELISA-array assay validated?", "output": "using cultured viruses and inoculated chicken eggs with patient sera" }, { "input": "In 2010, how many cases of tuberculosis were estimated in China?", "output": "108 per 100,000" }, { "input": "What is the population of Shandong province?", "output": "94 million" }, { "input": "What was the purpose of this study?", "output": "estimate the TB prevalence in Shandong" }, { "input": "What was the age range for the people surveyed?", "output": "15 years old or above" }, { "input": "How was the survey designed?", "output": "in accordance with WHO recommendations" }, { "input": "Was was the sample size?", "output": "52500" }, { "input": "How were the clusters selected?", "output": "A stratified multi stage random sampling" }, { "input": "How many people were in a community cluster?", "output": "1250 to 1750" }, { "input": "Who was excluded from the study?", "output": "Military barracks and prisons" }, { "input": "When was the study conducted?", "output": "March to June 2010" }, { "input": "Who conducted the study?", "output": "clinicians, public health doctors, radiologists, laboratory technicians and nurses" }, { "input": "What medium was used to collect the sputum samples?", "output": "L\u00f6wenstein-Jensen medium" }, { "input": "What was the response rate for the study?", "output": "95% to 97%" }, { "input": "What was the average age of a study participant?", "output": "46 years" }, { "input": "What was the prevalence rate in Shandong in 2010 for sputum positive cases of tuberculosis?", "output": "22.1" }, { "input": "What was the most striking finding of the study regarding tuberculosis patients?", "output": "a large proportion of TB patients did not present consistent cough" }, { "input": "How many cases of sputum positive tuberculosis patients had no persistent cough?", "output": "45%" }, { "input": "How many tuberculosis patients in Shandong were over 65 years old?", "output": "over half" }, { "input": "What enzymes have been reported to be linked with severity of infection and various pathological conditions caused by microorganisms?", "output": "cysteine proteases" }, { "input": "At what temperatures was the assay completed?", "output": "32uC, 37uC, 42uC" }, { "input": "What criteria sets the guideline for drug-like properties?", "output": "Lipinski's ''Rule of five''" }, { "input": "What could be novel candidates as potent inhibitors of papain like cysteine proteases in resistant microorganisms?", "output": "1-substituted pyridylimidazo[1,5-a]pyridine derivatives" }, { "input": "What method is useful in administering small molecules for systemic delivery to the body?", "output": "Intranasal" }, { "input": "Why is the nasal mucosa useful in the delivery of small molecules into the body?", "output": "the surface area can result in rapid absorption of the medication into the blood" }, { "input": "What are the most common methods of inhaled delivery of medications?", "output": "Metered dose inhalers (MDIs) and dry powder inhalers (DPIs)" }, { "input": "What medications have shown good promise to in vivo delivery via dry powder inhalers?", "output": "insulin [39] and low-molecular-weight heparin [40]" }, { "input": "How are siRNAs typically delivered for systemic effect?", "output": "intratracheal or intranasal delivery" }, { "input": "What structures form the human airway?", "output": "respiratory bronchioles, alveolar ducts, and alveolar sacs" }, { "input": "What size of particle has been shown to be most effective in the delivery to the lower airway?", "output": "1-5 \u03bcm" }, { "input": "What are the essential conditions in siRNA delivery to effectively produce gene silencing in the lungs?", "output": "delivered to their site of action, be stable, enter the target cells, and be present in the cytoplasm at sufficient concentration" }, { "input": "How long is the SAIBK gene?", "output": "27,534 nucleotides" }, { "input": "How many open reading frames are in the SAIBK gene?", "output": "10" }, { "input": "What virus has the closest genetic identity with the SAIBK gene?", "output": "Chinese IBV strain SC021202" }, { "input": "How many surgical masks or respirators have past studies projected will be required for a pandemic in the United States?", "output": "an estimated 7.3 billion" }, { "input": "What is the acronym MERS-CoV?", "output": "Middle East respiratory syndrome coronavirus" }, { "input": "What are the critical factors that determine the effect of an epidemic?", "output": "Transmissibility and severity" }, { "input": "When did the World Health Organization (WHO) officially declare the 2019-nCoV epidemic as a Public Health Emergency of International Concern?", "output": "January 30, 2020" }, { "input": "What influenza virus was identified in China in 2013?", "output": "H7N9" }, { "input": "What past research has been done on severe, single-wave pandemics?", "output": "After a new influenza virus (H7N9) was identified in China in 2013, a series of modeling articles described the effect of, and level of preparedness for, a severe, single-wave pandemic in the United States." }, { "input": "What is a clinical attack rate?", "output": "the proportion of individuals who become ill with or die from a disease in a population initially uninfected" }, { "input": "What was the clinical attack rate in the 2009 H1N1 pandemic?", "output": "20%" }, { "input": "What is the estimated R0 of COVID-19?", "output": "2.2" }, { "input": "How many ventilators have past studies projected will be required for a pandemic in the United States?\n", "output": "35\u202f000 to 60\u202f000" }, { "input": "How is exhaled breath condensate used in viral research?", "output": "the isolation of respiratory viruses" }, { "input": "How many patients were i this study?", "output": "102" }, { "input": "What was the conclusion of this study?", "output": "EBC collection using the RTube\u2122 is not reliable for diagnosis of respiratory infections" }, { "input": "How long did the patient breath into the RTube?", "output": "10 minutes" }, { "input": "What followed the reverse transcription step in the analysis?", "output": "denaturation step" }, { "input": "What was the last step in the analysis?", "output": "amplification step" }, { "input": "What percentage of the patients were between 20 and 30 years old in this study?", "output": "52%" }, { "input": "Why is EBC an attractive method for screening?", "output": "easy to perform and can be conducted in a home environment" }, { "input": "What is the leading cause of death among children after the age of 1 month?", "output": "Pneumonia remains the leading cause of death in children outside the neonatal period," }, { "input": "How has the number of childhood pneumonia been reduced?", "output": "New conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae have contributed to decreases in radiologic, clinical and complicated pneumonia cases" }, { "input": "What percentage of childhood deaths are due to pneumonia?", "output": " approximately 900,000 of the estimated 6.3 million child deaths in 2013 " }, { "input": "How has the childhood population grown in the last two decades?", "output": "global childhood population from 605 million in 2000 to 664 million in 2015 " }, { "input": "What is the reduction in the number of childhood pneumonia cases?", "output": "Recent data suggest that there has been a 25% decrease in the incidence of pneumonia, from 0.29 episodes per child year in low-and middle-income countries in 2000, to 0.22 episodes per child year in 2010 [3] . This is substantiated by a 58% decrease in pneumonia-associated disability-adjusted life years between 1990 and 2013, from 186 million to 78 million " }, { "input": "How much is the reduction in the childhood pneumonia deaths?", "output": "Pneumonia deaths decreased from 1.8 million in 2000 to 900,000 in 2013" }, { "input": "Childhood pneumonia rate for high income countries vs low and middle income countries.", "output": "The incidence in high-income countries is estimated at 0.015 episodes per child year, compared to 0.22 episodes per child year in low-and middle-income countries [3] . On average, 1 in 66 children in high-income countries is affected by pneumonia per year, compared to 1 in 5 children in low-and middle-income countries." }, { "input": "What percentage of childhood pneumonia deaths occur outside hospital in low and middle income countries?", "output": "up to 81% of severe pneumonia deaths occur outside a hospital " }, { "input": "Case Fatality Rates for Childhood Pneumonia in high income vs low and middle income countries.", "output": "the case fatality rate is estimated to be almost 10-fold higher in low-and middle-income countries as compared to high-income countries" }, { "input": "How can childhood pneumonia affect the subsequent health of a person?", "output": "Early life pneumonia can impair longterm lung health by decreasing lung function [6] . Severe or recurrent pneumonia can have a worse effect on lung function; increasing evidence suggests that chronic obstructive pulmonary disease might be related to early childhood pneumonia" }, { "input": "What is the increase in the risk of respiratory disease after having childhood pneumonia.", "output": "The risk of developing at least one of the major sequelae was estimated as 6% after an ambulatory pneumonia event and 14% after an episode of hospitalized pneumonia." }, { "input": "Which is the best method to identify pneumonia in a person?", "output": "Chest radiologic changes have been considered the gold standard for defining a pneumonia event" }, { "input": "What is responsible for the reduction of radiologic pneumonia?", "output": "Widespread use of pneumococcal conjugate vaccination and Haemophilus influenzae type B conjugate vaccination has decreased the incidence of radiologic pneumonia." }, { "input": "What is the percentage reduction in pneumonia cases due to vaccination?", "output": "Haemophilus influenzae type B conjugate vaccination in high-burden communities, the vaccination was associated with an 18% decrease in radiologic pneumonia [13] . Introduction of pneumococcal conjugate vaccination was associated with a 26% decrease in radiologic pneumonia in California between 1995 and 1998 [14] . In vaccine efficacy trials in low-and middle-income countries, pneumococcal conjugate vaccination reduced radiologic pneumonia by 37% in the Gambia [15] , 25% in South Africa [16] and 26% in the Philippines " }, { "input": "What is the revised WHO definition of Bacterial Pneumonia?", "output": " A revised case definition of \"presumed bacterial pneumonia\" has been introduced, and this definition includes pneumonia cases with WHO-defined alveolar consolidation, as well as those with other abnormal chest radiograph infiltrates and a serum C-reactive protein of at least 40 mg/L " }, { "input": "What is the reduction in bacterial pneumonia under the revised WHO definition of bacterial pneumonia?", "output": " Using the revised definition, the 10-valent pneumococcal conjugate vaccine (pneumococcal conjugate vaccination-10), had a vaccine efficacy of 22% in preventing presumed bacterial pneumonia in young children in South America [22] , and pneumococcal conjugate vaccination-13 had a vaccine efficacy of 39% in preventing presumed bacterial pneumonia in children older than 16 weeks who were not infected with human immunodeficiency virus (HIV) in South Africa [21]" }, { "input": "What caused the increase in the incidence of empyema in children in the recent past?", "output": " An increased incidence of empyema in children was noted in some high-income countries following pneumococcal conjugate vaccination-7 introduction, and this was attributed to pneumococcal serotypes not included in pneumococcal conjugate vaccination-7, especially 3 and 19A" }, { "input": "How have the incidence Empyema been reduced?", "output": "These trends have been reversed since the introduction of pneumococcal conjugate vaccination-13. Data from the United States suggest that empyema decreased by 50% in children younger than 5 years " }, { "input": "What pneumonia related or chest conditions indicate the need for child radiography?", "output": "chest radiography should not be routinely performed in children with ambulatory pneumonia [31] [32] [33] . Indications for chest radiography include hospitalization, severe hypoxemia or respiratory distress, failed initial antibiotic therapy, or suspicion for other diseases (tuberculosis, inhaled foreign body) or complications. " }, { "input": "What chest diseases and pneumonia were identified as leading causes prior to the availability of vaccines?", "output": "prior to availability of new conjugate vaccines confirmed S. pneumoniae and H. influenzae type B as the most important bacterial causes of pneumonia, with Staphylococcus aureus and Klebsiella pneumoniae associated with some severe cases. Respiratory syncytial virus was the leading viral cause, identified in 15-40% of pneumonia cases, followed by influenza A and B, parainfluenza, human metapneumovirus and adenovirus" }, { "input": "Why has pertussis immunity in infants has decreased in infants?", "output": "Because pertussis immunity after acellular pertussis vaccination is less long-lasting than immunity after wild-type infection or whole-cell vaccination, many women of child-bearing age have waning pertussis antibody levels. " }, { "input": "What is the effect of childhood tuberculosis in childhood pneumonia?", "output": "A recent systematic review of tuberculosis as a comorbidity of childhood pneumonia reported culture-confirmed disease in about 8% of cases [50] . Because intrathoracic tuberculosis disease is only culture-confirmed in a minority of cases, the true burden could be even higher; tuberculosis could therefore be an important contributor to childhood pneumonia incidence and mortality in high-prevalence areas" }, { "input": "What are the risk factors in childhood pneumonia?", "output": " incomplete or inadequate vaccination must be considered as a major preventable risk factor for childhood pneumonia. Other risk factors include low birth weight, which is associated with 3.2 times increased odds of severe pneumonia in low-and middle-income countries, and 1.8 times increased odds in high-income countries [51] . Similarly, lack of exclusive breastfeeding for the first 4 months of life increases odds of severe pneumonia by 2.7 times in low-and middle-income countries and 1.3 times in highincome countries. " }, { "input": "How does air pollution affect the incidence of childhood pneumonia?", "output": " Indoor air pollution from use of solid or biomass fuels increases odds of pneumonia by 1.6 times; lack of measles vaccination by the end of the first year of age increases odds of pneumonia by 1.8 times " }, { "input": "What is the strongest risk factor for childhood pneumonia?", "output": "The single strongest risk factor for pneumonia is HIV infection, which is especially prevalent in children in sub-Saharan Africa. HIV-infected children have 6 times increased odds of developing severe pneumonia or of death compared to HIV-uninfected children" }, { "input": "What is the global coverage of influenza and pneumonia vaccines?", "output": " By the end of 2015, Haemophilus influenzae type B conjugate vaccination had been introduced in 73 countries, with global coverage estimated at 68%. However, inequities are still apparent among regions: in the Americas coverage is estimated at 90%, while in the Western Pacific it is only 25%. By 2015, pneumococcal conjugate vaccination had been introduced into 54 countries, with global coverage of 35% for three doses of pneumococcal conjugate vaccination for infant populations" }, { "input": "Is influenza vaccination during pregnancy safe? How long does it protect the child?", "output": "Influenza vaccination during pregnancy is safe, provides reasonable maternal protection against influenza, and also protects infants for a limited period from confirmed influenza infection (vaccine efficacy 63% in Bangladesh [63] and 50.4% in South Africa [64] ). However as antibody levels drop sharply after birth, infant protection does not persist much beyond 8 weeks" }, { "input": "What is emphyema?", "output": "a rare complication of pneumonia" }, { "input": "How is the term end point consolidation described with regard to pneumonia diagnosis?", "output": "as a dense or fluffy opacity that occupies a portion or whole of a lobe, or the entire lung." }, { "input": "What factors make H5N1 a worldwide threat to public health?", "output": "rapid spread and high pathogenicity" }, { "input": "What are the symptoms of H5N1 infection in humans?", "output": "fever, encephalitis, pneumonia, and severe acute respiratory syndrome (SARS)" }, { "input": "Name some medications used to treat influenza.", "output": "zanamivir (Relenza) and oseltamivir (Tamiflu)" }, { "input": "Why have antiretrovirals medications had limited benefit in treating influenza?", "output": "drug-resistance and frequent antigenic mutation" }, { "input": "What is the focus of the current study?", "output": "effect of EAP against H5N1 influenza infection" }, { "input": "What is the result of the current study?", "output": "the anti-H5N1 effects of EAP offer an alternative strategy for developing antiinfluenza agents" }, { "input": "How do the polysaccharides in plants effect the immune response?", "output": "enhance the secretion of cytokines and chemokines, such as TNF-, IL-6, IL-8, and IL-12" }, { "input": "What does this study demonstrate?", "output": "EAP leaf extract is a prophylactic and immune enhancement agent against H5N1 influenza virus infection" }, { "input": "In this study, how did treatment of EAP after infection affect survival?", "output": "did not provide a survival advantage" }, { "input": "What viruses have been responsible for most common childhood acute respiratory track infections (ARTI)?", "output": "The most frequently reported viruses include respiratory syncytial virus (RSV), influenza viruses A and B (IAV, IBV), parainfluenza viruses (PIVs), human rhinovirus (HRV) and adenovirus (ADV), " }, { "input": "Are there any vaccines against to protect against respiratory viral infections?", "output": "Currently, there are no approved vaccines or medications available for most of the respiratory viruses" }, { "input": "Which type of bacteria are implicated in carrying genes of drug resistance?", "output": "Gammaproteobacteria" }, { "input": "What may be a likely cause of sink-to-sink spreading of pathogens in the hospital setting?", "output": "via a common sanitary pipe" }, { "input": "What types of acute respiratory infections can be screened and diagnosed with multiplex PCR?", "output": "influenza and parainfluenza viruses, RSV, adenovirus, rhinovirus, human metapneumovirus, enterovirus, bocavirus and coronavirus" }, { "input": "What is the role of antibodies during infection?", "output": "Antibodies against foreign antigens are a critical component of the overall immune response and can facilitate pathogen clearance during a primary infection and also protect against subsequent infections." }, { "input": "How can antibodies also create health problems?", "output": "Dysregulation of the antibody response can lead to an autoimmune disease, malignancy, or enhanced infection. " }, { "input": "Which technology invention produced antibodies that are clones of a unique parent cell?", "output": " in the 1970s with the development of hybridoma technology to produce monoclonal antibodies " }, { "input": "What mechanism is responsible for the creation of diversified repertoire for antibodies?", "output": "somatic rearrangement during B cell differentiation was responsible for antibody diversification " }, { "input": "What developments have been made possible by the study of B-cell repertoire?", "output": "(1) vaccine candidates that elicit protective antibodies; (2) antibodies that prevent disease when given prophylactically; and (3) antibodies that can be given as therapy after the onset of disease." }, { "input": "What motivates the study of the rare B-cells that produce Broadly Neutralizing Antibodies (bnAb)?", "output": "discovery of broadly neutralizing antibodies (bnAbs) that protect against infection across diverse viral isolates has intensified efforts to understand the developmental pathway of the rare B cells that produce these antibodies" }, { "input": "How has the study of B-cells helped the treatment for Respiratory syncytial virus (RSV)?", "output": "For RSV, stabilized versions of the fusion (F) protein in the pre-fusion conformation have led to insights in the B cell's response to infection and has generated potentially safer and more efficacious vaccine candidates" }, { "input": "How are the studies on B-cells helping the development of a universal influenza vaccine?", "output": "Influenza also performs fusion through the stem region of the hemagglutinin protein, and the identification of B cells that target this relatively conserved site has spurred research on the development of a universal influenza vaccine (" }, { "input": "What role B-cell play in malaria infection and prevention?", "output": " Rare memory B cells producing antibodies specific for the EBV fusion machinery have been isolated; these can neutralize both B cell and epithelial cell infection (20). A new paradigm in malaria vaccine development is also emerging with the discovery of IgM+ and IgD+ memory B cells targeting the Merozoite Surface Protein 1, that rapidly respond to malaria re-infection" }, { "input": "How can the study of B-cells help in the prevention and treatment of autoimmune diseases?", "output": "The study of autoantigen-specific B cells and a detailed analysis of B cell subsets with pathogenic potential in humans could lead to a better understanding of how to prevent and treat autoimmune diseases." }, { "input": "When was the Middle East Respiratory Syndrome Coronavirus isolated first?", "output": "(MERS-CoV) was first isolated in 2012, in a 60-year-old man who died in Jeddah, KSA due to severe acute pneumonia and multiple organ failure" }, { "input": "What is the Case fatality rate for MERS Coronavirus?", "output": "Recent fatality rate (CFR) of 21%" }, { "input": "How does gender influence MERS-COV infection?", "output": " MERS-CoV infects males more than females" }, { "input": "Which is the source animal for the MERS-COV?", "output": "Dromedary camels are the major animal source of MERS-CoV transmission to humans." }, { "input": "What is the median time until death in MERS-COV?", "output": "median time until death is 11-13 days (range 5-27 days) among severely ill patients" }, { "input": "What is the incubation period for MERS-COV?", "output": " incubation period of 16 days with a mean of 5-6 days [" }, { "input": "What is the treatment for MERS-COV?", "output": "ere is no specific treatment for MERS-CoV. Like most viral infections, the treatment options are supportive and symptomatic" }, { "input": "What age group had the most MERS-COV infections?", "output": "majority of confirmed cases of MERS-CoV were reported among people aged 40 and above" }, { "input": "Why are nucleosides analogs used for chemotheraphy?", "output": "they inhibit cellular DNA/RNA polymerases" }, { "input": "What nucleoside analog is the focus of the current study?", "output": "gemcitabine" }, { "input": "Gemcitabine has been shown to have antiviral activity against which viruses?", "output": "Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), HCV, poliovirus (PV), influenza A virus (IAV), HIV, and enteroviruses (EV)" }, { "input": "How does gemcitabine disrupt viral activity?", "output": "by targeting the salvage pathway of pyrimidine biosynthesis" }, { "input": "Why are cotton rats considered a strong animal model for biomedical research?", "output": "its well defined immunological and genetic information, costeffectiveness, and abundant inbred strains and research reagents" }, { "input": "What is the structure of the CD40 Ligand?", "output": "a sandwiched extracellular structure composed of a \u03b2-sheet, \u03b1-helix loop, and a \u03b2-sheet" }, { "input": "What is the effect of CD40L on Dendritic Cells?", "output": "it promotes cytokine production, the induction of cell surface co-stimulatory molecules, and facilitates the cross-presentation of antigen by these cells" }, { "input": "What is the effect of CD40L on B Cells?", "output": "it promotes germinal center formation, immunoglobulin (Ig) isotype switching, somatic hypermutation to enhance antigen affinity, and lastly, the formation of long-lived plasma cells and memory B cells" }, { "input": "What factor may influence viral replication and gene expression?", "output": "the average codon usage frequencies in the host genome" }, { "input": "What accounts for the variation of codon usage among open reading frameworks?", "output": "mutational pressure and translational selection" }, { "input": "What conditions are considered upper respiratory tracts infections?", "output": "common cold, pharyngitis, otitis, sinusitis, laryngotracheitis, epiglottitis" }, { "input": "What conditions are considered lower respiratory tract infections?", "output": "bronchitis, pneumonia and bronchiolitis" }, { "input": "What immune cells are primarily involved in eliminating virus-infected cells?", "output": "NK cells (CD3-/CD16+/CD56+)" }, { "input": "What molecules have been shown to hinder T cell responses to viral infections?", "output": "Excessive reactive oxygen species (ROS)" }, { "input": "The accumulation of what molecule hinders phagocytic activity in T cells?", "output": "reactive oxygen species (ROS)" }, { "input": "When did the last Director General of the WHO resign?", "output": "June 30, 2017" }, { "input": "Why might an organization like the WHO be necessary?", "output": "to promote, set standards in, and evaluate progress toward better health for people in all countries" }, { "input": "Where should the next Director General for the WHO come from?", "output": "a lowincome or middle-income country" }, { "input": "What traits should the new Director General of the WHO have?", "output": "open-minded and creative" }, { "input": "What is the Hepatitis C virus?", "output": "enveloped, positive-stranded RNA virus" }, { "input": "How many people have persistent hepatitis C virus?", "output": "170 million people worldwide" }, { "input": "What is the long-term risk of chronic hepatitis C infection?", "output": "cirrhosis and hepatocellular carcinoma" }, { "input": "What antiviral treatments are used for hepatitis C infection?", "output": "pegylated alpha-interferon and ribavirin" }, { "input": "What is the main cause of death in the neonatal period of calves?", "output": "Calf septicemia" }, { "input": "Where was hepcidin first discovered?", "output": "human urine" }, { "input": "What is hepcidin?", "output": "low molecular weight, antimicrobial peptide hormone" }, { "input": "What organ produces hepcidin?", "output": "liver" }, { "input": "What stimulates the release of hepcidin?", "output": "inflammatory reactions and high Fe concentrations" }, { "input": "What element does hepcidin play a roles in regulating during metabolism?", "output": "Fe" }, { "input": "Is hepcidin toxic?", "output": "potentially toxic" }, { "input": "Why is iron critical to bacteria?", "output": "bacteria utilize Fe for survival, growth and proliferation" }, { "input": "How does hepcidin work in the duodenum?", "output": "control of excessive Fe absorption" }, { "input": "How does hepcidin affect macrophages?", "output": "regulation of Fe release" }, { "input": "What leads to oxidative stress in the body?", "output": "production of ROS" }, { "input": "What parameter is used to measure antioxidant levels?", "output": "superoxide dismutase" }, { "input": "What is Acute hemorrhagic encephalomyelitis?", "output": "a rare form of acute disseminated encephalomyelitis" }, { "input": "What are the salient findings in Acute hemorrhagic encephalomyelitis?", "output": "fulminant encephalopathy with hemorrhagic necrosis" }, { "input": "What is RANBP2?", "output": "nuclear pore protein" }, { "input": "What is the suggested role of RANBP2 in the cell?", "output": "intracellular protein trafficking or energy maintenance and homeostasis of neuronal cells" }, { "input": "What is the hallmark finding of acute necrotizing encephalopathy?", "output": "multiple, symmetric brain lesions located in the thalami bilaterally, putamina, deep periventricular white matter, cerebellum, and brainstem" }, { "input": "What could trigger acute necrotizing encephalopathy?", "output": "viral infection in previously healthy children" }, { "input": "When did she present with rapidly progressive right-hand weakness?", "output": "1 month later" }, { "input": "Compounds from what framework have shown promising anticancer and antiviral properties?", "output": "quinazolin-4-one" }, { "input": "The replication of what virus is strongly inhibited by 2-(4-hydroxybenzyl)quinazolin-4(3H)-one (1)?", "output": "tobacco mosaic virus" }, { "input": "How many samples were obtained?", "output": "11,399" }, { "input": "What percentage of patients were positive for at least one respiratory pathogen?", "output": "49.2%" }, { "input": "What percentage of patients tested positive for HBoV1?", "output": "2.2%" }, { "input": "When was HBoV1 first identified?", "output": "2005" }, { "input": "What are the symptoms of HBoV1 infection?", "output": "cough, rhinitis, fever" }, { "input": "What are the ages of the patients in this study?", "output": "\u226414 years old" }, { "input": "What was the male to female ratio for this study?", "output": "1.82:1" }, { "input": "What causes acute respiratory illness in young children?", "output": "Human metapneumovirus (HMPV)" }, { "input": "What is the molecular structure of the Human metapneumovirus (HMPV)?", "output": "single-stranded RNA virus" }, { "input": "What virus is closely related to the human respiratory syncytial virus (RSV)?", "output": "Human metapneumovirus (HMPV)" }, { "input": "What diseases are caused by HMPV?", "output": "mild upper respiratory infection to bronchiolitis and pneumonia" }, { "input": "How large is the HMPV genome?", "output": "13 kb" }, { "input": "How many open reading frames are in the HMPV genome?", "output": "eight" }, { "input": "What are the two major genotypes of HMPV?", "output": "A and B" }, { "input": "What is the most common subgroup of HMPV?", "output": "HMPV A2" }, { "input": "Who accounted for 44% of HMPV positive cases in Kenya between 2007 and 2011?", "output": "children under 6 months of age" }, { "input": "What does this study describe?", "output": "a whole genome sequencing (WGS) approach for HMPV" }, { "input": "What was the difference in the group A and B genomes?", "output": "The length of the F-M2 intergenic region" }, { "input": "What was the purpose of this study?", "output": " to comprehensively investigate the viral epidemiology of adult RTIs" }, { "input": "How many control samples were used in this study?", "output": "27" }, { "input": "What was the prevalence of coinfection?", "output": "4.1% of cases" }, { "input": "What risks factors were associated with lower RTIs?", "output": "parainfluenza infection, old age, and immunosuppression" }, { "input": "What tests can simultaneously identify and subtype multiple respiratory viruses?", "output": "multilocus polymerase chain reaction coupled with electrospray ionization mass spectrometry" }, { "input": "What was the definition for an immunocompromised state in this study?", "output": "corticosteroid treatment, solid organ or hematopoietic stem cell recipient, or chemotherapy for an underlying malignancy during the past 6 months" }, { "input": "What was the length of the study?", "output": "9-month" }, { "input": "How many patients had acute RTIs?", "output": "263" }, { "input": "What was the most frequent coinfection?", "output": "rhinovirus" }, { "input": "What health regulations were changes due to the outbreak of C. burnetti?", "output": "forbid the display of sheep in the latter third of their pregnancy and require regular testing of animals for C. burnetii in petting zoos" }, { "input": "What was the median seropresence of C. burnetti in sheep flocks not linked to human outbreaks?", "output": "1%" }, { "input": "What important risk factors to infection were found during the second case-controlled study?", "output": "close proximity to the ewe and duration of exposure" }, { "input": "What was the interquartile range of the incubation period?", "output": "16 to 24 days" }, { "input": "How many controls were used in the second case study?", "output": "36" }, { "input": "What public event was linked with the outbreak?", "output": "farmers' market" }, { "input": "What causes Q fever?", "output": "Coxiella burnetii (C. burnetii)" }, { "input": "What is Coxiella burnetii?", "output": "small, gram-negative obligate intracellular bacterium" }, { "input": "What is the primary reservoir for Coxiella burnetii?", "output": "sheep, goat and cattle" }, { "input": "How are humans typically infected with Coxiella burnetii?", "output": "inhalation of contaminated aerosols from parturient fluids, placenta or wool" }, { "input": "What are critical to regulate cellular biological processes?", "output": "long non-coding RNAs" }, { "input": "How is the HeteSim measured used?", "output": "calculate the relatedness of objects with the same or different types" }, { "input": "What kind of data is included in the STRING database?", "output": "weighted protein interactions" }, { "input": "What is the function of MALAT1?", "output": "regulates cell cycle and survival" }, { "input": "What test can detect reduced anticoccidial efficacy in the field?", "output": "faecal oocyst count reduction test (FOCRT)" }, { "input": "What is toltrazuril used to treat?", "output": "anticoccidial" }, { "input": "What is multiple evanescent white dot syndrome?", "output": "a rare, sudden onset of unilateral chorioretinopathy" }, { "input": "What precedes about half of the reported cases of MEWDS?", "output": "flu-like illness" }, { "input": "What types of viruses can be diagnosed through serological testing?", "output": "herpes simplex virus (HSV) I-II, varicella zoster virus (VZV), West Nile virus, coxsackievirus, echovirus (subgroup of enterovirus), and corona virus" }, { "input": "What type of clinical test can differentiate multiple evanescent white dot syndrome (MEWDS) from optic neuritis?", "output": "multimodal imaging" }, { "input": "What were the most common viruses sampled from nasal swabs in Ilorin, Nigeria", "output": "Parainfluenza virus 4, respiratory syncytial virus B and enterovirus" }, { "input": "What was the most common virus detected in community members in this sample?", "output": "Coronavirus OC43" }, { "input": "How bad is the burden of disease in developing countries?", "output": "2-5 times higher than in developed countries" }, { "input": "Where do the majority of all infectious disease outbreaks happen?", "output": "Africa" }, { "input": "What are some risk factors for countries to experience a high prevalence of Acute Respiratory Infections?", "output": "age, sex, overcrowding, nutritional status, socio-economic status, and where study of ARIs is currently limited" }, { "input": "What symptoms are associated with acute respiratory infections?", "output": "sore throat, fever, couch, running nose, vomiting, body ache, leg pain, nausea, chills, shortness of breath " }, { "input": "What was the most common virus detected in community samples in Ilorin, Nigeria?", "output": "Coronavirus OC43" }, { "input": "What was the prevalence of Coronavirus OC43 in community samples in Ilorin, Nigeria?", "output": "13.3% (95% CI 6.9-23.6%)" }, { "input": "What was the prevalence of Coronavirus OC 229 E/NL63 in clinical subjects in Ilorin, Nigeria?", "output": "12.5%" }, { "input": "What was the difference between community and clinic cases of acute respiratory infections?", "output": "increased severity of illness in the clinical sample" }, { "input": "How can countries enhance public health surveillance?", "output": "active community surveillance" }, { "input": "Why do respiratory tract infections pose major public health problems?", "output": "world-wide occurrence, ease of transmission and considerable morbidity and mortality effecting people of all ages" }, { "input": "How much of a greater risk are children than adults to viral infections?", "output": "two to three times more frequently" }, { "input": "What is the most common infection in childhood?", "output": "acute RTI" }, { "input": "What can respiratory viruses cause?", "output": "common colds, pharyngitis, croup, bronchiolitis, viral pneumonia and otitis media" }, { "input": "When do respiratory infections usually happen?", "output": "during winter and early spring months" }, { "input": "What are the most common viruses?", "output": "respiratory syncytial virus (RSV), influenza A and B (INF-A, INF-B) viruses, parainfluenza viruses (PIVs), and human adenoviruses (HAdVs)" }, { "input": "What is the most common viral infection for infants up to 3 months old?", "output": "RSV" }, { "input": "What is the incidence of RSV in children older than 3 years of age?", "output": "13%" }, { "input": "What is the distance between the p4.7 and p12.7 genes in the Irish versus Japanese equine coronavirus variants?", "output": "544 base pairs" }, { "input": "What is the difference between the Tokachi09 and Irish coronavirus genomic sequences?", "output": "148-nucleotide insertion" }, { "input": "What suggests that Irish equine coronaviruses may have a low genetic diversity?", "output": "high level of homology between viruses" }, { "input": "Where have most outbreaks of equine coronavirus occurred in the United States?", "output": "adult riding, racing and show horses" }, { "input": "What kind of pertussis vaccine is used in middle and high income countries?", "output": "acellular" }, { "input": "Where is the highest rate of childhood pertussis globally?", "output": "Southeast Asia" }, { "input": "What type of pertussis vaccine has been recently recommended by the WHO?", "output": "whole cell pertussis vaccines" }, { "input": "What are the clinical symptoms of pertussis?", "output": "apnea, cyanosis, cough with vomit, or whoop/whooping cough" }, { "input": "What type of swabs are used to sample patients with pertussis?", "output": "mid-nasal nylon flocked" }, { "input": "How frequently do pertussis outbreaks peak?", "output": "every 2 to 4 years" }, { "input": "What is the WHO criteria for a pertussis infection?", "output": "a minimum of 2 weeks of cough, whoop, or posttussive vomiting" }, { "input": "What is used by the Canadian Public Health System to identify periods of influenza activity?", "output": "weekly proportion of