niryuu/sni-each-converted huggingface dataset:
In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-yearold, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved.
Output: Phenobarbital-induced anticonvulsant hypersensitivity syndrome in a cat
The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
Output: Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe pulmonary infection, with ∼35 % mortality. Spike glycoprotein (S) of MERS-CoV is a key target for vaccines and therapeutics because S mediates viral entry and membrane-fusion to host cells. Here, four different S subunit proteins, receptor-binding domain (RBD; 358-606 aa), S1 (1-751 aa), S2 (752-1296 aa), and SΔTM (1-1296 aa), were generated using the baculoviral system and immunized in mice to develop neutralizing antibodies. We developed 77 hybridomas and selected five neutralizing mAbs by immunization with SΔTM against MERS-CoV EMC/2012 strain S-pseudotyped lentivirus. However, all five monoclonal antibodies (mAb) did not neutralize the pseudotyped V534A mutation. Additionally, one mAb RBD-14F8 did not show neutralizing activity against pseudoviruses with amino acid substitution of L506 F or D509 G (England1 strain, EMC/2012 L506 F, and EMC/2012 D509 G), and RBD-43E4 mAb could not neutralize the pseudotyped I529 T mutation, while three other neutralizing mAbs showed broad neutralizing activity. This implies that the mutation in residue 506-509, 529, and 534 of S is critical to generate neutralization escape variants of MERS-CoV. Interestingly, all five neutralizing mAbs have binding affinity to RBD, although most mAbs generated by RBD did not have neutralizing activity. Additionally, chimeric antibodies of RBD-14F8 and RBD-43E4 with human Fc and light chain showed neutralizing effect against wild type MERS-CoV KOR/KNIH/002, similar to the original mouse mAbs. Thus, our mAbs can be utilized for the identification of specific mutations of MERS-CoV.
Output: Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein
Low cost, high throughput, easy quantitation, and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust "HTR communities" (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class, and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens, and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.
Output: Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses
Background: In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection. Methods: We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis. Results: Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052). Conclusions: Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.
Output: Hospitalized adult patients with 2009 influenza A (H1N1) in Beijing, China: risk factors for hospital mortality
Paramyxoviruses comprise a large number of diverse viruses which in part give rise to severe diseases in affected hosts. A new genotype of feline morbillivirus, tentatively named feline morbillivirus genotype 2 (FeMV-GT2), was isolated from urine of cats with urinary tract diseases. Whole genome sequencing showed about 78% nucleotide homology to known feline morbilliviruses. The virus was isolated in permanent cell lines of feline and simian origin. To investigate the cell tropism of FeMV-GT2 feline primary epithelial cells from the kidney, the urinary bladder and the lung, peripheral blood mononuclear cells (PBMC), as well as organotypic brain slice cultures were used for infection experiments. We demonstrate that FeMV-GT2 is able to infect renal and pulmonary epithelial cells, primary cells from the cerebrum and cerebellum, as well as immune cells in the blood, especially CD4 + T cells, CD20 + B cells and monocytes. The cats used for virus isolation shed FeMV-GT2 continuously for several months despite the presence of neutralizing antibodies in the blood. Our results point towards the necessity of increased awareness for this virus when clinical signs of the aforementioned organs are encountered in cats which cannot be explained by other etiologies.
Output: A New Genotype of Feline Morbillivirus Infects Primary Cells of the Lung, Kidney, Brain and Peripheral Blood
Avian infectious bronchitis virus (IBV) is a member of the group III coronaviruses, which differ from the other groups of coronaviruses in that they do not encode the essential pathogenic factor nonstructural protein 1 (nsp1) and instead start with nsp2. IBV nsp2 is one of the first replicase proteins to be translated and processed in the viral life cycle; however, it has an entirely unknown function. In order to better understand the structural details and functional mechanism of IBV nsp2, the recombinant protein was cloned, overexpressed in Escherichia coli, purified and crystallized. The crystals diffracted to 2.8 Å resolution and belonged to space group P2 1 , with unit-cell parameters a = 57.0, b = 192.3, c = 105.7 Å , = 90.8 . Two molecules were found in the asymmetric unit; the Matthews coefficient was 3.9 Å 3 Da À1 , corresponding to a solvent content of 68.2%.
