niryuu/sni-each-converted huggingface dataset:
Paragraph: The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection. 
 Title: Antiviral activity of silymarin against chikungunya virus
Output: True
Paragraph: Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation. 
 Title: High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan
Output: True
Paragraph: Phylogenomic analysis of SARS-CoV-2 as available from publicly available repositories suggests the presence of 3 prevalent groups of viral episomes (super-clades), which are mostly associated with outbreaks in distinct geographic locations (China, USA and Europe). While levels of genomic variability between SARS-CoV-2 isolates are limited, to our knowledge, it is not clear whether the observed patterns of variability in viral super-clades reflect ongoing adaptation of SARS-CoV-2, or merely genetic drift and founder effects. Here, we analyze more than 1100 complete, high quality SARS-CoV-2 genome sequences, and provide evidence for the absence of distinct evolutionary patterns/signatures in the genomes of the currently known major clades of SARS-CoV-2. Our analyses suggest that the presence of distinct viral episomes at different geographic locations are consistent with founder effects, coupled with the rapid spread of this novel virus. We observe that while cross species adaptation of the virus is associated with hypervariability of specific protein coding regions (including the RDB domain of the spike protein), the more variable genomic regions between extant SARS-CoV-2 episomes correspond with the 3' and 5' UTRs, suggesting that at present viral protein coding genes should not be subjected to different adaptive evolutionary pressures in different viral strains. Although this study can not be conclusive, we believe that the evidence presented here is strongly consistent with the notion that the biased geographic distribution of SARS-CoV-2 isolates should not be associated with adaptive evolution of this novel pathogen. 
 Title: Comparative genomics suggests limited variability and similar evolutionary patterns between major clades of SARS-CoV-2
Output: True
Paragraph: To study the influence of a linker rigidity and donor-acceptor properties, the P-CH 2 -O-CHR-fragment in acyclic nucleoside phosphonates (e.g., acyclovir, tenofovir) was replaced by the P-CH 2 -HN-C(O)-residue. The respective phosphonates were synthesized in good yields by coupling the straight chain of x-aminophosphonates and nucleobase-derived acetic acids with EDC. Based on the 1 H and 13 C NMR data, the unrestricted rotation within the methylene and 1,2-ethylidene linkers in phosphonates from series a and b was confirmed. For phosphonates containing 1,3-propylidene (series c) fragments, antiperiplanar disposition of the bulky O,O-diethylphosphonate and substituted amidomethyl groups was established. The synthesized ANPs P-X-HNC(O)-CH 2 B (X = CH 2 , CH 2 CH 2 , CH 2-CH 2 CH 2 , CH 2 OCH 2 CH 2 ) appeared inactive in antiviral assays against a wide variety of DNA and RNA viruses at concentrations up to 100 lM while marginal antiproliferative activity (L1210 cells, IC 50 = 89 ± 16 lM and HeLa cells, IC 50 = 194 ± 19 lM) was noticed for the analog derived from (5-fluorouracyl-1-yl)acetic acid and O,O-diethyl (2-aminoethoxy)methylphosphonate. O H N X (EtO) 2 (O)P X = CH 2 , CH 2 CH 2 , CH 2 CH 2 CH 2 , CH 2 OCH 2 CH 2 B = natural or modified nuclebases 
 Title: Acyclic nucleoside phosphonates containing the amide bond
Output: True
Paragraph: The neurotropic murine coronavirus, MHV-JHM (JHMV) causes encephalitis and paralytic-demyelinating disease in susceptible strains of mice and rats, serving as a model for human demyelinating diseases such as multiple sclerosis. In this communication, we report that a single intracerebral administration of the naturally occurring neuropeptide, fl-endorphin, reduced the incidence of JHMV-induced paralytic-demyelinating disease 40-50% in C57B1/6 mice. Protection from disease was accompanied by significantly reduced virus replication in the brain as early as 3 days post-infection and did not occur in irradiated, or immunoincompetent mice. The data suggest that fl-endorphin engages immune mechanisms of host resistance to JHMV infection to protect the mice from disease. 
