niryuu/sni-each-converted huggingface dataset:
Paragraph: Coronavirus genome replication is mediated by a multi-subunit protein complex that is comprised of more than a dozen virally encoded and several cellular proteins. Interactions of the viral replicase complex with cis-acting RNA elements located in the 5 and 3 -terminal genome regions ensure the specific replication of viral RNA. Over the past years, boundaries and structures of cis-acting RNA elements required for coronavirus genome replication have been extensively characterized in betacoronaviruses and, to a lesser extent, other coronavirus genera. Here, we review our current understanding of coronavirus cis-acting elements located in the terminal genome regions and use a combination of bioinformatic and RNA structure probing studies to identify and characterize putative cis-acting RNA elements in alphacoronaviruses. The study suggests significant RNA structure conservation among members of the genus Alphacoronavirus but also across genus boundaries. Overall, the conservation pattern identified for 5 and 3 -terminal RNA structural elements in the genomes of alpha-and betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements. 
 Title: RNA structure analysis of alphacoronavirus terminal genome regions
Output: False
Paragraph: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34 + stem cells, (2) fetal derived liver, thymus and CD34 + stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus. PLOS Neglected Tropical Diseases | https://doi.Onchocerciasis, caused by the filarial parasitic nematode Onchocerca volvulus, remains a significant source of morbidity throughout sub-Saharan Africa and is a primary cause of infectious blindness. Research on this disease has been hindered by an absence of suitable small animal hosts. Here we describe the development of humanized mouse models that are susceptible to O. volvulus infection supporting both growth and maturation of the parasite. These novel mouse models have enabled the identification of a number of new O. volvulus biomarkers with potential to play a role in the development of specific and sensitive diagnostic tests for presence of viable parasites. Development of Onchocerca volvulus in NSG mice PLOS Neglected Tropical Diseases | https://doi. 
 Title: Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum
Output: True
Paragraph: SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with over 400,000 recorded COVID-19 cases and greater than 19,000 recorded deaths by March 24 th , 2020 (www.WHO.org) (1). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2 (2). Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs (3). Rapid development and human testing of potential antivirals is greatly needed. A potentially quicker way to test compounds with antiviral activity is through drug re-purposing (2, 4). Numerous drugs are already approved for use in humans and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to test in COVID-19 patients. Here, we present data on 20 FDA approved drugs tested for antiviral activity against SARS-CoV-2 that we have previously found to inhibit SARS-CoV and MERS-CoV (4). We find that 17 of these . CC-BY-NC-ND 4.0 : bioRxiv preprint also inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. From these we specifically followed up with hydroxychloroquine sulfate and chloroquine phosphate. 
 Title: FDA approved drugs with broad anti-coronaviral activity inhibit SARS-CoV-2 in vitro
Output: False
Paragraph: Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes. 
 Title: Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity
Output: True
Paragraph: Background: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D 3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. Methods: We randomized 600 students into 4 treatment arms: 1) vitamin D 3 and gargling, 2) placebo and gargling, 3) vitamin D 3 and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. Results: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D 3 reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI 95 :0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI 95 :0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D 3 treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI 95 :0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log 10 viral copies/mL (mean difference: −0.89, CI 95: -1.7, −0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI 95 :0.53-1.26, p = 0.36). Conclusions: These results suggest that vitamin D 3 is a promising intervention for the prevention of URTI. Vitamin D 3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. Trial registration: Clinical Trials Registration: NCT01158560. 
 Title: Vitamin D 3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial
Output: True
Paragraph: Background: Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. Objective: We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. Methods: We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. Results: Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were viruspositive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF 25%-75% ), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. Conclusion: Urban children with asthma with high-symptom respiratory viral infections have reduced FEF 25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virusnegative illnesses. 