Output: Structural Biology and Crystallization Communications Purification, crystallization and preliminary X-ray analysis of nonstructural protein 2 (nsp2) from avian infectious bronchitis virus
A diverse group of cytolytic animal viruses encodes small, hydrophobic proteins to modify host cell membrane permeability to ions and small molecules during their infection cycles. In this study, we show that expression of the SARS-CoV E protein in mammalian cells alters the membrane permeability of these cells. Immunofluorescent staining and cell fractionation studies demonstrate that this protein is an integral membrane protein. It is mainly localized to the ER and the Golgi apparatus. The protein can be translocated to the cell surface and is partially associated with lipid rafts. Further biochemical characterization of the protein reveals that it is posttranslationally modified by palmitoylation on all three cysteine residues. Systematic mutagenesis studies confirm that the membrane permeabilizing activity of the SARS-CoV E protein is associated with its transmembrane domain.
Output: Biochemical and functional characterization of the membrane association and membrane permeabilizing activity of the severe acute respiratory syndrome coronavirus envelope protein
The importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P ‫؍‬ 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P ‫؍‬ 0.004 and P ‫؍‬ 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P < 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P < 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.
Output: Clinical and Vaccine Immunology p
| Despite the success of the WHO-led smallpox eradication programme a quarter of a century ago, there remains considerable fear that variola virus, or other related pathogenic poxviruses such as monkeypox, could re-emerge and spread disease in the human population. Even today, we are still mostly ignorant about why most poxvirus infections of vertebrate hosts show strict species specificity, or how zoonotic poxvirus infections occur when poxviruses occasionally leap into novel host species. Poxvirus tropism at the cellular level seems to be regulated by intracellular events downstream of virus binding and entry, rather than at the level of specific host receptors as is the case for many other viruses. This review summarizes our current understanding of poxvirus tropism and host range, and discusses the prospects of exploiting host-restricted poxvirus vectors for vaccines, gene therapy or tissue-targeted oncolytic viral therapies for the treatment of human cancers. ZOONOSIS
Output: POXVIRUS TROPISM
Recent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza. A case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252. We selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33-1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54-4.19)). The IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.
Output: Hospitalization Risk Due to Respiratory Illness Associated with Genetic Variation at IFITM3 in Patients with Influenza A(H1N1)pdm09 Infection: A Case-Control Study
Background: N95 filtering facepiece respirators (N95 respirators) may not provide adequate protection against respiratory infections during chest compression due to inappropriate fitting. Methods: This was a single-center simulation study performed from December 1, 2016, to December 31, 2016. Each participant underwent quantitative fit test (QNFT) of N95 respirators according to the Occupational Safety and Health Administration protocol. Adequacy of respirator fit was represented by the fit factor (FF), which is calculated as the number of ambient particles divided by the number inside the respirator. We divided all participants into the group that passed the overall fit test but failed at least one individual exercise (partially passed group [PPG]) and the group that passed all exercises (all passed group [APG]). Then, the participants performed three sessions of continuous chest compressions, each with a duration of 2 min, while undergoing real-time fit testing. The primary outcome was any failure (FF < 100) of the fit test during the three bouts of chest compression. Results: Forty-four participants passed the QNFT. Overall, 73% (n = 32) of the participants failed at least one of the three sessions of chest compression; the number of participants who failed was significantly higher in the PPG than in the APG (94% vs. 61%; p = 0.02). Approximately 18% (n = 8) of the participants experienced mask fit failures, such as strap slipping. Conclusions: Even if the participants passed the QNFT, the N95 respirator did not provide adequate protection against respiratory infections during chest compression.