 Title: /3-Endorphin protects mice from neurological disease induced by the murine coronavirus MHV-JHM
Output: True
Paragraph: The objective of this study was to develop quantitative real-time polymerase chain reaction (ReTi-PCR) tests for the detection of five economically important viruses in swine semen namely, pseudorabies virus (PRV), classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and porcine reproductive and respiratory syndrome virus (PRRSV). Each ReTi-PCR test was validated for specificity, analytical sensitivity (detection limits), and experimental infection studies were performed to compare the conventional virus isolation methods with the newly developed ReTi-PCR tests. All five developed ReTi-PCR tests are very rapid compared to virus isolation, highly specific, and even more sensitive (lower detection limits) than conventional virus isolation methods for the detection of mentioned viruses in semen. In semen of experimentally infected boars, viruses were detected much earlier after infection and more frequently by ReTi-PCR tests than by virus isolations. The high throughput of these rapid ReTi-PCR tests makes it possible to screen large number of semen samples for the presence of viruses prior to insemination. This is a substantial advantage, in particular for boar semen the quality of which deteriorates quickly after storage. In general, the newly developed ReTi-PCR tests are valuable tools for the early, reliable and rapid detection of five economically important viruses, namely PRV, CSFV, FMDV, SVDV, and PRRSV in boar semen. These ReTi-PCR tests will improve the control of viral diseases transmitted via semen. 
 Title: Detection of economically important viruses in boar semen by quantitative RealTime PCR TM technology
Output: True
Paragraph: Graphical Abstract Highlights d SARS-CoV causes a lethal respiratory infection in BALB/c mice d Robust SARS-CoV replication and delayed IFN-I signaling promote disease d IFN-I induces influx of pathogenic inflammatory monocytes and vascular leakage d Disease severity is ameliorated in the absence of IFN signaling SUMMARY Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (severe acute respiratory syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak, but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocytemacrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage, and impaired virus-specific T cell responses. Genetic ablation of the IFN-ab receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses. 
 Title: Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice Article Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice
Output: True
Paragraph: Middle East respiratory syndrome coronavirus (MERS-CoV) is an existential threat to global public health. The virus has been repeatedly detected in dromedary camels (Camelus dromedarius). Adult animals in many countries in the Middle East as well as in North and East Africa showed high (>90%) seroprevalence to the virus. Middle East respiratory syndrome coronavirus isolated from dromedaries is genetically and phenotypically similar to viruses from humans. We summarize current understanding of the ecology of MERS-CoV in animals and transmission at the animal-human interface. We review aspects of husbandry, animal movements and trade and the use and consumption of camel dairy and meat products in the Middle East that may be relevant to the epidemiology of MERS. We also highlight the gaps in understanding the transmission of this virus in animals and from animals to humans. 
 Title: Dromedary Camels and the Transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Output: False
Paragraph: Background: Timely identification of respiratory virus infection is essential to mitigate inappropriate antibiotic use and to implement appropriate treatment and/or infection control procedures. As such, multiplexed PCR assays have become standard in many virology laboratories. Objectives: To compare the Seeplex RV15 (test of record) with two newer generation multiplex assays, the Anyplex II RV16 and the xTAG respiratory virus panels. Study design: Two hundred and three retrospective and 36 prospective respiratory samples were tested by all three assays. Samples were deemed to be positive if they tested positive for a virus by at least two of the three respective assays. Negative samples also had to test negative by at least two of the three assays. Inconclusive samples were those that showed band signal intensity between 0 and 100 on the RV15, but had not been previously tested on the RV16 or xTAG. Results and conclusions: Overall sensitivity and specificity of all three assays were similar (∼85% and 100%, respectively). Given each assay can identify multiple different viruses, the targets reported by one assay did not always agree with each target from another assay. Partial discordant rates were 47% and 21% for positive and negative samples, respectively. These higher than expected partial discordant rates may be due to primer or chemistry differences amongst the three multiplex assays. 