laboratory tests that are positive for influenza" }, { "input": "Why is laboratory confirmation of influenza infection not commonly performed?", "output": "diagnosis will often not alter patient management, a paucity of real-time, accurate, inexpensive testing methods [4] and because influenza is not recognized as the etiology of the clinical presentation" }, { "input": "What types of viral infections are monitored through Canada's Respiratory Virus Detection Surveillance System (RVDSS)?", "output": "nfluenza, respiratory syncytial virus (RSV), para-influenza virus (PIV), and adenovirus" }, { "input": "What is discussed in this publication?", "output": "the potential anti-virus activity of inositol-requiring enzyme 1 (IRE1), a well characterized effector of the cellular homeostatic response to an overloading of the endoplasmic reticulum (ER) protein-folding capacity. IRE1, an ER-membrane-resident ribonuclease (RNase), upon activation catalyses regulated cleavage of select protein-coding and non-coding host RNAs, using an RNase domain which is homologous to that of the known anti-viral effector RNaseL. " }, { "input": "What is discussed in this publication?", "output": "The review first discusses the anti-viral mechanism of the OAS/RNaseL system and evasion tactics employed by different viruses. This is followed by a review of the RIDD pathway and its potential effect on the stability of viral RNAs. " }, { "input": "What is reported in this publication?", "output": "comparison of the enzymatic activity of the two RNases followed by deliberations on the physiological consequences of their activation." }, { "input": "What is the conclusion regarding IRE1 and RNaseL proteins?", "output": "In the context of a virus infection, the pathway leading from both these proteins have the potential to lead to cell death. Notwithstanding the fact that this might be an efficient way of virus clearance, it also portends pathological outcomes for the infected organism. Future research would probably lead to design of drugs targeting these proteins based on the structural homology of their effector domains, regulating the pathological denouement of their activation without compromising their anti-viral or potential anti-viral functions." }, { "input": "What is the structure of an Echovirus?", "output": "nonenveloped, single-stranded, positive-sense RNA" }, { "input": "What diseases are associated with echoviruses?", "output": "respiratory illness, hand-foot-and-mouth disease, and aseptic meningitis," }, { "input": "In California, to where are meningitis cases reported according to the California Code of Regulations?", "output": "California Department of Public Health (CDPH)" }, { "input": "According to the California Code of Regulations, when should a meningitis case be reported?", "output": "within 1 day of identification" }, { "input": "Where is the Viral and Rickettsial Disease Laboratory located?", "output": "CDPH" }, { "input": "What type of reference genome was used in the study?", "output": "E-30" }, { "input": "What was the read coverage for the E-30 genome in this study?", "output": "260-fold" }, { "input": "What are the structural regions of the enterovirus polyprotein in this study?", "output": "one structural (P1-capsid) and two nonstructural (P2 and P3) regions" }, { "input": "What can nuclear receptors regulate?", "output": "homeostasis, differentiation, embryonic development, and organ physiology" }, { "input": "What are associated with cancer, diabetes, inflammatory disease, and osteoporosis?", "output": "Nuclear receptors (NRs)" }, { "input": "What are nuclear receptors (NRs)?", "output": "class of ligand-inducible transcription factors" }, { "input": "What biological factors for nuclear receptors regulate?", "output": "homeostasis, differentiation, embryonic development, and organ physiology" }, { "input": "How many families are in the NR superfamily?", "output": "seven" }, { "input": "What is a prerequisite to make a molecular docking study feasible?", "output": "a reliable 3D (three dimensional) structure of the target protein" }, { "input": "What tool can be used to determine the 3D structure of proteins?", "output": "X-ray crystallography" }, { "input": "What are the shortcomings of X-ray crystallography?", "output": "time-consuming and expensive" }, { "input": "What types of proteins are difficult to crystallize?", "output": "membrane proteins" }, { "input": "Where were the data collected for this study?", "output": "KEGG (Kyoto Encyclopedia of Genes and Genomes)" }, { "input": "Who performed the sampling procedures?", "output": "veterinarians" }, { "input": "When were the fecal samples collected?", "output": "from November 2004 to November 2014" }, { "input": "What reference genome was used in the study?", "output": "BatCoV HKU10" }, { "input": "What is the length of the replicase gene ORF1ab?", "output": "20.4 kb" }, { "input": "What type of coronavirus was detected in R. affinis and R. sinicus species?", "output": "BtCoV/Rh/YN2012" }, { "input": "What is a natural reservoir of coronavirus?", "output": "Bats" }, { "input": "What is the genome size of the coronavirus?", "output": "26-32 kb" }, { "input": "What is the structure of the coronavirus?", "output": "enveloped, non-segmented, positive-strand RNA viruses" }, { "input": "What animals do gamma and delta coronavirus mainly infect?", "output": "birds" }, { "input": "How many types of coronaviruses are known to cause human disease?", "output": "Six" }, { "input": "What plays a role in regulating the immune response to a viral infection?", "output": "NF-\u03baB" }, { "input": "What is the conclusion of the coronavirus long-term surveillance studies?", "output": "Rhinolophus bats seem to harbor a wide diversity of CoVs" }, { "input": "What is the cause of Feline Infectious Peritonitis (FIP)?", "output": "FIP virus (FIPV)" }, { "input": "What is the molecular structure of Feline Infectious Peritonitis Virus?", "output": "enveloped virus with a nonsegmented, positive sense, single-stranded RNA genome" }, { "input": "How is FECV detected in cats?", "output": "shedding in their faeces" }, { "input": "What type of vaccine is used to protect against FIPV infection?", "output": "an attenuated, temperature-sensitive strain of type II FIPV" }, { "input": "Why is their controversy surrounding the FIPV vaccine?", "output": "the vaccine contains type 2 strain, whereas type 1 viruses are more prevalent in the field" }, { "input": "For how long was the denatured polyacrylamide gel polymerized?", "output": "30 minutes" }, { "input": "How was the binding strength measured?", "output": "nano Isothermal Titration Calorimeter (ITC)" }, { "input": "What was the focus of this study?", "output": " the anti-influenza A (H2N2) virus activity of patchouli alcohol" }, { "input": "What do neuroaminidase inhibitors target?", "output": "NA glycoproteins of influenza A and B virus" }, { "input": "What is the function of neuroaminidase in the influenza virus?", "output": "cleave the \u03b1-ketosidic linkage between terminal sialic acid and an adjacent sugar residue" }, { "input": "What is Tamiflu?", "output": "NA inhibitor" }, { "input": "What was the test for the level of cytotoxicity used in this study?", "output": "CC 50" }, { "input": "What method was used to measure the inhibition of viral replication?", "output": "MTT method" }, { "input": "What was the conclusion of this study?", "output": " patchouli alcohol possesses anti-influenza A (H2N2) virus activity" }, { "input": "Why have nucleic acid amplification tests been restricted to laboratory settings?", "output": "time, equipment, and technical expertise requirements" }, { "input": "What screening method was evaluated in this study?", "output": "HIV-1 RT-LAMP assay" }, { "input": "What was used to measure the performance of the NINA heaters?", "output": "whole blood specimens" }, { "input": "What percentage of HIV-infected people go undetected in the United States?", "output": "20%" }, { "input": "What percentage of patients do not return for followup after HIV testing?", "output": "35 to 50%" }, { "input": "What statistical tests were used to compare categorical variables?", "output": "Chi-square test and Fisher's exact test" }, { "input": "What was a severe limitation of this study?", "output": "unable to evaluate the levels of immunomodulators in the serum samples of a control group" }, { "input": "What followup is needed to confirm the results of the current study?", "output": "a larger, longitudinal study on the etiology and severity of pneumonia" }, { "input": "What is the conclusion of this study?", "output": "mixed respiratory infections and IP-10 may play major, interconnected roles in the pathogenesis of pneumonia" }, { "input": "What suggests that IP-10 plays a significant role on the pathogenesis of pneumonia?", "output": "highest serum IP-10 levels" }, { "input": "What cell types help prevent pneumococcal and influenza infection in the lungs?", "output": "airway epithelial cells 19 , resident alveolar macrophages (AMs) and blood monocytes-derived macrophages" }, { "input": "What is the most common, clinically-relevant multiresistant pathogen in both healthcare and community acquired infections?", "output": "Methicillin-resistant Staphylococcus aureus (MRSA)" }, { "input": "What is the treatment of choice for MRSA infections?", "output": "vancomycin" }, { "input": "What enzyme is essential for the metabolism of fatty acids?", "output": "isocitrate lyase" }, { "input": "What was the purpose of this research?", "output": "to assess the overall in vitro bactericidal activity of nine newly synthesized diamides" }, { "input": "What is the conclusion of the study?", "output": "the marmoset an appropriate animal model for biodefense-related pathogens" }, { "input": "Why makes the marmoset an appropriate animal model for pathogen research?", "output": "the small size of marmosets, their immune response to infection that is comparable to humans, and the ability to house more statistically relevant numbers within high containment" }, { "input": "How can the efficacy of DAAs be diminished?", "output": "the presence of resistance-associated substitutions" }, { "input": "Was is the response rate of the Hepatitis C virus to direct-acting antiviral treatments?", "output": "up to 98%" }, { "input": "How do nonnucleoside NS5B polymerase inhibitors work?", "output": "inhibit polymerase activity by allosteric mechanisms" }, { "input": "How many patients were studied?", "output": "31" }, { "input": "Was written consent obtained?", "output": "was obtained" }, { "input": "How much of the RNA template was in the reverse transcription reaction mixture?", "output": "5 \u03bcl" }, { "input": "How many RASs to NS5A inhibitors were identified?", "output": "2 strains out of 25 (8%)" }, { "input": "Why is the substitution E62D important in drug resistance?", "output": "confers a higher level of resistance than the one achieved by the RAS alone" }, { "input": "What are the key factors preventing the elimination of HCV infection in some patients?", "output": "baseline and emergent resistance variants" }, { "input": "What is needed to direct genetic mutations in RNA viruses?", "output": "Infectious cDNA clones" }, { "input": "What is the structure of the pestivirus?", "output": "single stranded positive sense RNA genomes" }, { "input": "What sequences are critical for the autonomous replication of the pestivirus genome?", "output": "5\u2032 and 3\u2032 untranslated regions (UTRs)" }, { "input": "What are the 4 structural proteins of the pestivirus polyprotein?", "output": "nucleocapsid protein C, envelope glycoproteins E rns , E1 and E2" }, { "input": "The BAC differed from the parental cDNA sequence by what amino acid substitutions?", "output": "aa" }, { "input": "What is the purpose of this research study?", "output": "to examine whether a relationship exists between operation volumes and SSIs" }, { "input": "Why are SSIs important to the overall burden on the healthcare system?", "output": "The total length of stay and expenditure for patients with SSIs after CABG surgery is significantly longer and higher than those without SSIs" }, { "input": "What is the \"Never Event\" policy?", "output": "hospitals would no longer receive higher payments for the additional costs associated with treating patients for certain healthcare-acquired infections" }, { "input": "Patients from how many medical centers were studied?", "output": "19" }, { "input": "Which patients were excluded from the study?", "output": "CABG patients under the age of 18 years or over 85 years" }, { "input": "What are the limitations of a deterministic model?", "output": "cannot reliably represent effects originating from stochasticity, from effects in small populations, or from heterogeneities" }, { "input": "How does PEDV spread?", "output": "fecal-oral contact" }, { "input": "How does PEDV cause illness?", "output": "destroys the lining of piglets' intestines" }, { "input": "What is the size of the PEDV genome?", "output": "26 to 32 kb" }, { "input": "Which viruses are part of the Old World complex of Arenaviridae?", "output": "Lassa and Lujo viruses" }, { "input": "How can Old World and New World Arenaviruses be differentiated?", "output": "through the use of serological assays" }, { "input": "What is the incubation period for arenavirus?", "output": "1-3 weeks" }, { "input": "What is the structure of the Arenavirus?", "output": "bisegmented, negative-sense, single stranded RNA genome" }, { "input": "What proteins does the Arenavirus produce?", "output": "a glycoprotein, a nucleoprotein (NP), a matrix protein (Z), and a polymerase (L)" }, { "input": "What diagnostic test has been show to have excellent sensitivity in detecting viral infections?", "output": "PCR assays" }, { "input": "What is the effect of oseltamivir and zanamivir?", "output": "neuraminidase inhibitors" }, { "input": "What is Glycyrrhizin?", "output": "a triterpene saponine" }, { "input": "What is the effect of Glycyrrhizin in viral infections?", "output": "interfere with replication and/or cytopathogenic effect (CPE) induction of many viruses" }, { "input": "What is another word for hypercytokinaemia?", "output": "cytokine storm'" }, { "input": "What has been correlated with the pathogenicity of the H5N1 infection?", "output": "caspase-dependent apoptosis in airway cells" }, { "input": "What is the conclusion of the study?", "output": "glycyrrhizin might also serve as lead structure for the development of novel anti-influenza drugs" }, { "input": "What is the mean duration of time from single lobe consolidation to bilateral multilobar lung infiltrates in human adenovirus type 55 (HAdV-55)?", "output": "2 days" }, { "input": "What is the mean duration of time from first positive chest x-ray to bilateral multilobar lung infiltrates in human adenovirus type 55 (HAdV-55)?", "output": "4.8 days" }, { "input": "What are the most frequent clinical manifestations of human adenovirus type 55 (HAdV-55) induced ARDS?", "output": "Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates" }, { "input": "What do we know about the genomics of human adenovirus type 55 (HAdV-55)?", "output": "This pathogen was fully characterized by whole-genome sequencing" }, { "input": "What are the clinical symptoms of human adenovirus type 55 (HAdV-55)?", "output": "Flulike symptoms, such as fever, cough and little sputum, were commonly observed at the onset of illness" }, { "input": "What is the mean time from onset of symptoms to dyspnea in human adenovirus type 55 (HAdV-55)?", "output": "5 days" }, { "input": "What is the mean time of onset of symptoms to ICU admission in human adenovirus type 55 (HAdV-55)?", "output": "9.6 days" }, { "input": "What is the mean rate of respiration upon admission to the ICU when admitted for human adenovirus type 55 (HAdV-55)?", "output": "43 breaths per minute" }, { "input": "What is the white blood cell count in severe cases of human adenovirus type 55 (HAdV-55)?", "output": " low or in the normal range" }, { "input": "What does a chest x-ray look like for a patient with a severe case of human adenovirus type 55 (HAdV-55)?", "output": "CXRs revealed multiple bilateral lobar or segment consolidation in the lungs of all five patients, and radiographic lesions progressed rapidly after ICU admission" }, { "input": "What are the high resolution pulmonary CT scan findings for patients with severe cases of human adenovirus type 55 (HAdV-55)?", "output": "Consolidations within a single lobe or several lobes with a clear border and air bronchogram were the most common findings on HRCT scans. Nodules, patches, pleural effusion, abscess and a cavity were also seen visualized by HRCT" }, { "input": "Where could a clinician acquire a positive viral sample in severe cases of human adenovirus type 55 (HAdV-55)?", "output": "All patients had HAdV-55 viremia. In four of the five patients, it was first detected in endotracheal aspirate (ETA) samples" }, { "input": "How long did it take for patients with positive human adenovirus type 55 (HAdV-55) endotracheal aspirates to develop a measurable viremia?", "output": "1 to 10 days" }, { "input": "Does blood type play a role in the severity of human adenovirus type 55 (HAdV-55) infection?", "output": " HAdV-55 may cause severe ARDS in immunocompetent young men with blood type B" }, { "input": "What are the most common clinical manifestations of severe human adenovirus type 55 (HAdV-55) induced ARDS?", "output": "Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates at the same time, are the most frequent clinical manifestations" }, { "input": "What is the mortality rate of severe ARDS from human adenovirus type 55 (HAdV-55)?", "output": "HAdV-55-induced severe ARDS has a very high mortality rate (80%) despite appropriate respiratory support." }, { "input": "What role does T-cell count play in severe human adenovirus type 55 (HAdV-55) infection?", "output": "a lower T-cell count may be a risk factor for HAdV-55 infection in young adults" }, { "input": "How successful are the use of invasive mechanical ventilation (IMV) and non-invasive positive pressure ventilation (NPPV) in the treatment of severe ARDS from human adenovirus type 55 infection?", "output": "we found that severe HAdV-55 infection could cause a rapid progression of respiratory failure, with a very high failure rate for NPPV and IMV" }, { "input": "How many patients were analyzed in the study?", "output": "Two hundred" }, { "input": "How many patients with community-acquired pneumonia are hospitalized each year?", "output": "600,000" }, { "input": "What chest X-ray findings are typically indicative of community-acquired pneumonia?", "output": "the presence of new parenchymal infiltrates" }, { "input": "When did WHO declare a pandemic of pH1N1/2009v influenza?", "output": "11 June 2009" }, { "input": "What is the classical cutoff value for antibody titers?", "output": "1/40" }, { "input": "What is meant by a protective HIA titer?", "output": "conferring 50% protection against a viral challenge" }, { "input": "What are the results of the study?", "output": "a substantial proportion of Reunion Island's population had pre-existing immunity to 2009 pandemic influenza virus" }, { "input": "What was the interpretation for the crossreactive antibodies?", "output": "the remote exposure of these individuals to H1N1 viruses circulating before 1957" }, { "input": "How long did the pH1N1/2009 viral outbreak last?", "output": "9 weeks" }, { "input": "What were the aims of this study?", "output": "to investigate the different pathogens involved in ILI and describe the associated symptoms" }, { "input": "What network of physicians provides real-time clinical data on the spread of influenza in France?", "output": "R\u00e9seau Sentinelles" }, { "input": "What are the criteria used to define an influenza-like illness in France?", "output": "a sudden fever above 39uC with myalgia and respiratory signs" }, { "input": "What virus was the most common among the H1N1v negative patients?", "output": "rhinovirus" }, { "input": "What was the aim of this study?", "output": "to elucidate the proximate causes of breeding failure behind the recent decline in productivity in the Spanish Pyrenees" }, { "input": "Where is the bearded vulture (Gypaetus barbatus) commonly found?", "output": "the Pyrenees" }, { "input": "What was the focus of this study?", "output": "the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells" }, { "input": "What is the third most prevalent cancer in females in the United States?", "output": "colorectal cancer" }, { "input": "What is the 1-year survival rate for colorectal cancer patients?", "output": "83.2%" }, { "input": "What is the 5-year survival rate for colorectal cancer patients?", "output": "64.3%" }, { "input": "How were nuclear morphological changes in HT-29 cells measured?", "output": "detection of nuclear condensation" }, { "input": "What is directly related to nuclear condensation?", "output": "apoptotic chromatin changes" }, { "input": "What morphological cell changes are most associated with apoptosis?", "output": "membrane permeability, cell shrinkage, disruption of the mitochondrial membrane, and chromatin condensation" }, { "input": "What types of cells are suitable for colon cancer studies?", "output": "HT-29 cells" }, { "input": "What was the goal of this study?", "output": "to explore the feasibility of DNA vaccination of poultry" }, { "input": "What is the conclusion of this study?", "output": "it is possible to develop a multivalent DNA vaccine for poultry that can protect against multiple HPAI H5N1 strains and that could keep pace with the continued evolution of avian influenza viruses" }, { "input": "What was the conclusion of this study?", "output": "Two E. coli W mutants were engineered that could effectively produce the bio-active flavonol glycosides hyperoside and quercitrin" }, { "input": "What are the implications of the novel fermentation-based glycosylation strategy described in this study?", "output": "the economically viable production of various glycosides" }, { "input": "What characteristics does glycosylation have on flavonoids?", "output": "solubility, stability and bio-activity" }, { "input": "What is fibrinogen-like protein 2 (FgI2)?", "output": "a pro-coagulant protein" }, { "input": "What represses murine hepatitis virus strain 3 (MHV-3) infection?", "output": "Fgl2 depletion" }, { "input": "What was the goal of this study?", "output": "to determine the role of CC10 in FH and the regulation of Fgl2 by CC10" }, { "input": "What is fulminant hepatitis?", "output": "a serious life-threatening disease characterized by massive hepatocyte necrosis" }, { "input": "How does Prothrombinase Fgl2 affect the coagulation process?", "output": "transforming prothrombin directly into thrombin," }, { "input": "How long after MHV-3 infection were liver samples taken?", "output": "72 h" }, { "input": "What is the relationship between urbanization and risk of emergence of flu-like diseases?", "output": " findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk." }, { "input": "What factors and characteristics of semi-urban landscapes promote viral transmission?", "output": " higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission" }, { "input": "What is the relationship between HIN1 viral transmission and poultry production.", "output": " landscapes where intensive and extensive forms of poultry production overlap were found at greater risk" }, { "input": "What is the principle behind infection Convergence Model ?", "output": "The convergence model can be so adapted by incorporating the dynamics of urban, agricultural, and natural ecosystem transformations proposed with this framework. These associated multifaceted interactions including feedbacks that affect ecological communities, hosts and pathogen populations, are the proximate drivers of disease emergence." }, { "input": "What is the Boosted Regression Tree method?", "output": "BRT utilizes regression trees and boosting algorithms to fit several models and combines them for improving prediction by performing iterative loop throughout the model " }, { "input": "What is the advantage of Boosted Regression Tree method?", "output": "The advantage of BRT is that it applies stochastic processes that include probabilistic components to improve predictive performance." }, { "input": "What is the relationship between land use and emergence of HPAI H5N1?", "output": " high land-use diversity landscapes, a variable not previously considered in spatial studies of HPAI H5N1, are at significantly greater risk for HPAI H5N1 outbreaks" }, { "input": "Where is the highest risk of HPAI H5N1 like disease emergence?", "output": "Emergence risk should be highest in the most rapidly transforming urban areas, peri-urban zones where mixes of urban-rural, modern-traditional land uses and poultry husbandry coincide most intensely." }, { "input": "How does land use fragmentation increase the risk of flu-like diseases?", "output": "Landscape fragmentation produces ecotones, defined as abrupt edges or transitions zones between different ecological systems, thought to facilitate disease emergence by increasing the intensity and frequency of contact between host species [31] Furthermore, fragmentation of natural habitat tends to interrupt and degrade natural processes, including interspecies interactions that regulate densities of otherwise opportunistic species that may serve as competent hosts" }, { "input": "What is the relationship between the outbreak of HPAI H5N1 like diseases and rice cultivation?", "output": " extent of rice cultivation is a risk factor, mainly due its association with free ranging ducks acting as scavengers" }, { "input": "What is the relationship between aquaculture and spread of H5N1 like diseases?", "output": "extent of aquaculture is a known risk factor [10] , possibly because water bodies offer routes for transmission and persistence of the virus" }, { "input": "What is the relationship between proximity ofwater bodies to agricultural lands and spread of H5N1 like diseases?", "output": "Proximity to water bodies increases the risk of outbreaks [47, [50] [51] [52] , possibly by increasing the chance of contact between wild water birds and domestic poultry." }, { "input": "What is the effect of diversity of chicken flock on H5N1 disease?", "output": "diversity of chicken flock-size had a strong association with HPAI H5N1 " }, { "input": "What is Compound Topological Index and how is it related to the risk of disease transmission?", "output": "Compound Topographical Index (CTI, also known as Topographical Wetness Index) is a measure of the tendency for water to pool. Studies in Thailand and elsewhere [54] have shown that the extent of surface water is a strong risk factor, possibly due to the role of water in long-range transmission and persistence of the virus. I" }, { "input": "In vitro comparison of antiviral activity of Chloroquine(CQ) and Hydroxychloroquine(HCQ) against COVID-19?", "output": "compare the antiviral activity of CQ versus HCQ, the dose-response curves" }, { "input": "What will be the drug of choice for treating COVID-19 between Chloroquine and Remdesivir?", "output": " two potential drugs, CQ appears to be the drug of choice for large-scale use due to its availability, proven safety record, and a relatively low cost." }, { "input": "Mechanism of action of Chloroquine(CQ) and Hydroxychloroquine(HCQ) against COVID-19?", "output": "CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles" }, { "input": "What is the effect of Chloroquine(CQ) and Hydroxychloroquine(HCQ) on endosomal maturation and endocytosis in COVID-19 treatment?", "output": "Since acidification is crucial for endosome maturation and function, we surmise that endosome maturation might be blocked at intermediate stages of endocytosis," }, { "input": "Evidence of Hydroxychloroquine(HCQ) being anti inflammatory in SARS-CoV-2 critically ill patients with elevated plasma cytokines?", "output": " HCQ is a safe and successful anti-inflammatory agent" }, { "input": "What proportion of healthcare workers reported symptoms of depression?", "output": "50.4%" }, { "input": "What proportion of healthcare workers reported symptoms of anxiety?", "output": "[44.6%" }, { "input": "What proportion of healthcare workers reported symptoms of insomnia?", "output": "34.0%" }, { "input": "What proportion reported distress?", "output": "[71.5%" }, { "input": "What were the Generalized Anxiety Disorder scale scores?", "output": "among men vs women: 2.0 [0-6.0] vs 4.0 [1.0-7.0]; P < .001" }, { "input": "What were the Insomnia Severity Index scores ?", "output": "among frontline vs second-line workers: 6.0 [2.0-11.0] vs 4.0 [1.0-8.0]; P < .001" }, { "input": "What were the Impact of Event Scale\u2013Revised scores?", "output": " 21.0 [8.5-34.5] vs 18.0 [6.0-28.0] in Hubei outside Wuhan and 15.0 [4.0-26.0] outside Hubei; P < .001)." }, { "input": "What were the results of analysis?", "output": "participants from outside Hubei province were associated with lower risk of experiencing symptoms of distress compared with those in Wuhan (odds ratio [OR], 0.62; 95% CI, 0.43-0.88; P = .008)" }, { "input": "What were the results of analysis?", "output": "Frontline health care workers engaged in direct diagnosis, treatment, and care of patients with COVID-19 were associated with a higher risk of symptoms of depression (OR, 1.52; 95% CI, 1.11-2.09; P = .01), anxiety (OR, 1.57; 95% CI, 1.22-2.02; P < .001), insomnia (OR, 2.97; 95% CI, 1.92-4.60; P < .001), and distress (OR, 1.60; 95% CI, 1.25-2.04; P < .001)." }, { "input": "What are the conclusions of this study?", "output": "In this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19." }, { "input": "What are microtubule severing enzymes?", "output": "a family of AAA-ATPase proteins" }, { "input": "What genetic mutation is associated with hereditary spastic paraplegia?", "output": "SPG4" }, { "input": "What genetic mutation is associated with cerebral malformations?", "output": "KATNB1" }, { "input": "What genetic mutation is associated with autism?", "output": "KATNAL2" }, { "input": "What is KATNAL1?", "output": "microtubule severing enzyme" }, { "input": "What organ is most associated with the KATNAL1 gene?", "output": "central nervous system" }, { "input": "What CNS functions can be measured by studying the movement of mice in a T-maze?", "output": "working memory and spatial memory" }, { "input": "What CNS functions are changed by mutations in the KATNAL1 gene?", "output": "circadian rhythms, sleep and behaviour" }, { "input": "How is Japanese encephalitis transmitted?", "output": "arthropod" }, { "input": "What element is essential to promoting JEV infection?", "output": "calcium" }, { "input": "Where is Q130 located in the NS4B protein?", "output": "transmembrane domain 3" }, { "input": "What is the mechanism of action for manidipine?", "output": "voltage-gated Ca(2+) channel (VGCC) inhibitor" }, { "input": "How many different pathogens are members of the Flaviviridae family of virus?", "output": "70" }, { "input": "What is the size of a flavivirus?", "output": "11-kb" }, { "input": "How many open reading frames are in the flavivirus genome?", "output": "single" }, { "input": "What are the structural protein elements of a flavivirus?", "output": "capsid (C), membrane (premembrane [prM] and membrane [M] ), and envelope (E)" }, { "input": "What is the function of the nonstructural protein elements of the flavivirus?", "output": "viral replication, virion assembly, and virus escape from immune surveillance." }, { "input": "What are RVPs?", "output": "Recombinant viral particles" }, { "input": "What is HTS?", "output": "high-throughput screening" }, { "input": "What is the selective index in high throughput screening?", "output": "the 50% cytotoxic concentration" }, { "input": "What is the structure of a recombiant viral particle?", "output": "a natural virus-like envelope on the outside and a replicon on the inside" }, { "input": "What measure is used in high-throughput screening to identify potential antiviral compounds?", "output": "selective index of >10" }, { "input": "How many known species of Rotavirus exist?", "output": "nine species" }, { "input": "Is Rotavirus single or double-stranded?", "output": "double-stranded ribonucleic acid" }, { "input": "What structural proteins are coded by Rotavirus?", "output": "VP1-VP4, VP6 and VP7" }, { "input": "What non-structural proteins are coded by Rotavirus?", "output": "NSP1-NSP5/NSP6" }, { "input": "What is qRT-PCR?", "output": "qualitative real-time polymerase chain reaction" }, { "input": "What is required to establish a secondary immune response to a viral infection?", "output": "the generation of antigen-specific \"memory\" B and T lymphocytes" }, { "input": "What do immunoglobulin isotype recombination and somatic hyper mutation depend on?", "output": "expression of AID" }, { "input": "What was used to quantify the amount of IgM secreting cells?", "output": "ELISpot technique" }, { "input": "Where was the coronavirus discovered?", "output": "Wuhan, China" }, { "input": "What is the number of confirmed cases reached on 8 February 2020?", "output": "34,598" }, { "input": "What is presented in this study?", "output": "new forecasting model to estimate and forecast the number of confirmed cases of COVID-19 in the upcoming ten days based on the previously confirmed cases recorded in China" }, { "input": "What is the proposed model?", "output": "an improved adaptive neuro-fuzzy inference system (ANFIS) using an enhanced flower pollination algorithm (FPA) by using the salp swarm algorithm (SSA)" }, { "input": "When is SSA generally employed?", "output": "to improve FPA to avoid its drawbacks (i.e., getting trapped at the local optima)" }, { "input": "What is the main idea behind the proposed model?", "output": "to improve the performance of ANFIS by determining the parameters of ANFIS using FPASSA." }, { "input": "What is the proposed model called?", "output": " FPASSA-ANFIS" }, { "input": "How is FPASSA-ANFIS model evaluated?", "output": "using the World Health Organization (WHO) official data of the outbreak of the COVID-19 to forecast the confirmed cases of the upcoming ten days." }, { "input": "What did the comparison of the FPASSA-ANFIS model with several existing models, show?", "output": "it showed better performance in terms of Mean Absolute Percentage Error (MAPE), Root Mean Squared Relative Error (RMSRE), Root Mean Squared Relative Error (RMSRE), coefficient of determination ( R 2 ), and computing time. " }, { "input": "How was the proposed model tested?", "output": " using two different datasets of weekly influenza confirmed cases in two countries, namely the USA and China" }, { "input": "What were the outcomes of the test?", "output": "showed good performances" }, { "input": "What are the large family of viruses, called coronaviruses?", "output": " pathogens for human beings, which infect respiratory, hepatic, gastrointestinal, and neurologic diseases." }, { "input": "Among whom are the coronaviruses distributed?", "output": " among humans, birds, livestock, mice, bats, and other wild animals " }, { "input": "In what the Adaptive Neuro-Fuzzy Inference System (ANFIS) [22] is widely applied?", "output": " in time series prediction and forecasting problems" }, { "input": "What does ANFIS offer?", "output": "flexibility in determining nonlinearity in the time series data, as well as combining the properties of both artificial neural networks (ANN) and fuzzy logic systems." }, { "input": "In which applications has it been applied?", "output": "in various forecasting applications, for example, in [23] , a stock price forecasting model was proposed using ANFIS and empirical mode decomposition" }, { "input": "What is SI?", "output": "swarm intelligence" }, { "input": "What is PSO?", "output": "particle swarm optimization" }, { "input": "What is SCA?", "output": "sine-cosine algorithm" }, { "input": "What is MVO?", "output": "multi-verse optimizer" }, { "input": "For what SCA algorithm was applied to improve the ANFIS model ?", "output": "to forecast oil consumption in three countries, namely, Canada, Germany, and Japan." }, { "input": "What may be a problem with individual SI algorithm?", "output": "may stock at local optima" }, { "input": "What is OWA?", "output": " ordered weighted averaging" }, { "input": "What is proposed in the current study?", "output": "an improved ANFIS model based on a modified flower pollination algorithm (FPA) using the salp swarm algorithm (SSA)." }, { "input": "What is the FPA optimization algorithm inspired by?", "output": "inspired by the flow pollination process of the flowering plants." }, { "input": "What is the SSA optimization algorithm inspired by?", "output": "inspired by the behavior of salp chains" }, { "input": "What is the proposed FPASSA method?", "output": " is a hybrid of FPA and SSA, in which the SSA is applied as a local search method for FPA" }, { "input": "How does the proposed FPASSA start?", "output": " by receiving the historical COVID-19 dataset." }, { "input": "What do the authors propose?", "output": "an efficient forecasting model to forecast the confirmed cases of the COVID-19 in China for the upcoming ten days based on previously confirmed cases." }, { "input": "What is vacuolar-type H(+)-ATPase (v-ATPase)?", "output": "the major proton pump that acidifies intracellular compartments of eukaryotic cells" }, { "input": "What is archazolid?", "output": "v-ATPase inhibitor" }, { "input": "How many complexes are within v-ATPase?", "output": "two" }, { "input": "What is the role of v-ATPase in the plasma membrane of osteoclasts and renal epithelial cells?", "output": "they pump protons into the extracellular space" }, { "input": "What does angiogenesis depend on?", "output": "the proliferation, migration and differentiation of endothelial cells" }, { "input": "How were untreated MDA-MB-231 cells labeled?", "output": "CellTracker Green CMFDA Dye" }, { "input": "What was the goal of the study?", "output": "describe GE and RTI outbreaks with infection and all-cause lethality rates according to the individual characteristics of nursing home residents" }, { "input": "What was the reported infection rate for influenza?", "output": "30.0%" }, { "input": "How many times more likely was an infection found in patients over 85 years old?", "output": "1.5 to 1.6 times" }, { "input": "What can be the main challenges in managing a hospital outbreak of COVID-19?", "output": " (1) early identification of outbreak, (2) rapid expansion of patients, (3) high risk of nosocomial transmission, (4) unpredictability of size impacted, and (5) lack of backup resource." }, { "input": "Why early identification