 Title: Impact of community respiratory viral infections in urban children with asthma
Output: True
Paragraph: The tripartite motif (TRIM)-containing proteins usually exert important regulatory roles during multiple biological processes. TRIM8 has been demonstrated to be a RING domain-containing E3 ubiquitin ligase which plays critical roles in inflammation and cancer. In this study, a TRIM8 homolog from grouper, Epinephelus coioides (EcTRIM8) was cloned, and its effects on fish virus replication were investigated. The full-length EcTRIM8 cDNA encoded a polypeptide of 568 amino acids with 92% identity to TRIM8 homolog from large yellow croaker (Larimichthys crocea). Sequence alignment analysis indicated that EcTRIM8 contained conserved RING finger, B-box and coiled-coil domain. Expression patterns analysis showed that EcTRIM8 was predominant in kidney, gill, fin, liver, spleen and brain. After challenging with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C), the EcTRIM8 transcript was significantly increased at the early stage of injection. Under fluorescence microscopy, we observed different distribution patterns of EcTRIM8 in grouper spleen (GS) cells, including punctate fluorescence evenly situated throughout the cytoplasm and bright aggregates. The ectopic expression of EcTRIM8 in vitro significantly inhibited the replication of SGIV and red spotted grouper nervous necrosis virus (RGNNV), evidenced by the obvious reduction in the severity of cytopathic effect (CPE) and the significant decrease in viral gene transcription and protein synthesis. Moreover, the transcription of the proinflammatory factors and interferon related immune factors were differently regulated by EcTRIM8 during SGIV or RGNNV infection. In addition, overexpression of EcTRIM8 significantly increased the transcription of interferon regulator factor 3 (IRF3) and IRF7, and enhanced IRF3 or IRF7 induced interferon-stimulated response element (ISRE) promoter activity. Together, our results firstly demonstrated that fish TRIM8 could exert antiviral function through the regulation of the expression of proinflammatory cytokines and interferon related transcription factors in response to fish viruses. 
 Title: Fish TRIM8 exerts antiviral roles through regulation of the proinflammatory factors and interferon signaling
Output: False
Paragraph: Restriction factors are antiviral components of intrinsic immunity which constitute a first line of defense by blocking different steps of the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed by several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate antiviral interferon-stimulated genes (ISGs). Several studies suggest a link between these two types of immunity. Indeed, restriction factors, that are generally interferon-inducible, are able to modulate immune responses. This review highlights recent knowledge of the interplay between restriction factors and immunity inducing antiviral defenses. Counteraction of this intrinsic and innate immunity by HIV viral proteins will also be discussed. of PAMPs by PRRs induces signaling cascades and leads to the transcription of pro-inflammatory cytokines and type I interferons (IFN-I), the most powerful antiviral effectors. Once produced by cells in which PRRs have been activated, IFN-I are secreted and bind, in an autocrine or paracrine manner, to the membrane receptor IFNAR (IFN-α/β receptor chain) to induce signal transduction driving the transcription of interferon-stimulated genes (ISGs). There are hundreds of ISGs encoding antiviral proteins such as the protein kinase R (PKR) or the 2 -5 -oligoadenylate synthetase 1 (OAS1) [13, 14] . Thus, ISGs are crucial to switch cells into an antiviral state. Interestingly, even if HIV restriction factors have been described as intrinsic immune effectors, most of them are IFN-inducible and can be defined as ISGs linking intrinsic and innate immunity. Moreover, by exerting their antiviral functions or by additional pathways, some restriction factors have been described to shape innate and adaptive immune responses highlighting an intimate relationship between restriction factors and immunity [15, 16] . In this review, we summarize the recent knowledge of the interplay between restriction factors and immunity focusing only on restriction factors that belong to the ISG family. After a description of restriction factors antiviral mechanisms and their induction by IFN, we will discuss how they can modulate immunity, in particular, innate immune responses. Moreover, since HIV-1 proteins are able to counteract many restriction factors, we will also mention viral mechanisms used to escape from intrinsic and innate immunity. Taken together, this review will allow a better understanding of the intricate interplay between restriction factors-mediated intrinsic immunity and innate immunity. 