 Title: Evaluation of three commercial multiplex assays for the detection of respiratory viral infections
Output: True
Paragraph: Background: Influenza is a severe contagious disease especially in children, elderly and immunocompromised patients. Beside vaccination, the discovery of new anti-viral agents represents an important strategy to encounter seasonal and pandemic influenza A virus (IAV) strains. The bacterial extra-cellular ribonuclease binase is a well-studied RNase from Bacillus pumilus. Treatment with binase was shown to improve survival of laboratory animals infected with different RNA viruses. Although binase reduced IAV titer in vitro and in vivo, the mode of action (MOA) of binase against IAV at the molecular level has yet not been studied in depth and remains elusive. Methods: To analyze whether binase impairs virus replication by direct interaction with the viral particle we applied a hemagglutination inhibition assay and monitored the integrity of the viral RNA within the virus particle by RT-PCR. Furthermore, we used Western blot and confocal microscopy analysis to study whether binase can internalize into MDCK-II cells. By primer extension we examined the effect of binase on the integrity of viral RNAs within the cells and using a mini-genome system we explored the effect of binase on the viral expression. Results: We show that (i) binase does not to attack IAV particle-protected viral RNA, (ii) internalized binase could be detected within the cytosol of MDCK-II cells and that (iii) binase impairs IAV replication by specifically degrading viral RNA species within the infected MDCK-II cells without obvious effect on cellular mRNAs. Conclusion: Our data provide novel evidence suggesting that binase is a potential anti-viral agent with specific intra-cellular MOA. 
 Title: Bacterial ribonuclease binase exerts an intra-cellular anti-viral mode of action targeting viral RNAs in influenza a virus- infected MDCK-II cells
Output: False
Paragraph: Background: The relation between weather conditions, viral transmission and seasonal activity of respiratory viruses is not fully understood. Objectives: To investigate the impact of outdoor weather in a temperate climate setting on the seasonal epidemiology of viruses causing respiratory tract infections, particularly influenza A (IFA). Study design: In total, 20,062 clinical nasopharyngeal swab samples referred for detection of respiratory pathogens using a multiplex PCR panel, between October 2010 and July 2013, were included. Results of PCR detection were compared with local meteorological data for the same period. Results: Low temperature and vapor pressure (VP) were associated with weekly incidence of IFA, respiratory syncytial virus, metapneumovirus, bocavirus and adenovirus but no association with relative humidity was found. The incidence of human rhinovirus and enterovirus was independent of temperature. During seasonal IFA outbreaks, the weekly drop of average temperature (compared with the week before) was strongly associated with the IFA incidence recorded the following week. Conclusion: A sudden drop in outdoor temperature might activate the annual influenza epidemic in a temperate climate by facilitating aerosol spread in dry air. These conditions also seem to affect the incidence of other respiratory pathogens but not human rhino-or enterovirus, suggesting that routes of infection other than aerosol may be relevant for these agents. 
 Title: A four year seasonal survey of the relationship between outdoor climate and epidemiology of viral respiratory tract infections in a temperate climate
Output: False
Paragraph: While the ferret is a valuable animal model for a number of human viral infections, such as influenza, Hendra and Nipah, evaluating the cellular immune response following infection has been hampered by the lack of a number of species-specific immunological reagents. Interleukin 2 (IL-2) is one such key cytokine. Ferret recombinant IL-2 incorporating a C-terminal histidine tag was expressed and purified and the three-dimensional structure solved and refined at 1.89 Å by X-ray crystallography, which represents the highest resolution and first non-human IL-2 structure. While ferret IL-2 displays the classic cytokine fold of the four-helix bundle structure, conformational flexibility was observed at the second helix and its neighbouring region in the bundle, which may result in the disruption of the spatial arrangement of residues involved in receptor binding interactions, implicating subtle differences between ferret and human IL-2 when initiating biological functions. Ferret recombinant IL-2 stimulated the proliferation of ferret lymph node cells and induced the expression of mRNA for IFN-g and Granzyme A. Crown 
 Title: Structural and functional characterisation of ferret interleukin-2
Output: True