of COVID-19 patients can be difficult?", "output": "Early identification of 2019-nCoV infection presents a major challenge" }, { "input": "What are the steps that a hospital should take after COVID-19 outbreak?", "output": "2019-nCoV patients should be admitted" }, { "input": "Why exposure risk of COVID-19 is very high for ICU staff and what precautions should be taken?", "output": " substantial exposure risk for ICU staff because of the following reasons" }, { "input": "Use of SIR/SEIR model in Statistics-Based Predictions of Coronavirus Epidemic Spreading?", "output": "susceptible persons is S, infected (persons who are sick and spread the infection) -I, removed (persons who do not spread the infection anymore, this number is the sum of isolated, recovered and dead people) -R; the infection and immunization rates " }, { "input": "What virus are used by the most successful neuronal circuit tracing methods?", "output": "Pseudorabies (PRV) and Rabies viruses (RABV)" }, { "input": "In what direction does the Vesicular stomatitis virus spread through the nervous system?", "output": "anterograde" }, { "input": "What determines the whether the spread of Vesicular stomatitis virus is monosynaptic or polysynaptic?", "output": "method of delivery of the G gene" }, { "input": "What types of viruses can be used to study the connectivity of neuronal circuitry?", "output": "rVSV vectors" }, { "input": "What is Carrageenan?", "output": "a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections" }, { "input": "What is a potential therapeutic benefit of carageenan?", "output": "carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7)" }, { "input": "What is the optimal window for initiating treatment with carageenan and Zanamivir?", "output": "72 hours post infection" }, { "input": "What was the mortality rate of influenza a virus subtype h7n9 (avian or bird flu)?", "output": "more than 35%" }, { "input": "How many human cases were there of influenza a virus subtype h7n9?", "output": "more than 400 human cases" }, { "input": "How did most patients contract influenza a virus subtype h7n9?", "output": "Most patients with A(H7N9) infections had contact with poultry or visited live animal markets" }, { "input": "Can influenza a virus subtype h7n9 be transmit human to human?", "output": "some sporadic cases seemed to be a result of human to human transmissions" }, { "input": "What kind of disease is caused by influenza?", "output": " influenza is an acute respiratory disease" }, { "input": "How many severe cases are there for annual influenza epidemics?", "output": " Worldwide, annual epidemics result in about three to five million cases of severe illness" }, { "input": "How many deaths occur annually as a result of annual influenza epidemics?", "output": "250,000 to 500,000" }, { "input": "Is coinfection common in influenza infection?", "output": "influenza virus infections are often accompanied by other viral pathogens" }, { "input": "What percentage of people infected with influenza have a viral coinfection?", "output": "Analysis by qRT-PCR revealed that 54.5-83.3% of influenza A or B positive patients were found to have at least one concomitant respiratory viral infection [9] [10] [11] [12] . The detection frequency with immunofluorescence was found to be even higher (90-100%) [13, 14] . " }, { "input": "What are common concamitant infections during the course of influenza infection?", "output": "human rhinovirus (hRV), respiratory syncytial virus, adenovirus, human coronavirus, human metapneumovirus and parainfluenza virus" }, { "input": "What is the anti-viral mechanism of action for carrageenan?", "output": "The antiviral mechanism of carrageenan is based on the interference with viral attachment; as a consequence, viral entry is inhibited " }, { "input": "What is the hypothetical mechanical benefit for carageenan in preventing and treating upper respiratory infections?", "output": "a protective physical barrier in the nasal cavity" }, { "input": "What is carageenan?", "output": "a high molecular weight sulfated polymer derived from red seaweed (Rhodophyceae) that has been extensively used in food, cosmetic and pharmaceutical industry and is generally recognized as safe by the FDA " }, { "input": "What is the recovery benefit of carageenan in patients with any respiratory virus?", "output": "1.9 day faster recovery from common cold symptoms than placebo treated patients in the intention-to-treat population" }, { "input": "What is the anti-influenza benefit of carageenan?", "output": "anti-influenza activity was shown by subgroup analysis of 49 influenza infected patients who benefited from a 3.3 days faster recovery from symptoms" }, { "input": "What is the association between influenza viral load and carageenan?", "output": "a significant reduction of the influenza viral load in nasal fluids and a significant increase in the number of virus free patients within the treatment period of 7 days" }, { "input": "Is Oseltamivir effective when taken intranasally?", "output": "In contrast to Oseltamivir, which needs to be activated by metabolic conversion, Zanamivir is directly applied as active drug and can also be administered intranasally" }, { "input": "What is the effect of intranasal Zanamivir on laboratory confirmed infleunza infection?", "output": "challenge trials showed that treatment starting before and up to 36 hours post virus inoculation was associated with prevention of laboratory confirmed influenza and febrile illness as well as a reduction in viral titers, duration of shedding and symptoms" }, { "input": "Do carageenan and Zanamivir delivered intranasally have a benefit when taken for influenza subtype H7N7 infection?", "output": "the combination of two effective, established mono-therapies resulted in a significantly enhanced survival in lethally H7N7 infected mice" }, { "input": "Do carageenan and Zanamivir delivered intranasally have a benefit when taken for influenza subtype H1N1 infection?", "output": "carrageenan and Zanamivir starting 72 hpi significantly protects lethally influenza H1N1(09)pdm infected mice" }, { "input": "Is there a dose-dependent response to carageenan and Zanamavir intranasal therapy?", "output": "While H1N1(09)pdm was highly sensitive to inhibition by both substances alone, H7N7 required much higher concentrations of carrageenan and Zanamivir, respectively, to achieve similar inhibition efficiencies" }, { "input": "Do carageenan and Zanamavir together have a greater benefit than either in monotherapy?", "output": "the H1N1(09)pdm model the combination of carrageenan with 1 mg/kg BW/day Zanamivir showed statistically significant enhanced survival in comparison to placebo treatment even after a treatment start 72 hpi" }, { "input": "Did the use of carageenan play a role in pandemic's caused by novel viruses?", "output": "A second scope of this combination is the protection against newly emerging pandemic viruses during the time until identification of the virus followed by manufacturing and distribution of vaccines" }, { "input": "How was ILI defined?", "output": "as a sudden onset of fever more than 38 degrees Celsius and cough, associated or not with other symptoms such as breathing difficulty, headache, etc. " }, { "input": "What is this assay based on?", "output": "on the multiplex ligation-dependent probe amplification (MLPA) technology." }, { "input": "How was random sampling performed?", "output": " with Excel 1 using the anonymized surveillance database of the Cire OI. The sampling frame contained identification number of swab assigned by Cire OI, laboratory identification number, sex, age, date of onset of symptoms, date of swab collection and result of influenza RT-PCR." }, { "input": "What used to detect pathogens?", "output": " Respifinder 1 Smart 22 kits a multiplex RT-PCR (PathoFinder, Maastricht, The Netherlands) which can detect 22 respiratory pathogens. " }, { "input": "What does the retrospective study use?", "output": "nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012." }, { "input": "How many swabs were randomly selected and analyzed?", "output": "250 " }, { "input": "How were the swabs analyzed?", "output": " by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria." }, { "input": "What viruses were detected?", "output": "respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). " }, { "input": "What co-infections were found?", "output": "Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses." }, { "input": "What seasonal differences were found?", "output": "seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter." }, { "input": "What does the study highlight?", "output": " a substantial circulation of multiple respiratory pathogens in R\u00e9union Island throughout the year. I" }, { "input": "What does the study show?", "output": "that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI." }, { "input": "Which are identified as major viruses mostly responsible for ILI and pneumonia in several studies?", "output": "Influenza viruses, Respiratory Syncytial viruses (RSV) and Parainfluenza viruses" }, { "input": "What percentage of these infections are identified?", "output": "less than 50%" }, { "input": "What is Reunion Island?", "output": " a French overseas territory" }, { "input": "What is the number of inhabitants of Reunion Island?", "output": " 850,000" }, { "input": "Where is Reunion Island located?", "output": "n the southern hemisphere between Madagascar and Mauritius in the Indian Ocean (Latitude: 21\u00b005.2920 S Longitude: 55\u00b036.4380 E.)" }, { "input": "What is the island's health care system similar to?", "output": " to mainland France and epidemiological surveillance has been developed by the regional office of the French Institute for Public Health Surveillance (Cire OI), based on the surveillance system of mainland France" }, { "input": "When does influenza activity increase?", "output": " during austral winter, corresponding to summer in Europe" }, { "input": "When does the influenza vaccination campaign in Reunion Island start?", "output": "April " }, { "input": "What is the clinical and biological influenza surveillance has been based on?", "output": "a sentinel practitioner's network" }, { "input": "What is this network composed of?", "output": "58 general practitioners (GPs) spread over the island and represented around 7% of all R\u00e9union Island GPs." }, { "input": "How are the influenza tests carried out?", "output": " Nasal swabs are randomly collected all along the year and are tested by RT-PCR for influenza viruses" }, { "input": "What do 40-50% of the samples test positive for?", "output": " for influenza A virus, A(H1N1)pdm09 or B virus" }, { "input": "What are the ILI samples wich test negative for influence?", "output": "are of unknown etiology" }, { "input": "What tool has been developed to identify several viruses simultaneously?", "output": ", multiplex reverse transcriptase polymerase chain reaction (RT-PCR) " }, { "input": "What are the objectives of the study?", "output": "to characterize respiratory pathogens responsible for ILI consultations in sentinel GPs in 2011 and 2012. Secondary objectives were to highlight seasonal trends on respiratory pathogens circulation and to describe occurrence of co-infections, especially during the flu season." }, { "input": "On which system the reverse transcription and preamplification steps were performed?", "output": "on the epgradient Mastercycler 1 (Eppendorf) and the hybridization, ligation and detection steps on the LightCycler 1 480 system (Roche Applied Science)." }, { "input": "Which two seasons were identified for trends in virus circulation??", "output": "winter season during weeks 23 to 39 between June and September and summer season during the rest of the year." }, { "input": "Which were the most frequently identified respiratory pathogens?", "output": " rhinovirus (23.4%), influenza A not H1N1 (21.2%) and influenza B (12.6%) " }, { "input": "What were detected only in summer?", "output": "Human Metapneumovirus, RSV A and B, and influenza A(H1N1)pdm09" }, { "input": "What viruses were identified only in winter?", "output": "Parainfluenza 1,2 and 4 viruses" }, { "input": "Respiratory viral pathogens were present in what percentage of samples?", "output": "76.1" }, { "input": "What did the study highlight?", "output": "several co-infections, showing that concomitant the multiple etiology of ILI" }, { "input": "How many swabs remained without etiology?", "output": " 53 swabs, representing 24% of the sample" }, { "input": "What hypotheses can explain this result?", "output": " a poor quality of swabs, preventing from identifying a pathogen, noninfectious causes or other pathogens not included in the multiplex PCR." }, { "input": "What could not be tested for?", "output": "RNAse P, a marker of human cells," }, { "input": "What does this study highlight?", "output": " circulation of multiple pathogens in R\u00e9union Island throughout the year." }, { "input": "What does the study show?", "output": "that ILI is not specific to influenza and so it is essential to have biological results in order to establish the differential diagnosis and thus explain the etiology of symptoms." }, { "input": "What would be interesting to do?", "output": "to repeat this study every 3 or 5 years adding clinical data to monitor the evolution of respiratory pathogens in R\u00e9union Island over time." }, { "input": "What is it most similar to?", "output": "bat beta-coronaviruses, with the highest being >96% identity " }, { "input": "How many people were affected as of Feb. 10, 2020?", "output": "greater than 40,000" }, { "input": "How is the SARS-CoV-2 referred to?", "output": " as coronavirus disease discovered in 2019 (COVID-19)" }, { "input": "How much similarity the SARS-COV-2 genome sequence has with SARS-COV?", "output": "\u223c80% identity with SARS-CoV" }, { "input": "what similarity human SARS-COV and palm civet SARSlike COV share?", "output": " 99.8% homology, with a total of 202 single-nucleotide (nt) variations (SNVs) identified across the genome " }, { "input": "How much is the difference between the human SARS-CoV-2 and the bat RaTG13-CoV?", "output": "greater than 1,100 nt " }, { "input": "Why is it highly unlikely that RaTG13 CoV is the immediate source of SARS-CoV-2. ", "output": "are distributed throughout the genome in a naturally occurring pattern following the evolutionary characteristics typical of CoVs" }, { "input": "What are the most revealing signs that SARS-CoV-2 evolved by natural evolution. ", "output": "The absence of a logical targeted pattern in the new viral sequences and a close relative in a wildlife species (bat" }, { "input": "What did the Nature Medicine paper report?", "output": "the construction of a chimeric CoV with a bat CoV S gene (SHC014) in the backbone of a SARS CoV that has adapted to infect mice (MA15) and is capable of infecting human cells" }, { "input": "Why does the claim lack any scientific basis?", "output": " because of significant divergence in the genetic sequence of this construct with the new SARS-CoV-2 (>5,000 nucleotides)." }, { "input": "How was the mouse-adapted SARS virus (MA15) generated?", "output": "by serial passage of an infectious wildtype SARS CoV clone in the respiratory tract of BALB/c mice." }, { "input": "How did the SARS-CoV gain elevated replication and lung pathogenesis in aged mice ?", "output": "due to six coding genetic mutations associated with mouse adaptation. " }, { "input": "Why is it likely that MA15 is highly attenuated to replicate in human cells?", "output": "due to the mouse adaptation." }, { "input": "Why were civets proposed to be an intermediate host of the bat-CoVs, capable of spreading SARS CoV to humans?", "output": "t was proposed that the S gene from bat-derived CoV, unlike that from human patients-or civetsderived viruses, was unable to use human ACE2 as a receptor for entry into human cells " }, { "input": "What was the finding in 2013?", "output": "several novel bat coronaviruses were isolated from Chinese horseshoe bats and the bat SARS-like or SL-CoV-WIV1 was able to use ACE2 from humans, civets and Chinese horseshoe bats for entry " }, { "input": " Why is it proposed that some bat SL-CoVs may be able to directly infect human hosts?", "output": "Combined with evolutionary evidence that the bat ACE2 gene has been positively selected at the same contact sites as the human ACE2 gene for interacting with SARS CoV [" }, { "input": "What was done to test if an intermediate host may not be necessary and that some bat SL-CoVs may be able to directly infect human hosts. T", "output": " the exact S gene from bat coronavirus SL-SHC014 was synthesized and used to generate a chimeric virus in the mouse adapted MA15 SARS-CoV backbone. " }, { "input": "What were the results of this test?", "output": "The resultant SL-SHC014-MA15 virus could indeed efficiently use human ACE2 and replicate in primary human airway cells to similar titres as epidemic strains of SARS-CoV. While SL-SHC014-MA15 can replicate efficiently in young and aged mouse lungs, infection was attenuated, and less virus antigen was present in the airway epithelium as compared to SARS MA15, which causes lethal outcomes in aged mice" }, { "input": "Why were experiments with SL-SHC014-MA15 chimeric virus were later restricted?", "output": "as gain of function (GOF) studies under the US government-mandated pause policy " }, { "input": "Why is there no credible evidence to support the claim that the SARS-CoV-2 is derived from the chimeric SL-SHC014-MA15 virus?", "output": "upon careful phylogenetic analyses by multiple international groups [5, 14] , the SARS-CoV-2 is undoubtedly distinct from SL-SHC014-MA15, with >6,000 nucleotide differences across the whole genome." }, { "input": "What did the rumour that the virus was made by humans in the lab, claim?", "output": "that SARS-CoV-2 has HIV sequence in it and was thus likely generated in the laboratory. I" }, { "input": "What was reported in a rebuttal paper led by an HIV-1 virologist Dr. Feng Gao?", "output": " they used careful bioinformatics analyses to demonstrate that the original claim of multiple HIV insertions into the SARS-CoV-2 is not HIV-1 specific but random " }, { "input": "What happened to the report with initial claims?", "output": " Because of the many concerns raised by the international community, the authors who made the initial claim have already withdrawn this report." }, { "input": "What is the difference between evolution and synthetic constructs?", "output": "Evolution is stepwise and accrues mutations gradually over time, whereas synthetic constructs would typically use a known backbone and introduce logical or targeted changes instead of the randomly occurring mutations that are present in naturally isolated viruses such as bat CoV RaTG13." }, { "input": "What is the conclusion of this report?", "output": " there is currently no credible evidence to support the claim that SARS-CoV-2 originated from a laboratory-engineered CoV. It is more likely that SARS-CoV-2 is a recombinant CoV generated in nature between a bat CoV and another coronavirus in an intermediate animal host. " }, { "input": "What is the conclusion of this report?", "output": "More studies are needed to explore this possibility and resolve the natural origin of SARS-CoV-2. We should emphasize that, although SARS-CoV-2 shows no evidence of laboratory origin, viruses with such great public health threats must be handled properly in the laboratory and also properly regulated by the scientific community and governments." }, { "input": "what is the clinical manifestation similar to?", "output": "to that of the severe acute respiratory syndrome (SARS) caused by SARS-CoV. " }, { "input": "What was the purpose of the research?", "output": "to evaluate the effectiveness of zinc supplementation on diarrhea and average daily weight gain (ADG) in pre-weaned dairy calves" }, { "input": "What preventative measure has been taken to decrease the incidence of diarrhea in children?", "output": "Zinc supplementation" }, { "input": "What led to a great increase in their study among virologists worldwide?", "output": "an outbreak in 1993\u201394 in the southwestern United States" }, { "input": "How many hantaviral genotypes have been described", "output": "Well over 40" }, { "input": "How many of them are pathogenic for humans?", "output": "nearly half of them" }, { "input": "What do Hantaviruses cause in their reservoir hosts?", "output": "persistent infections" }, { "input": "What does hantavirus human disease manifest as?", "output": " a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS)" }, { "input": "What is the case-fatality ratios, for the most common viral serotypes? ", "output": "between 30% and 40%" }, { "input": " What are among the factors that may have increased the human caseload of HCPS between 1993 and the present?", "output": " Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change," }, { "input": "What do authors consider in this study?", "output": " the features that influence the structure of host population dynamics that may lead to viral outbreaks" }, { "input": "What do authors consider in this study?", "output": "the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity." }, { "input": "Which diseases are a major concern among scientists studying infectious diseases?", "output": " emerging zoonotic diseases" }, { "input": "What may alter population disease dynamics and lead to the emergence of zoonotic infections? ", "output": "Changes in biotic and abiotic conditions" }, { "input": "Which are among the conspicuous examples which challenge prevention and control measures of public health systems?", "output": " influenza A, Ebola virus, hepatitis C virus, severe adult respiratory distress (SARS), coronavirus, and human immunodeficiency virus" }, { "input": "More recently, what did outbreaks of several viral-related diseases that have emerged or re-emerged, involve?", "output": "hantaviruses, and the expansion of the geographic range of West Nile virus." }, { "input": "What did, In the last century, outbreaks of viral-related diseases that have emerged or re-emerged, involve?", "output": "arenaviruses and dengue viruses" }, { "input": "Among zoonotic diseases, what are hosts of several pathogenic RNA viruses?", "output": "small mammals" }, { "input": "Which pathogenic RNA viruses are hosted by small mammals?", "output": " Arenaviridae and Bunyaviridae: Hantavirus " }, { "input": "When did Hantavirus infections became a concern in the Americas?", "output": " disease, hantavirus cardiopulmonary syndrome, HCPS (or hantavirus pulmonary syndrome), was linked to " }, { "input": " What was the hantavirus cardiopulmonary syndrome, HCPS (or hantavirus pulmonary syndrome), linked to?", "output": "infection by the newly-discovered Sin Nombre virus (SNV)" }, { "input": "What was identified as the reservoir of SNV?", "output": " the rodent Peromyscus maniculatus (deer mouse)" }, { "input": " What did a review of ancient Chinese writings in 960 AD, reveal?", "output": "descriptions closely resembling hemorrhagic fever with renal syndrome (HFRS), the syndrome caused by Old World hantaviruses" }, { "input": "How was HFRS first brought to the attention of western medicine ?", "output": "with an outbreak that occurred among United Nations troops during the Korean conflict between 1951 and 1954" }, { "input": "What is HTNV?", "output": " etiologic agent, Hantaan virus" }, { "input": "Where was HTNV isolated from?", "output": " from the striped field mouse Apodemus agrarius," }, { "input": "Which new genus was the virus later found to represent?", "output": "Hantavirus of the family Bunyaviridae" }, { "input": "Which was the first hantavirus to be isolated?", "output": "The categorization of hantaviruses as belonging to the family Bunyaviridae is due in part to" }, { "input": "What is the categorization of hantaviruses as belonging to the family Bunyaviridae due in part to?", "output": " the consistent presence of three RNA genomes that are circularized in vivo as a result of the presence of terminal complementary nucleotides that help fold the genome into a -hairpin\u2016 morphology," }, { "input": "What was the hairpin morphology first described for?", "output": "Uukuniemi phlebovirus " }, { "input": "How is the the precursor form GPC processed, during virus maturation?", "output": "a membrane -bound protease into Gn and Gc, a cleavage that occurs" }, { "input": "When does the cleavage appear to be signaled?", "output": "after the conserved peptide signal WAASA at the C-terminal of Gn " }, { "input": "Why must the two proteins Gn and Gc be co-expressed?", "output": "to allow them stability so that the two can be assembled correctly in the Golg" }, { "input": "Which two distinct cellular receptors the glycoproteins are the known or presumed ligands for?", "output": " the \uf0623 integrin chain and decay accelerating factor, or DAF" }, { "input": "What is the underlying premise for many of these studies?", "output": " blunt any pathological response in the host [" }, { "input": "What is the premise for apathogenic forms to blunt any pathological response in the host?", "output": "would tend to induce an earlier innate response that would render it more likely that the virus would be quickly cleared or rendered less competent in its replication" }, { "input": "Which proteins and mRNAs prominently induced by hantaviruses include?", "output": "hantaviruses have been identified as adversely affecting" }, { "input": " What have hantaviruses been identified as adversely affect?", "output": "endothelial migration over substrata " }, { "input": " What have hantaviruses been identified in potentiating?", "output": " VEG-F-induced endothelial permeability" }, { "input": "What is N-protein?", "output": "a structural component of the viral nucleocapsid" }, { "input": "What does the N-protein, as an RNA-binding protein, do?", "output": "engages the hairpin termini of the genomic segments with high affinity" }, { "input": "As an RNA-binding protein that engages the hairpin termini of the genomic segments, what does the N-protein of hantavirus do?", "output": " it limits the access of the RNA to host nucleases " }, { "input": "As an RNA-binding protein that engages the hairpin termini of the genomic segments, what does the N-protein of hantavirus do?", "output": " helps to render viral replication a closed process within the cytoplasm" }, { "input": "What does the N-protein act as?", "output": "a peripheral membrane protein" }, { "input": " What can some of the other activities of N have, be linked to?", "output": " to the interference with an array of the intracellular processes of the normal cell" }, { "input": " What can some of the other activities of N have, be linked to?", "output": " to fundamental requirements of replication" }, { "input": "What is N also reported to interact with?", "output": "with actin microfilaments, and the SUMO-1 protein" }, { "input": "How do the viral RNAs become concentrated in P bodies during hantavirus infection?", "output": " through their interaction with N and DCP1" }, { "input": "What have confocal microscopy and biochemical-inhibitor studies shown?", "output": " that N tracks along microtubules" }, { "input": "What have confocal microscopy and biochemical-inhibitor studies shown on what N tracks?", "output": "not with actin filaments " }, { "input": "What is the ultimate destination for N, for its assembly into viral particles?", "output": "the Golgi" }, { "input": "How does it traffic?", "output": " via the endoplasmic reticulum-Golgi intermediate complex (ERGIC), also known as vesicular-tubular cluster " }, { "input": "What is a dominant negative inhibitor?", "output": " dynamitin" }, { "input": "What is dynamitin associated with?", "output": "dynein-mediated transport" }, { "input": "What is dynamitin associated with?", "output": " reduced N's accumulation in the Golgi" }, { "input": "What does recent data indicate?", "output": " that microtubular transport is indeed utilized for the New World hantavirus SNV" }, { "input": "Why have Hantavirus diseases of man been suspected of having an immunopathogenic basis?", "output": "plasma viral RNA with" }, { "input": "What is a critical feature of both?", "output": " a transient (~ 1-5 days) capillary leak involving the kidney and retroperitoneal space in HFRS and the lungs in HCPS" }, { "input": "What is the character of he resulting leakage?", "output": "is exudative in character, with chemical composition high in protein and resembling plasma." }, { "input": "Which is an especially attractive candidate as an important in vivo receptor for hantaviruses?", "output": " \u03b23 integrin" }, { "input": "What is the likely way that hantaviruses arrive at their target tissues?", "output": "through uptake by regional lymph nodes, perhaps with or within an escorting lung histiocyte" }, { "input": "What does the virus seed?", "output": "local endothelium" }, { "input": "What happens with the viral seeding at the local endothelium?", "output": " the first few infected cells give rise, ultimately, to a primary viremia" }, { "input": "How long does the process of giving rise to primary viremia for hantavirus infections?", "output": "appears to take a long time " }, { "input": "What happens by the time that secondary viremia emerges?", "output": " the agents of the more severe forms of HFRS and HCPS have begun to achieve sufficient mass" }, { "input": "How is the the expression of proinflammatory cytokines induced?", "output": " through PAMP-PRR interactions and other means" }, { "input": " For HCPS, what does that expression favor?", "output": "the pulmonary bed and lymphoid organs" }, { "input": " For HCPS, what does that expression spare?", "output": "the retroperitoneum and, in general, the kidney" }, { "input": "What happens for HFRS?", "output": " For HCPS, that expression favors the pulmonary bed and lymphoid organs, yet, for unknown reasons, spares the retroperitoneum and, in general, the kidney. In HFRS the situation is reversed," }, { "input": "What is considered to be a requirement for the development of systemic disease symptoms?", "output": "Local elaboration of inflammatory and chemotactic mediators " }, { "input": "What do those abnormalities sometimes culminate in?", "output": "shock and death" }, { "input": "What leads to death in most fatal cases of HCPS?", "output": " not hypoxemia, due to the prominent pulmonary edema" }, { "input": "What leads to death in most fatal cases of HCPS?", "output": "intoxication of the heart by as-yet-undefined mediators that leads to the low cardiac output state and the associated shock syndrome " }, { "input": "What potential mechanism, could be presumed to underlie the pathogenesis of HCPS?", "output": " Innate immune mechanisms." }, { "input": "What potential mechanism, could be presumed to underlie the pathogenesis of HCPS?", "output": "Direct viral effects" }, { "input": "What potential mechanism, could be presumed to underlie the pathogenesis of HCPS?", "output": "Pathogenic effects caused by the activities of specific viral macromolecules." }, { "input": "What explanation have some investigators favored for much of the capillary leak?", "output": "direct viral toxicity, acting through the inhibition of endothelial cell barrier function" }, { "input": " What animal models exist for both the asymptomatic carriage of PUUV and SNV?", "output": "their native carrier rodents, the bank vole Myodes glareolus and the deer mouse P. maniculatus" }, { "input": "For what can the Syrian hamster model used?", "output": "ANDV or the related Maporal virus from Venezuela, for which an HCPS-mimetic disease is observed" }, { "input": "What does the hamster model for HCPS caused by?", "output": "by capillary leak that results in pulmonary edema and the production of a pleural effusion with exudative characteristics" }, { "input": " Typically how long do the hamsters die post-inoculation?", "output": "11 and 14-d" }, { "input": "What does the microscopic examination of the lung reveal, as with human HCPS?", "output": "abundant fibrin deposition, thickened alveolar septa, and viral antigen expressed abundantly in the microvascular endothelium." }, { "input": "What do ANDV-infected hamsters fitted with physiologic monitoring devices exhibit?", "output": "diminished pulse pressures, tachycardia, and hypotension" }, { "input": "What do diminished pulse pressures, tachycardia, and hypotension in ANDV infected hamsters appear to closely mimic?", "output": "the shock that is believed to be the proximate cause of demise in patients who succumb to HCPS " }, { "input": "Compared to humans, what do ANDV infected hamsters exhibit?", "output": "exceptionally high titers of live ANDV in their tissues, with much of the viral replication occurring in hepatocytes" }, { "input": "With what have three studies correlated plasma viral RNA?", "output": "with disease severity for HCPS and HFRS," }, { "input": "What are examples of delivery vectors for commercial anti-Salmonella vaccines?", "output": "Ty21a for typhoid fever in humans, several Salmonella serovars against salmonellosis in chickens and other animals" }, { "input": "What can be a factor in using common vectors for the delivery of vaccines?", "output": "commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. " }, { "input": "Is a pre-existing immune response to commonly used delivery vector an advantage or a disadvantage?", "output": "for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses." }, { "input": "What bacterial delivery vectors have been tested in animal hosts?", "output": " attenuated bacteria, including Escherichia coli, Vibrio cholerae, lactic acid bacteria (LAB), specifically Lactococcus lactis, Mycobacterium, Listeria, Shigella and Salmonella, have been tested for the targeted delivery of heterologous antigens of bacterial, viral and parasitic origin into a variety of animal hosts" }, { "input": "Which bacteial delivery vectors have gained favor for vaccines?", "output": "Bacteria such as E. coli and lactic acid bacteria " }, { "input": "Why are E Coli and lactic acid are safe choices as delivery vectors for vaccines?", "output": "E. coli is a commensal and lactic acid bacteria are present in most fermented food items and are therefore naturally present in the host. They are also a much safer option than traditional attenuated vaccines in children and immunecompromised people." }, { "input": "What is Listeria?", "output": " Listeria species are Gram-positive intracellular food-borne pathogens" }, { "input": "What is the advantage of Listeria as a delivery vector for vaccines?", "output": "The advantages of Listeria are that it can invade a variety of cells, including antigen presenting cells (APCs). After invading the host cell, Listeria resides inside the phagosome; however, it can escape the phagosome with the help of listeriolysin O (LLO; Hly) and reside in the cytoplasm of the cells, thereby efficiently presenting antigen to both CD8 and CD4 T cells " }, { "input": "What are examples of viral vectors for delivering vaccines?", "output": "recombinant vaccines are based on both DNA viruses (such as fowlpox virus-based vaccines which target avian influenza virus and fowlpox virus, or vaccinia virusbased vectors against the rabies virus in wildlife) and RNA viruses [such as Newcastle disease virus-based vaccines to be used in poultry or yellow fever virus (YFV)-based vaccines to be used in horses against West Nile virus] " }, { "input": "Which viral vaccine delivery vector was first licensed?", "output": "YFV (YF-17D strain) was the first to be licensed for use in humans, where the cDNAs encoding the envelope proteins of YFV were replaced with the corresponding genes of an attenuated Japanese encephalitis virus strain, SA14-14-2" }, { "input": "What are examples of attenuated poxvirus vaccine delivery vectors?", "output": "modified vaccinia virus Ankara (MVA) and New York attenuated vaccinia virus NYVAC strains" }, { "input": "What is the connection between chicken and Salmonella?", "output": "Chickens (Gallus gallus) are a natural animal reservoir for Salmonella, which makes them an important source of Salmonella-associated gastroenteritis in humans. " }, { "input": "Why are some poxvirus ideally suited as vaccine delivery vectors?", "output": "They are ideal candidate vectors due to their large DNA-packing capacity and their thermal and genetic stability " }, { "input": "What is the advantage of adenovirus as vaccine delivery vector?", "output": "adenovirus (Ad) vector is another of the most widely evaluated vectors to date to express heterologous antigens, due to ease of production, safety profile, genetic stability, the ease of DNA genome manipulation, and the ability to stimulate both innate and adaptive immune responses and induce both T and B cell responses " }, { "input": "What are important criteria for selecting vaccine delivery vectors?", "output": "a vaccine should be inexpensive, so that it can be administered to a large population at minimal cost" }, { "input": "What are important criteria for selecting vaccine delivery vectors?", "output": "Safety is a major concern, as even a low level of toxicity is unacceptable " }, { "input": "What are important criteria for selecting vaccine delivery vectors?", "output": "long-lasting cellular and (where appropriate) humoral immune responses to the vectored antigen must be induced following administration of these vaccines, preferably with a single dose" }, { "input": "What happens when a recipient of a vaccine has immune response to the delivery vector?", "output": "considering a vector such as Salmonella, if a host has previously been infected there will exist robust B and T memory responses, and as such, when a vaccination is delivered, an anamnestic response to the Salmonella antigens will be induced (while the response to the vectored antigen will be a primary response)" }, { "input": "What is the effect of host immune response to the delivery vector on the efficacy of vaccination?", "output": "for virally vectored antigens, the existence of pre-existing immunity to the vector (particularly neutralizing antibody) will restrict delivery of the virus into cells, thereby effectively reducing the dose of the vectored antigen. Again, this might be expected to result in a reduction in the antigenicity of the vectored antigen." }, { "input": "What is the effect of host immune response to the delivery vector on the efficacy of vaccination?", "output": "theoretically reduce the exposure of the heterologous antigen to the immune system, as the vector is rapidly cleared." }, { "input": "What is an example of the effect of immunity to the delivery vector on the efficacy of vaccination?", "output": "mice that had been primed with Salmonella alone, and then boosted with Salmonella expressing tetC, induced much lower anti-tetC responses than mice that had not been primed. This argues strongly that prior immunological immunity to the vector can seriously dampen subsequent antigen-specific humoral responses." }, { "input": "What is the effect of host immune response to viral delivery vectors in the efficacy of vaccination?", "output": "pre-existing immunity is a major obstacle of many viralvectored vaccines, such as Ad serotype 5 or herpes simplex virus type 1 (HSV-1), where the rate of seroprevalence to these viruses is very high [40-45 % and 70 % (or more) of the US population, respectively] " }, { "input": "What is the effect of host immune response to the viral delivery vector on the efficacy of vaccination?", "output": "Vector-specific antibodies may impede the induction of immune responses to the vaccine-encoded antigens, as they may reduce the dose and time of exposure of the target cells to the vaccinated antigens" }, { "input": "What is the effect of host immune response to the delivery vector on the efficacy of vaccination?", "output": " In a large-scale clinical trial (STEP) of an Ad serotype 5 (AdHu5)-based HIV-1 vaccine, the vaccines showed a lack of efficacy and tended to increase the risk of HIV-1 infection in vaccine recipients who had pre-existing neutralizing antibodies to AdHu5 (" }, { "input": "What are methods to avoid the effect vector immunity on the efficacy of vaccination?", "output": " the use of vectors derived from nonhuman sources, using human viruses of rare serotypes (Kahl et al., 2010; Lasaro & Ertl, 2009) , heterologous prime-boost approaches (Liu et al., 2008) , homologous reimmunization (Steffensen et al., 2012) and removing key neutralizing epitopes on the surface of viral capsid proteins (Gabitzsch & Jones, 2011; Roberts et al., 2006) " }, { "input": "What are methods to avoid the effect of vector immune response on the efficacy of vaccination?", "output": "The inhibitory effect of pre-existing immunity can also be avoided by masking the Ad vector inside dendritic cells (DCs) (Steffensen et al., 2012) . In addition, mucosal vaccination or administration of higher vaccine doses can overcome pre-existing immunity problems (Alexander et al., 2012; Belyakov et al., 1999; Priddy et al., 2008; Xiang et al., 2003) .