 Title: cells Interplay between Intrinsic and Innate Immunity during HIV Infection
Output: False
Paragraph: A Cucumber green mottle mosaic virus (CGMMV) was used to present a truncated dengue virus type 2 envelope (E) protein binding region from amino acids 379 to 423 (EB4). The EB4 gene was inserted at the terminal end of the CGMMV coat protein (CP) open reading frame (ORF). Read-through sequences of TMV or CGMMV, CAA-UAG-CAA-UUA, or AAA-UAG-CAA-UUA were, respectively, inserted in between the CP and the EB4 genes. The chimeric clones, pRT, pRG, and pCG+FSRTRE, were transcribed into full-length capped recombinant CGMMV transcripts. Only constructs with the wild-type CGMMV read-through sequence yielded infectious viruses following infection of host plant, muskmelon (Cucumis melo) leaves. The ratio of modified to unmodified CP for the read-through expression clone developed was also found to be approximately 1:1, higher than what has been previously reported. It was also observed that infectivity was not affected by differences in pI between the chimera and its wild counterpart. Analysis of recombinant viruses after 21-days-postinculation (dpi) revealed that deletions occurred resulting in partial reversions of the viral population to near wild type and suggesting that this would be the limiting harvest period for obtaining true to type recombinants with this construct. 
 Title: Virus-Specific Read-Through Codon Preference Affects Infectivity of Chimeric Cucumber Green Mottle Mosaic Viruses Displaying a Dengue Virus Epitope
Output: True
Paragraph: Background. Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading pediatric pathogens. However, risk factors for severe hMPV disease remain unknown. We comparatively assessed environmental, host, and viral determinants for severe hMPV and RSV infections. Methods. We studied a prospective cohort of >1000 children aged <3 years hospitalized in or presenting to a pediatric clinic for acute respiratory infection. We collected clinical data at enrollment and 1-month follow-up and tested nasopharyngeal secretions for respiratory viruses. Disease severity was defined as hospitalization and was also assessed with a severity score (1 point/variable) calculated on the basis of fraction of inhaled O 2 ≥ 30%, hospitalization >5 days, and pediatric intensive care unit admission. Results. hMPV was identified in 58 of 305 outpatient children (19.0%) and 69 of 734 hospitalized children (9.4%), second only to RSV (48.2% and 63.6%, respectively). In multivariate regression analysis of hMPV cases, age <6 months and household crowding were associated with hospitalization. Among hospitalized patients, risk factors for severe hMPV disease were female sex, prematurity, and genotype B infection. Age <6 months, comorbidities, and household crowding were risk factors for RSV hospitalization; breast-feeding and viral coinfection were protective. Age <6 months and prematurity were associated with severe RSV cases among hospitalized children. Conclusions. hMPV and RSV severity risk factors may differ slightly. These findings will inform hMPV prevention strategies. 
 Title: Comparison of Risk Factors for Human Metapneumovirus and Respiratory Syncytial Virus Disease Severity in Young Children
Output: True
Paragraph: publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. 49. Corvin AJ, et al: Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse. Dev Dyn 212:385-393, 1998. 50. Olutoye OO, et al: Lower cytokine release by fetal porcine platelets: a possible explanation for reduced inflammation after fetal wounding. J Pediatr Surg 31:91-95, 1996. 51. Olutoye OO, et al: Hyaluronic acid inhibits fetal platelet function: implications in scarless healing. 