Paragraph: A plethora of new development goals and funding institutions have greatly increased the demand for internationally comparable health estimates in recent years, and have brought important new players into the field of health estimate production. These changes have rekindled debates about the validity and legitimacy of global health estimates. This paper draws on country case studies and personal experience to support our opinion that the production and use of estimates are deeply embedded in specific social, economic, political and ideational contexts, which differ at different levels of the global health architecture. Broadly, most global health estimates tend to be made far from the local contexts in which the data upon which they are based are collected, and where the results of estimation processes must ultimately be used if they are to make a difference to the health of individuals. Internationally standardised indicators are necessary, but they are no substitute for data that meet local needs, and that fit with local ideas of what is credible and useful. In other words, data that are both technically and socially robust for those who make key decisions about health. We suggest that greater engagement of local actors (and local data) in the formulation, communication and interpretation of health estimates would increase the likelihood that these data will be used by those most able to translate them into health gains for the longer term. Besides strengthening national information systems, this requires ongoing interaction, building trust and establishing a communicative infrastructure. Local capacities to use knowledge to improve health must be supported. ARTICLE HISTORY 
 Title: In the eye of the beholder: to make global health estimates useful, make them more socially robust Bringing the indicators home: Country perspective on the utility of global 40 estimates for health indicators (WHO)
Output: True
Paragraph: A recombinant vaccinia virus producing the bacteriophage T7 RNA polymerase was used to express foreign genes in eukaryotic cells. Translation efficiency in this expression system was enhanced significantly by employing the encephalomyocarditis virus (EMCV) 5'-untranslated region (UTR) which confers cap-independent translation by directing internal initiation of translation. The enhancement was accomplished by fusing open reading frames (ORFs) to the N terminus of the EMCV polyprotein coding region, thus utilizing its highly efficient translation initiation site. Expression vectors were constructed to allow cloning in all three reading frames. As reporter genes, we used the IucZ gene and a number of genes encoding coronavirus structural proteins: among others the genes encoding glycoproteins with N-terminal signal sequences. The signal sequences of these glycoproteins are located internally in the primary translation product. We demonstrated that this did not interfere with translocation and glycosylation and yields biologically active proteins. The usefulness of sequences that direct internal initiation was extended by using EMCV UTR s to express two and three ORFs from polycistronic mRNAs. 
 Title: Enhancement of the vaccinia virus/phage T7 RNA polymerase expression system using encephalomyocarditis virus 5'-untranslated region sequences
Output: True
Paragraph: Biomolecular NMR now contributes routinely to every step in the development of new chemical entities ahead of clinical trials. The versatility of NMR -from detection of ligand binding over a wide range of affinities and a wide range of drug targets with its wealth of molecular information, to metabolomic profiling, both ex vivo and in vivo -has paved the way for broadly distributed applications in academia and the pharmaceutical industry. Proteomics and initial target selection both benefit from NMR: screenings by NMR identify lead compounds capable of inhibiting protein-protein interactions, still one of the most difficult development tasks in drug discovery. NMR hardware improvements have given access to the microgram domain of phytochemistry, which should lead to the discovery of novel bioactive natural compounds. Steering medicinal chemists through the lead optimisation process by providing detailed information about protein-ligand interactions has led to impressive success in the development of novel drugs. The study of biofluid compositionmetabonomics -provides information about pharmacokinetics and helps toxicological safety assessment in animal model systems. In vivo, magnetic resonance spectroscopy interrogates metabolite distributions in living cells and tissues with increasing precision, which significantly impacts the development of anticancer or neurological disorder therapeutics. An overview of different steps in recent drug discovery is presented to illuminate the links with the most recent advances in NMR methodology. 
 Title: Biomolecular NMR: a chaperone to drug discovery This review comes from a themed issue on Combinatorial chemistry and molecular diversity Edited
Output: True
Paragraph: Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. , et al. 2010. Identification of a severe acute respiratory syndrome coronavirus-like virus in a leaf-nosed bat in Nigeria. mBio 1(4): Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson's leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs. IMPORTANCE Bats (order Chiroptera, suborders Megachiroptera and Microchiroptera) are reservoirs for a wide range of viruses that cause diseases in humans and livestock, including the severe acute respiratory syndrome coronavirus (SARS-CoV), responsible for the global SARS outbreak in 2003. The diversity of viruses harbored by bats is only just beginning to be understood because of expanded wildlife surveillance and the development and application of new tools for pathogen discovery. This paper describes a new coronavirus, one with a distinctive genomic organization that may provide insights into coronavirus evolution and biology. 