\n" }, { "input": "How does cell-mediated immunity to viral delivery vector, reduce the immune response to vaccine?", "output": " this is because viruses will induce neutralizing antibody on the first dose, and in subsequent doses this antibody will limit the number of transduced cells, therefore limiting the responses. This is particularly a problem with a common viral vector such as Ad, where a large proportion of the population will have immunological memory against common serotypes" }, { "input": "How can vectors for which host has immunity, be used differently to increase the efficacy of vaccination?", "output": " it will be possible to utilize such vectors only by developing vaccines from alternative serotypes. It may be that a vector such as Pre-existing immunity against vaccine vectors attenuated influenza virus, with the ability to easily develop reassortants, will be useful in this context.\n\nIn addition, immunological memory in the form of opsonizing antibody certainly plays an important role in the early uptake of Salmonella by macrophages and DC. This may be beneficial, as the live bacterial vector used for delivery purposes harbours mutations in genes encoding proteins responsible for their survival in the animal host. This not only encumbers their ability to cause disease, making them safe live vectors, but also limits the number of replications. The presence of opsonizing antibodies should mean a higher level of bacterial uptake, leading to higher presentation to the immune system and therefore a better immune response." }, { "input": "How does the PED virus transmit between animals?", "output": "fecal\u2013oral contact" }, { "input": "How can Bacilius subtilis be used as an oral vaccine?", "output": "recombinant vaccine carrier" }, { "input": "What cells are infected by the PED virus?", "output": "intestine epithelial cells" }, { "input": "What kind of immune responses are most effective in preventing PED virus?", "output": "mucosal" }, { "input": "What intestinal factors may reduce the effectiveness of orally-administered immunizations?", "output": "gastric acids, pepsin, and trypsin" }, { "input": "What is Bacillus subtilis?", "output": "Gram-positive bacterium" }, { "input": "What is the role of dendritic cells in the immune response?", "output": "antigen-presenting cells" }, { "input": "Where do dendritic cells exist in the body?", "output": "gut-associated lymphoid tissue (GALT)" }, { "input": "What are the components of the gut-associated lymphoid tissue?", "output": "Peyer's patches (PPs), isolated lymphoid follicles (ILFs), mesenteric lymph nodes (MLNs), and scatter throughout the subepithelial lamina propria (LP) of the small intestine and colon" }, { "input": "What type of cells form the intestinal mucosal barrier?", "output": "lymphoid cells" }, { "input": "What factors determine an effective mucosal immune response?", "output": "serum IgG and mucosal SIgA" }, { "input": "What is an effective indicator of a vaccine's ability to generate an immune response?", "output": "cytokines" }, { "input": "What is interleukin-1Beta?", "output": "pro-inflammatory cytokines" }, { "input": "When was the first case of COVID-19 identified?", "output": "Wuhan City, China" }, { "input": "Where did SARS-CoV-2 originate?", "output": "Wuhan City, China" }, { "input": "In what year did the first SARS epidemic occur?", "output": " rapid and transparent sharing of information between countries and agencies" }, { "input": "When was World Health Organization (WHO) first notified about the SARS-CoV-2 epidemic in Wuhan City, China?", "output": "31 December" }, { "input": "When did we discover that SARS-CoV-2, which causes COVID-19, was a novel coronavirus?", "output": "26 January 2020" }, { "input": "How long did it take to identify the cause of COVID-19?", "output": "4 weeks" }, { "input": "What type of test was initially developed to screen for SARS-CoV-2?", "output": " reverse transcription polymerase chain reaction" }, { "input": "How big was the temporary hospital built in Wuhan City for treatment of COVID-19 patients?", "output": "1000 bed hospital" }, { "input": "How long did it take China to build the temporary hospital in Wuhan for COVID-19 patients?", "output": "10 days" }, { "input": "What is a key factor in managing emerging infectious disease threats?", "output": "transparent sharing of information between countries and agencies" }, { "input": "In what year did the MERS epidemic occur?", "output": "2012" }, { "input": "How long did it take to publish the full genomic sequence of SARS-CoV-2 after it was identified?", "output": "2 weeks" }, { "input": "What was the fatality rate for SARS-CoV?", "output": "10%" }, { "input": "What was the fatality rate for MERS?", "output": "34%" }, { "input": "What are some challenges associated with using media and social media to capture information about an emerging epidemic?", "output": "the volume and diversity of the information available and the relative lack of verification mechanisms" }, { "input": "What are the risks of health workers failing to wash hands?", "output": "autoinfection, but also in infection of patients hospitalised for other causes when they provide care" }, { "input": "Who is at risk when health workers fail to wash their hands?", "output": " the health worker, but also for their families and the communities in which they live" }, { "input": "What was the R0 of SARS in absence of control measures?", "output": "3" }, { "input": "What is superspreading?", "output": "where a case infected significantly more contacts than the average" }, { "input": "How many people may have left Wuhan before travel restrictions were imposed?", "output": "5 m people" }, { "input": "How many severe cases of influenza-related illnesses are reported per year?", "output": "Between 3-5 million" }, { "input": "How many influenza-related deaths are reported each year?", "output": "over 250 000" }, { "input": "What is the mortality rate of the H5N1 strain of influenza?", "output": "53%" }, { "input": "What cells are the main target of the influenza A virus in the lungs?", "output": "primary human alveolar epithelial type II (ATII) cells" }, { "input": "How many extracellular domains are in the CEAMCAM1 protein?", "output": "four" }, { "input": "Where is CEACAM1 expressed in the body?", "output": "epithelial and endothelial cells 11 , as well as B cells, T cells, neutrophils, NK cells, macrophages and dendritic cells (DCs)" }, { "input": "What motifs are absent in the short form of CEACAM1 protein?", "output": "immunoreceptor tyrosine-based inhibitory motifs (ITIMs)" }, { "input": "What are the most common isoforms of CEACAM1?", "output": "CEACAM1-4L and CEACAM1-3L" }, { "input": "How do CEACAM1 and CEACAM5 interact?", "output": "heterophilically" }, { "input": "What are the SRC-family of kinases? ", "output": "signaling molecules" }, { "input": "What triggers the release of pro-inflammatory cytokines/chemokines to assist in viral clearance?", "output": "pattern recognition receptors (PRRs)" }, { "input": "What mediates the anti-apoptosis of neutrophils?", "output": "Phosphorylation of CEACAM1 ITIM motifs and activation of caspase-3" }, { "input": "How do natural killer cells fight influenza viruses?", "output": "by recognizing and killing infected cells" }, { "input": "How do influenza viruses escape binding by the natural killer cell activating receptors?", "output": "modification of influenza hemagglutinin (HA) glycosylation" }, { "input": "What is Enfuvirtide?", "output": "HIV fusion inhibitor" }, { "input": "What is labeled in red?", "output": "residues corresponding to the NHR pocket region" }, { "input": "What is marked in blue?", "output": "residues for the PBD" }, { "input": "What is marked in green?", "output": "MT-hook residues adjacent to the N terminus of PBD" }, { "input": "What is labeled in pink?", "output": "mutant residues in PBD of AP2 and AP3" }, { "input": "How many times was the experiment repeated?", "output": "twice" }, { "input": "What was the main finding in the study?", "output": "AP3, exhibited improved antiviral activity, drug resistance profile and pharmacological properties over T20" }, { "input": "What do the results suggest?", "output": "AP3 has potential for development as a new anti-HIV drug" }, { "input": "What enhanced anti-HIV1 activity?", "output": "adding two amino acids of Met and Thr to the N-terminus of a CHR-peptide " }, { "input": "What figure shows that AP3 exhibited higher inhibitory activities on infection by HIV-1 IIIB and HIV-1 Bal strains?", "output": "Fig. 1b" }, { "input": "What is the serum half-life of T20?", "output": "about 2 h" }, { "input": "What kind of model best describes the pharmacokinetic profiles of AP3 and AP2?", "output": "non-compartment model" }, { "input": "What is the in vivo elimination half-life of AP3?", "output": "6.02 h" }, { "input": "Why did the T20/N36 complex not show a typical alpha helical conformation?", "output": "Because T20 lacks the pocket-binding domain (PBD)" }, { "input": "What mutations have been typically associated with T20-resistant HIV-1 variants?", "output": "GIV motif (residues 36-45: GIVQQQNNLL) in the gp41 NHR domain 10" }, { "input": "What are main steps for mitigating the COVID -19 transmission during transport of suspected and confirmed patients?", "output": "firstly, early recognition of the deteriorating patient; secondly, HCW safety; thirdly, bystander safety; fourthly, contingency plans for medical emergencies during transport; fifthly, post-transport decontamination" }, { "input": "How many deaths each year are caused by gastroenteritis?", "output": "two to three million" }, { "input": "What percentage of sporadic diarrhea are caused by norovirus?", "output": "60%" }, { "input": "What is the most common cause of viral gastroenteritis in children?", "output": "Rotavirus" }, { "input": "Which types of adenovirus are associated with diarrhea?", "output": "type 40 and 41" }, { "input": "When was the first tissue culture system developed?", "output": "1907" }, { "input": "What are the most common DNA-based techniques for detecting viruses?", "output": "1. Universal primer-PCR [41] ; 2. Random priming-based PCR [42] ; 3. Virus Discovery cDNA, Amplified Fragment Length Polymorphism (VIDISCA) [43] ; and 4. Sequence-Independent Single Primer Amplification (SISPA)" }, { "input": "What is Universal primer-PCR used for in viral studies?", "output": "detect novel variants" }, { "input": "What is Koch's first postulate?", "output": "The microbe occurs in every case of the disease in question and under circumstances which can account for the pathological changes and clinical course of the disease" }, { "input": "What is Koch's second postulate?", "output": "the microbe occurs in no other disease as a fortuitous and nonpathogenic parasite" }, { "input": "What is Koch's third postulate?", "output": "after being fully isolated from the body and repeatedly grown in pure culture, the microbe can induce the disease anew" }, { "input": "If all 3 of Koch's postulates are met, what does this indicate?", "output": "microbe is the cause of the disease" }, { "input": "Is Koch's postulate applicable to enteric viruses?", "output": "not applicable" }, { "input": "What changes do viruses make to be unrecognizable to previously neutralizing antibodies?", "output": "point mutations on immunodominant regions of surface proteins" }, { "input": "What is hepatitis C?", "output": "positive-sense single stranded RNA enveloped virus" }, { "input": "How large is the HCV genome?", "output": "3,000 aminoacids" }, { "input": "What are the non-structural proteins encoded by the HCV genome?", "output": "p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B" }, { "input": "Why has it been difficult to develop a therapy for the Hepatitis C virus?", "output": "high mutation rate" }, { "input": "An antibody response to which proteins correlates with reduced HCV levels?", "output": "glycoproteins E1 and E2" }, { "input": "How are type A, B, and C viruses determined?", "output": "antigenic differences of their nucleoprotein and matrix protein" }, { "input": "Which type of influenza causes epidemics and pandemics?", "output": "influenza A" }, { "input": "When did lions first occupy Europe?", "output": "By Mid Pleistocene (,500,000 years ago)" }, { "input": "What was the purpose of this study?", "output": "to assess the evolutionary history of lion" }, { "input": "What has been the application of phage display technology?", "output": "protein\u2013protein interactions." }, { "input": "What makes phage display technology useful for other applications?", "output": " inherent biological, biochemical, and biophysical properties of filamentous bacteriophage, as well as the ease of its genetic manipulation" }, { "input": "What are the advantages of phage as a vaccine carrier?", "output": "high immunogenicity, relative antigenic simplicity and ability to activate a range of immune responses" }, { "input": "What is the potential of phage for infectious and chronic diseases?", "output": "prophylactic and therapeutic agent" }, { "input": "What is the regularity of the virion major coat protein lattice useful for?\n", "output": " enables a variety of bioconjugation and surface chemistry applications, particularly in nanomaterials" }, { "input": "Why is the phage ab excellent model system for directed protein evolution?", "output": "the phage\u2019s large population sizes and fast generation times" }, { "input": "What are filamentous bacteriophages genera Inovirua and Plectrovirus?", "output": "non-enveloped, rod-shaped viruses of Escherichia coli whose long helical capsids encapsulate a single-stranded circular DNA genome." }, { "input": "What invention has made bacteriophage useful for research?", "output": "principle of modifying the filamentous phage genome to display polypeptides as fusions to coat proteins on the virion surface " }, { "input": "What has the bacteriphage technology and the library of folded protein variants enabled?", "output": "the ability to seamlessly connect genetic information with protein function for a large number of protein variants simultaneously, and has been widely and productively exploited in studies of proteinprotein interactions" }, { "input": "What are the potential novel applications of the filamentous phage?", "output": "(i) filamentous phage as a vaccine carrier; (ii) engineered filamentous phage as a therapeutic biologic agent in infectious and chronic diseases; (iii) filamentous phage as a scaffold for bioconjugation and surface chemistry; and (iv) filamentous phage as an engine for evolving variants of displayed proteins with novel functions. " }, { "input": "What themes are common in the applications of filamentous phage?", "output": " unique biological, immunological, and physicochemical properties of the phage, its ability to display a variety of biomolecules in modular fashion, and its relative simplicity and ease of manipulation" }, { "input": "What do applications of filamentous phage depend on?", "output": "its ability to display polypeptides on the virion's surface as fusions to phage coat proteins " }, { "input": "What characteristics are determined by the display mode?", "output": " maximum tolerated size of the fused polypeptide, its copy number on the phage, and potentially, the structure of the displayed polypeptide" }, { "input": "How may the display be achieved?", "output": " by fusing DNA encoding a polypeptide of interest directly to the gene encoding a coat protein within the phage genome (type 8 display on pVIII, type 3 display on pIII, etc.)" }, { "input": "What does the term \"phage display\" refer to?", "output": " a recombinant filamentous phage displaying a single polypeptide sequence on its surface (or more rarely, bispecific display achieved via fusion of polypeptides to two different capsid proteins)" }, { "input": "What does the term \"phage displayed library\" refer to?", "output": "a diverse pool of recombinant filamentous phage displaying an array of polypeptide variants (e.g., antibody fragments; peptides)" }, { "input": "What characteristic of filamentous phage has been demonstrated?", "output": "is highly immunogenic in the absence of adjuvants (Meynell and Lawn, 1968 ) and that only the major coat protein, pVIII, and the minor coat protein, pIII, are targeted by antibodies" }, { "input": "What application is a natural extension of the ability to display recombinant exogenous sequences on its surface?", "output": "as carrier to elicit antibodies against poorly immunogenic haptens or polypeptide" }, { "input": "What makes it an attractive vaccine carrier?", "output": "The phage particle's low cost of production, high stability and potential for high valency display of foreign antigen" }, { "input": "What does the display mode determine?", "output": " the maximum tolerated size of the fused polypeptide, its copy number on the phage, and potentially, the structure of the displayed polypeptide. " }, { "input": "Why are antibody epitope based peptide vaccines are no longer an active research area?", "output": "(i) in many cases, peptides incompletely or inadequately mimic epitopes on folded proteins (Irving et al., 2010 ; see below); (ii) antibodies against a single epitope may be of limited utility, especially for highly variable pathogens (Van Regenmortel, 2012); and (iii) for pathogens for which protective immune responses are generated efficiently during natural infection, peptide vaccines offer few advantages over recombinant subunit and live vector vaccines, which have become easier to produce over time." }, { "input": "What phage may be useful in allergy immunotherapy?", "output": "Phage displaying peptide ligands of an anti-IgE antibody elicited antibodies that bound purified IgE molecules" }, { "input": "Which are some phage based contraceptive vaccines for animals?", "output": " immunization with phage displaying follicle-stimulating hormone peptides on pVIII elicited antibodies that impaired the fertility of mice and ewes " }, { "input": "Which are some phage based contraceptive vaccines for animals?", "output": "Phage displaying or chemically Rubinchik and Chow (2000) conjugated to sperm antigen peptides or peptide mimics (Samoylova et al., 2012a,b) and gonadotropin-releasing hormone (Samoylov et al., 2012) are also in development." }, { "input": "What is one reason for the lack of success of immunization phage displayed peptides with native protein?", "output": " it seems that peptide antigens elicit a set of topologically restricted antibodies that are largely unable to recognize discontinuous or complex epitopes on larger biomolecules. While the peptide may mimic the chemistry of a given epitope on a folded protein (allowing it to crossreact with a targeted antibody), being a smaller molecule, it cannot mimic the topology of that antibody's full epitope." }, { "input": "Despite shortcomings, what has the filamentous phage has been useful for?", "output": "as a carrier for peptides with relatively simple secondary structures, which may be stablilized via anchoring to the coat proteins (Henry et al., 2011) . This may be especially true of peptides with poor inherent immunogenicity, which may be increased by high-valency display and phage-associated adjuvanticity" }, { "input": "What is the result of all species tests of phage particles?", "output": " is immunogenic without adjuvant in all species tested to date, including mice (Willis et al., 1993) , rats (Dente et al., 1994) , rabbits (de la Cruz et al., 1988) , guinea pigs (Frenkel et al., 2000; Kim et al., 2004) , fish (Coull et al., 1996; Xia et al., 2005) , non-human primates (Chen et al., 2001) , and humans (Roehnisch et al., 2014) " }, { "input": "What are the results of filamentous phage immunizations in mice?", "output": "serum antibody titers against the phage typically reach 1:10 5 -1:10 6 after 2-3 immunizations, and are maintained for at least 1 year postimmunization (Frenkel et al., 2000) . " }, { "input": "What is the primary antibody response against the phage?", "output": "composed of a mixture of IgM and IgG2b isotypes in C57BL/6 mice, while secondary antibody responses are composed primarily of IgG1 and IgG2b isotypes, with a lesser contribution of IgG2c and IgG3 isotypes (Hashiguchi et al., 2010) ." }, { "input": "Why is phage self-adjuvanting?", "output": "Host cell wall-derived LPS enhances the virion's immunogenicity, and its removal by polymyxin B chromatography reduces antibody titers against phage coat proteins (Grabowska et al., 2000) . The phage's singlestranded DNA genome contains CpG motifs and may also have an adjuvant effect. " }, { "input": "On what does the antibody response to phage depend on?", "output": "MyD88 signaling and is modulated by stimulation of several Toll-like receptors (Hashiguchi et al., 2010) , indicating that innate immunity plays an important " }, { "input": "What do biodistribution studies of the phage after intravenous injection show?", "output": " it is cleared from the blood within hours through the reticuloendothelial system (Molenaar et al., 2002) , particularly of the liver and spleen, where it is retained for days (Zou et al., 2004) , potentially activating marginal-zone B-cell responses. " }, { "input": "What are the merits of the filamentous phage carriers?", "output": " the filamentous phage is not only a highly immunogenic carrier, but by virtue of activating a range of innate and adaptive immune responses, serves as an excellent model virus-like particle antigen." }, { "input": "What is a future potential of filamentous phage?", "output": " as elements of combination therapeutics against certain drug-resistant infections." }, { "input": "What were more potent inhibitors of Staphylococcus aureus growth than high-concentration free chloramphenicol?", "output": "M13 or fd phage displaying either a targeting peptide or antibody fragment and tethered to chloramphenicol by a labile crosslinker " }, { "input": "What killed prostate cancer cells in vitro?", "output": "M13 phage loaded with doxorubicin and displaying a targeting peptide on pIII" }, { "input": "What was the effect of phage displaying peptides on tumor?", "output": "Using the B16-OVA tumor model, Eriksson et al. (2007) showed that phage displaying peptides and/or Fabs specific for tumor antigens delayed tumor growth and improved survival, owing in large part to activation of tumor-associated macrophages and recruitment of neutrophils to the tumor site (Eriksson et al., 2009) " }, { "input": "Why is the phage displaying an scFv against \u03b2-amyloid fibrils is a good diagnostic for Alzheimers and Parkinson's disease?", "output": " ability of the phage to penetrate into brain tissue (Ksendzovsky et al., 2012) " }, { "input": "What is the structure of a filamentous phage particle?", "output": "is enclosed by a rod-like protein capsid, \u223c1000 nm long and 5 nm wide, made up almost entirely of overlapping pVIII monomers, each of which lies \u223c27 angstroms from its nearest neighbor and exposes two amine groups as well as at least three carboxyl groups (Henry et al., 2011)" }, { "input": "What makes filamentous phage ideal scaffold for bioconjugation?", "output": "The regularity of the phage pVIII lattice and its diversity of chemically addressable groups" }, { "input": "What trials have been done to demonstrate the potential of phage in applications for nanomaterials?", "output": "Lee et al. (2002) engineered M13 phage to display a ZnS-binding peptide on pIII and showed that, in the presence of ZnS nanoparticles, they selfassemble into highly ordered film biomaterials that can be aligned using magnetic fields." }, { "input": "What trials have been done to demonstrate the potential of phage in applications for nanomaterials?", "output": "Taking advantage of the ability to display substrate-specific peptides at known locations on the phage filament Hess et al., 2012) , this pioneering FIGURE 3 | Chemically addressable groups of the filamentous bacteriophage major coat protein lattice. " }, { "input": "What is the filamentous phage varion is made of?", "output": "made up of \u223c2,500-4,000 overlapping copies of the 50-residue major coat protein, pVIII, arranged in a shingle-type lattice. Each monomer has an array of chemically addressable groups available for bioorthogonal conjugation, including two primary amine groups (shown in red), three carboxyl groups (show in blue) and two hydroxyl groups (show in green). The 12 N-terminal residues generally exposed to the immune system for antibody binding " }, { "input": "What demonstrate the potential of phage in applications for nanomaterials?", "output": "construction of two-and threedimensional nanomaterials with more advanced architectures, including semiconducting nanowires (Mao et al., 2003 (Mao et al., , 2004 , nanoparticles , and nanocomposites (Oh et al., 2012; Chen et al., 2014)" }, { "input": "What was investigated in this study?", "output": "The capacities of nanopore sequencing for viral diagnostics" }, { "input": "What was the range of genomic sequencing depths?", "output": "19.2 to 103.5X" }, { "input": "Which q-score reads were eliminated from the analysis?", "output": "lower than 7" }, { "input": "What was the mean length of the sequenced read?", "output": "816 nt" }, { "input": "Which strain was similar to other Belgian porcine kobuvirus isolates?", "output": "17V079" }, { "input": "What is Clodstridium difficile?", "output": "Gram positive, anaerobic bacterium" }, { "input": "What is sporulation?", "output": "adaptive strategy that enables bacteria to survive harsh environmental conditions for prolonged periods of time" }, { "input": "What is the key regulator to sporulation?", "output": "Spo0A" }, { "input": "What are the main virulence factors in C. difficle?", "output": "toxins A and B" }, { "input": "What laboratory test can be used to monitor protein expression?", "output": "Western blot" }, { "input": "How is Venezuelan equine encephalitis virus transmitted?", "output": "by mosquitoes" }, { "input": "What are the symptoms of Venezuelan equine encephalitis virus?", "output": "fever, malaise, and vomiting" }, { "input": "What is the mortality rate of Venezuelan equine encephalitis virus in children?", "output": "35%" }, { "input": "What is the mortality rate of Venezuelan equine encephalitis virus in adults?", "output": "10%" }, { "input": "What vaccine can be used to prevent Venezuelan equine encephalitis virus?", "output": "TC83" }, { "input": "What can RNA sequencing be used to monitor?", "output": "changes in gene expression" }, { "input": "What activates the UPR pathway in the cell?", "output": "protein misfolding" }, { "input": "What indicators does the UPR pathway use to regulate protein folding and secretion in the cell?", "output": "inositolrequiring enzyme 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6)" }, { "input": "Where does EGR1 accumulate in the cell?", "output": "nucleus" }, { "input": "What is EGR1?", "output": "a transcription factor" }, { "input": "What is disease resilience?", "output": " the ability of a given host to tolerate an infection, and to return to a state of health" }, { "input": "What family of virus does SARS reside in?", "output": "coronavirus" }, { "input": "What family of virus does MERS reside in?", "output": "coronavirus" }, { "input": "When was SARS-CoV first identified?", "output": "2003" }, { "input": "How many people did SARS-CoV infect?", "output": "8000" }, { "input": "What percentage of people infected with MERS-CoV died?", "output": "35-50%" }, { "input": "What percentage of people infected with SARS-CoV died?", "output": "10%" }, { "input": "What was the reservoir for SARS-CoV and MERS-CoV?", "output": "animal reservoirs" }, { "input": "What was the primary threatening clinical finding in patients infected with SARS-CoV and MERS-CoV?", "output": "severe lung pathology" }, { "input": "What is the relationship between SARS-CoV and acute lung injury (ALI)?", "output": "Many infected patients have acute lung injury (ALI)" }, { "input": "What is the relationship between SARS-CoV and acute respiratory distress syndrome (ARDS)?", "output": " In some patients there is a progression to the more severe form of ALI, acute respiratory distress syndrome (ARDS)" }, { "input": "What is required for a person to survive a serious SARS-CoV infection?", "output": " a successful host must not only be able to clear the pathogen, but tolerate damage caused by the pathogen itself and also by the host's immune response" }, { "input": "How does cell-entry differ between SARS-CoV and MERS-CoV?", "output": "SARS-CoV uses the ACE2 receptor to gain entry to cells, while MERS-CoV uses the ectopeptidase DPP4" }, { "input": "What is a major difference in clinical progression between SARS-CoV and MERS-CoV?", "output": "Unlike SARS-CoV infection, which causes primarily a severe respiratory syndrome, MERS-CoV infection can also lead to kidney failure" }, { "input": "How does transmission differ between SARS-CoV and MERS-CoV?", "output": " SARS-CoV also spreads more rapidly between hosts, while MERS-CoV has been more easily contained, but it is unclear if this is due to the affected patient populations and regions" }, { "input": "How do SARS-CoV and MERS-CoV evade the immune system sensing it's genome?", "output": "SARS-CoV and MERS-CoV are contained in double membrane vesicles" }, { "input": "What role does initial viral titer play in the prognosis of SARS-CoV and MERS-CoV?", "output": "In patients with high initial viral titers there is a poor prognosis" }, { "input": "What is the timeline of the type I interferon (IFN) response in SARS-CoV infection?", "output": "In a mouse model of SARS-CoV infection, the type I IFN response is delayed" }, { "input": "How do SARS-CoV viral proteins interact with the immune response?", "output": "several viral proteins suppress the type I IFN response, and other aspects of innate antiviral immunity" }, { "input": "What was the role of corticosteroid use in hospitalized patients with SARS-CoV?", "output": "Retrospective analysis revealed that, when given at the correct time and to the appropriate patients, corticosteroid use could decrease mortality and also length of hospital stays" }, { "input": "What is the role of interferon's (IFNs) in the treatment of SARS-CoV?", "output": " there is some evidence that simultaneous treatment with IFNs could increase the potential benefits" }, { "input": "What are some negative effects of decreasing immunopathology by immunomodulation?", "output": "decreasing immunopathology by immunomodulation is problematic because it can lead to increased pathogen burden, and thus increase virus-induced pathology" }, { "input": "What is the role of topoisomerase I in improving host resilience in viral lung infections?", "output": "A recent paper demonstrates that topoisomerase I can protect against inflammation-induced death from a variety of viral infections including IAV" }, { "input": "What is the role of complement 5a (C5a) in increasing host resilience to viral lung infection?", "output": "Blockade of C5a complement signaling has also been suggested as a possible option in decreasing inflammation during IAV infection" }, { "input": "What is the role of statins in increasing host resilience to viral lung infections?", "output": "They act to stabilize the activation of aspects of the innate immune response and prevent excessive inflammation" }, { "input": "Which medical comorbidities most profoundly influenced MERS-CoV outcomes?", "output": "if they were obese, immunocompromised, diabetic or had cardiac disease" }, { "input": "Which immune factors were associated with increased SARS-CoV morbidity and mortality?", "output": "a higher neutrophil count and low T-cell counts" }, { "input": "What is the prognostic role of coinfection in SARS-CoV and MERS-CoV infections?", "output": "One factor that increased disease for patients infected with SARS-CoV and MERS-CoV was infection with other viruses or bacteria" }, { "input": "Can host resilience be predicted?", "output": "A recent study looking at malaria infections in animal models and human patients demonstrated that resilient hosts can be predicted" }, { "input": "Can biomarkers be used to predict outcomes in acute respiratory distress (ARDS) patients?", "output": "Clinical studies have started to correlate specific biomarkers with disease outcomes in ARDS patients" }, { "input": "What work has been carried out this study?", "output": "A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. " }, { "input": "How many confirmed cases were identified in February 2020?", "output": " 25,000" }, { "input": "What was the case fatality rate?", "output": " 2%" }, { "input": "Who are the majority of cases?", "output": "males with a median age of 55 years and linked to the Huanan Seafood Wholesale Market " }, { "input": "What are the symptoms at the onset?", "output": "fever, cough, and myalgia or fatigue." }, { "input": "What type of virus is 2019-nCOV?", "output": "betacoronavirus" }, { "input": "What clade does it belong to?", "output": " forms a clade within the subgenus sarbecovirus of the Orthocoronavirinae subfamily " }, { "input": "What other betacoronaviruses are zoonotic in origin?", "output": "The severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)" }, { "input": "How does the pathogenicity of 2019-nCOV compare with other viruses?", "output": "Based on current evidence, pathogenicity for 2019-nCoV is about 3%, which is significantly lower than SARS-CoV (10%) and MERS-CoV (40%)" }, { "input": "How does the transmissibility of 2019-nCOV compare with other viruses?", "output": "2019-nCoV has potentially higher transmissibility (R0: 1.4-5.5) than both SARS-CoV (R0: [2] [3] [4] [5] and MERS-CoV (R0: <1)" }, { "input": "Which electronic databases were used for this study?", "output": "PubMed, Embase and Cochrane Library" }, { "input": "What was the purpose of the search?", "output": " to identify published studies examining the diagnosis, therapeutic drugs and vaccines for Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019-nCoV), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines." }, { "input": "What topics were searched for?", "output": "randomized controlled trials (RCTs) and validation trials (for diagnostics test) published in English, that measured (a) the sensitivity and/or specificity of a rapid diagnostic test or a point-of-care testing kit, (b) the impact of drug therapy or (c) vaccine efficacy against either of these diseases with no date restriction applied. For the 2019-nCoV, we searched for all in vitro, animal, or human studies published in English between 1 December 2019 and 6 February 2020, on the same outcomes of interest. " }, { "input": "What studies were excluded?", "output": " Studies that examined the mechanisms of diagnostic tests, drug therapy or vaccine efficacy against SARS, MERS and 2019-nCoV" }, { "input": "What did the searches yield?", "output": "A Google search for 2019-nCoV diagnostics (as of 6 February 2020; Table S2 ) yielded five webpage links from government and international bodies with official information and guidelines (WHO, Europe CDC, US CDC, US FDA), three webpage links on diagnostic protocols and scientific commentaries, and five webpage links on market news and press releases. Six protocols for diagnostics using reverse transcriptase polymerase chain reaction (RT-PCR) from six countries were published on WHO's website [9] . Google search for 2019-nCoV vaccines yielded 19 relevant articles." }, { "input": " What is the the primary means for diagnosing the new virus strain?", "output": "real time RT-PCR" }, { "input": "What are roles of the period and type of specimens?", "output": "It was found that the respiratory specimens were positive for the virus while serum was negative in the early period. It has also suggested that in the early days of illness, patients have high levels of virus despite the mild symptoms." }, { "input": "What are some of the other diagnostic methods?", "output": "reverse transcription loop-mediated isothermal amplification (RT-LAMP), RT-insulated isothermal PCR (RT-iiPCR) and a one-step rRT-PCR assay based on specific TaqMan probes." }, { "input": "How does RT-LAMP compare with other methods?", "output": " RT-LAMP has similar sensitivity as real time RT-PCR. It is also highly specific and is used to detect MERS-CoV. It is comparable to the usual diagnostic tests and is rapid, simple and convenient." }, { "input": "How do RT-iiPCR and a one-step rRT-PCR compare with other methods?", "output": " have also shown similar sensitivity and high specificity for MER-CoV." }, { "input": " Why is RT-PCR not the best method sometimes?", "output": "high levels of PCR inhibition may hinder PCR sensitivity " }, { "input": "What did the comparison between the molecular test and serological test show?", "output": " that the molecular test has better sensitivity and specificity. " }, { "input": "What enhancements to the molecular tests were looked at?", "output": "Studies looked at using nested PCR to include a pre-amplification step or incorporating N gene as an additional sensitive molecular marker to improve on the sensitivity " }, { "input": "What is the threshold sensitivity of Real time PCR?", "output": "10 genome equivalents per reaction" }, { "input": "How is the reproducibility of real time PCR?", "output": "has a good reproducibility with the inter-assay coefficients of variation of 1.73 to 2.72%." }, { "input": "What are potential vaccines based on?", "output": "messenger RNA, DNA-based, nanoparticle, synthetic and modified virus-like particle)" }, { "input": "Which kit is currently used in China?", "output": " kit developed by the BGI have passed emergency approval procedure of the National Medical Products Administration, and are currently used in clinical and surveillance centers of China" }, { "input": "Why were only four studies included?", "output": "Most studies on SARS and MERS vaccines were excluded as they were performed in cell or animal models " }, { "input": "Which four studies were included?", "output": " Phase I clinical trials on SARS or MERS vaccines" }, { "input": "What is te safety of the vaccines?