Output: N95 filtering facepiece respirators do not reliably afford respiratory protection during chest compression: A simulation study
Objective: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical (hospital) surveillance in Nigeria. Results: Children were selected via convenience sampling from communities and a tertiary care center (n = 91) during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority (79.1%) of subjects were under 6 years old, of whom 46 were infected (63.9%). A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% (15/16) of clinical subjects, and 6.7% (5/75) of community subjects (significant difference, p < 0.001). Coronavirus OC43 was the most common virus detected in community members (13.3%, 10/75). A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic (2/16) and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of respiratory infections.
Output: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria
Macrolide have enjoyed continued use for over 40 years, being increasingly usedfor the treatment ofre :piratory tract infection. Newer macrolide have been introduced that show improved ab orption after oral administration, better gastrointestinal tolerance, and delivery of increased amount ofdrug to the infection ite. Macrolides are commonly used in community-acquired pneumonia, as ,'.'ell as in atypical pneumonia and legionello is. The newer macrolides, in comparative studies, have been shown to be as effective as the conventional therapies for treating acute otitis media, acute sinusitis and acute pharyngitis, with a low incidence of side-effect. HOlvever, dosing can be simplified because of their unique pharmacokinetic properties. Limitations in the use of macrolides for respiratory infections include rather marginal activity in the most severe cases ofHaemophilu influenzae infections, lack of activity against Kleb iella and other coliforms, which precludes their lise as single agents in the therapy of pneumonia in patient with Significant underlying disease or in the elderly, and development of resistance in treptococci and taphylococci.
Output: The use of macrolides in respiratory tract infections
Autophagy and autophagy-related processes are fundamentally important in human health and disease. These processes are viewed primarily as cellular degradative pathways that recycle macromolecules and dysfunctional or redundant organelles into amino acids, sugars and lipids, especially during starvation. However, the ubiquitin-like autophagy proteins and other components of the autophagic machinery additionally participate in cellular reprogramming. We highlight these non-autophagic roles of autophagy proteins with the aim of drawing attention to this growing, but unexplored, research topic. We focus on the non-autophagic functions of autophagy proteins in cell survival and apoptosis, modulation of cellular traffic, protein secretion, cell signalling, transcription, translation and membrane reorganization.
Output: review review Non-autophagic roles of autophagy-related proteins
Bio-aerosols originate from different sources and their potentially pathogenic nature may form a hazard to healthcare workers and patients. So far no extensive review on existing evidence regarding bio-aerosols is available. This study aimed to review evidence on bio-aerosols in healthcare and the dental setting. The objectives were 1) What are the sources that generate bio-aerosols?; 2) What is the microbial load and composition of bio-aerosols and how were they measured?; and 3) What is the hazard posed by pathogenic micro-organisms transported via the aerosol route of transmission? Systematic scoping review design. Searched in PubMed and EMBASE from inception to 09-03-2016. References were screened and selected based on abstract and full text according to eligibility criteria. Full text articles were assessed for inclusion and summarized. The results are presented in three separate objectives and summarized for an overview of evidence. The search yielded 5,823 studies, of which 62 were included. Dental hand pieces were found to generate aerosols in the dental settings. Another 30 sources from human activities, interventions and daily cleaning performances in the hospital also generate aerosols. Fiftyfive bacterial species, 45 fungi genera and ten viruses were identified in a hospital setting and 16 bacterial and 23 fungal species in the dental environment. Patients with certain risk factors had a higher chance to acquire Legionella in hospitals. Such infections can lead to irreversible septic shock and death. Only a few studies found that bio-aerosol generating procedures resulted in transmission of infectious diseases or allergic reactions.