 Title: 53. Sporn MB, Roberts AB: Transforming growth factor-β: recent progress and new challenges
Output: True
Paragraph: We have synthesized and characterized a series of compounds containing the 3azatetracyclo[5.2.1.1 5,8 .0 1,5 ]undecane scaffold designed as analogs of amantadine, an inhibitor of the M2 proton channel of influenza A virus. Inhibition of the wild-type (wt) M2 channel and the amantadine-resistant A/M2-S31N and A/M2-V27A mutant ion channels were measured in Xenopus oocytes using two-electrode voltage clamp (TEV) assays. Most of the novel compounds inhibited the wt ion channel in the low micromolar range. Of note, several compounds inhibited the A/M2 V27A mutant ion channel, one of them with submicromolar IC 50 . None of the compounds was found to inhibit the S31N mutant ion channel. The antiviral activity of three novel dual wt and A/M2-V27A channels inhibitors was confirmed by influenza virus yield assays. Amantadine; cage compounds; influenza A virus; M2 proton channel; drug design c MCC: minimum cytotoxic concentration, or concentration producing minimal alterations in cell morphology after 72 hr incubation with compound. d CC 50 : 50% cytotoxic concentration, as determined by the MTS cell viability test. Values shown are the mean of 2-3 determinations. J Med Chem. 
 Title: 3-Azatetracyclo[5.2.1.1 5,8 .0 1,5 ]undecane derivatives: from wild- type inhibitors of the M2 ion channel of influenza A virus to derivatives with potent activity against the V27A mutant NIH Public Access
Output: True
Paragraph: Mis-secreted glycoproteins (LGI1, reelin) are emerging causes of epilepsy. LMAN2L belongs to a glycoprotein secretion chaperone family. One recessive LMAN2L missense mutation predicted to impair the chaperone's interaction with glycoproteins was reported in a family with intellectual disability (ID) and remitting epilepsy. We describe four members of a family with autosomal dominant inheritance of a similar phenotype. We show that they segregate a NM_001142292.1:c.1073delT mutation that eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane. LMAN2L mislocalization, like impaired glycoprotein interaction, disturbs brain development, including generation of developmentally restricted epilepsy. 
 Title: Dominant LMAN2L mutation causes intellectual disability with remitting epilepsy
Output: True
Paragraph: Vitamin A (VA) has pleiotropic effects on the immune system and is critical for mucosal immune function and intestinal lymphocyte trafficking. We hypothesized that oral VA supplementation of porcine epidemic diarrhea virus (PEDV)infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV challenge. Gilts received daily oral retinyl acetate (30 000 IU) starting at gestation day 76 throughout lactation. At 3-4 weeks pre-partum, VA-supplemented (PEDV + VA) and non-supplemented (PEDV) gilts were PEDV or mock inoculated (mock + VA and mock, respectively). PEDV + VA gilts had decreased mean PEDV RNA shedding titers and diarrhea scores. To determine if lactogenic immunity correlated with protection, all piglets were PEDV-challenged at 3-5 days post-partum. The survival rate of PEDV + VA litters was 74.2% compared with 55.9% in PEDV litters. Mock and mock + VA litter survival rates were 5.7% and 8.3%, respectively. PEDV + VA gilts had increased PEDV IgA antibody secreting cells and PEDV IgA antibodies in serum pre-partum and IgA + β7 + (gut homing) cells in milk post piglet challenge compared with PEDV gilts. Our findings suggest that oral VA supplementation may act as an adjuvant during pregnancy, enhancing maternal IgA and lactogenic immune protection in nursing piglets. 