\n", "output": " All vaccine candidates for SARS and MERS were reported to be safe, " }, { "input": "What was the performance of the vaccine candidates?", "output": "well-tolerated and able to trigger the relevant and appropriate immune responses in the participants" }, { "input": "How many clinical trials are registered?", "output": "nine" }, { "input": "What is the status of the nine trials?", "output": " five studies on hydroxychloroquine, lopinavir plus ritonavir and arbidol, mesenchymal stem cells, traditional Chinese medicine and glucocorticoid therapy usage have commenced recruitment. The remaining four studies encompass investigation of antivirals, interferon atomization, darunavir and cobicistat, arbidol, and remdesivir usage for 2019-nCoV patients" }, { "input": "What are the results on seroconversion?", "output": " Seroconversion measured by S1-ELISA occurred in 86% and 94% participants after 2 and 3 doses, respectively, and was maintained in 79% participants up to study end at week 60." }, { "input": "What were the results on antibodies?", "output": "Neutralising antibodies were detected in 50% participants at one or more time points during the study, but only 3% maintained neutralisation activity to end of study." }, { "input": "What were the T-cell responses?", "output": " detected in 71% and 76% participants after 2 and 3 doses, respectively." }, { "input": "What were the differences in immune responses?", "output": "no differences in immune responses between dose groups after 6 weeks and vaccine-induced humoral and cellular responses were respectively detected in 77% and 64% participants at week 60" }, { "input": "What is the observed benefit of the molecules?", "output": "Molecules developed by the university scientists inhibit two coronavirus enzymes and prevent its replication. The discovered drug targets are said to be more than 95% similar to enzyme targets found on the SARS virus. " }, { "input": "What is the ongoing randomized trial investigating?", "output": "It investigates the usage of Lopinavir/Ritonavir and Interferon Beta 1B." }, { "input": "What are the many prospective and restrospective studies conducted on?", "output": " usage of ribavirin with lopinavir/ritonavir/ribavirin, interferon, and convalescent plasma usage." }, { "input": "What was the result of the phase 1 trial of IgG immunoglobin?", "output": "The trial conducted in the United States in 2017 demonstrated SAB-301 to be safe and well-tolerated at single doses. " }, { "input": "What role rapid diagnostics plays?", "output": "enables prompt and accurate public health surveillance, prevention and control measures. Local transmission and clusters can be prevented or delayed by isolation of laboratory-confirmed cases and their close contacts quarantined and monitored at home" }, { "input": "What other measures rapid diagnostics facilitates?", "output": "specific public health interventions such as closure of high-risk facilities and areas associated with the confirmed cases for prompt infection control and environmental decontamination " }, { "input": "What are ways to perform laboratory diagnostics?", "output": " (a) detecting the genetic material of the virus, (b) detecting the antibodies that neutralize the viral particles of interest, (c) detecting the viral epitopes of interest with antibodies (serological testing), or (d) culture and isolation of viable virus particles." }, { "input": "What are key limtations of genetic detection?", "output": "lack of knowledge of the presence of viable virus, the potential cross-reactivity with non-specific genetic regions and the short timeframe for accurate detection during the acute infection phase." }, { "input": "What is a key limitation of serological testing?", "output": "the need to collect paired serum samples (in the acute and convalescent phases) from cases under investigation for confirmation to eliminate potential cross-reactivity from non-specific antibodies from past exposure and/or infection by other coronaviruses." }, { "input": "What is the limitation in virus testing?", "output": " the long duration and the highly specialized skills required of the technicians to process the samples. " }, { "input": "What was the result of the treatment?", "output": "Significantly shorted time from the disease onset to the symptom improvement in treatment (5.10 \u00b1 2.83 days) compared to control group (7.62 \u00b1 2.27 days) (p < 0.05) No significant difference in blood routine improvement, pulmonary chest shadow in chest film improvement and corticosteroid usgae between the 2 groups. " }, { "input": "What superiority did the treatment with integrative chinese and western medicine treatment have compared with using control treatment alone?", "output": "in the respect of improving clinical symptoms, elevating quality of life, promoting immune function recovery, promoting absorption of pulmonary inflammation, reducing the dosage of cortisteroid and shortening the therapeutic course" }, { "input": " What was a characteristic of SARS-CoV and MERS-CoV, specimens collected from the lower respiratory tract such as sputum and tracheal aspirates?", "output": "have higher and more prolonged levels of viral RNA because of the tropism of the virus. " }, { "input": "How do severe cases compare with mild cases?", "output": "viral loads are also higher for severe cases and have longer viral shedding compared to mild cases" }, { "input": "What is the disadvantage of upper respiratory tract specimens?", "output": "hey have potentially lower viral loads and may have higher risk of false-negatives among the mild MERS and SARS cases [102, 103] , and likely among the 2019-nCoV cases.\n" }, { "input": "What are the existing practices in detecting genetic material of viruses?", "output": "(a) reverse transcription-polymerase chain reaction (RT-PCR), (b) real-time RT-PCR (rRT-PCR), (c) reverse transcription loop-mediated isothermal amplification (RT-LAMP) and (d) real-time RT-LAMP [104] . " }, { "input": "Why are Nucleic amplification tests (NAAT) usually preferred as in the case of MERS-CoV diagnosis?", "output": "it has the highest sensitivity at the earliest time point in the acute phase of infection " }, { "input": "Where was the first validated diagnostic test designed?", "output": " in Germany" }, { "input": "How were the assays selected ?", "output": "based on the match against 2019-nCoV upon inspection of the sequence alignment. " }, { "input": "How were the assays used?", "output": "Two assays were used for the RNA dependent RNA polymerase (RdRP) gene and E gene where E gene assay acts as the first-line screening tool and RdRp gene assay as the confirmatory testing. " }, { "input": "What were the results?", "output": "All assays were highly sensitive and specific in that they did not cross-react with other coronavirus and also human clinical samples that contained respiratory viruses " }, { "input": "What did the trial on SAB-301 demonstrate?", "output": " to be safe and well-tolerated at single doses." }, { "input": "What conditions are caused by Staphylococcus aureus?", "output": "mild skin infections to fatal necrotizing pneumonia" }, { "input": "What percentage of healthy adults are asymptotically colonized by pneumococcus bacteria?", "output": "8-30%" }, { "input": "What types of cells follow epithelial cells in the immune response to infections in the lung?", "output": "alveolar macrophages" }, { "input": "What enhances the expression of type I interferon?", "output": "The subsequent infection with Gram-positive bacteria" }, { "input": "What reduces the antimicrobial activities of alveolar macrophages?", "output": "Reduced TNF\u03b1 production by NK cells" }, { "input": "What is Pneumolysin?", "output": "a pneumococcal pore-forming toxin" }, { "input": "What factors make bacterial and viral co-infections so lethal?", "output": "epithelial barrier damage, exaggerated innate immune response, and cytokine storm" }, { "input": "What are inovirus-associated vectors?", "output": "engineered, non-lytic, filamentous bacteriophages" }, { "input": "How can random peptide libraries be used in applications?", "output": "the identification of peptide ligands by receptors, the mapping of substrate sites for enzymes, and the creation of antibody peptide libraries" }, { "input": "Which Lactobacililus casei strain does not have the cholera toxin subunit A1 (CTA1) on the surface?", "output": "pgsA-sM2/L. casei" }, { "input": "What is the most effective treatment against influenza?", "output": "Vaccination" }, { "input": "What is the percentage decrease in influenza antibodies after 8 months after inoculation with the inactivated vaccine?", "output": "75%" }, { "input": "Why is matrix protein 2 (M2) an attractive target for a universal influenza vaccine?", "output": "highly conserved among influenza A virus strains" }, { "input": "Why have M2-based vaccines been ineffective?", "output": "low immunogenicity" }, { "input": "Why are lactic acid bacteria considered an attractive delivery system for a live influenza vaccine?", "output": "considered safe and exhibits an adjuvant-like effect on mucosal and systemic immunity" }, { "input": "What primer pairs were used for PCR?", "output": "59-GGGGTACCTCATTATTAACA-39, and 59-ACGTCGACT-CATTATTCAAGTTCAATAATG AC-39" }, { "input": "What is considered essential to boost the interaction of the influenza vaccine with the mucosal immune system?", "output": "the incorporation of an adjuvant" }, { "input": "Name some adjuvants that have been used with an influenza vaccine.", "output": "liposomes, nanoparticles, and immunostimulating complexes (ISCOMs)" }, { "input": "What was found in the lungs of the control mice in this study?", "output": "severe pneumonitis" }, { "input": "What did this study show?", "output": "recombinant L. casei expressing CTA1-sM2 induced long-lasting immunity and conferred protection against lethal infections by influenza" }, { "input": "What regulates the secretion of proinflammatory cytokines?", "output": "Nod-like receptor family, pyrin domain-containing 3" }, { "input": "Where does the NLRP3 inflammasome activate after a SARS-CoV infection?", "output": "in lipopolysaccharide-primed macrophages" }, { "input": "What ion channel is essential for 3a-mediated IL-1Beta secretion?", "output": "ion channel activity of the 3a protein" }, { "input": "What are viroporins?", "output": "transmembrane pore-forming viral proteins" }, { "input": "What is the genus of the SARS coronavirus?", "output": "Betacoronavirus" }, { "input": "What is the family of the SARS coronavirus?", "output": "Coronaviridae" }, { "input": "Is the SARS coronavirus enveloped?", "output": "enveloped" }, { "input": "Is the SARS coronavirus single-stranded or double-stranded?", "output": "single-stranded" }, { "input": "How many laboratory-confirmed cases of SARS coronavirus infections were reported between November 2002 and July 2003?", "output": "At least 8,098" }, { "input": "What was the fatality rate of the SARS coronavirus outbreak between November 2002 and July 2003?", "output": "9.6%" }, { "input": "What are examples of proinflammatory cytokines?", "output": "tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-1\u03b2, and IL-6" }, { "input": "How does NLRP3 detect RNA viral infection?", "output": "by sensing the cellular damage or distress induced by viroporins" }, { "input": "How many amino acids are in the SARS-CoV E protein?", "output": "76 amino acids" }, { "input": "What type of ion channels are formed by the SARS-CoV E protein?", "output": "Ca 2+ -permeable" }, { "input": "What does the SARS-CoV protein activate?", "output": "NLRP3 inflammasome" }, { "input": "What is critical to the development of a protective granuloma in tuberculosis infections?", "output": "tumor necrosis factor-\u03b1" }, { "input": "What is tumor necrosis factor-alpha?", "output": "cytokines" }, { "input": "What regulates the activity of MAPK activity?", "output": "MAPK phosphatase-1" }, { "input": "What causes tuberculosis?", "output": "Mycobacterium tuberculosis" }, { "input": "What percentage of the world has been infected by tuberculosis?", "output": "one third of the world's population" }, { "input": "How many new tuberculosis cases are there each year worldwide?", "output": "9.2 million" }, { "input": "What are some mitogen activated protein kinases?", "output": "extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK)" }, { "input": "How is MAPK activated?", "output": "phosphorylation" }, { "input": "What enzymes are involved with phosphorylation?", "output": "tyrosine phosphatases, serine/threonine phosphatases, and dual-specificity phosphatases (DUSPs)" }, { "input": "How many MAPK phosphatases exist?", "output": "at least 10" }, { "input": "What is lipopolysaccharide?", "output": "a cell wall component of Gram-negative bacteria" }, { "input": "What is Staph aureus?", "output": "Gram positive bacteria" }, { "input": "What protein is in the critical path of immunity and cytokine expression?", "output": "MAPK" }, { "input": "What diminishes the effectiveness of annual influenza vaccinations?", "output": "Constant evolution of circulating influenza virus strains and the emergence of new strains" }, { "input": "what new type of influenza vaccines are needed?", "output": "efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines." }, { "input": "What alternatives to classical vectored vaccines are needed?", "output": "Recombinant virus-vectored vaccines" }, { "input": "What is the advantage of virus vectored vaccine?", "output": "a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract " }, { "input": "What is the advantage of virus vectored vaccines?", "output": " virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. " }, { "input": "What is one of the issues with present vaccines?", "output": " low efficacy in the populations at greatest risk of complications from influenza virus infection, i.e., the young and elderly" }, { "input": "What general types of vaccines are available?", "output": "trivalent inactivated influenza vaccine (TIV), quadrivalent influenza vaccine (QIV), and live attenuated influenza vaccine (LAIV; in trivalent and quadrivalent forms)" }, { "input": "What inactivated vaccines are available?", "output": "whole virus inactivated, split virus inactivated, and subunit vaccines." }, { "input": "How is the split virus inactivated?", "output": "the virus is disrupted by a detergent" }, { "input": "How is the TIV administered?", "output": "intramuscularly " }, { "input": "What does the TIV contain?", "output": " three or four inactivated viruses, i.e., two type A strains (H1 and H3) and one or two type B strains. " }, { "input": "How is the TIV efficacy measured?", "output": "humoral responses to the hemagglutinin (HA) protein," }, { "input": "Which is the major surface and attachment glycoprotein on influenza virus?", "output": "hemagglutinin (HA) protein," }, { "input": "How is the serum antibody response measured?", "output": " by the hemagglutination-inhibition (HI) assay," }, { "input": "What is a gold standard for correlation with immunity to influenza?", "output": "strain-specific HI titer " }, { "input": "What is the indication for protection to influenza?", "output": " a four-fold increase in titer post-vaccination, or a HI titer of \u22651:40 is considered protective " }, { "input": "What gives protection against clinical disease?", "output": "serum antibodies" }, { "input": "What can give protection against clinical disease?", "output": "mucosal IgA antibodies also may contribute to resistance against infection" }, { "input": "How is the LAIV administered?", "output": "nasal spray" }, { "input": "What does the LAIV contain?", "output": "the same three or four influenza virus strains as inactivated vaccines but on an attenuated vaccine backbone " }, { "input": "Do LAIV replicate at body temperature?", "output": "they do not replicate effectively at core body temperature" }, { "input": "What is a characteristic of LAIV?", "output": "LAIV are temperature-sensitive and cold-adapted " }, { "input": "Where do the LAIV replicate?", "output": "replicate in the mucosa of the nasopharynx" }, { "input": "What does LAIV immunization do?", "output": "LAIV immunization induces serum antibody responses, mucosal antibody responses (IgA), and T cell responses." }, { "input": "What do the inactivated vaccines rely on?", "output": "specific antibody responses to the HA, and to a lesser extent NA proteins for protection." }, { "input": "What enables virus invasion from immunity?", "output": "The immunodominant portions of the HA and NA molecules undergo a constant process of antigenic drift, a natural accumulation of mutations" }, { "input": "When does the vaccine strain selection occur in the northern hemisphere?", "output": "in February" }, { "input": "What is the efficacy of LAIV?", "output": "it is generally considered to be as effective as inactivated vaccines and may be more efficacious in children " }, { "input": "What does LAIV rely on?", "output": "antigenic match" }, { "input": "What is the LAIV replacement schedule?", "output": " the HA and NA antigens are replaced on the same schedule as the TIV" }, { "input": "Why LAIV may provide broader broader protection than TIV?", "output": "due to the diversity of the immune response consistent with inducing virus-neutralizing serum and mucosal antibodies, as well as broadly reactive T cell responses" }, { "input": "What has raised the possibility of universal influenza vaccine?", "output": "improved understanding of immunity to conserved influenza virus antigens" }, { "input": "What is the advantage of recombinant DNA systems?", "output": "allow ready manipulation and modification of the vector genome" }, { "input": "What is the advantage of recombinant DNA system?", "output": "enables modification of the vectors to attenuate the virus or enhance immunogenicity" }, { "input": "What is the advantage of recombinant DNA systems?", "output": "adding and manipulating the influenza virus antigens" }, { "input": "What is the issue with each of these vaccines?", "output": "is either replication-defective or causes a self-limiting infection" }, { "input": "What is a concern with these vaccines?", "output": " like LAIV, safety in immunocompromised individuals" }, { "input": "How many serotypes of adenovirus are there?", "output": "53 " }, { "input": "Why adenovirus may be the safest vaccine vector?", "output": " A live adenovirus vaccine containing serotypes 4 and 7 has been in use by the military for decades" }, { "input": "Which is the most studied serotype?", "output": "Adenovirus 5 (Ad5) " }, { "input": "Why is Ad5 is the most studied serotype? ", "output": "having been tested for gene delivery and anti-cancer agents, as well as for infectious disease vaccines" }, { "input": "Why are adenovirus vectors most attractive?", "output": "their genome is very stable and there are a variety of recombinant systems available which can accommodate up to 10 kb of recombinant genetic material " }, { "input": "What is the advantage of the adenovirus ?", "output": "is a non-enveloped virus which is relatively stable and can be formulated for long-term storage at 4 \u00b0C, or even storage up to six months at room temperature " }, { "input": "What is the advantage of adenovirus vector?", "output": "Adenovirus vaccines can be grown to high titers, exceeding 10 1\u00b0 plaque forming units (PFU) per mL when cultured on 293 or PER.C6 cells " }, { "input": "What is the advantage of adenovirus?", "output": "the virus can be purified by simple methods " }, { "input": "What is the advantage of adenovirus vaccines?", "output": " Adenovirus vaccines can also be delivered via multiple routes, including intramuscular injection, subcutaneous injection, intradermal injection, oral delivery using a protective capsule, and by intranasal delivery." }, { "input": "What is the advantage of oral capsule and intranasal deliveries?", "output": "induce robust mucosal immune responses and may bypass preexisting vector immunity " }, { "input": "What did the first report on adenovirus as a vector demonstrate?", "output": "immunogenicity of recombinant adenovirus 5 (rAd5) expressing the HA of a swine influenza virus, A/Swine/Iowa/1999 (H3N2)" }, { "input": "Which rAd5 delivery has been tested?", "output": "A rAd5-HA expressing the HA from A/Puerto Rico/8/1934 (H1N1; PR8) was delivered to humans epicutaneously or intranasally " }, { "input": "What was the result of the rAd5-HA testing?", "output": "The vaccine was well tolerated and induced seroconversion with the intranasal administration had a higher conversion rate and higher geometric meant HI titers " }, { "input": "What is the result of rAd5 trials?", "output": "clinical trials with rAd vectors have overall been successful, demonstrating safety and some level of efficacy," }, { "input": "What is an example of failure of rAd5?", "output": " a gene therapy examination where high-dose intravenous delivery of an Ad vector resulted in the death of an 18-year-old male" }, { "input": "What was the failure of rAd5 vaccine for inducing HIV-1 specific T cell response?", "output": "the study was stopped after interim analysis suggested the vaccine did not achieve efficacy and individuals with high preexisting Ad5 antibody titers might have an increased risk of acquiring HIV-1 " }, { "input": "What does immunization with adenovirus induce?", "output": "potent cellular and humoral immune responses that are initiated through toll-like receptor-dependent and independent pathways which induce robust pro-inflammatory cytokine responses" }, { "input": "What is the advantage of inclusion of non-HA antigens to HA based vaccines?", "output": " to improve immunogenicity and broaden breadth of both humoral and cellular immunity" }, { "input": "What is the disadvantage of inclusion of non-HA antigens to HA based vaccines?", "output": "as both CD8 + T cell and neutralizing antibody responses are generated by the vector and vaccine antigens, immunological memory to these components can reduce efficacy and limit repeated use " }, { "input": "What was the first reported baculovirus vector based vaccine for influenza?", "output": " using Autographa californica nuclear polyhedrosis virus (AcNPV) expressing the HA of PR8 under control of the CAG promoter (AcCAG-HA) " }, { "input": "What is a drawback of Ad5 vector?", "output": "preexisting immunity," }, { "input": "What alternatives to Ad5 vector have been explored?", "output": "adenovirus serotypes have been explored as vectors, particularly non-human and uncommon human serotypes" }, { "input": "What animal adenoviruses have been shown to induce immunity comparable to rdA5-HA?", "output": "Swine, NHP and bovine adenoviruses expressing H5 HA antigens " }, { "input": "what can evade anti-Ad5 response and also provide effective antigen delivery and immunogenicity?", "output": " Low prevalence serotypes such as adenovirus types 3, 7, 11, and 35" }, { "input": "What additional strategies have been explored to avoid preexisting immunity?", "output": "Prime-boost strategies, using DNA or protein immunization in conjunction with an adenovirus vaccine booster immunization" }, { "input": "What is the advantage of AAV vector?", "output": "Like rAd vectors, rAAV have broad tropism infecting a variety of hosts, tissues, and proliferating and non-proliferating cell types " }, { "input": "What is the advantage of the AAV vector?", "output": " The wild type viruses are non-pathogenic and replication incompetent in humans and the recombinant AAV vector systems are even further attenuated " }, { "input": "What is the advantage of AAV vector?", "output": "As members of the parvovirus family, AAVs are small non-enveloped viruses that are stable and amenable to long-term storage without a cold chain." }, { "input": "What is the advantage of AAV vector?", "output": "While there is limited preexisting immunity, availability of non-human strains as vaccine candidates eliminates these concerns." }, { "input": "Has AAV been studied as vectors for influenza?", "output": "There are limited studies " }, { "input": "What are alphaviruses?", "output": "positive-sense, single-stranded RNA viruses of the Togaviridae family" }, { "input": "What are some alphavirus vectors that have been developed?", "output": "Semliki Forest virus (SFV), Sindbis (SIN) virus, Venezuelan equine encephalitis (VEE) virus, as well as chimeric viruses incorporating portions of SIN and VEE viruses" }, { "input": "How do the alphavirus vectors work?", "output": " The replication defective vaccines or replicons do not encode viral structural proteins, having these portions of the genome replaces with transgenic material." }, { "input": "How do the alphavirus vectors work?", "output": "The structural proteins are provided in cell culture production systems." }, { "input": "What is an important feature of the replicon system?", "output": "the self-replicating nature of the RNA. Despite the partial viral genome, the RNAs are self-replicating and can express transgenes at very high levels" }, { "input": "How did the VEE based replicon system incorporating HA from PR8perform?", "output": "demonstrated to induce potent HA-specific immune response and protected from challenge in a murine model, despite repeated immunization with the vector expressing a control antigen, suggesting preexisting immunity may not be an issue for the replicon vaccine" }, { "input": "Why is the VEE replicon system particularly appealing?", "output": "the VEE targets antigen-presenting cells in the lymphatic tissues, priming rapid and robust immune responses" }, { "input": "What is the advantage of the VEE replicon system?", "output": "VEE replicon systems can induce robust mucosal immune responses through intranasal or subcutaneous immunization [72] [73] [74] , and subcutaneous immunization with virus-like replicon particles (VRP) expressing HA-induced antigen-specific systemic IgG and fecal IgA antibodies " }, { "input": "What were the VRPs derived from VEE developed for?", "output": "as candidate vaccines for cytomegalovirus (CMV)" }, { "input": "What did the clinical trial with CMV VRP show?", "output": "vaccine was immunogenic, inducing CMV-neutralizing antibody responses and potent T cell responses. Moreover, the vaccine was well tolerated and considered safe " }, { "input": "What did the clinical trial with VRP show?", "output": "vaccine was safe and despite high vector-specific immunity after initial immunization, continued to boost transgene-specific immune responses upon boost " }, { "input": "Which baculovirus vaccine has been approved for \n human use?", "output": "baculovirus-derived recombinant HA vaccine was approved for human use and was first available for use in the United States for the 2013-2014 influenza season" }, { "input": "What is the advantage of baculoviruses?", "output": "readily manipulated" }, { "input": "What is the advantage of baculovirus vectors?", "output": "The vectors can accommodate large gene insertions, show limited cytopathic effect in mammalian cells, and have been shown to infect and express genes of interest in a spectrum of mammalian cells" }, { "input": "How can baculovirus vectors be improved?", "output": "While the insect promoters are not effective for mammalian gene expression, appropriate promoters can be cloned into the baculovirus vaccine vectors." }, { "input": "what baculovirus vector based immunization provided protection from lethal challenge?", "output": "only intranasal immunization" }, { "input": "What was the benefit of the robust innate immune response to baculovirus vector?", "output": " non-specific protection from subsequent influenza virus infection" }, { "input": "What is the Newcastle disease virus?", "output": "a single-stranded, negative-sense RNA virus that causes disease in poultry. " }, { "input": "What are the appealing qualities of the NDV vector?", "output": "As an avian virus, there is little or no preexisting immunity to NDV in humans and NDV propagates to high titers in both chicken eggs and cell culture. " }, { "input": "What is the appealing quality of the NDV vector?", "output": "As a paramyxovirus, there is no DNA phase in the virus lifecycle reducing concerns of integration events, and the levels of gene expression are driven by the proximity to the leader sequence at the 3' end of the viral genome. This gradient of gene expression enables attenuation through rearrangement of the genome, or by insertion of transgenes within the genome." }, { "input": "What is the appealing quality of the NDV vector?", "output": "pathogenicity of NDV is largely determined by features of the fusion protein enabling ready attenuation of the vaccine vector" }, { "input": "What did the first report on the NDV vector test conclude?", "output": "it induced a robust serum antibody response and protected against homologous influenza virus challenge in a murine model of infection " }, { "input": "What is the added protection of NDV vector?", "output": "providing protection against both the influenza virus and NDV infection." }, { "input": "What have the limited NDV human trails shown?", "output": "the NDV vector is well-tolerated, even at high doses delivered intravenously " }, { "input": "What are the attractive features of the PIV5 vector?", "output": " PIV5 has a stable RNA genome and no DNA phase in virus replication cycle reducing concerns of host genome integration or modification. PIV5 can be grown to very high titers in mammalian vaccine cell culture substrates and is not cytopathic allowing for extended culture and harvest of vaccine virus [98, 99] . Like NDV, PIV5 has a 3'-to 5' gradient of gene expression and insertion of transgenes at different locations in the genome can variably attenuate the virus and alter transgene expression [100] . PIV5 has broad tropism, infecting many cell types, tissues, and species without causing clinical disease, although PIV5 has been associated with -kennel cough\u2016 in dogs" }, { "input": "What was the result of the test of efficacy of PIV5 in murine challenge?", "output": "Mice intranasally vaccinated with a single dose of PIV5-H5 vaccine had robust serum and mucosal antibody responses, and were protected from lethal challenge. Notably, although cellular immune responses appeared to contribute to protection, serum antibody was sufficient for protection from challenge" }, { "input": "What opportunity has the termination of smallpox vaccination provided?", "output": "has resulted in a large population of poxvirus-na\u00ef ve individuals that provides the opportunity for the use of poxviruses as vectors without preexisting immunity concerns " }, { "input": "What vaccinia vectors were created to address safety concerns?", "output": "The modified vaccinia virus Ankara (MVA) strain was attenuated by passage 530 times in chick embryo fibroblasts cultures. The second, New York vaccinia virus (NYVAC) was a plaque-purified clone of the Copenhagen vaccine strain rationally attenuated by deletion of 18 open reading frames" }, { "input": "How safe is MVA?", "output": "MVA has undergone extensive safety testing and shown to be attenuated in severely immunocompromised animals and safe for use in children, adults, elderly, and immunocompromised persons. With extensive pre-clinical data, recombinant MVA vaccines expressing influenza antigens have been tested in clinical trials and been shown to be safe and immunogenic in humans " }, { "input": "What is the status of MVA influenza vaccine?", "output": "results combined with data from other (non-influenza) clinical and pre-clinical studies support MVA as a leading viral-vectored candidate vaccine." }, { "input": "What is NYVAC?", "output": "The NYVAC vector is a highly attenuated vaccinia virus strain. NYVAC is replication-restricted" }, { "input": "How is NYVAC grown?", "output": "in chick embryo fibroblasts and Vero cells enabling vaccine-scale production. In non-permissive cells, critical late structural proteins are not produced stopping replication at the immature virion stage " }, { "input": "How safe is NYVAC?", "output": " NYVAC is very attenuated and considered safe for use in humans of all ages" }, { "input": "What would limit the use of poxvirus vectored vaccines?", "output": "current influenza vaccination strategies rely upon regular immunization with vaccines matched to circulating strains" }, { "input": "what is the advantage of the NYVAC as an influenza virus?", "output": "immunization with this vector induces weaker vaccine-specific immune responses compared to other poxvirus vaccines, a feature that may address the concerns surrounding preexisting immunity " }, { "input": "Where is poxvirus vaccine being used?", "output": " licensed poxvirus for veterinary use that include fowlpox-and canarypox-vectored vaccines for avian and equine influenza viruses, respectively " }, { "input": "What have the studies on NP shown for the protection against influenza challege?", "output": " immunization with NP expressed by AAV, rAd5, alphavirus vectors, MVA, or other vector systems induces potent CD8 + T cell responses " }, { "input": "What is the goal of vaccine?", "output": "protect against infection and disease, while inducing population-based immunity to reduce or eliminate virus transmission within the population" }, { "input": "What has enabled the development of one size fits all vaccine?", "output": " recent ability to probe the virus-host interface through RNA interference approaches that facilitate the identification of host genes affecting virus replication, immunity, and disease." }, { "input": "Why is a revision of current vaccines is needed?", "output": "strategies for at-risk populations, particularly those at either end of the age spectrum" }, { "input": "What is an example of an improved vaccine regime?", "output": "a vectored influenza virus vaccine that expresses the HA, NA and M and/or NP proteins for the two currently circulating influenza A subtypes and both influenza B strains so that vaccine take and vaccine antigen levels are not an issue in inducing protective immunity" }, { "input": "What can provide an improved vaccine regime?", "output": "Recombinant live-attenuated or replication-deficient influenza viruses" }, { "input": "What features can be created for creating vectored vaccines?", "output": "full-length influenza virus proteins, as well as generate conformationally restricted epitopes, features critical in generating appropriate humoral protection." }, { "input": "How can sustained immunity be generated?", "output": "induce immunity at sites of inductive immunity to natural infection, in this case the respiratory tract" }, { "input": "What is the advantage of vectored vaccines?", "output": "generate antigen for weeks after immunization, in contrast to subunit vaccination. This increased presence and level of vaccine antigen contributes to and helps sustain a durable memory immune response, even augmenting the selection of higher affinity antibody secreting cells" }, { "input": "What is the enhanced memory immune response linked to?", "output": "intrinsic augmentation of immunity induced by the vector." }, { "input": "What cellular process is the Tat protein essential to?", "output": "HIV-1 replication" }, { "input": "Where does the Tat protein move to in cells?", "output": "nucleoplasm and the nucleolus" }, { "input": "What is a nucleolus?", "output": "a highly dynamic and structured membrane-less sub-nuclear compartment" }, { "input": "Where are rRNA and ribosomes created?", "output": "nucleolus" }, { "input": "How many proteins were shown to change the amount of Jurkat T-cell nucleolus significantly?", "output": "49" }, { "input": "What cellular processes occur in the nucleolus?", "output": "RNA-polymerase-I-directed rDNA transcription, rRNA processing mediated by small nucleolar ribonucleoproteins (soRNPs) and ribosome assembly" }, { "input": "Which viruses target the nucleolus as part of their replication strategy?", "output": "HIV-1, hCMV, HSV and KSHV" }, { "input": "What nucleolar antigen is essential of localization of Tat and Rev proteins?", "output": "B23" }, { "input": "What was studied in this report?", "output": "systematically analysed the nucleolar proteome perturbations occurring in Jurkat T-cells" }, { "input": "What was studied in this report?", "output": "the quantitative changes in the nucleolar proteome of Jurkat T cells constitutively expressing HIV-1 Tat (86aa) versus their Tat-negative counterpart," }, { "input": "Which isotope labeled arginine?", "output": "light (R0K0)" }, { "input": "Which isotope labeled lysine?", "output": "heavy (R6K6)" }, { "input": "How many cells were harvested from each culture?", "output": "85 million" }, { "input": "How long is the nuclear protein PARP-1?", "output": "113 kDa" }, { "input": "How long is the protein Alpha-tubulin?", "output": "50 kDa" }, { "input": "Where