Output: A scoping review on bio-aerosols in healthcare and the dental environment
Viruses serve as infectious agents for all living entities. There have been various research groups that focus on understanding the viruses in terms of their hostviral relationships, pathogenesis and immune evasion. However, with the current advances in the field of science, now the research field has widened up at the 'omics' level. Apparently, generation of viral sequence data has been increasing. There are numerous bioinformatics tools available that not only aid in analysing such sequence data but also aid in deducing useful information that can be exploited in developing preventive and therapeutic measures. This chapter elaborates on bioinformatics tools that are specifically designed for animal viruses as well as other generic tools that can be exploited to study animal viruses. The chapter further provides information on the tools that can be used to study viral epidemiology, phylogenetic analysis, structural modelling of proteins, epitope recognition and open reading frame (ORF) recognition and tools that enable to analyse host-viral interactions, gene prediction in the viral genome, etc. Various databases that organize information on animal and human viruses have also been described. The chapter will converse on overview of the current advances, online and downloadable tools and databases in the field of bioinformatics that will enable the researchers to study animal viruses at gene level.
Output: 23 Bioinformatics Applications in Advancing Animal Virus Research
that were admitted either to a general ward or the intensive care unit compared to 44.3 % (66/149) of single SeasFlu A virus infections (OR 2.5 95 % CI 0.67-9.34, p = 0.17). In a stratified analysis, there was a trend towards higher association between FluA, hCoV and hBoV with increasing age (especially in patients aged 24-45 years and >65 year old). Conclusion Our hCoV RT-PCR protocol appeared to be of adequate analytical sensitivity for diagnosis. More and larger studies are needed to confirm the role of hCoV, hBoV in causing severe disease when they co-infect with influenza A viruses. Influenza A viruses are a significant cause of acute lower respiratory tract infections (ALRI), with 13.0 % of all children with influenza infection developing ALRI-equivalent to 20 million (95 % CI 13-32 million) ALRI cases per year [1]; and according to these authors, in 2008, between 28,000 and 111,500 children younger than 5 years died of influenza-associated ALRI. Among potential co-pathogens, human coronaviruses (hCoV) and human bocavirus (hBoV) are important emerging respiratory viruses [2, 3] . Coronaviruses infect a wide variety of hosts (animals and humans); Alphacoronaviruses and Betacoronaviruses infect mammals, whereas Gammacoronaviruses infect birds [4] . Most of the human coronaviruses (Alphacoronaviruses 229E and NL63 and Betacoronaviruses OC43, HKU1) cause mild influenza like illnesses, however in 2003, the severe acute respiratory syndrome (SARS) Purpose Influenza A viruses, human coronaviruses (hCoV) and human bocavirus (hBoV) are emerging respiratory viruses. This study investigated the association between influenza A viruses co-infection with hBoV and hCoV and severity and the sensitivity of a real-time polymerase chain reaction (RT-PCR) assay for identification of 15 coronaviruses. Methodology Published sequences for the 15 human coronaviruses were used to design a consensus PCR targeting the replicase open reading frame 1b. A previously published PCR targeting the NS1 Gene of all known human bocavirus strains was also utilized. A series of 217 samples from patients aged 37.7 (SD ± 30.4)] with seasonal influenza A viruses (SeasFluA) identified between 06/2011 and 06/2012 in NW England were tested for hCoV and hBoV using RT-PCR. Association between coinfection and disease outcome was assessed using logistic regression. Results The limit of detection of hCoV RT-PCR assay was 2 copies/µl of human coronavirus RNA template, a sensitivity comparable to a previously published SYBR green assay for human coronaviruses. A total of 12 hCoV and 17 hBoV were identified in the 217 influenza A positive samples. A higher proportion (61.5 %; 8/13) of SeasFluA/hBoV co-infections were identified in patients
Output: Pan-human coronavirus and human bocavirus SYBR Green and TaqMan PCR assays; use in studying influenza A viruses co-infection and risk of hospitalization