 Title: Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets
Output: True
Paragraph: Relevant pandemic-spread scenario simulations provide guiding principles for containment and mitigation policy developments. Here we devise a simple model to predict the effectiveness of different mitigation strategies. The model consists of a set of simple differential equations considering the population size, reported and unreported infections, reported and unreported recoveries and the number of Covid-19-inflicted deaths. For simplification, we assume that Covid-19 survivors are immune (e.g. mutations are not considered) and that the virus can only be passed on by persons with undetected infections. While the latter assumption is a simplification (it is neglected that e.g. hospital staff may be infected by detected patients with symptoms), it was introduced here to keep the model as simple as possible. Moreover, the current version of the model does not account for age-dependent differences in the death rates, but considers higher mortality rates due to temporary shortage of intensive care units. Some of the model parameters have been fitted to the reported cases outside of China 1 from January 22 to March 12 of the 2020 Covid-19 pandemic. The other parameters were chosen in a plausible range to the best of our knowledge. We compared infection rates, the total number of people getting infected and the number of deaths in six different scenarios. Social distancing or increased testing can contain or drastically reduce the infections and the predicted number of deaths when compared to a situation without mitigation. We find that mass-testing alone and subsequent isolation of detected cases can be an effective mitigation strategy, alone and in combination with social distancing. However, unless one assumes that the virus can be globally defeated by reducing the number of infected persons to zero, testing must be upheld, albeit at reduced intensity, to prevent subsequent waves of infection. The model suggests that testing strategies can be equally effective as social distancing, though at much lower economical costs. We discuss how our mathematical model may help to devise an optimal mix of mitigation strategies against the Covid-19 pandemic. The website corona-lab.ch provides an interactive simulation tool based on the presented model. The Covid-19 pandemic is a serious threat that can be mitigated by different strategies. Social isolation is currently practiced in most countries in Europe, at least until alternative mitigation strategies can be implemented or therapies and vaccines become available. We have formulated a simple mathematical model to estimate how well social isolation or improved identification of Covid-19 infected people can slow down virus spread and reduce the death toll. 
 Title: Dynamic Modeling to Identify Mitigation Strategies for Covid-19 Pandemic
Output: False
Paragraph: A population of Persian cats experienced an epidemic of feline infectious peritonitis (FIP) over 2 years. Twelve cases of FIP occurred in litters born during this period. Cats contracting FIP were all genetically related through the sire. Feline coronavirus (FCoV) genomic RNA was detected consistently in this study in biologic samples from adult cats, kittens suffering from FIP, and their siblings. Analysis of viral 7a/7b open reading frame (ORFs) were analyzed and revealed two distinct virus variants circulating in the population, one with an intact 7a ORF and one with two major deletions in the 7a ORF. The 7b ORFs were intact and similar among all virus isolates, although point mutations resulting in amino acid changes were present. The sire was determined to be infected with both variants, and was persistently virus-infected. We speculate the deletion variant arose from the non-deletion variant during viral replication in this population, possibly in the sire. # 
 Title: Deletions in the 7a ORF of feline coronavirus associated with an epidemic of feline infectious peritonitis
Output: False
Paragraph: Many factors influence the choice of methods used to develop antibody to infectious agents. In this paper, we review the current status of the main technologies used to produce monoclonal antibodies (mAbs) from the B cells of antigen-sensitized animals. While companies are adopting advanced high-throughput methods, the major technologies used by veterinary and medical research laboratories are classical hybridoma fusion and recombinant library selection techniques. These methods have inherent advantages and limitations but have many common aspects when using immunized rodents. Laboratories with expertise in both methods of antibody development have a distinct advantage in their ability to advance mAb technology. New and re-emerging infectious threats in todayÕs world emphasize the need for quality immunoreagents and the need to maintain expertise in mAb development. We provide examples of some common applications for mAb reagents used to identify pathogens such as the SARS-coronavirus (SARS-CoV), Bacillus anthracis, and foot-and-mouth disease (FMD) virus. We also outline a framework for investigators to make rational decisions concerning which method to use to develop mAbs based upon characteristics of the pathogen under study and the intended downstream application. Lastly, we provide parameters for the immunisation of mice and a classification system which describes the expected outcome for mAb development strategies when using classes of immunogens to generate mAbs with desired activities. Crown Abbreviations: mAb; monoclonal antibody; SARS-CoV; severe acute respiratory syndrome coronavirus; FMD virus; foot-and-mouth disease virus; PA; protective antigen of Bacillus anthracis; BSA; bovine serum albumin; FBS; fetal bovine serum; HAT; hypoxanthine-aminopterin-thymidine; scFv; single chain variable fragment; Fab; fragment responsible for antigen binding; PBL; peripheral blood leucocytes; VP-1; viral protein 1 or 1D viral protein of FMD virus; IEM; immuno-electron microscopy; IHC; immunohistochemistry; IFA; immunoflourescence; V-genes; immunoglobulin variable region genes, responsible for encoding the antigen contact domains. * 