was alpha-tubulin found most abundantly in the cell?", "output": "cytoplasmic" }, { "input": "Where was alpha-tubulin found least abundantly in the cell?", "output": "nuclear" }, { "input": "What is shown in Table S1?", "output": "The fully annotated list of the quantified nucleolar proteins" }, { "input": "What types of cells are used to study Tat-mediated pathogenesis?", "output": "Jurkat T-cells" }, { "input": "How many proteins displayed a significant fold change?", "output": "49" }, { "input": "What is the significance of this study?", "output": "the first proteomic analysis of dynamic composition of the nucleolus in response to HIV-1 Tat expression" }, { "input": "How are Mammarenaviruses spread from rodents to humans?", "output": "mucosal exposure to aerosols or by direct contact of abraded skin with infectious material" }, { "input": "What are the main groups for Mammarenaviruses?", "output": "Old World (OW) and New World (NW)" }, { "input": "What is the cause of Lassa fever?", "output": "OW Lassa virus (LASV)" }, { "input": "What type of vaccine is JUNV, Candid#1?", "output": "live attenuated" }, { "input": "Why was the human A549 cell line chosen for this study?", "output": "lung epithelial cells are one of the initial cell targets of humans following inhalation of mammarenavirions" }, { "input": "For how long were the cells infected before analysis?", "output": "48 h" }, { "input": "What drug is used to treat congestive heart failure?", "output": "ouabain" }, { "input": "What does ouabain inhibit?", "output": "ATP1A1" }, { "input": "What method can significantly alleviate the emergence of drug-resistant variants in RNA viral infections?", "output": "Combination therapy" }, { "input": "What factors did this study attribute to the efficient multiplication of mammarenaviruses?", "output": "ATP1A1 and PHB" }, { "input": "How do the authors suggest that ATP1A1 and PHB contribute to the efficient multiplication of mammarenaviruses?", "output": "using genetics and pharmacological inhibition of the genes" }, { "input": "Which are the most abundant biological entities on Earth?", "output": "Viruses " }, { "input": "What contributed to a large part of mammalian genomic sequence?", "output": "Retroviruses " }, { "input": "What were the earliest replicating entities that fulfill several criteria for life?", "output": "ribozymes or viroids" }, { "input": "What are some examples of autonomous bacteria that lost their independence and became intracellular parasites or endosymbionts?", "output": "mitochondria, chloroplasts, Rickettsia " }, { "input": "What entities with no genes satisfy the criteria for life?", "output": "ribozymes, catalytic RNAs closely related to viroids" }, { "input": "Which group of RNA quasispecies satisfy criteria for life?", "output": " catalytically active members, enzymatically active ribozymes. The sequence space for 220-mer RNAs is about 3 \u00d7 10 132 (" }, { "input": "How are the ribozymes able to replicate, join and create peptide bonds?", "output": " They can polymerize progeny chemically, allow for mutations to occur and can evolve. One molecule serves as catalyst, the other one as substrate. Replication of ribozymes was demonstrated in the test tube (Lincoln and Joyce, 2009) . Ribozymes can form peptide bonds between amino acids (Zhang and Cech, 1997) . Thus, small peptides were available by ribozyme activity. " }, { "input": "Does RNA replication need polymerase enzymes?", "output": "Replication of RNA molecules can be performed chemically from RNA without polymerase enzymes." }, { "input": "How can DNA arise chemically from RNA?", "output": "deoxyribozymes can form from ribonucleotides (Wilson and Szostak, 1999) . Thus, DNA can arise from RNA chemically, without the key protein enzyme, the reverse transcriptase." }, { "input": "What do ribozymes consist of?", "output": "circular single-stranded RNAs" }, { "input": "What do ribozymes lack?", "output": "the genetic triplet code and do not encode proteins" }, { "input": "What do ribozymes exhibit?", "output": "structural information by hairpin-loops that form hydrogen bonds between incomplete double strands, and loops free to interact with other molecules." }, { "input": "What is CHIKV marked by?", "output": "severe joint pain, contorting its victims into unusual postures " }, { "input": "What does Chikungunya cause?", "output": " fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia" }, { "input": "What is Chikungunya virus?", "output": "a mosquito-borne emerging pathogen" }, { "input": "Is there a treatment?", "output": "Currently, there is no vaccine or antiviral treatmen" }, { "input": "What conclusion is drawn in this report?", "output": "With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine." }, { "input": "What is Chikungunya virus?", "output": "a mosquito-borne pathogen listed by National Institute of Allergy and Infectious Diseases (NIAID) as a Category C Priority Pathogen that causes Chikungunya fever (CHIKF)" }, { "input": "What is CHIKV?", "output": "an arthropod-borne virus (arbovirus" }, { "input": "How is CHIKV propagated to humans?", "output": "primarily by Aedes aegypti, the infamous yellow fever propagator" }, { "input": "From what language the disease gets its name?", "output": "Kimakonde vernacular language of Tanzania and Mozambique" }, { "input": "What is the word Chikungunya mean?", "output": "'that which contorts or bends up'" }, { "input": "What does Chikungunya mean in Swahili?", "output": "the illness of the bended walker" }, { "input": "How is CHIKV maintained in Africa?", "output": " in a sylvatic cycle among forest-dwelling Aedes spp. mosquitoes, wild primates, squirrels, birds, and rodents" }, { "input": "What is it vectored by, in Asia?", "output": " Ae. aegypti and Ae. albopictus" }, { "input": "How does the transmission in Asia occur?", "output": "in an urban cycle whereby the mosquito spreads the disease from an infected human to an uninfected human, following an epidemiological pattern similar to dengue fever" }, { "input": "What spurred the discovery of the new vector Ae. albopictus?", "output": "The 2005-2006 epidemic of CHIKV in La Reunion islands in the Indian Ocean," }, { "input": "In the epidemic peak how many cases per week were there on the island?", "output": "46,000" }, { "input": "What does this review detail?", "output": "the epidemiology and global expansion of CHIKV" }, { "input": "What dose this review describe?", "output": " its clinical features and pathogenesis and its symptoms and complications, and finally nominates a possible vaccine approach against CHIKV infection." }, { "input": "How many genotypes of CHIKV have been isilated?", "output": " three genotypes based on phylogenetic studies." }, { "input": "What are the genotypes based on?", "output": "the gene sequences of an Envelope protein (E1), are Asian, East/Central/ South African, and West African" }, { "input": "hen did Asian genotype emerge?", "output": "between 50 and 310 y ago," }, { "input": "When didthe Asian genotype diverge from African genotype?", "output": " between 100 and 840 y ago" }, { "input": "What is the status of Asian CHIKV since its emergence?", "output": "has come a long way, with several mutations incorporated, and has continued to wreak epidemics in several regions" }, { "input": "What are the recent activities of CHIKV?", "output": " the Indian epidemic in 2005-2006, which was followed by a sudden explosion of cases in 2007. An estimated 1.3 million people across 13 states were reported to be infected in India [12, 16] , and CHIKV was also widespread in Malaysia, Sri Lanka, and Indonesia [17] . In July-August of 2007, CHIKV was reported in Italy, probably brought in by travelers from CHIKV-prone regions of India, Africa, and Indian Ocean islands such as Mauritius, Madagascar, and Seychelles." }, { "input": "How was the Italian isolation found to have evolved from?", "output": "from the Kerala isolate, which was associated with a A226V shift in E1 gene that represents a successful evolutionary adaptation in the mosquito vector similar to the ones observed in Reunion Island [" }, { "input": "How many days is the incubation period?", "output": "2-6 d" }, { "input": "In how many days do the symptoms arise?", "output": "4-7 " }, { "input": "What are exhibited in the two phases?", "output": "The first stage is acute, while the second stage, experienced by most but not all, is persistent, causing disabling polyarthritis. Characteristics of the acute phase include an abrupt onset of fever, arthralgia, and in some cases, maculopapular rash [6, 23] . The acute phase causes such intense joint and muscular pain that makes movement very difficult and prostrates its victims [" }, { "input": "What are consequences of infection?", "output": "Ninety-five percent of infected adults are symptomatic after infection, and of these, most become disabled for weeks to months as a result of decreased dexterity, loss of mobility, and delayed reaction." }, { "input": "What percentage of the patients still have the CHIKV IgM after eighteen months?", "output": "The chronic stage of CHIKF is characterized by" }, { "input": "What is te chronic stage characterized by?", "output": " by polyarthralgia that can last from weeks to years beyond the acute stage" }, { "input": "What is affected by CHIKV?", "output": "fibroblasts" }, { "input": "What explains the pain associated with CHIKV?", "output": " The high number of nociceptive nerve endings found within the joints and muscle connective tissues" }, { "input": "What percentage of people suffering from the CHIKF are over 65 years old?", "output": "50%" }, { "input": "What percentage die?", "output": "33% " }, { "input": "What other group is disproportionately affected?", "output": "children" }, { "input": "What complications are associated with CHIKV?", "output": "from most common to least common, include respiratory failure, cardiovascular decompensation, meningoencephalitis, severe acute hepatitis, severe cutaneous effects, other central nervous system problems, and kidney failure" }, { "input": "What happens after host infection?", "output": "CHIKV undertakes a complex replication cycle upon host infection (Figure 2 ), which makes its genome susceptible to mutations " }, { "input": "What did the Ae.Aegypti which is responsible for epidemics in Kenya, Comoros and Seychelles carry?", "output": "CHIKV with an alanine in the 226 position of the E1 gene (E1-A226)" }, { "input": "what was the result of the decline in population of Ae. Aegyptus when the virus struck the Reunion Islands, due to massive use dichlorodiphenyltrichloroethane usage?", "output": " in an ecological pressure, favoring replacement of alanine at position 226 with valine (E1-A226V) " }, { "input": "What did this mutation allow?", "output": "CHIKV's secondary vector species, Ae. albopictus, to supplement Ae. aegypti as its primary vector" }, { "input": "What vectored the large epidemic in La Reunion Islands?", "output": " Ae. albopictus" }, { "input": "What percentage of population was affected?", "output": "34% " }, { "input": "Where were the CHIKV strain found?", "output": "All of the CHIKV strains isolated from Mayotte carried the E1-A226V mutation, and the mutation was also found in Madagascar in 2007 [" }, { "input": "What is the finding on E1-A226V in Indian Ocean?", "output": "mutation was not present at the beginning of the Indian Ocean Islands outbreak (before September 2005). However, more than 90% of later viral strains found there had incorporated the mutation (December-March 2006), indicating a genotype switch during the winter season" }, { "input": "What has the E1-A226V enabled?", "output": "an increase in infectivity of Ae. albopictus when compared to its infectivity of Ae. aegypti " }, { "input": "What has become the preferred and lethal vector?", "output": "Ae. albopictus" }, { "input": "What was the finding on the Green Fluorescent tagged E1-A226V?", "output": " E1-A226V virus was 100 times more infective to Ae. albopictus than it was to Ae. aegypti" }, { "input": "What became the main vector in the Indian Ocean within 1-2 y after CHIKV was introduced?", "output": "Ae. albopictus" }, { "input": "how long Ae. aegypti been established in North America?", "output": "for over 300 " }, { "input": "What is the presence of Ae.albopictus in North America?", "output": "has been in many areas of the US, since 1985, primarily in Florida [32] and since then has expanded its range in the country." }, { "input": "What percentage of newborns were infected from their mother?", "output": "50%" }, { "input": "What has been some instances of mother to fetus transmission?", "output": "congenital illness and fetal death" }, { "input": "What did the studies reveal regarding transmission from mothers during perinatal period?", "output": "During the 2005-2006 La Reunion Island outbreaks, Ramful et al. discovered that mothers could transmit CHIKV to their progeny during the perinatal period (Day 24 to Day +1) [33, 34] , and it is associated with a high degree of morbidity. By mean Day 4 of life, all of the neonates were symptomatic for CHIKV, exhibiting common CHIKF symptoms." }, { "input": "What is theorized regarding transmission?", "output": "motherto-child transmission most likely happens transplacentally shortly before delivery" }, { "input": "What did the study report?", "output": "neonatal infection associated with intrapartum maternal viremia that progressed to develop encephalitis owing to vertical transmission from infected mothers " }, { "input": "What is a conclusion of this report?", "output": " DNA vaccines could play a major role in combating CHIKV" }, { "input": "What is a conclusion of this report?", "output": "Vaccines are literally a critical component of CHIKV disease control and therefore research in this area is highly encouraged. " }, { "input": "What is the NIAID designation of CHIKV?", "output": "as a Category C pathogen alongside the influenza and SARS-CoV viruses " }, { "input": "What are the strengths and advantages of DNA based vaccine?", "output": " its ability to induce cross-reactive immune responses against the three distinct phylogenetic groups of CHIKV. Also DNA-based vaccines can be produced more rapidly than protein-based vaccines." }, { "input": "How many facilities were monitored in this study?", "output": "two" }, { "input": "What percentage of facilities believed they were adequately equipped to handle Ebola virus disease?", "output": "25.74%" }, { "input": "How many facilities believed they were adequately equipped to handle Ebla virus disease?", "output": "26" }, { "input": "How many healthcare workers would be willing to continue working during the Ebola virus outbreak?", "output": "less than 50%" }, { "input": "What does the study suggest would make healthcare workers more willing to care for patients during an Ebola virus outbreak?", "output": "if HCWs are assured or guaranteed that they and or their families would be taken care of in case of death or while taking care of an EVD case," }, { "input": "What causes avian infectious bronchitis?", "output": "infectious bronchitis virus (IBV)" }, { "input": "What differentiated the two chicken lines used in this study?", "output": "serum concentration of mannose-binding lectin (MBL)" }, { "input": "Which organ was used for the RNA sequencing samples?", "output": "spleen" }, { "input": "What is needed to elucidate zoonotic emergence?", "output": "A mechanistic understanding of the impact of bats\u2019 virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics" }, { "input": "What is the conclusion of this report?", "output": " heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats." }, { "input": "Why have bats received attention in recent years?", "output": "for their role as reservoir hosts for emerging viral zoonoses, including rabies and related lyssaviruses, Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS coronavirus " }, { "input": "What difference bats demonstrate compared to most non-Chiropteran mammals?", "output": "no obvious disease symptoms upon infection with pathogens that are highly virulent in non-volant mammals (Schountz et al., 2017) but may, instead, support viruses as longterm persistent infections, rather than transient, immunizing pathologies" }, { "input": "What suite of species-specific mechanisms do bats have to limit viral load?", "output": "host receptor sequence incompatibilities for some bat-virus combinations (Ng et al., 2015; Takadate et al., 2020) and constitutive expression of the antiviral cytokine" }, { "input": "How are mammalian cells typically rendered antiviral?", "output": " the presence of viral RNA or DNA in the cytoplasm of mammalian cells will induce secretion of type I interferon proteins (IFN-a and IFN-b), which promote expression and translation of interferon-stimulated genes (ISGs) in neighboring cells " }, { "input": "In non-flying mammals, what what would be elicited by IFN expression upon viral infection?", "output": "widespread inflammation and concomitant immunopathology upon viral infection" }, { "input": "What do the bats do instead?", "output": "bats support unique adaptations to combat inflammation" }, { "input": "Why may the bats have this unique adaptation?", "output": "to mitigate metabolic damage induced during flight" }, { "input": "Why was the field of virus dynamics developed?", "output": "to describe the mechanistic underpinnings of long-term patterns of steady-state viral load exhibited by patients in chronic phase infections with HIV, who appeared to produce and clear virus at equivalent rates " }, { "input": "How are bats connected to fatal viral diseases?", "output": "bats are natural reservoirs for viruses that have some of the highest fatality rates of any viruses that people acquire from wild animals -including rabies, Ebola and the SARS coronavirus." }, { "input": "What is an example of anti-viral defense in bats?", "output": "some bats have an antiviral immune response called the interferon pathway perpetually switched on" }, { "input": "What would be caused by this hyper-vigilance in most other mammals?", "output": " harmful inflammation" }, { "input": "How are bats different?", "output": "Bats, however, have adapted anti-inflammatory traits that protect them from such harm, include the loss of certain genes that normally promote inflammation." }, { "input": "What bat species cells were compared?", "output": "-the black flying fox -in which the interferon pathway is always on, and another -the Egyptian fruit bat -in which this pathway is only activated during an infection." }, { "input": "What was the conclusion of the study ?", "output": " In both bat species, the strongest antiviral responses were countered by the virus spreading more quickly from cell to cell. This suggests that bat immune defenses may drive the evolution of faster transmitting viruses, and while bats are well protected from the harmful effects of their own prolific viruses, other creatures like humans are not." }, { "input": "What would be the benefit of learning more about bat's defenses and how they drive virus evolution?", "output": "help scientists develop better ways to predict, prevent or limit the spread of viruses from bats to humans. " }, { "input": "Which cells are IFN-defective and therefore limited in antiviral capacity?", "output": "demonstrate idiosyncratic induced interferon responses upon viral challenge" }, { "input": "What cells demonstrate idiosyncratic interferon response?", "output": "RoNi/7.1 (Rousettus aegyptiacus) cells" }, { "input": "Which cells express constitutive IFN-a?", "output": "PaKiT01 (Pteropus alecto) cell" }, { "input": "How were the spread of GFP-expressing virus-infected cells across tissue monolayers tracked via inverted fluorescence microscopy?", "output": "Because plaque assays restrict viral transmission neighbor-to-neighbor in two-dimensional cellular space " }, { "input": "How were the spread of GFP-expressing virus-infected cells tracked?", "output": " For each infection trial, we monitored and re-imaged plates for up to 200 hr of observations or until total monolayer destruction, processed resulting images, and generated a time series of the proportion of infectious-cell occupied plate space across the duration of each trial (see Materials and methods). We used generalized additive models to infer the time course of all cell culture replicates and construct the multi-trial dataset to which we eventually fit our mechanistic transmission model for each cell line-virus-specific combinatio" }, { "input": "How was the modeling carried out?", "output": "an innovative combination of in vitro experimentation and within-host modeling to explore the impact of unique bat immunity on virus dynamics." }, { "input": "What was the finding in this study?", "output": "that bat cell lines demonstrated a signature of enhanced interferon-mediated immune response, of either constitutive or induced form, which allowed for establishment of rapid within-host, cell-to-cell virus transmission rates " }, { "input": "What supports the results?", "output": "by both data-independent bifurcation analysis of our mean field theoretical model, as well as fitting of this model to viral infection time series established in bat cell culture." }, { "input": "What was additionally demonstrated?", "output": "the antiviral state induced by the interferon pathway protects live cells from mortality in tissue culture, resulting in in vitro epidemics of extended duration that enhance the probability of establishing a long-term persistent infection." }, { "input": "What do the studies suggest?", "output": "that viruses evolved in bat reservoirs possessing enhanced IFN capabilities could achieve more rapid within-host transmission rates without causing pathology to their hosts. Such rapidly-reproducing viruses would likely generate extreme virulence upon spillover to hosts lacking similar immune capacities to bats." }, { "input": "What was the methodology for this study?", "output": "we first developed a novel, within-host, theoretical model elucidating the effects of unique bat immunity, then undertook bifurcation analysis of the model's equilibrium properties under immune absent, induced, and constitutive assumptions. We considered a cell line to be constitutively immune if possessing any number of antiviral cells at disease-free equilibrium but allowed the extent of constitutive immunity to vary across the parameter range for \", the constitutive rate of antiviral acquisition. " }, { "input": "What was demonstrated in deriving the equation for R 0?", "output": " invasion threshold is elevated at high values of constitutive antiviral acquisition," }, { "input": "What is a conclusion of the modeling?", "output": "Constitutive immune processes can thus prohibit pathogen invasion, while induced responses, by definition, can only control infections post-hoc." }, { "input": "What is a conclusion of the study?", "output": "Regardless of mechanism (induced or constitutive), interferon-stimulated antiviral cells appear to play a key role in maintaining longer term or persistent infections by safeguarding susceptible cells from rapid infection and concomitant cell death. " }, { "input": "What do fits to rVSV-MARV infections on PaKiT01 cells suggest?", "output": "that the constitutive IFN-a expression characteristic of P. alecto cells may represent more of a constitutive immune priming process than a perpetual, functional, antiviral defense." }, { "input": "What do the findings indicate?", "output": "enhanced IFN-mediated immune pathways in bat reservoirs may promote elevated within-host virus replication rates prior to cross-species emergence. " }, { "input": "What is presented in this study?", "output": "general methods to study cross-scale viral dynamics, which suggest that within-host persistence is supported by robust antiviral responses characteristic of bat immune processes. " }, { "input": "What is a conclusion of this study?", "output": " Viruses which evolve rapid replication rates under these robust antiviral defenses may pose the greatest hazard for cross-species pathogen emergence into spillover hosts with immune systems that differ from those unique to bats. " }, { "input": "What age group has the highest rate of severe outcomes?", "output": "people 85 years and older" }, { "input": "How is COVID-19 spread?", "output": "person-to-person" }, { "input": "How many states in the U.S. have reported cases of COVID-19?", "output": "50" }, { "input": "When did the White House launch the \"15 Days to Slow the Spread\" program?", "output": "March 16" }, { "input": "What should mildly-ill patients do?", "output": "isolate at home during their illness" }, { "input": "What type of virus is SARS-CoV-2?", "output": "betacoronavirus" }, { "input": "What viruses are similar to the COVID-19 coronavirus?", "output": "MERS-CoV and SARS-CoV." }, { "input": "What are the phases of a pandemic?", "output": "investigation phase, followed by recognition, initiation, and acceleration phases" }, { "input": "At which phase does the peak of the pandemic occur?", "output": "at the end of the acceleration phase" }, { "input": "People with which medical conditions have a higher rate of severe illness?", "output": "People who have serious chronic medical conditions like:\nHeart disease\nDiabetes\nLung disease" }, { "input": "What kind of test can diagnose COVID-19?", "output": "rRT-PCR test" }, { "input": "In what species did the COVID-19 virus likely originate?", "output": "bats" }, { "input": "What risk factors should be considered in addition to clinical symptoms?", "output": "Does the patient have recent travel from an affected area?\nHas the patient been in close contact with someone with COVID-19 or with patients with pneumonia of unknown cause?\nDoes the patient reside in an area where there has been community spread of COVID-19?" }, { "input": "What is the acronym SARS-CoV-2?", "output": "severe acute respiratory syndrome coronavirus 2 " }, { "input": "When was SARS-CoV-2 first identified?", "output": "December 2019" }, { "input": "Where was SARS-CoV-2 first identified?", "output": "Wuhan, capital of Hubei Province, China" }, { "input": "What factor positively correlates with imported-and-reported cases counts of SARS-CoV-2 infection?", "output": "daily air travel volume" }, { "input": "What is the doubling time of the COVID-19 pandemic?", "output": "\u22486 days" }, { "input": "When did the first known cases of Middle East respiratory syndrome (MERS) occur?", "output": " in 2012 " }, { "input": "Where did the first known cases of Middle East respiratory syndrome (MERS) occur?", "output": "in Jordan" }, { "input": "Where was the the case first to be publicly reported was from ?", "output": "Jeddah, in the Kingdom of Saudi Arabia (KSA)" }, { "input": "In what animals MERS-CoV sequences have been found ?", "output": "in a bat and in many dromedary camels (DC)." }, { "input": "Where is MERS-CoV is enzootic in DC?", "output": "across the Arabian Peninsula and in parts of Africa" }, { "input": "What does MERS-COV cause?", "output": " mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections." }, { "input": "Precisely how does the virus transmit to humans?", "output": "remains unknown" }, { "input": "What appears to be a requirement for transmission?", "output": "close and lengthy exposure" }, { "input": "What is a focal point of MERS?", "output": "The KSA " }, { "input": "What is MERS mostly known as?", "output": "lower respiratory tract (LRT) disease " }, { "input": "What does the MERS LRT disease involve?", "output": "fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. " }, { "input": "Where else MERS-COV has also been detected?", "output": " in mild and influenza-like illnesses and in those with no signs or symptoms." }, { "input": "Who suffers severe diseases from MERS?", "output": "Older males" }, { "input": " Compared to severe acute respiratory syndrome (SARS) and another sometimes- fatal zoonotic coronavirus disease, how does MERS affect the patients?", "output": "MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal." }, { "input": "To what have most human cases of MERS been linked?", "output": "to lapses in infection prevention and control (IPC) in healthcare settings" }, { "input": "Among whom 20% of the virus detection are reported?", "output": " among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. " }, { "input": "What have sero-surveys of MERS virus found?", "output": "widespread evidence of past infection in adult camels and limited past exposure among humans." }, { "input": "How was the first culture of the new Coronavirus announced?", "output": "An email from Dr Ali Mohamed Zaki, an Egyptian virologist working at the Dr Soliman Fakeeh Hospital in Jeddah in the Kingdom of Saudi Arabia (KSA)" }, { "input": "Where was the Email published?", "output": "on the website of the professional emerging diseases (ProMED) network" }, { "input": "When was the Email published?", "output": "20 th September 2012 " }, { "input": "Whose was the first reported case?", "output": "a 60 year old man from Bisha in the KSA" }, { "input": "How many viral RNA or virus-specific antibodies been detected?", "output": "1,493" }, { "input": "What is the death rate from MERS-COV?", "output": "over a third of the positive people dying (at least 527, 35 %)" }, { "input": "What did the discovery process over two to three years reveal?", "output": "a virus that had infected over 90 % of adult dromedary camels (DC; Camelus dromedarius) in the KSA [4] , also DCs across the Arabian Peninsula and parts of Africa that are a source of DC imports for the KSA " }, { "input": "What does subsequent transmission of MERS-CoV to other humans require?", "output": " relatively close and prolonged exposure " }, { "input": "What would restrict access to both the virus and to viral diagnostics ?", "output": "The first viral isolate was patented " }, { "input": "How was the virus then made freely available? ", "output": " sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics were quickly described " }, { "input": "What has epidemiology and research identified the MERS-CoV's cell receptor is?", "output": "as exopeptidase dipeptidyl peptidase 4 (DPP4; also called CD26)" }, { "input": "How does MERS-CoV compare with SARS-CoV?", "output": "eliciting a more proinflammatory response than SARS-CoV" }, { "input": "How does MERS-CoV compare with SARS-CoV?", "output": "MERS kills its human host more often than SARS did (20-40 % versus 9 % for SARS " }, { "input": "How does MERS-CoV spread among people?", "output": "From intermittent animal-to-human spill-over events" }, { "input": "Who gets more severe disease from MERS?", "output": "among older adults, especially males, with pre-existing diseases. " }, { "input": "What is the spread of MERS-CoV among humans, associated with?", "output": "with outbreaks in hospitals, with around 20 % of all cases to date involving healthcare workers (HCWs)." }, { "input": "What do the DCs suffer with MERS-CoV infection?", "output": " the equivalent of a 'common cold' from MERS-CoV infection," }, { "input": "What happens to humans infected by MERS-CoV virus?", "output": " the virus can be a more serious and opportunistic pathogen associated with the death of up to 40 % of reported cases." }, { "input": "What is the incubation period of MERS?", "output": " five to six days, ranging from two to 16 days" }, { "input": "What is the duration between when illness begins in one person and subsequently spreads to another?", "output": "13 to 14 days" }, { "input": "What is the median time to death in case of progressive illness?", "output": "11 to 13 days" }, { "input": "What is the progression of symptoms to disease?", "output": "Fever and gastrointestinal symptoms may form a prodrome, after which symptoms decline, only to be followed by a more severe systemic and respiratory syndrome " }, { "input": "What did the later WHO definition of MERS clearly state?", "output": "a confirmed case included any person whose sample was RT-PCR positive for MERS-CoV, or who produced a seroconversion, irrespective of clinical signs and symptoms." }, { "input": "What percentage of cases KSA has been a source of?", "output": " 79 % " }, { "input": "What is severe MARS noted for?", "output": "its impact among older men with comorbid diseases including diabetes mellitus, cirrhosis and various lung, renal and cardiac conditions " }, { "input": "What symptoms appear among the confirmed cases of MERS?", "output": "fever, cough and upper respiratory tract (URT) signs and symptoms usually occur first, followed within a week by progressive LRT distress and lymphopaenia" }, { "input": "What do patients often present to a hospital with, in cases of MERS?", "output": " pneumonia" }, { "input": "What can MERS disease progress to?", "output": "acute respiratory distress syndrome and multiorgan system failure" }, { "input": "What percentage of all reported cases has MERS reportedly killed ?", "output": " 35 % " }, { "input": "What percentage of of all reported cases has MERS reportedly killed in KSA?", "output": "42 %" }, { "input": "What was mortality in South Korea from MERS disease?", "output": "ranged from 7 % among younger age groups to 40 % among those aged 60 years and above" }, { "input": "Which are the preferred method for MERS-CoV detection?", "output": " PCR-based techniques " }, { "input": "What have become a key diagnostic and taxonomic target for CoV species identification?", "output": "The first open reading frames " }, { "input": "Why it can be concluded that MERS-COV is a novel and distinct virus?", "output": " less than 80 % identity between the amino acid sequence of MERS ORF 1ab and betacoronavirus relatives, Tylonycteris bat HKU4 and Pipistrellus bat HKU5" }, { "input": "What indicates the likely presence of infectious virus?", "output": " Detection of viral proteins rather than viral RNA" }, { "input": "What is the sensitivity with which immunochromatographic tool could detect recombinant MERS-CoV nucleocapsid protein?", "output": "94 %" }, { "input": "What is the specificity with which immunochromatographic tool could detect recombinant MERS-CoV nucleocapsid protein?", "output": "100 % " }, { "input": "What is a different approach for the detection?", "output": "monoclonal antibody-based capture ELISA targeting the MERS-CoV nucleocapsid protein" }, { "input": "What is usual in serology testing?", "output": " to detect a viral footprint, in the form of antibodies" }, { "input": "How have some sero-assays bypassed the risks of working with infectious virus?", "output": " by creating transfected cells expressing recombinant portions of the MERS-CoV nucleocapsid and spike proteins [" }, { "input": "How have some sero-assays bypassed the risks of working with infectious virus?", "output": "using a recombinant lentivirus expressing MERS-CoV spike protein and luciferase" }, { "input": "What is the detection of MERS-CoV infection using ELISA or S1 subunit protein microarray [84] is usually followed by?", "output": "by confirmatory IFA and/ or a plaque-reduction neutralization (PRNT) [69, 70, 85] or MNT test." }, { "input": "What does the confirmatory process aim to ensure?", "output": "the antibodies detected are able to specifically neutralize the intended virus and are not more broadly reactive to other coronaviruses found in DCs (bovine CoV, BCoV) or humans (HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, SARS-CoV)." }, { "input": "When does generally MERS infection does not trigger a detectable immune response?", "output": "if only mild disease or asymptomatic infection results" }, { "input": "When does the WHO recommend samlinf from the LRT?", "output": " when sample collection is delayed by a week or more after onset of symptoms" }, { "input": "What do the recommended samples include?", "output": "are recommended when URT sampling is to be conducted" }, { "input": "What are recommended when URT sampling is to be conducted?", "output": " an oropharyngeal and throat swab or a nasopharyngeal aspirate/wash" }, { "input": "What paired sera are preferable?", "output": " collected two to three weeks apart" }, { "input": " When is a single sample suggested to be sufficient?", "output": "Human urine and stool have been found to contain MERS-CoV RNA" }, { "input": "How long human urine and stool have been found to contain MERS-CoV RNA?", "output": "12 to 26 days after symptom onset " }, { "input": "What do individual studies report on viral shedding?", "output": " long periods of viral shedding, sometimes intermittently and not necessarily linked to the presence of disease symptoms." }, { "input": "What fraction of MERS cases shed viral RNA in their LRT specimens (tracheal aspirates and sputum) ?", "output": "Over three quarters of" }, { "input": "How long MERS cases shed viral RNA in their LRT specimens (tracheal aspirates and sputum)? ", "output": "at least 30 days" }, { "input": "What percentage of contacts were still shedding RNA in their URT specimens?", "output": "30 %" }, { "input": "What samples returned the highest MERS viral load values?", "output": " the proportion of deaths among those infected with MERS-CoV is much higher than that known for the HCoVs NL63, HKU1, 229E or" }, { "input": "What is NPA?", "output": " nasopharyngeal aspirates" }, { "input": "What is NPA?", "output": "URT sample" }, { "input": "What is BAL?", "output": "bronchoalveolar lavage" }, { "input": "What is the the proportion of deaths among those infected with MERS-CoV?", "output": " is much higher than that known for the HCoVs NL63, HKU1, 229E or OC43" }, { "input": "What is the the proportion of deaths among those infected with MERS-CoV?", "output": " above that for SARS-CoV" }, { "input": "What has prevented worldwide spread of MERS-COV?", "output": "the low transmission rate" }, { "input": "What must be reported to the world organization for animal health as an emerging disease ?", "output": "animal MERS-CoV infections" }, { "input": "What are juvenile DCs more often positive for?", "output": "virus or viral RNA" }, { "input": "What are older DCs are more likely to be positive for?", "output": "seropositive and RNA or virus negative" }, { "input": "When does the camel calving season?", "output": "t" }, { "input": "Why is there an increased risk to humans of spill-over during calving season?", "output": "due to new infections among na\u00efve DC populations" }, { "input": "Which may be an occupational group with significantly higher incidence of seropositivity to MERS-CoV ?", "output": "slaughterhouse workers who kill both younger and older DCs" }, { "input": "How long after Infectious MERS-CoV added to DC, goat or cow milk and stored at 4\u00b0C could be recovered?", "output": " up to 48 h" }, { "input": "How long after Infectious MERS-CoV added to DC, goat or cow milk and stored at 22\u00b0C could be recovered?", "output": "up to 48 h" }, { "input": "What ablated MERS-COV infection completely?", "output": "pasteurization" }, { "input": "How long MERS-CoV remained viable at high ambient temperature (30\u00b0C) and low RH (30 %) ?", "output": "for 24 h" }, { "input": "How long can pathogenic bacteria remain viable and airborne in a coughed aerosol?", "output": " for 45 min" }, { "input": "How far can pathogenic bacteria spread in a coughed aerosol?", "output": "4 m" }, { "input": "What is considered the mechanism of human-to-human transmission of MERS-COV?", "output": "Droplet spread between humans" }, { "input": "What is the transmission of MERS-CoV is defined as?", "output": "sporadic " }, { "input": "What is the transmission of MERS-CoV is defined as?", "output": "intra-familial," }, { "input": "What is the transmission of MERS-CoV is defined as?", "output": "often healthcare associated" }, { "input": "What is the transmission of MERS-CoV is defined as?", "output": "inefficient " }, { "input": "What is the transmission of MERS-CoV is defined as?", "output": "requiring close and prolonged contact" }, { "input": "What is the the rate of general transmission, even in outbreaks?", "output": "readily transmit to more than one other human" }, { "input": "What do the majority of human cases of MERS-CoV seem not to do?", "output": "readily transmit to more than one other human " }, { "input": "What is the basic reproduction number (R 0)?", "output": "the average number of infections caused by one infected individual in a fully susceptible population" }, { "input": "What is the basic reproduction number (R 0 ) for MERS-COV?", "output": "close to one" }, { "input": "Why has MERS had a constant presence in the Arabian Peninsula?", "output": "due to ongoing, sporadic spill-over events from DCs amplified by poorly controlled hospital outbreaks.