 Title: Identification of a Severe Acute Respiratory Syndrome Coronavirus- Like Virus in a Leaf-Nosed Bat in Nigeria
Output: True
Paragraph: We evaluated the role of vaccine candidate surface proteins, PhtD and PhtE as antigens with functional importance for Streptococcus pneumoniae (pneumococci) in adherence to nasopharyngeal (D562) and lung (A549) epithelial cell lines. Comparing TIGR4 to PhtD and PhtE-deleted isogenic mutants, a 40% (p=0.001) and 42% (p=0.002) drop in the number of epithelial cells with adherent pneumococci was observed to both cells lines with the mutants, as quantitated using flow cytometry. We expressed PhtD and PhtE on the surface of E coli and demonstrated that when PhtD and PhtE were surface expressed on E coli adherence increased to D562 and A549 cells, compared with the E coli parent strain (p = 0.005, 0.013 for D562 and p=0.034, p=0.035 for A549). Using flow cytometry and confocal microscopy we found that pneumococci aggregated in the presence of human serum IgG, leading to a non-specific drop in adherence. Therefore IgG Fab fragments were prepared to study the functional role of PhtD and PhtE-specific Fabs in blocking adherence. The addition of 1 μg of IgG Fab from adult sera led to a 34% reduction (p= 0.002) and from children a 20% (p= 0.023) reduction in D562 epithelial cells with adherent pneumococci. In purified IgG from adult sera, the depletion of PhtD and PhtE specific Fab from total IgG Fab resulted in a significant increase in the number of D562 epithelial cells with adherent pneumococci (p=0.005 for PhtD and p=0.024 for PhtE). We conclude that antibody directed to PhtD and PhtE are adhesins of pneumococci, if raised by vaccination, may function to prevent pneumococcal adherence to human airway epithelial cells. 
 Title: Vaccine Candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans
Output: False
Paragraph: The outbreaks of Middle East respiratory syndrome (MERS) previously in Middle East and recently in South Korea have raised serious concerns world-wide, reinforcing the importance of developing effective and safe vaccines against MERS-coronavirus (MERS-CoV). A number of vaccine candidates have been developed on the basis of viral vectors, recombinant proteins, DNAs, nanoparticles, and recombinant MERS-CoV, and some of them have shown efficacy in laboratory animals. However, the paucity of financial support has made it difficult to transfer effective candidates from the preclinical stage to clinical trials. Here, we summarize currently available MERS vaccine candidates and illustrate strategies for future development, with the aim of provoking government agencies and Big Pharma to invest more funds for developing efficacious and safe MERS vaccines. 
 Title: Middle East respiratory syndrome: current status and future prospects for vaccine development
Output: False
Paragraph: Background: Developing methods to reconstruct transmission histories for viral outbreaks could provide critical information to support locating sources of disease transmission. Phylogenetic methods used to measure the degree of relatedness among sequenced viral samples have proven useful in identifying potential outbreak sources. The complex nature of infectious disease, however, makes it difficult to assign a rigorously defined quantitative confidence value assessing the likelihood of a true direct transmission event using genetic data alone. Results: A new method is presented to calculate a confidence value assessing the likelihood of a transmission event using both phylogenetic inference and limited knowledge of incubation and infectious duration times. The method is applied to simulations of a foot and mouth disease (FMD) outbreak to demonstrate how the combination of both phylogenetic and epidemiology data can be used to strengthen the assessment of the likelihood of direct transmission over methods using just phylogenetic data or infection timing data alone. The method is applied to a previous FMD outbreak to identify areas where over confidence in previously inferred direct transmission may exist. Conclusion: Combining knowledge from viral evolution and epidemiology within a single integrated transmission inference framework is an important approach to assess the potential likelihood of transmission events and makes clear how specific features of a virus' spread through the course of an outbreak will directly determine the potential for confidence in inferred host transmission links. Background Developing methods to protect against RNA virus outbreaks in the face of constantly changing disease dynamics remains one of the great public health challenges of our time. One small piece of this problem involves determining the host-pathogen transmission history to identify an outbreak's origin. In recent cases such as the 2003 SARS outbreak [1, 2], H5N1 influenza [3] infection in humans and Marburgvirus [4], phylogenetic inference has been used to help identify potential outbreak sources. Typically, a collection of sequences from candidate related sources are compared to infer transmission links between the most closely related sequences. These methods have been used beyond the public health domain to provide evidence in HIV [5, 6] and other forensic investigations [7] to help infer when a suspect is involved in infecting a victim. P (δ, σ|M ) rather than P (δ|M ). This reflects the desire to estimate the probability of observing the genetic relation δ in conjunction with infection related timing values for the transmission hypothesis M . The σ parameter values are motivated by a SEIR type infection concept [22], which describes a host in one of four 5 . CC-BY-ND 4.0 International license is made available under a 
 Title: Mapping a viral phylogeny onto outbreak trees to improve host transmission inference
Output: False
Paragraph: Dengue virus (DENV) of the Flaviviridae family is a single positive-stranded RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The objective of this study was to investigate the use of chloroquine (CLQ) as an antiviral drug against dengue virus in monkeys. To analyze the action of the drug in vivo, nonhuman primates groups (Aotus azarai infulatus) were inoculated with a subcutaneous injection of a virulent strain of DENV-2, treated and untreated CLQ. Blood hematological, viremia, and serum biochemical values were obtained from 16 DENV-2-inoculated, treated and untreated; four received only CLQ and one mock-infected Aotus monkeys. Monkey serum samples (day 0-10 post-inoculation) were assayed by reverse transcription polymerase chain reaction and Cytometric Bead Array for determination of viremia and inflammatory cytokines, respectively. Additionally, body temperature and activity levels were determined. In the present work, CLQ was effective on replication of DENV-2 in Aotus monkeys; a time viremia reduction was observed compared with the controls. The concentration of tumor necrosis factor alpha and interferon gamma in the serum of the animals had a statistically significant reduction in the groups treated with CLQ after infection compared with the controls. A significant decrease in systemic levels of the liver enzyme aspartate aminotransferase (AST) was also observed in the animals treated with CLQ after infection compared with the controls. These results suggest that CLQ interferes in DENV-2 replication in Aotus monkeys. 