 Title: Rational monoclonal antibody development to emerging pathogens, biothreat agents and agents of foreign animal disease: The antigen scale
Output: False
Paragraph: Lonicera japonica Thunb. is an important medicinal plant. The secondary metabolites in L. japonica are diverse and vary in levels during development, leading to the ambiguous evaluation for its medical value. In order to reveal the regulatory mechanism of secondary metabolites during the flowering stages, transcriptomic, proteomic, and metabolomic analyses were performed. The integration analysis of omic-data illustrated that the metabolic changes over the flower developmental stages were mainly involved in sugar metabolism, lipopolysaccharide biosynthesis, carbon conversion, and secondary metabolism. Further proteomic analysis revealed that uniquely identified proteins were mainly involved in glycolysis/phenylpropanoids and tricarboxylic acid cycle/ terpenoid backbone pathways in early and late stages, respectively. Transketolase was commonly identified in the 5 developmental stages and 2-fold increase in gold flowering stage compared with juvenile bud stage. Simple phenylpropanoids/flavonoids and 1-deoxy-D-xylulose-5-phosphate were accumulated in early stages and upregulated in late stages, respectively. These results indicate that phenylpropanoids were accumulated attributing to the activated glycolysis process in the early stages, while the terpenoids biosynthetic pathways might be promoted by the transketolase-contained regulatory circuit in the late stages of L. japonica flower development. Biological Significance: Lonicera japonica Thunb. is a native species in the East Asian and used in traditional Chinese medicine. In order to reveal the regulatory mechanism of secondary metabolites during the flowering stages, transcriptomic, proteomic, and metabolomic analyses were performed. The integration analysis of omicdata illustrated that the metabolic changes over the flower developmental stages were mainly involved in sugar metabolism, lipopolysaccharide biosynthesis, carbon conversion, and secondary metabolism. Our results indicate that phenylpropanoids were accumulated attributing to the activated glycolysis process in the early stages, while the terpenoids biosynthetic pathways might be promoted by the transketolase-contained regulatory circuit in the late stages of L. japonica flower development. 
 Title: Integrative omics of Lonicera japonica Thunb. Flower development unravels molecular changes regulating secondary metabolites
Output: True
Paragraph: In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV. 
 Title: Development of a Poliovirus Neutralization Test with Poliovirus Pseudovirus for Measurement of Neutralizing Antibody Titer in Human Serum ᰔ Downloaded from
Output: False
Paragraph: Interferons (IFNs) are generally considered antiviral cytokines, yet the newly discovered IFN-l4 is linked with the failure to clear hepatitis C virus (HCV) infection either spontaneously or in response to treatment. IFN-l4 can be generated only by individuals who carry the IFNL4-DG allele (rs368234815), which is the strongest known host factor for predicting clearance of HCV. The ancestral IFNL4-DG allele is the major variant in Africans while the minor variant in Asians, suggesting very strong negative genetic selection for this allelemost likely driven by an infectious agent other than HCV. IFN-l4 most closely resembles IFN-l3, but these proteins share only 29% amino-acid identity, and, in contrast to IFN-l3, IFN-l4 is only weakly secreted. Nevertheless, IFN-l4 signals through the IFN-l receptor complex and induces expression of IFN-stimulated genes via the Janus kinase-signal transducer and activator of transcription signaling pathway. Although the IFNL4-DG variant is strongly associated with the failure to clear HCV infection, HCV-infected patients who carry this allele have lower baseline HCV RNA levels in the absence of treatment. Resolving the paradoxical functions of IFN-l4, which appears to induce antiviral activity yet impair effective clearance of HCV, may yield critical new insights into the immunologic response to HCV infection and IFN biology. 
 Title: IFN-l4: The Paradoxical New Member of the Interferon Lambda Family
Output: False
Paragraph: Background. Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. Methods. In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. Results. Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04-2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI, .16-.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI, .003-.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39-16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. Conclusions. Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI. 