\n" }, { "input": "What was the first known MERS human-to-human transmission event was one characterized by?", "output": "acute LRT disease" }, { "input": "Where was the first known MERS human-to-human transmission event?", "output": "in a healthcare setting in Jordan" }, { "input": "Approximately what percentage of MERS cases were fatal in KSA?", "output": "21 %" }, { "input": "Approximately what percentage of MERS cases were died outside KSA?", "output": "21 %" }, { "input": "What percentage of HCWs comprised of MERS cases in the KSA and South Korea?", "output": "16 %" }, { "input": "How has most of the analysis of MERS-CoV genetics been performed?", "output": "using high throughput or \"deep\" sequencing methods for complete genome deduction" }, { "input": "What does Clade A contain?", "output": "only human-derived MERS-CoV genomes" }, { "input": "What does clade B comprise?", "output": "the majority of human and camel genomes deduced thus far" }, { "input": "How many clades have become apparent in genome of MERS-COV from humans and DCs?", "output": "has had more MERS cases than any other region of the KSA" }, { "input": "Which city has had has had more MERS cases than any other region of the KSA ?", "output": "Riyadh" }, { "input": "Which city harbours a wide range of MERS-CoV variants ", "output": " Riyadh" }, { "input": "How has the vast majority of MERS-CoV transmission occurred?", "output": "from infected to uninfected humans in close and prolonged contact " }, { "input": "How were the transmission circumstances created?", "output": "by poor infection control in health care settings" }, { "input": "What percentage of humans have died among all humans reported to be infected?", "output": " nearly 40 %" }, { "input": "What would aid accurate calculation of a case fatality ratio?", "output": "Global alignment of case definitions" }, { "input": "How does MARS-COV differ from SARS-COV?", "output": "MERS-CoV has a broader tropism, grows more rapidly in vitro, more rapidly induces cytopathogenic change, triggers distinct transcriptional responses, makes use of a different receptor, induces a more proinflammatory state and has a delayed innate antiviral response compared to SARS-CoV.\n" }, { "input": "Is there any evidence that MERS-CoV is a virus of pandemic concern?", "output": "There is no evidence that MERS-CoV is a virus of pandemic concern" }, { "input": "How did the first WHO case definition define probable cases of MERS?", "output": "based on the presence of febrile illness, cough and requirement for hospitalization with suspicion of lower respiratory tract (LRT) involvement." }, { "input": "What is PHEIC?", "output": "Public Health Emergency of International Concern'" }, { "input": "How is PHEIC defined?", "output": "an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response" }, { "input": "What platform was instrumental in rapid sharing of COVID-19 information?", "output": "Global Initiative on Sharing All Influenza Data (GISAID)" }, { "input": "What's the recommended procedure to disinfect at CT scanner after a COVID-19 exposure?", "output": "The equipment in the contaminated area are wiped with\n2000mg/L chlorine-containing disinfectant. The DR and CT gantry in the contaminated\narea are wiped with 75% ethanol. The equipment in the buffer area is wiped with\n500-1000mg/L chlorine-containing disinfectant or alcohol-containing disposable\ndisinfectant wipes twice a day." }, { "input": "What's the recommended method to disinfect floors for COVID-19?", "output": "The ground is wiped with 1000mg/L chlorine-containing\ndisinfectant, once /4 hours." }, { "input": "What is the role of computed tomography (CT) in COVID-19?", "output": "diagnosing and categorizing\nCOVID-19 on the basis of case definitions issued by the WHO" }, { "input": "What kind of masks are recommended to protect healthcare workers from COVID-19 exposure?", "output": "N95 mask" }, { "input": "What thickness of layers is recommended for CT image reconstruction in COVID-19 assessment?", "output": "1 mm-thick layers" }, { "input": "What must the data gathering include?", "output": "up-to-date case definitions and information about\nconfirmatory tests to all staff with direct patient contact to allow appropriate barrier precautions\nto be taken." }, { "input": "What must be done to assist in recognition of the disease on images and to allow accurate reporting\nof these findings?\n", "output": "All typical and atypical imaging features of the disease should be made known to\nall radiologists" }, { "input": "What is the major role of chest CT?", "output": "to understand the\nextent and dynamic evolution of lung lesions induced by COVID-19" }, { "input": "What is the reason to adopt low-dose CT?", "output": " low-dose chest CT has been\nwidely used in the screening of early lung cancer. It is well known that many early lung cancers\nare ground-glass opacities (GGO), so we believe that low-dose screening is also applicable for\nCOVID-19. In addition, considering the rapid development of COVID-19, many CT\n14\nexaminations may be conducted in the same individual to monitor disease progress. Low-dose\nscanning can reduce the radiation damage to patients." }, { "input": "What did the EMICT responsibilities include?", "output": " (1) coordination between the\nhospital\u2019s management and planning of infection control and radiology departments; (2)\ncollection of the most up-to-date protection-related information to educate and train staff in the\ndepartment; (3) reallocation of staff according to the actual situation; (4) establishment of the\nCT procedures for patients with COVID-19; and (5) establishment of an emergency\nmanagement plan for the radiology department to ensure that the department would run\nnormally." }, { "input": "How were the radiology department areas divided?", "output": "contaminated, semicontaminated,\nbuffer, and clean areas" }, { "input": "How was the contaminated area connected to the CT room and other facilities?", "output": "connected to the fever clinic and\nincludes the fever accessway, the CT examination room, and the DR examination room for\n6\nconfirmed and suspected cases. One CT scanner and one DR system closest to the emergency\ndepartment are designated the fever-CT and fever-DR to examine patients with suspected and\nconfirmed COVID-19. There is a separate dedicated access between the contaminated area and\nthe fever screening tents. " }, { "input": "What does the clean area include?", "output": "he clean area\nincludes the administrative office and the diagnostic room." }, { "input": "What does the semicontaminated area include?", "output": " the fever-CT control room,\nfever-DR control room, and other patient examination access areas. " }, { "input": "What does the buffer area include?", "output": "access areas for medical personnel and a dressing area for technologists. " }, { "input": "How was the wearing and removing of the equipment performed?", "output": "under the supervision of\nthe infection control nurse." }, { "input": "What can lower the physical and mental stress levels of staff members?", "output": " periodically taking time off " }, { "input": "Who must be assigned to the clean area?", "output": "Pregnant staff " }, { "input": "What responses must EMICT consider once a disease has been identified?", "output": "data gathering, collaboration, needs assessment, and expert advice " }, { "input": "What is the conclusion of the report?", "output": "Strategic planning and adequate protections can help protect patients and staff\nagainst a highly infectious disease while maintaining function at a high volume capacity.\nKeywords: Coronavirus, COVID-19, novel coronavirus pneumonia, infection control" }, { "input": "What were the number of cases in mainland china as of March 11th?", "output": "80,793 " }, { "input": "How many COVID deaths occurred in Chinese mainland as of March 11th?", "output": "3,169 " }, { "input": "How many people have come in contact and how many of these are in observation?", "output": "677,243 people have been identified as having had close contact with\ninfected patients of whom13,701 " }, { "input": "When was the novel Coronavirus first reported?", "output": "December 2019" }, { "input": "When did China detect the first human case of H7N9 infection?", "output": "February 2013" }, { "input": "How many deaths were associated with MERS-CoV as of July 2014?", "output": "288" }, { "input": "What illness is caused by the 2019-nCOV Coronavirus?", "output": "The novel coronavirus (2019-nCoV) infection caused pneumonia. " }, { "input": "In addition to oral swabs, which tests detected the presence of 2019-nCOV virus?", "output": "the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). " }, { "input": "What is the relationship between the presence of virus in blood and anal swabs and disease severity?", "output": "all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage." }, { "input": "Which patients were classified as severe in Chinese guidelines?", "output": "Patients who were with at least one of the following symptom should be diagnosed to be severe case, 1) distress of respiratory with respiratory rate > = 30/min; 2) Oxygen saturation < = 93% in the rest state, and 3) arterial oxygen tension (PaO\u2082) over inspiratory oxygen fraction (FIO\u2082) of less than 300 mm Hg. In the blood detection cohort (Figure 1 (A)), patients who had at less one serum sample measurement with the PCR method were included. " }, { "input": "What is the relationship between the presence of virus in blood sample and disease severity?", "output": " In the 57, 6 cases were detected to be blood positive, all of them (100%) were severe in symptom requiring special care attention, and the blood of the rest 51 cases was without detectable virus in the blood, only 12 of them (23.5%) were severe cases." }, { "input": "What test could give an indication for special care for 2019-nCOV patients?", "output": "presence of viral RNA outside of the respiratory tract might herald the severity of the disease and alarm the requirement of special care" }, { "input": "What is the relationship between the presence of virus in anal swabs and disease severity in 2019-nCOV?", "output": "In the anal swab cohort (Figure 1 (B)), 11 of 28 cases were detected to be anal swab positive, 8 of them (72.7%) were with severe symptoms, which was significantly higher than that 4 (23.5%) of the rest 17 cases without detectable virus in anal were severe cases" }, { "input": "What could be the implication of 2019-nCOV virus in anal swabs?", "output": "digestive tract might be one extrapulmonary site for virus replication" }, { "input": "What could account for the high transmission rate of the 2019-nCOV virus?", "output": "Intensive structural analysis of the S protein of 2019-nCoV with the SARS-Coronavirus suggested that several critical residues in the viral spike protein might confer favourable interaction with human ACE2 [7] . Of note, ACE2 is also abundantly present in humans in the epithelia of the small intestine besides the respiratory tract and is ubiquitously present in endothelial cells [8] , which might provide possible routes of transmission, and might account for the high transmission capacity of the new virus. " }, { "input": "What could account for the dissemination of the 2019-nCOV virus across the whole body?", "output": "We propose that rampant coronavirus replication in pulmonary alveolus results in the breakdown of the alveolar vessel and the subsequent virus leakage into the blood flow, through which the virus is disseminated across the whole body. Then the virus succeeds in establishing reinfection in the digestive tract by using the highly expressed ACE2 receptor, which exacerbated the disease vice versa" }, { "input": "When did the World Health Organization declare the Ebola epidemic in West Africa as a Public Health Emergency of International Concern?", "output": "8 August 2014" }, { "input": "What is PPE?", "output": "Personal Protective Equipment" }, { "input": "Where did the 2014 Ebola epidemic in West Africa spread to?", "output": "neighbouring sub-Saharan countries, North America, and Europe" }, { "input": "What are the prerequisites for successful emergency preparedness for an epidemic?", "output": "connectedness between health professionals, technological devices, and knowledge" }, { "input": "What is the structure of a coronavirus?", "output": "large, non-segmented, positive sense and single stranded RNA animal viruses" }, { "input": "What method is developed in this study?", "output": "a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. " }, { "input": "What is the model simplified to?", "output": "Reservoir-People (RP) transmission network model" }, { "input": "What is the estimate of R 0?", "output": "The value of R 0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.5" }, { "input": "What is the conclusion of this study?", "output": "Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea." }, { "input": "What was the focus of the study?", "output": "Huanan Seafood Wholesale Market (reservoir) to people," }, { "input": "What were the model assumptions?", "output": "the virus transmitted among the bats, and then transmitted to unknown hosts (probably some wild animals). The hosts were hunted and sent to the seafood market which was defined as the reservoir of the virus. People exposed to the market got the risks of the infection " }, { "input": "What compartments were the bats divided into?", "output": "susceptible bats (S B ), exposed bats (E B ), infected bats (I B ), and removed bats (R B )." }, { "input": "What compartments were the host animals divided into?", "output": "The hosts were also divided into four compartments: susceptible hosts (S H ), exposed hosts (E H ), infected hosts (I H ), and removed hosts (R H )" }, { "input": "What was the SARS-COV-2 reservoir?", "output": "the seafood market" }, { "input": "What were the people divided into?", "output": " into five compartments:\n\nsusceptible people (S P ), exposed people (E P ), symptomatic infected people (I P ), asymptomatic infected people (A P ), and removed people (R P ) including recovered and death people." }, { "input": "What was the mean incubation period?", "output": "5.2 days (95% confidence interval [CI]: 4.1-7.0) " }, { "input": "What was the mean delay from symptom onset to detection/hospitalization of a case?", "output": " 5-day" }, { "input": "How long after onset, the cases detected in Thailand and Japan were hospitalized?", "output": " from 3 to 7 days" }, { "input": "What was the duration from illness onset to first medical visit ?", "output": "a mean of 5.8 days (95% CI: 4.3-7.5)" }, { "input": "What was the assumption of transmissibility of asymptomatic infection?", "output": "0.5 times that of symptomatic infection (\u03ba = 0.5), which was the similar value as influenza " }, { "input": "As of January 17, how many people were tested for body temperature?", "output": " 0.3 million people" }, { "input": "What is mobile population in Wuhan?", "output": "about 2.87 million" }, { "input": "What was the R0 of SARS?", "output": "2.7-3.4 or 2-4 in Hong Kong" }, { "input": "What was the value of R0 in other researches?", "output": "R 0 of SARS was about 2.1 in Hong Kong, China, 2.7 in Singapore, and 3.8 in Beijing, China" }, { "input": "What is the reported value of R0 for MERS?", "output": "0.8-1.3 " }, { "input": "What was R0 for the high transmissibility in South Korea?", "output": " 2.5-7.2" }, { "input": "What is important for containing the transmission?", "output": " to decrease R 0" }, { "input": "What did this model show?", "output": " the transmissibility of SARS-CoV-2 might be higher than MERS in the Middle East countries, similar to SARS, but lower than MERS in the Republic of Korea." }, { "input": "What was the objective of the study?", "output": "provide a mathematical model for calculating the transmissibility of SARS-CoV-2" }, { "input": "What are coronaviruses?", "output": "s are spherical, enveloped, and the largest of positive-strand RNA v" }, { "input": "What animals can carry coronavirus?", "output": "uding birds, farm animals, pets, camels, an" }, { "input": "How many COVID-19 cases were confirmed on the Diamond Princess cruise ship?", "output": "199" }, { "input": "What was the time period of peak infection of COVID-19 on the Diamond Princess cruise ship?", "output": "2 to 4 February 2020," }, { "input": "With the intervention of movement restrictions starting on 5th February 2020, what were the confirmed cases for COVID-19, were limited to?", "output": "102 and 47 cases, respectively." }, { "input": "Who was the first COVID-19 identified case patient on the Diamond Princess cruise ship?", "output": "case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards." }, { "input": "When was the first passenger patient on the Diamond Princess cruise ship diagnosed with COVID-19?", "output": "he case was diagnosed on 1 February" }, { "input": "How many COVID-19 cases were confirmed on the Diamond Princess cruise ship?", "output": "Out of a total of 3711 persons (consisting of 2666 passengers and 1045 crew members), 199 symptomatic cases have been diagnosed on board as of 24 February, and additional asymptomatic infections and symptomatic cases after disembarkation have also been reported" }, { "input": "What is the estimated mean incubation period for COVID-19 infection on the Diamond Princess cruise ship?", "output": "about 5.0 days" }, { "input": "What was the effect of movement restriction policy on the Diamond Princess cruise ship started on 5th February 2020.", "output": "highly successful in greatly reducing the number of secondary transmissions on board." }, { "input": "What would have the number of confirmed cases on the Diamond Princess cruise ship, without a movement restriction starting on the 5th February 2020?", "output": " the cumulative incidence with and without close contact would have been as large as 1373 (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases," }, { "input": "When was the a cluster of pneumonia cases were first reported ?", "output": "31 December 2019," }, { "input": "What is the number of inbound passengers from China?", "output": " 63.1 million per year in 2017 " }, { "input": "What percent of inbound passengers from China were from Wuhan?", "output": "2.1%" }, { "input": "What is the mechanism of action for rupintrivir?", "output": "prevents cleavage of viral proteins required for replication" }, { "input": "Has rupintrivir been shown to reduce the symptoms of a rhinoviral infection?", "output": "in studies of natural infection, it did not significantly affect viral loads or symptom severity" }, { "input": "What is the primary etiology of acute respiratory infection?", "output": "viral" }, { "input": "What is RSV?", "output": "respiratory syncytial virus" }, { "input": "What virus is most commonly associated with acute respiratory infections?", "output": "human rhinovirus" }, { "input": "What viruses are most frequently associated with acute respiratory infections?", "output": "HRVs, coronaviruses (CoV), influenza, respiratory syncytial virus (RSV) and parainfluenza viruses (PIV)" }, { "input": "What are the clinical characteristics of asthma?", "output": "chronic airway inflammation, and a history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough" }, { "input": "What risk factor was associated with hospitalization and death during the 2009 H1N1 influence pandemic?", "output": "morbid obesity" }, { "input": "How many surface proteins are on the H1N1 influenza virus?", "output": "two" }, { "input": "What are the 2 surface proteins on the H1N1 influenza virus?", "output": "haemagglutinin (HA) and the neuraminidase (NA) " }, { "input": "What pharmaceutical targets the NA glycoprotein of the H1N1 influenza virus?", "output": "oseltamivir" }, { "input": "What genetic mutation decreases a person's susceptibility to the H1N1 influenza virus?", "output": "H275Y" }, { "input": "Why is ribavirin treatment limited?", "output": "difficulty with aerosol delivery, cost and potential harm to healthcare workers" }, { "input": "To what the lack of exposure report could be attributed?", "output": " lack of awareness or recall bias" }, { "input": "Why is the determination of asymptomatic or pre-symptomatic transmission, an urgent priority?", "output": " it has direct implications for public health and hospital infection control" }, { "input": "When does the infectivity of SARS-COV peak?", "output": "10 days after illness onset [7] , consistent with the peak in viral load at around that time" }, { "input": "How can the 2019-nCov spread?", "output": " from person to person," }, { "input": "What is the estimate of the basic reproduction number?", "output": "2.2" }, { "input": "What is assumed for the mean serial interval?", "output": " 7.5 days" }, { "input": "What would a shorter mean serial interval mean?", "output": "slightly lower basic reproductive number." }, { "input": "What should have reduced the basic reproduction number in January?", "output": "Control measures and changes in population behaviou" }, { "input": "What are the delays between infection to illness and illness to laboratory confirmatiion?", "output": " around 5\u20136 days, with an upper limit of around 11-14 days [2,5], and delays from illness onset to laboratory confirmation added a further 10 days on average" }, { "input": "What is the estimate of number of infections in Wuhan on 25 January 2020?", "output": "75,000" }, { "input": "when is viral shedding the highest?", "output": "on the day of illness onse" }, { "input": "How does the transmission of the respiratory virus happen?", "output": "through large respiratory droplets, " }, { "input": "How do some respiratory viruses spread?", "output": " through fine particle aerosols" }, { "input": "What can also play a role?", "output": "indirect transmission via fomites" }, { "input": "What can play a role in the infection of gastrointestinal tract?", "output": " faecal-oral transmission " }, { "input": "What was attributed to the spread of SARS-COV at Amoy Gardens?", "output": "through pressure differentials between contaminated effluent pipes, bathroom floor drains and flushing toilets " }, { "input": "How were the first human infections identified?", "output": "through a surveillance system for pneumonia of unknown aetiology" }, { "input": "What do mild clinical presentations of 2019-nCOV indicate?", "output": "that there could be many more mild infections than severe infections" }, { "input": "Why is important to determine the spectrum of clinical manifestations of 2019-nCoV infections?", "output": "because it determines the strength of public health response required." }, { "input": "What, beyond the assessment of severity, is important?", "output": " to determine high risk groups." }, { "input": "For whom would the infections be more severe?", "output": "older adults, obese individuals or those with underlying medical conditions," }, { "input": "When is this especially true?", "output": "when not all exacerbation events occurred during the viral infection but may also occur well after viral clearance (Kim et al., 2008; Stolz et al., 2019) in particular the late onset of a bacterial infection" }, { "input": "What is the current understanding on viral-induced exacerbations?", "output": "that viral infection increases airway inflammation which aggravates disease symptoms." }, { "input": "What have evoked new understandings as to the mechanisms of viral exacerbations?", "output": "Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models" }, { "input": "What is one of the major sources of exacerbation of chronic airway inflammatory diseases?", "output": "Respiratory virus infection" }, { "input": "What is the focus of this review?", "output": " recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways." }, { "input": "What have the authors reviewed?", "output": "the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases." }, { "input": "What is summarized?", "output": "how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations." }, { "input": "What is highlighted by the authors?", "output": "the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection." }, { "input": "What is consolidated in this review?", "output": "the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases." }, { "input": "What is this disease characterized by ?", "output": " airway inflammation leading to complications such as coughing, wheezing and shortness of breath. " }, { "input": "Where can this disease manifest?", "output": " in both the upper airway (such as chronic rhinosinusitis, CRS) and lower airway (such as asthma and chronic obstructive pulmonary disease, COPD)" }, { "input": "Why do treatment and management vary in efficacy?", "output": "due to the complexity and heterogeneity of the disease." }, { "input": "What complicates this further?", "output": "the effect of episodic exacerbations of the disease, defined as worsening of disease symptoms including wheeze, cough, breathlessness and chest tightness " }, { "input": "What are such exacerbations due to?", "output": "the effect of enhanced acute airway inflammation impacting upon and worsening the symptoms of the existing disease" }, { "input": "What do the acute exacerbations cause?", "output": "morbidity and sometimes mortality in patients, as well as resulting in major economic burdens worldwide" }, { "input": "What are acute exacerbations usually due to ?", "output": "the presence of environmental factors such as allergens, pollutants, smoke, cold or dry air and pathogenic microbes in the airway" }, { "input": "What does the immune response elicited by these agents lead to?", "output": " infiltration of activated immune cells that further release inflammatory mediators that cause acute symptoms such as increased mucus production, cough, wheeze and shortness of breath. " }, { "input": "Among these agents which is a major driver?", "output": "viral infection is one of the major drivers of asthma exacerbations accounting for up to 80-90% and 45-80% of exacerbations in children and adults respectively" }, { "input": "What is the viral involvement in COPD exacerbation? ", "output": "30-80% of acute COPD exacerbations" }, { "input": "What is the reason for the involvement of respiratory viruses in exacerbation?", "output": "their ease of transmission and infection" }, { "input": "What does the involvement of respiratory viruses contribute to?", "output": " important to identify the exact mechanisms underpinning viral exacerbations in susceptible subjects" }, { "input": "Why is it important to identify the exact mechanisms underpinning viral exacerbations in susceptible subjects?", "output": " to properly manage exacerbations via supplementary treatments that may alleviate the exacerbation symptoms or prevent severe exacerbations." }, { "input": "What is the lower airway the site of?", "output": "dysregulated inflammation in most chronic airway inflammatory diseases" }, { "input": "Where is the the first point of contact with sources of exacerbation", "output": "the upper airway" }, { "input": "What is the focus of this review?", "output": " recent findings of viral interaction with the upper airway." }, { "input": "What is complied by the authors?", "output": "how viral induced changes to the upper airway may contribute to chronic airway inflammatory disease exacerbations, to provide a unified elucidation of the potential exacerbation mechanisms initiated from predominantly upper airway infections." }, { "input": "Before linking respiratory viruses, what was linked to acute exacerbations?", "output": "Despite being a major cause of exacerbation, reports linking respiratory viruses to acute exacerbations only start to emerge in the late 1950s (Pattemore et al., 1992) ; with bacterial infections previously considered as the likely culprit for acute exacerbation " }, { "input": "What did the advent of PCR technology lead to?", "output": " viruses were recovered during acute exacerbations events and reports implicating their role emerged in the late 1980s" }, { "input": "What are the predominant viruses linked to airway inflammatory diseases?", "output": "Rhinovirus (RV) and respiratory syncytial virus (RSV) " }, { "input": "What other viruses are implicated in acute exacerbations but to a much lesser extent?", "output": "parainfluenza virus (PIV), influenza virus (IFV) and adenovirus (AdV)" }, { "input": "What other viruses have been recently reported as contributing to acute exacerbations?", "output": " viruses including bocavirus (BoV), human metapneumovirus (HMPV), certain coronavirus (CoV) strains, a specific enterovirus (EV) strain EV-D68, human cytomegalovirus (hCMV) and herpes simplex virus (HSV)" }, { "input": "What are the common feature of these viruses share?", "output": "they can infect both the upper and/or lower airway, further increasing the inflammatory conditions in the diseased airway" }, { "input": "Where do the respiratory viruses primarily infect and replicate?", "output": "within airway epithelial cells " }, { "input": "What happens during the replication process?", "output": "the cells release antiviral factors and cytokines that alter local airway inflammation and airway niche " }, { "input": "What does the inflammation lead to in healthy airways?", "output": "leads to type 1 inflammatory responses consisting of activation of an antiviral state and infiltration of antiviral effector cells. This eventually results in the resolution of the inflammatory response and clearance of the viral infection " }, { "input": "How may the responses be different in a chronically inflamed airway?", "output": " the responses against the virus may be impaired or aberrant, causing sustained inflammation and erroneous infiltration, resulting in the exacerbation of their symptoms (Mallia and Johnston, 2006; Dougherty and Fahy, 2009; Busse et al., 2010; Britto et al., 2017; Linden et al., 2019) . This is usually further compounded by the increased susceptibility of chronic airway inflammatory disease patients toward viral respiratory infections, thereby increasing the frequency of exacerbation as a whole" }, { "input": "What will the review focus on?", "output": "compiling and collating the current known mechanisms of viral-induced exacerbation of chronic airway inflammatory diseases; as well as linking the different viral infection pathogenesis to elucidate other potential ways the infection can exacerbate the disease" }, { "input": "How will this review serve?", "output": "to provide further understanding of viral induced exacerbation to identify potential pathways and pathogenesis mechanisms that may be targeted as supplementary care for management and prevention of exacerbation." }, { "input": "Why is this approach significant?", "output": "due to the current scarcity of antiviral drugs for the management of viral-induced exacerbations." }, { "input": "What happens upon infection?", "output": "viruses evoke an inflammatory response as a means of counteracting the infection." }, { "input": "How does the infected airway cell respond?", "output": "Generally, infected airway epithelial cells release type I (IFN\u03b1/\u03b2) and type III (IFN\u03bb) interferons, cytokines and chemokines such as IL-6, IL-8, IL-12, RANTES, macrophage inflammatory protein 1\u03b1 (MIP-1\u03b1) and monocyte chemotactic protein 1 (MCP-1) (Wark and Gibson, 2006; Matsukura et al., 2013) ." }, { "input": "What does the epithelial proteins cause?", "output": "enable infiltration of innate immune cells and of professional antigen presenting cells (APCs) that will then in turn release specific mediators to facilitate viral targeting and clearance, including type II interferon (IFN\u03b3), IL-2, IL-4, IL-5, IL-9, and IL-12 (Wark and Gibson, 2006; Singh et al., 2010; Braciale et al., 2012) ." }, { "input": "What is the effect of these factors?", "output": "These factors heighten local inflammation and the infiltration of granulocytes, T-cells and B-cells (Wark and Gibson, 2006; Braciale et al., 2012) . The increased inflammation, in turn, worsens the symptoms of airway diseases." }, { "input": "What additional effects are caused in patients with asthma and patients with CRS with nasal polyp ?", "output": "viral infections such as RV and RSV promote a Type 2-biased immune response (Becker, 2006; Jackson et al., 2014; Jurak et al., 2018) . This amplifies the basal type 2 inflammation resulting in a greater release of IL-4, IL-5, IL-13, RANTES and eotaxin and a further increase in eosinophilia, a key pathological driver of asthma and CRSwNP" }, { "input": "What is the result of increased eosinophilia?", "output": "worsens the classical symptoms of disease and may further lead to life-threatening conditions due to breathing difficulties" }, { "input": "What are the effects for patients with COPD and patients with CRS without nasal polyp (CRSsNP) ?", "output": "are more neutrophilic in nature due to the expression of neutrophil chemoattractants such as CXCL9, CXCL10, and CXCL11 (Cukic et al., 2012; Brightling and Greening, 2019) . The pathology of these airway diseases is characterized by airway remodeling due to the presence of remodeling factors such as matrix metalloproteinases (MMPs) released from infiltrating neutrophils (Linden et al., 2019) . Viral infections in such conditions will then cause increase neutrophilic activation; worsening the symptoms and airway remodeling in the airway thereby exacerbating COPD, CRSsNP and even CRSwNP in certain cases " }, { "input": " Which are the type 2 inflammatory cytokines expressed by the epithelial cells upon injury to the epithelial barrier?", "output": " IL-25, IL-33 and TSLP " }, { "input": "Which cells lacking both B and T cell receptors but play a crucial role in secreting type 2 cytokines to perpetuate type 2 inflammation when activated ?", "output": " ILC2s are a group of lymphoid cells" }, { "input": "What is the effect cell death and injury to the epithelial barrier due to infection?", "output": "induce the expression of IL-25, IL-33 and TSLP, with heighten expression in an inflamed airway" }, { "input": "What happens when the 3 cytokines are expressed?", "output": "These 3 cytokines then work in concert to activate ILC2s to further secrete type 2 cytokines IL-4, IL-5, and IL-13 which further aggravate the type 2 inflammation in the airway causing acute exacerbation (" }, { "input": "What happens in the case of COPD?", "output": " increased ILC2 activation, which retain the capability of differentiating to ILC1, may also further augment the neutrophilic response and further aggravate the exacerbation" }, { "input": "What happens during viral infection of healthy individuals?", "output": " these factors are not released to any great extent and do not activate an ILC2 response during viral infection in healthy individuals (Yan et al., 2016; Tan et al., 2018a) ; despite augmenting a type 2 exacerbation in chronically inflamed airways (Jurak et al., 2018) . These classical mechanisms of viral induced acute exacerbations are summarized in Figure 1 " }, { "input": "What happens upon viral infection in the airway?", "output": "antiviral state will be activated to clear the invading pathogen from the airway. Immune response and injury factors released from the infected epithelium normally would induce a rapid type 1 immunity that facilitates viral clearance. " }, { "input": "What is the effect of the inflammation of the airway?", "output": " However, in the inflamed airway, the cytokines and chemokines released instead augmented the inflammation present in the chronically inflamed airway, strengthening the neutrophilic infiltration in COPD airway, and eosinophilic infiltration in the asthmatic airway. The effect is also further compounded by the participation of Th1 and ILC1 cells in the COPD airway; and Th2 and ILC2 cells in the asthmatic airway." }, { "input": "What increases the severity of exacerbations in the airway?", "output": "the synergistic effect of viral infection with other sensitizing agents " }, { "input": "Why viruses do not need to directly infect the lower airway to cause an acute exacerbation?", "output": "he nasal epithelium remains the primary site of most infections." }, { "input": "what is suggested by the fact that not all viral infections of the airway lead to acute exacerbations?", "output": "a more complex interplay between the virus and upper airway epithelium which synergize with the local airway environment in line with the \"united airway\" hypothesis " }, { "input": "What is the effect of chronic airway inflammatory disease in patients?", "output": "viral infections or their components persist in patients" }, { "input": "What is the effect of chronic