 Title: Antiviral Activity of Chloroquine Against Dengue Virus Type 2 Replication in Aotus Monkeys
Output: False
Paragraph: To examine the relationship of impairments of the liver and kidney with viral load after nephropathogenic infectious bronchitis virus (NIBV) infection in embryonic chickens, 120 specific-pathogenfree Leghorn embryonated chicken eggs were randomly divided into two groups (infected and control), with three replicates per group and 20 eggs in each replicate. The eggs in the infected and control groups were challenged with 0.2 mL of 10 5.5 ELD 50 NIBV and sterile saline solution, respectively. The embryonic chickens' plasma and liver and kidney tissues were collected at 1, 3, and 5 days post-inoculation (dpi), the liver and kidney functional parameters were quantified, and the tissue viral loads were determined with real-time PCR. The results showed that plasma potassium, sodium, chlorine, magnesium, calcium, and phosphorus levels were increased. The infected group exhibited significantly higher plasma uric acid, blood urea nitrogen, and creatinine levels than the control group at 3 dpi. The plasma concentrations of aspartate aminotransferase and alanine aminotransferase were significantly increased in the infected group. The total protein, albumin, and globulin levels in the infected group were significantly lower than those in the control group. The liver-kidney viral load in the infected group peaked at 3 dpi, at which time the kidney viral load was significantly higher than that of the liver. Our results indicated that NIBV infection caused liver and kidney damage in the embryonic chickens, and the results also demonstrated that the liver and kidney damage was strongly related to the tissue viral load following NIBV infection in embryonic chickens. 
 Title: The relationship between liver-kidney impairment and viral load after nephropathogenic infectious bronchitis virus infection in embryonic chickens
Output: False
Paragraph: Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. , sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 9-10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. 
 Title: Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records
Output: True
Paragraph: Background: Human adenovirus type 55 is a re-emerging human respiratory pathogen that is associated with several respiratory infections outbreaks in military and school populations. In this study, we describe the first HAdV55-associated hospital outbreak documented in Guangdong, China. Active surveillance was conducted in the involved neurosurgical inpatient department. All staff and patients in the involved neurosurgical department were surveyed for any symptoms of fever (≥38°C) and enlarged tonsils during the outbreak period. Throat swabs and demographic information were collected for all cases. For each specimen, assays for common respiratory viruses were performed using one-step reverse transcription-polymerase chain reaction. HAdV-positive samples were inoculated onto Hep-2 cells for isolation. Hexon genes, fiber genes, penton genes, and whole genomes were sequenced. A phylogenetic tree was constructed. Forty-three cases, including 24 laboratory-confirmed cases and 19 possible cases, were identified. Nurses had the highest attack rate of infection, with a rate of 36.4%. The attack rate for doctors and inpatients was 20.0% and 16.7%, respectively. HAdV55 was the sole pathogen identified during this outbreak. The hexon, fiber, and penton genes from seven isolated HAdV55 stains were sequenced. All these genes showed 100% homology and fell into the HAdV55 [P14H11F14] cluster, indicating that HAdV55 was the single viral strain for the outbreak. While not conclusive, the epidemic investigation revealed that the outbreak was introduced by nurses from sources outside the hospital. It was likely that a transmission from staff to inpatients had occurred. hospital infection, human adenovirus type 55, respiratory disease | 329 YI et al. 