 Title: The Journal of Infectious Diseases Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children
Output: False
Paragraph: Positive-strand RNA viruses exist as a quasi-species due to the incorporation of mutations into the viral genome during replication by the virus-encoded RNA-dependent RNA polymerase (RdRP). Therefore, the RdRP is often described as a low-fidelity enzyme. However, until recently, a complete description of the kinetic, thermodynamic and structural basis for the nucleotide incorporation fidelity of the RdRP has not been available. In this article, we review the following: (i) the steps employed by the RdRP to incorporate a correct nucleotide; (ii) the steps that are employed by the RdRP for nucleotide selection; (iii) the structure-based hypothesis for nucleotide selection; (iv) the impact of sites remote from the active site on polymerase fidelity. Given the recent observation that RNA viruses exist on the threshold of error catastrophe, the studies reviewed herein suggest novel strategies to perturb RdRP fidelity that may lead ultimately to the development of antiviral agents to treat RNA virus infection. 
 Title: Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective ଝ
Output: False
Paragraph: General medical training programs are aimed at promoting competency in general practice skills with a holistic perspective of patient-centered medicine for the new generation of physicians. The faculty development program was implemented to promote learning and application of the six core competencies established by the Accreditation Council for Graduate Medical Education. This article describes the implementation and outcome of the current faculty development program. Additional assessment tools of the faculty development program are recommended to evaluate different perspectives of outcome. Our experience suggests that OSTEs are a realistic and well-received approach for faculty development that merits further investigation. According to the clinical instructors' response, our faculty development program effectively increased familiarity with various teaching and assessment skills needed to teach PGY 1 residents and ACGME competencies, and these clinical instructors also then subsequently applied these skills. 
 Title: Faculty development program for general medicine in Taiwan: Past, present, and future
Output: False
Paragraph: Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the Arf GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to BFA, an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism. 
 Title: Poliovirus Replication Requires the N-terminus but not the Catalytic Sec7 Domain of ArfGEF GBF1
Output: True
Paragraph: The death morphology commonly known as apoptosis results from a post-translational pathway driven largely by specific limited proteolysis. In the last decade the structural basis for apoptosis regulation has moved from nothing to 'quite good', and we now know the fundamental structures of examples from the initiator phase, the pre-mitochondrial regulator phase, the executioner phase, inhibitors and their antagonists, and even the structures of some substrates. The field is as well advanced as the best known of proteolytic pathways, the coagulation cascade. Fundamentally new mechanisms in protease regulation have been disclosed. Structural evidence suggests that caspases have an unusual catalytic mechanism, and that they are activated by apparently unrelated events, depending on which position in the apoptotic pathway they occupy. Some naturally occurring caspase inhibitors have adopted classic inhibition strategies, but other have revealed completely novel mechanisms. All of the structural and mechanistic information can, and is, being applied to drive therapeutic strategies to combat overactivation of apoptosis in degenerative disease, and underactivation in neoplasia. We present a comprehensive review of the caspases, their regulators and inhibitors from a structural and mechanistic point of view, and with an aim to consolidate the many threads that define the rapid growth of this field. 