airway inflammatory disease?", "output": "may further alter the local environment and contribute to current and future exacerbations" }, { "input": "Why should future studies be performed using metagenomics in addition to PCR analysis ?", "output": "to determine the contribution of the microbiome and mycobiome to viral infections." }, { "input": "What is highlighted by the authors in this review?", "output": " recent data regarding viral interactions with the airway epithelium that could also contribute to, or further aggravate, acute exacerbations of chronic airway inflammatory diseases." }, { "input": "Who has impaired or reduced ability of viral clearance ?", "output": "Patients with chronic airway inflammatory diseases " }, { "input": "What does their impairment stems from?", "output": "a type 2-skewed inflammatory response which deprives the airway of important type 1 responsive CD8 cells that are responsible for the complete clearance of virusinfected cells " }, { "input": "Where is this especially evident?", "output": "in weak type 1 inflammation-inducing viruses such as RV and RSV" }, { "input": "What are other effects?", "output": "there are also evidence of reduced type I (IFN\u03b2) and III (IFN\u03bb) interferon production due to type 2-skewed inflammation, which contributes to imperfect clearance of the virus resulting in persistence of viral components, or the live virus in the airway epithelium " }, { "input": "What is the effect of viral components remaining in the airway?", "output": "antiviral genes such as type I interferons, inflammasome activating factors and cytokines remained activated resulting in prolong airway inflammation" }, { "input": "What do these factors do?", "output": "enhance granulocyte infiltration thus prolonging the exacerbation symptoms. Such persistent inflammation may also be found within DNA viruses such as AdV, hCMV and HSV, whose infections generally persist longer (Imperiale and Jiang, 2015) , further contributing to chronic activation of inflammation when they infect the airway" }, { "input": "What is also linked with the chronic inflammation that precedes the malignancies?", "output": "human papilloma virus (HPV), a DNA virus highly associated with head and neck cancers and respiratory papillomatosis," }, { "input": "What should be investigated in the future?", "output": " the role of HPV infection in causing chronic inflammation in the airway and their association to exacerbations of chronic airway inflammatory diseases, which is scarcely explored" }, { "input": "What further can viral persistence lead to?", "output": "viral persistence which lead to continuous expression of antiviral genes may also lead to the development of steroid resistance, which is seen with RV, RSV, and PIV infection" }, { "input": "What effect the use of steroids to suppress inflammation can have?", "output": "may also cause the virus to linger longer in the airway due to the lack of antiviral clearance" }, { "input": "What should be further focus of research?", "output": "The concomitant development of steroid resistance together with recurring or prolong viral infection " }, { "input": "Which viruses may not cause prolonged inflammation due to strong induction of antiviral clearance?", "output": "viruses that induce strong type 1 inflammation and cell death such as IFV (Yan et al., 2016; Guibas et al., 2018) and certain CoV (including the recently emerged COVID-19 virus)" }, { "input": "What do these infections cause?", "output": "massive damage and cell death to the epithelial barrier, so much so that areas of the epithelium may be completely absent post infection (Yan et al., 2016; Tan et al., 2019) . Factors such as RANTES and CXCL10, which recruit immune cells to induce apoptosis, are strongly induced from IFV infected epithelium " }, { "input": "What do the necroptotic factors such as RIP3 do?", "output": " further compounds the cell deaths in IFV infected epithelium . The massive cell death induced may result in worsening of the acute exacerbation due to the release of their cellular content into the airway, further evoking an inflammatory response in the airway " }, { "input": "What may the destruction of the epithelial barrier cause?", "output": " further contact with other pathogens and allergens in the airway which may then prolong exacerbations or results in new exacerbations." }, { "input": "What may the epithelial destruction cause?", "output": "may also promote further epithelial remodeling during its regeneration as viral infection induces the expression of remodeling genes such as MMPs and growth factors . Infections that cause massive destruction of the epithelium, such as IFV, usually result in severe acute exacerbations with non-classical symptoms of chronic airway inflammatory diseases." }, { "input": "What is recommended that patients with chronic airway inflammatory disease?", "output": " receive their annual influenza vaccination as the best means to prevent severe IFV induced exacerbation." }, { "input": "What is another mechanism that viral infections use to drive acute exacerbations?", "output": "the induction of vasodilation or tight junction opening factors which may increase the rate of infiltration. " }, { "input": "What does infection of respiratory viruses cause?", "output": "disruption of tight junctions with the resulting increased rate of viral infiltration. This also increases the chances of allergens coming into contact with airway immune cells." }, { "input": "What is an example of this?", "output": " IFV infection was found to induce oncostatin M (OSM) which causes tight junction opening (Pothoven et al., 2015; Tian et al., 2018) . Similarly, RV and RSV infections usually cause tight junction opening which may also increase the infiltration rate of eosinophils and thus worsening of the classical symptoms of chronic airway inflammatory diseases " }, { "input": "What are also associated with viral infections and pneumonia development, which may worsen inflammation in the lower airway?", "output": " the expression of vasodilating factors and fluid homeostatic factors such as angiopoietin-like 4 (ANGPTL4) and bactericidal/permeabilityincreasing fold-containing family member A1 (BPIFA1)" }, { "input": "What is another area of interest?", "output": "the relationship between asthma and COPD exacerbations and their association with the airway microbiome." }, { "input": "What is usually linked with the development of chronic airway inflammatory diseases?", "output": "specific bacterial species in the microbiome which may thrive in the inflamed airway environment " }, { "input": "What follows in the event of a viral infection such as RV infection?", "output": " the effect induced by the virus may destabilize the equilibrium of the microbiome present (Molyneaux et al., 2013; Kloepfer et al., 2014; Kloepfer et al., 2017; Jubinville et al., 2018; van Rijn et al., 2019) . In addition, viral infection may disrupt biofilm colonies in the upper airway (e.g., Streptococcus pneumoniae) microbiome to be release into the lower airway and worsening the inflammation" }, { "input": "What does the viral infection alter?", "output": "the nutrient profile in the airway through release of previously inaccessible nutrients that will alter bacterial growth" }, { "input": "What is the destabilization is further compounded by?", "output": " impaired bacterial immune response, either from direct viral influences, or use of corticosteroids to suppress the exacerbation symptoms" }, { "input": "What does all this gradually lead to?", "output": "more far reaching effect when normal flora is replaced with opportunistic pathogens, altering the inflammatory profiles " }, { "input": "Why do these changes may result in more severe and frequent acute exacerbations ?", "output": "due to the interplay between virus and pathogenic bacteria in exacerbating chronic airway inflammatory diseases " }, { "input": "How effective are microbiome based trial therapies?", "output": " have shown efficacy in the treatments of irritable bowel syndrome by restoring the intestinal microbiome (" }, { "input": "What can viral infections cause?", "output": "the disruption of mucociliary function, an important component of the epithelial barrier. " }, { "input": "Which is the primary contact/infection site of most respiratory viruses?", "output": "The upper airway epithelium" }, { "input": "What does the destruction of epithelial barrier, mucociliary function and cell death of the epithelial cells do?", "output": "serves to increase contact between environmental triggers with the lower airway and resident immune cells." }, { "input": "What are viral infections are usually accompanied with?", "output": "oxidative stress which will further increase the local inflammation in the airway. " }, { "input": "What is the dysregulation of inflammation can be further compounded by?", "output": "modulation of miRNAs and epigenetic modification such as DNA methylation and histone modifications that promote dysregulation in inflammation" }, { "input": "What does the change in the local airway environment and inflammation promote?", "output": "growth of pathogenic bacteria that may replace the airway microbiome. " }, { "input": "What does the the inflammatory environment dispersal of upper airway commensals into the lower airway cause?", "output": "inflammation and alteration of the lower airway environment, resulting in prolong exacerbation episodes following viral infection. " }, { "input": "Which are the most commonly studied viruses in chronic airway inflammatory diseases?", "output": "RV, RSV, and IFV" }, { "input": "What do the infections such as RSV are shown to do?", "output": " to directly destroy the cilia of the ciliated cells and almost all respiratory viruses infect the ciliated cells" }, { "input": "What does mucus overproduction do?", "output": " disrupt the equilibrium of the mucociliary function following viral infection, resulting in symptoms of acute exacerbation" }, { "input": "What does the disruption of the ciliary movement during viral infection may cause?", "output": "MicroRNAs (miRNAs)" }, { "input": "What are MicroRNAs(miRNA)?", "output": "short non-coding RNAs involved in post-transcriptional modulation of biological processes, and implicated in a number of diseases " }, { "input": "What are miRNAs found to be induced by?", "output": " viral infections and may play a role in the modulation of antiviral responses and inflammation " }, { "input": "What were linked to the exacerbation of the airway inflammation disease?", "output": "circulating miRNA changes" }, { "input": "Where might such miRNA changes have originated from?", "output": "from the infected epithelium and responding immune cells, which may serve to further dysregulate airway inflammation leading to exacerbations." }, { "input": "What are both IFV and RSV infections shown to do?", "output": " to increase miR-21 and augmented inflammation in experimental murine asthma models, which is reversed with a combination treatment of anti-miR-21 and corticosteroids" }, { "input": "What are IFV infection shown to do?", "output": " increase miR-125a and b, and miR-132 in COPD epithelium which inhibits A20 and MAVS; and p300 and IRF3, respectively, resulting in increased susceptibility to viral infections " }, { "input": "What happens in in asthmatic epithelium in IFV infection?", "output": "miR-22 was shown to be suppressed in asthmatic epithelium in IFV infection which lead to aberrant epithelial response, contributing to exacerbations " }, { "input": "What do non-coding RNAs present as?", "output": "as targets to modulate viral induced airway changes as a means of managing exacerbation of chronic airway inflammatory diseases." }, { "input": "What mechanisms, other than miRNA modulation play a role?", "output": "epigenetic modification such as DNA methylation " }, { "input": "What have recent epigenetic studies indicated?", "output": "the association of epigenetic modification and chronic airway inflammatory diseases, and that the nasal methylome was shown to be a sensitive marker for airway inflammatory changes (Cardenas et al., 2019; Gomez, 2019) ." }, { "input": " What have these studies also shown?", "output": " viral infections such as RV and RSV alters DNA methylation and histone modifications in the airway epithelium which may alter inflammatory responses, driving chronic airway inflammatory diseases and exacerbations" }, { "input": "What has Spalluto et.al. have shown?", "output": "that antiviral factors such as IFN\u03b3 epigenetically modifies the viral resistance of epithelial cells." }, { "input": " What infections such as RV and RSV that weakly induce antiviral responses may result in?", "output": " an altered inflammatory state contributing to further viral persistence and exacerbation of chronic airway inflammatory diseases " }, { "input": "What can viral infection result in?", "output": " enhanced production of reactive oxygen species (ROS), oxidative stress and mitochondrial dysfunction in the airway epithelium " }, { "input": "What sustains the inflammation in the airway?", "output": "state of constant oxidative stress " }, { "input": "What may viral infections of the respiratory epithelium by viruses such as IFV, RV, RSV and HSV do?", "output": "may trigger the further production of ROS as an antiviral mechanism" }, { "input": "What can happen in response to the infection such as neutrophils?", "output": " infiltrating cells in response to the infection such as neutrophils will also trigger respiratory burst as a means of increasing the ROS in the infected region. The increased ROS and oxidative stress in the local environment may serve as a trigger to promote inflammation thereby aggravating the inflammation in the airway " }, { "input": "In addition to worsening disease symptoms, what do viral-induced exacerbations do?", "output": " also may alter the management of the disease or confer resistance toward treatments that worked before. " }, { "input": "What may studies in natural exacerbations and in viral-challenge models using RNA-sequencing (RNA-seq) or single cell RNA-seq on a range of time-points provide?", "output": "important information regarding viral pathogenesis and changes induced within the airway of chronic airway inflammatory disease patients to identify novel targets and pathway for improved management of the disease." }, { "input": "What analysis functions may be useful?", "output": " epithelial cell models such as the air-liquid interface, in vitro airway epithelial model that has been adapted to studying viral infection and the changes it induced in the airway " }, { "input": "For what purpose animal based models aare developed for?", "output": "to identify systemic mechanisms of acute exacerbation" }, { "input": "What can be used unravel the immune profile of a viral infection in healthy and diseased condition?", "output": " the humanized mouse model that possess human immune cells " }, { "input": "For what purpose controlled in vivo human infections can be performed for mild viruses?", "output": "the best mode of verification of the associations of the virus with the proposed mechanism of viral induced acute exacerbations " }, { "input": "Why may the mechanisms of exacerbation vary considerably?", "output": " due to the complex interactions between the host and the exacerbation agents" }, { "input": "What clinical condition is caused by Hantaan virus?", "output": "hemorrhagic fever with renal syndrome" }, { "input": "What is the structure of Hantaan virus?", "output": "enveloped, negative-sense RNA virus" }, { "input": "What the animal vector reservoir for Hantaan virus?", "output": "rodents" }, { "input": "What diagnostic test is correlated with the severity of HFRS?", "output": "plasma viral load" }, { "input": "How is Interferon used in practice?", "output": "an antiviral medicine" }, { "input": "What genotypes are associated with the severity of HFRS?", "output": "rs12252 C allele and CC genotype" }, { "input": "Which IFITM proteins have been shown to possess antiviral activity?", "output": "IFITM1, 2, and 3" }, { "input": "What is the hypothesized mechanism by which IFITMs work?", "output": "restrict viral infection at the stage of cellular entry" }, { "input": "What genotype causes truncation of the IFITM3 protein?", "output": "rs12252 C allele" }, { "input": "What can cause a slowing growth in daily reported deaths?", "output": "significant impact\nof interventions implemented several weeks earlier." }, { "input": "When did Italy go into Iockdown?", "output": "11th March" }, { "input": "Approximately how many deaths have been averted in Western Europe with current non-pharmaceutical interventions remaining in place until the end of March?", "output": "59,000 deaths" }, { "input": "What are some non-pharmaceutical interventions?", "output": "case isolation, the closure of schools and\nuniversities, banning of mass gatherings and/or public events, and most recently, widescale social\ndistancing including local and national Iockdowns" }, { "input": "Type of model used to infer the impact non-pharmaceutical interventions?", "output": "semi-mechanistic Bayesian hierarchical model" }, { "input": "How can a semi-mechanistic Bayesian hierarchical model estimate changes to the reproductive number?", "output": "calculating backwards from the deaths observed over time to estimate transmission that\noccurred several weeks prior, allowing for the time lag between infection and death." }, { "input": "What is a key assumption of a semi-mechanistic Bayesian hierarchical model used for coronavirus?", "output": "each intervention has the same effect on the\nreproduction number across countries and over time" }, { "input": "What is the time lag between when transmission changes occur and when their impact can be\nobserved in trends in mortality?", "output": "2-3 weeks" }, { "input": "What is the key aim of non-pharmaceutical interventions?", "output": "reduce the effective reproduction number" }, { "input": "What happens if the reproduction number is greater then 1?", "output": "infections will increase (dependent on how much greater than 1 the reproduction number is)" }, { "input": "When did China introduce strict movement restrictions and other measures including case isolation and quarantine?", "output": "23rd January" }, { "input": "What was the result of China's interventions introduced in January?", "output": "downward trend in the number of\nconfirmed new cases during February" }, { "input": "What are examples of social distancing?", "output": "banning large gatherings and advising individuals not to socialize outside\ntheir households" }, { "input": "What was the estimated effect on China's reproduction number in March based on the intervention introduced in January?", "output": "from\naround 2-4 during the uncontrolled epidemic down to below 1" }, { "input": "Why is it challenging to estimate the reproduction number?", "output": "high proportion of\ninfections not detected by health systems\u201d7 and regular changes in testing policies," }, { "input": "What is an alternative way to estimate the course of an epidemic?", "output": "back-calculate infections from\nobserved deaths" }, { "input": "What is the estimated attack rate in Italy?", "output": "9.8% [3.2%-25%] of the population" }, { "input": "As of the end of March what is the proportion of Spain's population to be infected?", "output": "15.0% (7.0 [18-19] million people)" }, { "input": "Which Western European country is estimated to have the lowest attack rate?", "output": "Germany" }, { "input": "What is Austria's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "1.1% [0.36%-3.1%]" }, { "input": "What is Belgium's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "3.7% [1.3%-9.7%]" }, { "input": "What is Denmark's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "1.1% [0.40%-3.1%]" }, { "input": "What is France's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "3.0% [1.1%-7.4%]" }, { "input": "What is Germany's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "0.72% [0.28%-1.8%]" }, { "input": "What is Italy's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "9.8% [3.2%-26%]" }, { "input": "What is Norway's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "0.41% [0.09%-1.2%]" }, { "input": "What is Spain's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "15% [3.7%-41%]" }, { "input": "What is Spain's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "3.1% [0.85%-8.4%]" }, { "input": "What is Switzerland's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "3.2% [1.3%-7.6%]" }, { "input": "What is United Kingdom's estimated mean percentage [95% credible interval] of total population infected as of 28th March?", "output": "2.7% [1.2%-5.4%]" }, { "input": "What is the estimated averaged initial reproduction number [95% credible interval] for Western Europe as of 28th March?", "output": "3.87 [3.01-4.66]" }, { "input": "Why is there high uncertainty in estimating the impact of interventions against the coronavirus?", "output": "too early to detect substantial\nintervention impact in many countries at earlier stages of their epidemic" }, { "input": "Why is it statistically impossible to determine which individual intervention had the greatest effect on reducing the coronavirus reproduction number?", "output": "close spacing of interventions in time" }, { "input": "What is estimated to drop immediately after an introduction of a non-pharmaceutical intervention?", "output": " number of daily infections" }, { "input": "One way to understand the impact of interventions?", "output": "fit a counterfactual model without the interventions\nand compare this to the actual model" }, { "input": "What is a lockdown?", "output": "banned gatherings of more than 2 people" }, { "input": "Why is it hard to know the true incidence of infections number?", "output": "underreporting as well as systematic and country-specific changes in testing" }, { "input": "What is an example of a case-based measure against coronavirus?", "output": "strong recommendations or laws to the general\npublic and primary care about self\u2014isolation when showing COVID-19-like symptoms" }, { "input": "What is an example of containment phase intervention?", "output": "isolation if travelling back from an epidemic country" }, { "input": "What does a public events ban intervention mean?", "output": "banning all public events of more than 100 participants" }, { "input": "An example of social distancing", "output": "work from home wherever possible" }, { "input": "Example of social distancing", "output": "reducing use ofpublictransport" }, { "input": "What is a lockdown?", "output": "regulations/legislations regarding strict face-to-face social interaction" }, { "input": "What is an infection-to-onset-distribution?", "output": "time from infection to the onset\nof symptoms" }, { "input": "What is an onset-to-death distribution?", "output": "time from the onset of symptoms to death" }, { "input": "What is the population-averaged infection fatality ratio?", "output": "adjusted for the age structure and contact patterns of\neach country" }, { "input": "What is the time-varying reproduction number a function of?", "output": " initial reproduction number before interventions and the effect sizes from\ninterventions" }, { "input": "What is an incubation period?", "output": "infection to onset of symptoms" }, { "input": "What is an incubation period?", "output": "infection-\nto-onset" }, { "input": "What are the descriptive statistics for the onset-to-death for coronavirus?", "output": "Gamma distributed with a mean of 18.8 days and a\ncoefficient of va riation 0.45" }, { "input": "What are the descriptive statistics for the incubation period for coronavirus?", "output": "distribution is Gamma distributed with mean 5.1 days and coefficient of variation\n0.86" }, { "input": "What is the estimated infection-to-death distribution's mean for coronavirus?", "output": "23.9 days" }, { "input": "What is a well known approach to model the true number of infected individuals?", "output": "discrete renewal process" }, { "input": "What is a way to measure virus transmission?", "output": "reproductive number" }, { "input": "What term describes when a majority of the population has built an immunity to a virus?", "output": "herd immunity" }, { "input": "What is the estimated number of people in Italy infected with coronavirus by March 28th?", "output": "cumulatively, 5.9 [1.9-15.2] million people have been\ninfected as of March 28th" }, { "input": "In 2009 what was the reported H1N1 vaccination rate in China?", "output": "10.8%" }, { "input": "What is the highest alert level given by the World Health Organization to a pandemic?", "output": "phase 6" }, { "input": "What does it mean for a pandemic to have a WHO alert level of 6?", "output": "spread in more than two continents" }, { "input": "What was the estimated economic impact in the U.S. from the 2009 SARS pandemic?", "output": "estimated at $30-$100 billion" }, { "input": "How is 2019-nCOV transmitted?", "output": "2019-nCoV was transmitted through respiratory tract and then induced pneumonia," }, { "input": "What are ways in which 2019-nCOV is transmitted?", "output": "We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral\u2013fecal route." }, { "input": "Is oral swab for detecting 2019-nCOV infection, sufficient?", "output": "the current strategy for the detection of viral RNA in oral swabs used for 2019-nCoV diagnosis is not perfect. The virus may be present in anal swabs or blood of patients when oral swabs detection negative." }, { "input": "Is oral swab for detecting 2019-nCOV infection, sufficient?", "output": " patients infected with 2019-nCoV may harbour the virus in the intestine at the early or late stage of disease. It is also worth to note none of the patients with viremia blood had positive swabs. These patients would likely be considered as 2019-nCoV negative through routine surveillance, and thus pose a threat to other people." }, { "input": "What other tests should be considered for 2019-nCOV epidemiology?", "output": "serology should be considered for 2019-nCoV epidemiology." }, { "input": "What tests should be done before a 2019-nCOV infected patient is discharged?", "output": "we cannot discharge a patient purely based on oral swabs negative, who may still shed the virus by oral-fecal route. Above all, we strongly suggest using viral IgM and IgG serological test to confirm an infection, considering the unreliable results from oral swabs detection" }, { "input": "What is a Hantavirus?", "output": "zoonotic diseases" }, { "input": "What plays a role in innate immunity to Hantavirus infection?", "output": "long noncoding RNAs (lncRNAs)" }, { "input": "What evidence suggests that RIG-I and DDX60 collaborate to exert antiviral effects?", "output": "colocalized after HTNV infection" }, { "input": "What was the major contribution of this study?", "output": "the first study to describe the role of NEAT1 in HTNV infection" }, { "input": "What symptoms were reported?", "output": "Of the remaining 29, 20 reported fever, 14 reported cough and eight reported weakness. Additional symptoms reported included headaches (6 cases), sore throat (2), rhinorrhoea (2), shortness of breath (2), myalgia (1), diarrhoea (1) and nausea (1)" }, { "input": "What did the collected data include?", "output": "demographics, history of recent travel to affected areas, close contact with a probable or confirmed COVID-19 case, underlying conditions, signs and symptoms of disease at onset, type of specimens from which the virus was detected, and clinical outcome. " }, { "input": "When was COVID surveillance implemented in European region?", "output": "27 January 2020" }, { "input": "As of 21 February, how many cases were reported?", "output": "47" }, { "input": "Where were the cases that were studied?", "output": "21 were linked to two clusters in Germany and France, 14 were infected in China" }, { "input": "What was the median case age?", "output": "42 years" }, { "input": "How many were male?", "output": " 25 " }, { "input": "How many cases were there on 5 March?", "output": "4,250 " }, { "input": "When did the Chinese authorities share the sequence of a novel coronavirus ?", "output": "12 January 2020" }, { "input": "What is the name of the disease caused buy SARS-COV-2?", "output": "coronavirus disease 2019 (COVID -19)" }, { "input": "What country does this study exclude?", "output": "United Kingdom (UK)" }, { "input": "What does the study include?", "output": "a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission." }, { "input": "What did the ECDC and WHO regional office ask the countries?", "output": " to complete a WHO standard COVID-19 case report form for all confirmed and probable cases according to WHO criteria" }, { "input": "What was the overall aim of the surveillance?", "output": " to support the global strategy of containment of COVID-19 with rapid identification and follow-up of cases linked to affected countries in order to minimise onward transmission." }, { "input": "What were the surveillance objectives?", "output": "to: describe the key epidemiological and clinical characteristics of COVID-19 cases detected in Europe; inform country preparedness; and improve further case detection and management. " }, { "input": "What is the adopted WHO case definition?", "output": "a confirmed case was a person with laboratory confirmation of SARS-CoV-2 infection (ECDC recommended two separate SARS-CoV-2 RT-PCR tests), irrespective of clinical signs and symptoms, whereas a probable case was a suspect case for whom testing for SARS-CoV-2 was inconclusive or positive using a pan-coronavirus assay" }, { "input": "When was the first reported death in France?", "output": "15 February" }, { "input": "What is the presumed incubation period?", "output": " up to 14 days [" }, { "input": "What were the places of infection?", "output": " 35 cases (missing for three cases), of whom 14 were infected in China (Hubei province: 10 cases; Shandong province: one case; province not reported for three cases). The remaining 21 cases were infected in Europe. " }, { "input": "What places were linked to these?", "output": "14 were linked to a cluster in Bavaria, Germany, and seven to a cluster in Haute-Savoie, France " }, { "input": "How many cases were hospitalised?", "output": "All but two cases were hospitalised (35 of 37 where information on hospitalisation was reported)" }, { "input": "Why were they hospitalised?", "output": " it is likely that most were hospitalised to isolate the person rather than because of severe disease. " }, { "input": "What was time from onset to hospitalisation?", "output": "ranged between 0 and 10 days with a mean of 3.7 days " }, { "input": "What was the duration of hospitalisation?", "output": "The mean number of days to hospitalisation was 2.5 days for cases imported from China, but 4.6 days for those infected in Europe." }, { "input": "Why was this?", "output": "This was mostly a result of delays in identifying the index cases of the two clusters in France and Germany. In the German cluster, for example, the first three cases detected locally were hospitalised in a mean of 5.7 days, whereas the following six took only a mean of 2 days to be hospitalised." }, { "input": "How many cases reported symptoms at this point?\n", "output": " 31 cases" }, { "input": "How many cases were asymptomatic?", "output": "Two cases " }, { "input": "What were the asymptomatic cases tested as?", "output": "as part of screening following repatriation and during contact tracing respectively. " }, { "input": " For how many cases Fever reported as the sole symptom?", "output": " nine cases" }, { "input": "In how many cases the symptoms at diagnosis were consistent with the case definition for acute respiratory infection?", "output": "In 16 of 29 symptomatic cases" }, { "input": "How many cases had data on preexisting conditions?", "output": "seven cases" }, { "input": "How many cases had no pre-existing conditions?", "output": "five" }, { "input": "What other data on pre-existing conditions were reported?", "output": "one was reported to be obese and one had pre-existing cardiac disease. No data on clinical signs e.g. dyspnea etc. were reported for any of the 38 cases." }, { "input": "How many reported viral pneumonia?", "output": "two reported in Italy and two reported in France" }, { "input": "What was the clinical evolution of the hospitalised cases?", "output": "All hospitalised cases had a benign clinical evolution except four," }, { "input": "What happened to three cases who were aged 65 years or over?", "output": "were admitted to intensive care and required respiratory support and one French case died." }, { "input": "What happened to the case who died?", "output": "was hospitalised for 21 days and required intensive care and mechanical ventilation for 19 days" }, { "input": "What was the duration of hospitalisation reported for 16 cases ?", "output": "a median of 13 days (range: 8-23 days)" }, { "input": "How were the assays confirmed?", "output": "according to specific assays targeting at least two separate genes (envelope (E) gene as a screening test and RNA-dependent RNA polymerase (RdRp) gene or nucleoprotein (N) gene for confirmation) " }, { "input": "What were the specimen types for 21 cases?", "output": "15 had positive nasopharyngeal swabs, nine had positive throat swabs, three cases had positive sputum, two had a positive nasal swab, one case had a positive nasopharyngeal aspirate and one a positive endotracheal aspirate." }, { "input": "As of 5 March 2020, what are the cases in the WHO European region?", "output": "there are 4,250 cases including 113 deaths reported among 38 countries" }, { "input": "What were the two contexts for transmission?", "output": "sporadic cases among travellers from China (14 cases) and cases who acquired infection due to subsequent local transmission in Europe (21 cases)." }, { "input": "What does the analysis show on the difference between locally acquired cases vs imported cases?", "output": "that the time from symptom onset to hospitalisation/case isolation was about 3 days longer for locally acquired cases than for imported cases." }, { "input": "What is required for locally acquired cases?", "output": "significant resources for contact tracing and quarantine, and countries should be prepared to allocate considerable public health resources during the containment phase, should local clusters emerge in their population. In addition, prompt sharing of information on cases and contacts through international notification systems such as the International Health Regulations (IHR) mechanism and the European Commission's European Early Warning and Response System is essential to contain international spread of infection.\n" }, { "input": "What was common to all imported cases?", "output": "had a history of travel to China" }, { "input": "What testing and detection are needed?", "output": "Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection of local circulation of COVID-19, including through testing of severe acute respiratory infections in hospitals irrespectively of travel history as recommended in the WHO case definition updated on 27 February 2020 " }, { "input": "What did the finding prompt ECDC to do?", "output": "include fever among several clinical signs or symptoms indicative for the suspected case definition." }, { "input": "Why is understanding the infection-severity critical ?", "output": "to help plan for the impact on the healthcare system and the wider population." }, { "input": "Why are serological tests vital?", "output": "to understand the proportion of cases who are asymptomatic." }, { "input": "How can hospital based surveillance help?", "output": "help estimate the incidence of severe cases and identify risk factors for severity and death" }, { "input": "How can present systems of surveillance be used?", "output": "Established hospital surveillance systems that are in place for influenza and other diseases in Europe may be expanded for this purpose. In addition, a number of countries in Europe are adapting and, in some cases, already using existing sentinel primary care based surveillance systems for influenza to detect community transmission of SARS-CoV-2" }, { "input": "How will this approach used?", "output": "will be used globally to help identify evidence of widespread community transmission and, should the virus spread and containment no longer be deemed feasible, to monitor intensity of disease transmission, trends and its geographical spread." }, { "input": "Why is additional research needed?", "output": " to complement surveillance data to build knowledge on the infectious period, modes of transmission, basic and effective reproduction numbers, and effectiveness of prevention and case management options also in settings outside of China." }, { "input": "What growing dysjunction has been witnessed?", "output": "a 'Valley of Death' 1,2 no less, between broadening strides in fundamental biomedical research and their incommensurate reach into the clinic. " }, { "input": "What is aiming to incorporate pathways to translation at the earliest stages?", "output": " recent changes in the structure of government funding, 2 new public and private joint ventures and specialist undergraduate and postgraduate courses" }, { "input": "How much have the number of biomedical research publications targeting 'translational' concepts has increased ?", "output": "exponentially, up 1800%" }, { "input": "What ways to solve the issues are outlined?", "output": "by creatively leveraging the so-called 'strengths' of viruses. Viral RNA polymerisation and reverse transcription enable resistance to treatment by conferring extraordinary genetic diversity. " }, { "input": "How do these exact processes ultimately restrict viral infectivity?", "output": " by strongly limiting virus genome sizes and their incorporation of new information. " }, { "input": "What does the author coin this evolutionary dilemma as?", "output": "'information economy paradox'." }, { "input": "How do many viruses resolve this ?", "output": "by manipulating multifunctional or multitasking host cell proteins (MMHPs), thereby maximising host subversion and viral infectivity at minimal informational cost." }, { "input": "How may this \"Achilles Heel\" be safely targeted?", "output": " via host-oriented therapies to impose devastating informational and fitness barriers on escape mutant selection." }, { "input": "Why may MMHP-targeting therapies exhibit both robust and broadspectrum antiviral efficacy?", "output": "since MMHPs are often conserved targets within and between virus families," } ] }