 Title: A cluster of adenovirus type B55 infection in a neurosurgical inpatient department of a general hospital in Guangdong, China Background: Human adenovirus type 55 is a re-emerging human respiratory pathogen
Output: False
Paragraph: Accurate quantification of impurities existing as separate crystalline phases at trace levels in drug materials is an important issue in the pharmaceutical industry. In the present study, a thermoanalytical approach previously developed for quantifying trace levels of polymorphic impurity (form II metastable nuclei) in commercial salmeterol xinafoate powders has been successfully applied with slight modifications to ribavirin, an antiviral drug exhibiting roughly similar polymorph-dependent crystallization kinetics in melts to that of salmeterol xinafoate. Essentially, the approach involved modeling of the crystallization kinetics of both tested and reference drug materials in melts using the Avrami-Erofe'ev (AE) rate expression, derivation of a mathematical equation for relating the AE kinetic constant to the composition of reference polymorph mixtures, and the use of this derived equation (in the form of a calibration curve) to calculate the impurity contents of the tested samples from their computed AE constants. For ribavirin, modification of the latter equation by incorporation of an empirical exponent was found necessary to account for the compositiondependent changes in crystallization kinetics of the reference mixtures. Such modification has made possible the determination of polymorphic impurity content of as low as 0.004% (w/w) in ribavirin samples induced by different forms of grinding treatment. 
 Title: An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
Output: True
Paragraph: Bluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide 27 range of wild and domestic ruminants. In this report, we showed that BTV, through its virulence 28 non-structural protein NS3 (BTV-NS3), is able to activate the MAPK/ERK pathway. In 29 response to growth factors, the MAPK/ERK pathway activates cell survival, differentiation, 30 proliferation and protein translation but can also lead to the production of several inflammatory 31 cytokines. By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis 32 from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein 33 kinase B-Raf (BRAF), a crucial player of the MAPK/ERK pathway, as a new cellular interactor 34 of BTV-NS3. BRAF silencing led to a significant decrease of the MAPK/ERK activation by 35 BTV supporting a model where BTV-NS3 interacts with BRAF to activate this signaling 36 cascade. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the 37 MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be 38 specific to BTV compared to other members of Orbivirus genus. Inhibition of MAPK/ERK 39 pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its 40 own replication. Therefore, the activation of the MAPK/ERK pathway by BTV-NS3 could 41 benefit to BTV replication by promoting its own viral protein synthesis but could also explain 42 the deleterious inflammation associated with tissue damages as already observed in severe cases 43 of BT disease. Altogether, our data provide molecular mechanisms to explain the role of BTV-44 NS3 as a virulence factor and determinant of pathogenesis. 45 author/funder. All rights reserved. No reuse allowed without permission. Bluetongue Virus (BTV) is responsible of the non-contagious arthropod-borne disease 48 Bluetongue (BT) transmitted to ruminants by blood-feeding midges. Despite the fact that BTV 49 has been extensively studied, we still have little understanding of the molecular determinants 50 of BTV virulence. In this report, we found that the virulence protein NS3 interacts with BRAF, 51 a key component of the MAPK/ERK pathway. In response to growth factors, this pathway 52 promotes cell survival, increases protein translation but also contributes to the production of 53 inflammatory cytokines. We showed that BTV-NS3 enhances the MAPK/ERK pathway and 54 this activation is BRAF-dependent. Our results demonstrate, at the molecular level, how a 55 single virulence factor has evolved to target a cellular function to ensure its viral replication. 56 On the other hand, our findings could also explain the deleterious inflammation associated with 57 tissue damages as already observed in severe cases of BT disease. 58 author/funder. All rights reserved. No reuse allowed without permission. 