 Title: The protein structures that shape caspase activity, specificity, activation and inhibition
Output: True
Paragraph: This study investigated the heterogeneity and plasticity of porcine alveolar macrophages (PAM) and pulmonary interstitial macrophages (IM) isolated from healthy pigs, including phenotype, function and gene expression. Dynamic changes of nitric oxide (NO) levels secreted by PAM and IM with stimulation of different doses of lipopolysaccharide (LPS) were investigated by Griess method, and the viability of the PAM and IM cells was investigated by MTT assay. Flow cytometry, fluorescence quantitative PCR and ELISA techniques were used to measure cell phenotype, gene expression and cytokine secretion, respectively. The PAM and IM cells in normal healthy pigs showed heterogeneity with 95.42±1.51% and 31.99±5.84% of CD163+ macrophage, respectively. The NO level in IM was significantly higher versus PAM after LPS treatment. Consistently, the ratio of Arg I/iNOS in IM was much lower than that in PAM, suggesting that the PAM belong to M2 macrophages and the IM belong to M1 macrophages. The PAM and IM cells in normal healthy pigs also showed plasticity. The Arg I/iNOS ratio and TIMP1/MMP12 ratio were significantly decreased in LPS-or LPS+IFNγ-treated PAM and IM, suggesting that cells were polarized towards M1 macrophages under LPS or LPS+IFNγ stimulation. On the contrary, IL-4 and IL-13 stimulation on PAM and IM lead to M2 polarization. A similar result was found in IL-1β gene expression and TNFα secretion. In conclusion, porcine macrophages have shown heterogeneity and plasticity on polarization under the stimulation of LPS, IFNγ, IL-4 and IL-13. 
 Title: Heterogeneity and plasticity of porcine alveolar macrophage and pulmonary interstitial macrophage isolated from healthy pigs in vitro
Output: True
Paragraph: Previous estimates of a generic level phylogeny for the ubiquitous parasitoid wasp subfamily Microgastrinae (Hymenoptera) have been problematic due to short internal branches deep in the phylogeny. These short branches might be attributed to a rapid radiation among the taxa, the use of genes that are unsuitable for the levels of divergence being examined, or insuYcient quantity of data. We added over 1200 nucleotides from four nuclear genes to a dataset derived from three genes to produce a dataset of over 3000 nucleotides per taxon. While the number of well-supported short branches in the phylogeny increased, we still did not obtain strong bootstrap support for every node. Parametric and nonparametric bootstrap simulations projected that an enormous, and likely unobtainable, amount of data would be required to get bootstrap support greater than 50% for every node. However, a marked increase in the number of well-supported nodes was seen when we conducted a Bayesian analysis of a combined dataset generated from morphological characters added to the seven gene dataset. Our results suggest that, in some cases, combining morphological and genetic characters may be the most practical way to increase support for short branches deep in a phylogeny. 
 Title: Dissecting the ancient rapid radiation of microgastrine wasp genera using additional nuclear genes
Output: False
Paragraph: The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin. . 2 The abbreviations used are: C3, C3 exoenzyme derived from Clostridium botulinum; RGD, Arg-Gly-Asp; SARS, severe acute respiratory syndrome; ANOVA, analysis of variance; aa, amino acid(s). 
 Title: The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg-Gly-Asp motif
Output: False
Paragraph: Avian infectious bronchitis virus (IBV), a coronavirus, causes infectious bronchitis leading to enormous economic loss in the poultry industry worldwide. Hypericin (HY) is an excellent compound that has been investigated in antiviral, antineoplastic, and antidepressant. To investigate the inhibition effect of HY on IBV infection in chicken embryo kidney (CEK) cells, 3 different experimental designs: pre-treatment of cells prior to IBV infection, direct treatment of IBV-infected cells, and pre-treatment of IBV prior to cell infection were used. Quantitative real-time PCR (qRT-PCR), immunofluorescence assay (IFA), flow cytometry, and fluorescence microscopy were performed and virus titer was determined by TCID 50 . The re-sults revealed that HY had a good anti-IBV effect when HY directly treated the IBV-infected cells, and virus infectivity decreased in a dose-dependent manner. Furthermore, HY inhibited IBV-induced apoptosis in CEK cells, and significantly reduced the mRNA expression levels of Fas, FasL, JNK, Bax, Caspase 3, and Caspase 8, and significantly increased Bcl-2 mRNA expression level in CEK cells. In addition, HY treatment could decrease IBV-induced reactive oxygen species (ROS) generation in CEK cells. These results suggested that HY showed potential antiviral activities against IBV infection involving the inhibition of apoptosis and ROS generation in CEK cells. 
 Title: Protective effects of hypericin against infectious bronchitis virus induced apoptosis and reactive oxygen species in chicken embryo kidney cells
Output: False