Coronaviruses (CoVs) continuously threaten human health. However, to date, the evolutionary mechanisms that govern CoV strain persistence in human populations have not been fully understood. In this study, we characterized the evolution of the major antigen-spike (S) gene in the most prevalent human coronavirus (HCoV) OC43 using phylogenetic and phylodynamic analysis. Among the five known HCoV-OC43 genotypes (A to E), higher substitution rates and dN/dS values as well as more positive selection sites were detected in the S gene of genotype D, corresponding to the most dominant HCoV epidemic in recent years. Further analysis showed that the majority of substitutions were located in the S1 subunit. Among them, seven positive selection sites were chronologically traced in the temporal evolution routes of genotype D, and six were located around the critical sugar binding region in the N-terminal domain (NTD) of S protein, an important sugar binding domain of CoV. These findings suggest that the genetic drift of the S gene may play an important role in genotype persistence in human populations, providing insights into the mechanisms of HCoV-OC43 adaptive evolution. Coronaviruses (CoVs) are widely found in humans as well as in mammalian and avian species, causing asymptomatic infections or respiratory tract disorders, and gastroenteritis of varying severity 1 . CoVs belong to the genus Coronavirus of family Coronaviridae, and are classified into four genera, Alphacoronavirus (α -CoV), Betacoronavirus (ß-CoV), Gammacoronavirus, and Deltacoronavirus based on phylogenetics and serology 1 . To date, α -CoV [including human CoV (HCoV)-229E and NL63] and ß-CoV [including HCoV-OC43, HKU1, Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV)] are known to infect human beings 1 . Interspecies transmission is a common phenomenon for CoVs that may be responsible for generation of new CoV epidemics during viral evolution 2-5 . For instance, the feline CoV (FCoV) type II, a member of α -CoV, might be generated by a double recombination between FCoV type I and canine CoV 4 . Interestingly, porcine hemagglutinating encephalomyelitis virus, bovine CoV (BCoV) and HCoV-OC43 of ß-CoV are thought to have evolved from the same common ancestor 5 . During evolution, high frequencies of homologous RNA recombination and gene mutations are considered the main forces that push CoVs to adapt to specific hosts. Such events can lead to emergence of new strains or genotypes within a certain species, and even to new species, causing epidemic or zoonotic outbreaks that continuously threaten human health 2,3 . This phenomenon is exemplified by the recent emergence of SARS-CoV and MERS-CoV 6,7 . However, the detailed evolutionary mechanism of interspecies transmission and the persistence of CoVs in specific hosts have yet to be fully elucidated.
Output: Genetic drift of human coronavirus OC43 spike gene during adaptive evolution OPEN
A coronavirus vector based on the genome of the porcine transmissible gastroenteritis virus (TGEV) expressing the rotavirus VP7 protein was constructed to immunize and protect against rotavirus infections in a murine model. The tropism of this TGEV-derived vector was modified by replacing the spike S protein with the homologous protein from mouse hepatitis virus (MHV). The rotavirus gene encoding the VP7 protein was cloned into the coronavirus cDNA. BALB/c and STAT1-deficient mice were inoculated with the recombinant viral vector rTGEV S-MHV -VP7, which replicates in the intestine and spreads to other organs such as liver, spleen and lungs. TGEV-specific antibodies were detected in all the inoculated BALB/c mice, while rotavirusspecific antibodies were found only after immunization by the intraperitoneal route. Partial protection against rotavirus-induced diarrhea was achieved in suckling BALB/c mice born to dams immunized with the recombinant virus expressing VP7 when they were orally challenged with the homotypic rotavirus strain.
Output: Transmissible gastroenteritis virus (TGEV)-based vectors with engineered murine tropism express the rotavirus VP7 protein and immunize mice against rotavirus
Adenoviruses have been identified in humans and a wide range of vertebrate animals, but not previously from the polar region. Here, we report the entire 26,340-bp genome of a novel adenovirus, detected by PCR, in tissues of six of nine South Polar skuas (Catharacta maccormicki), collected in Lake King Sejong, King George Island, Antarctica, from 2007 to 2009. The DNA polymerase, penton base, hexon and fiber genes of the South Polar skua adenovirus (SPSAdV) exhibited 68.3%, 75.4%, 74.9% and 48.0% nucleotide sequence similarity with their counterparts in turkey hemorrhagic enteritis virus. Phylogenetic analysis based on the entire genome revealed that SPSAdV belonged to the genus Siadenovirus, family Adenoviridae. This is the first evidence of a novel adenovirus, SPSAdV, from a large polar seabird (family Stercorariidae) in Antarctica.