 Title: Novel Function of Bluetongue Virus NS3 Protein in Regulation of the MAPK/ERK Signaling Pathway 2 3
Output: False
Paragraph: Due to its excessively high capacity for human-to-human transmission, the 2019 novel coronavirus disease , first reported in Wuhan in China, spread rapidly to the entire nation and beyond, and has now been declared a global public health emergency. Understanding the transmission pattern of the virus and the efficacy of transmission control measures is crucial to ensuring regional and global disease control. Here we propose a simple model based on exponential infectious growth, but with a timevarying, largely damping, transmission rate. This model provides an excellent fit to the existing data from the 102 countries and regions which have reported cases for more than 6 days, and, we think, has largely captured the transmission patterns of the COVID-19 outbreak under a variety of intervention and control measures. We found that the damping rate, defined as the rate of the exponential decline in transmission rate, ranged from -0.125 to 0.513 d -1 globally (a negative damping rate represents acceleration in spread). The estimated peak time (when the fastest spread occurs) and the final number of infections were found to be greatly affected by the damping rate. Successful control measures, such as those implemented in China and South Korea, have resulted in a clear pattern of exponential damping in the viral spread (also shown during the 2003 outbreak of Severe Acute Respiratory Syndrome, SARS). The damping rate, therefore, could be used as an indicator for the efficacy of implemented control measures. Our model suggests that the COVID-19 outbreak is currently accelerating worldwide, especially rapidly in certain countries (e.g. USA and Australia) where exponential damping is yet to emerge. Consistent with the message from the World Health Organisation (WHO), we thus strongly suggest all countries to take active measures to contain this global pandemic. Slight increments in the damping rate from additional control efforts, especially in countries showing weak or no exponential damping in COVID-19 transmission, could lead to a radically more positive outcome in the fight to contain the pandemic. 
 Title: Exponential damping: The key to successful containment of COVID-19
Output: True
Paragraph: The major isoform of myelin basic protein (MBP) in the healthy adult central nervous system is the 18.5-kDa protein which is produced by mRNA derived from exons 1, 3, 4, 5, 6 and 7 of the MBP gene. Since isoforms containing exon 2-encoded protein (X2MBP) are expressed during myelin formation, we examined T cell reactivity specific for X2MBP in a disease characterized by remyelination subsequent to demyelination, multiple sclerosis (MS). T cell lines specific for X2MBP were derived from three MS patients as well as one healthy control. This suggests that candidate autoantigens in demyelinating/remyelinating diseases should include not only the major isoforms of myelin proteins, but also isoforms expressed aberrantly during a disease process since they too may be the target of a T cell-mediated autoimmune process. 
 Title: T-lymphocyte recognition of a portion of myelin basic protein encoded by an exon expressed during myelination
Output: True
Paragraph: Background: Both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important viral pathogens causing respiratory tract infection (RTI) in the pediatric population. However, the clinical manifestations of RSV and hMPV infections are similar. Therefore, a reliable and rapid diagnostic tool is needed for diagnostic performance. Methods: In order to optimize diagnosis efficiency of RTI, the aim of this study is to establish a rapid and advanced method for simultaneous detecting RSV and hMPV in nasopharyngeal aspirates specimens from patients. We designed a one-step triplex real-time RT-PCR (qRT-PCR) protocol using TaqMan probes for detecting RSV and hMPV. The plasmid clones containing RSV nucleoprotein gene and hMPV fusion gene were established as reference standards. We used virus culture supernatants from 86 known pediatric RTI patient to test the specificity and sensitivity of our assay. Then we used total 222 nasopharyngeal aspirates specimens from pediatric patients hospitalized with respiratory symptoms to evaluate our assay. Results: Our one-step triplex qRT-PCR assay showed 100% sensitivity and specificity in testing RSV and hMPV in 86 known virus culture supernatants, with excellent linearity (R 2 > 0.99) and reliable reproducibility (CV lower than 1.04%). This assay has a wide dynamic range 10 2 -10 9 copies/reaction (limit of detection; LOD = 100 copies/reaction). A total of 222 patients hospitalized with respiratory symptoms were enrolled for clinical evaluation. In these samples, our qRT-PCR assay detected 68 RSV positive and 18 hMPV positive cases. However, standard virus culture only detected 8 RSV positive cases and 0 hMPV cases. Based on this improved triplex qRT-PCR assay, we found that RSV infection was associated with severe inflammation by chest X-ray and occurrence of pneumonia which were not observed previously. In summary, we have developed a highly specific and sensitive one-step triplex qRT-PCR assay to detect hMPV and RSV simultaneously. This assay offers a valuable tool for routine diagnosis. 
 Title: Simultaneous detection of respiratory syncytial virus and human metapneumovirus by one-step multiplex real-time RT-PCR in patients with respiratory symptoms
Output: False