Output: Full genome analysis of a novel adenovirus from the South Polar skua (Catharacta maccormicki) in Antarctica
Feline oral squamous cell carcinoma (FOSCC) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (HNSCC). HNSCC can be broadly divided into human papillomavirus (HPV)negative cancers and HPV-positive cancers where HPV is the causative agent. Previous studies in FOSCC have used both species-specific and species-nonspecific PCR primers that may be insensitive to the detection of PVs and other viruses that may be divergent from known sequences. ViroCap is a targeted capture and next generation sequencing tool that was designed to identify all known vertebrate DNA and RNA viruses. In this study we used a metagenomic approach using ViroCap for DNA viruses in 20 FOSCC, 9 normal feline oral mucosal, and 8 suspected PV positive control samples. We tested the hypothesis that viruses would be enriched in FOSCC compared to normal oral mucosa. The virome of the FOSCC and normal feline oral mucosa consisted of feline foamy virus in 7/20 and 2/9 (35% and 22%), feline torque teno virus in 2/20 and 0/9 (10% and 0%), alphaherpesvirus in 2/10 and 0/9 (10% and 0%), FIV (0% and 22%), Epstein-Barr virus in 1/20 and 0/9 (5% and 0%) and feline papillomavirus in 1/20 and 0/9 samples (5% and 0% respectively). Felis catus papillomavirus-3 was found in 1 of 20 FOSCC samples. A virus was not associated consistently with FOSCC. If PVs have a role in FOSCC it is at most a supplementary or uncommon role. FOSCC appears most closely related to HPV-negative HNSCC. Future research on FOSCC should focus on identifying genetic and environmental causes. (S. Chu). Veterinary Microbiology 240 (2020) 108491 0378-1135/ Published by Elsevier B.V. T
Output: A virome sequencing approach to feline oral squamous cell carcinoma to evaluate viral causative factors
Genomic RNA fingerprints of infectious bronchitis virus (IBV) strains M41 and Conn46 were prepared to identify Tl RNase-resistant oligonucleotides 'unique' to each of the two IBV strains. Such oligonucleotides were subsequently eluted from the gels and their nucleotide sequences determined. When oligonucleotide probes of those sequences were synthesized and used in a dot-blot hybridization assay, the probes lacked IBV strain-speciticity and reacted with the RNAs of homologous as well as heterologous IBV strains. Based on these results, the methods used in this study need to be applied to a large number of oligonucleotide probes, to find one or a few that might be suitable as IBV strain-or serotype-specific oligonucleotide probes. IBV strain M41; IBV strain Conn46; Monoclonal antibody; Nucleic acid probe;
Output: Oligonucleotide probes in infectious bronchitis virus diagnosis and strain identification
Carbocyclic nucleosides (À)-5 0 -homocarbovir and (þ)-epi-4 0 -homocarbovir were prepared from an acylnitroso-derived hetero DielseAlder cycloadduct. A kinetic enzymatic resolution generated an enantiopure aminocyclopentenol and Pd(0)-mediated decarboxylative allylations of allyl 2,2,2-trifluoroethyl malonates were used to install the 4 0 -hydroxyethyl groups. Late stage derivatization gave access to the cyclopropylamine analogs, (À)-5 0 -homoabacavir, and (þ)-epi-4 0 -homoabacavir. All carbonucleoside target molecules were evaluated for antiviral activity.
Output: Enantioselective syntheses of carbocyclic nucleosides 5 0 -homocarbovir, epi-4 0 -homocarbovir, and their cyclopropylamine analogs using facially selective Pd-mediated allylations
The main peptidase (M pro ) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M pro by an aza-peptide epoxide (APE; k inact /K i Z 1900(G400) M K1 s K1 ). The crystal structures of the M pro :APE complex in the space groups C2 and P2 1 2 1 2 1 revealed the formation of a covalent bond between the catalytic Cys145 S g atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M pro in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M pro in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M pro are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M pro in the space group P2 1 .
Output: Crystal Structures of the Main Peptidase from the SARS Coronavirus Inhibited by a Substrate-like Aza-peptide Epoxide
The nucleotide sequence of the unique region of coronavirus MHV-A59 mRNA 2 has been determined. Two open reading frames (ORF) are predicted: ORFl potentially encodes a protein of 261 amino acids; its amino acid sequence contains elements which indicate nucleotide binding properties. ORF2 predicts a 413 amino acids protein; it lacks a translation initiation codon and is therefore probably a pseudogene. The amino acid sequence of ORF2 shares 300/o homology with the HA1 hemagglutinin sequence of influenza C virus. A short stretch of nucleotides immediately upstream of ORF2 shares 83O/0 homology with the MHC class I nucleotide sequences. We discuss the possibilitythat both similarities are the result of recombinations and present a model for the acquisition and the subsequent inactivation of ORF2; the model applies also to MHV-A59-related coronaviruses in which we expect ORF2 to be still functional.
Output: Sequence of Mouse Hepatitis Virus A59 mRNA 2: Indications for RNA Recombination between Coronaviruses and Influenza C Virus
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing ribavirin are reviewed. Ribavirin is highly soluble, but its permeability characteristics are not well defined. Therefore according to the Biopharmaceutical Classification System, and taking a "worst case" approach, ribavirin should be assigned to class III. As ribavirin is transported across the brush border membrane of the human jejunum by hCNT2, it shows saturable uptake in the intestine. However, no common excipients have been shown to compete for ribavirin absorption, nor have problems with BE of immediate release ribavirin formulations containing different excipients and produced by different manufacturing methods been reported in the open literature. So the risk of bioinequivalence caused by these factors appears to be low. Ribavirin is considered a narrow therapeutic index drug, as judged by comparing the minimum effective concentration and minimum toxic concentrations in blood. Although ribavirin would not be eligible for approval via a Biopharmaceutical Classification Systemebased biowaiver procedure according to today's guidances due to its narrow therapeutic index, the risks of biowaiving should be weighed against the considerable risks associated with studying BE of ribavirin products in healthy subjects.
Output: General Commentary Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ribavirin
Ninety-six Jersey calves were used to evaluate the effects of housing and method of colostrum feeding on serum Ig concentrations, incidence and severity of scours, intake, and BW changes from birth to 35 d of age. Calves were separated from the dam and fed 2 L of colostrum in nipple-bottles or allowed to nurse the dam for 3 d. Calves were housed in individual hutches or wooden pens in a bam. Intake of colostrum by calves allowed to nurse the dam was not controlled. Serum IgG and IgM concentrations at 24 h of age were greater for calves that nursed the dam. Scours were less severe when calves were housed in hutches, but number of days scouring was unaffected by treatment. Calves fed colostrum in nipple-bottles and housed in the bam consumed more starter than did other calves from 3 to 5 wk of age. The BW were greater for calves allowed to nurse the dam and housed in hutches. Feed efficiency over the 35-d study was Received May 5. 1994. Accepted December 6. 1994 in part by the American Jersey Cattle Club, 6486 East Main Street. Reynoldsburg. OH 43068-2362. 2Reprint requests. improved when calves nursed the dam. Optimal transfer of passive immunity and housing in hutches appeared to maximize health and growth in this study. (
Output: Effects of Housing and Colostrum Feeding on Serum Immunoglobulins, Growth, and Fecal Scores of Jersey Calves 1
The grass carp accounts for a large proportion of aquacultural production in China, but the hemorrhagic disease caused by grass carp reovirus (GCRV) infection often causes huge economic losses to the industry. Interleukin 17 (IL-17) is an important cytokine that plays a critical role in the inflammatory and immune responses. Although IL-17 family members have been extensively studied in mammals, our knowledge of the activity of IL-17 proteins in teleosts in response to viral infection is still limited. In this study, the role of IL-17 in GCRV infection and its mechanism were investigated. The expression levels of IL-17AF1, IL-17AF2, and IL-17AF3 in Ctenopharyngodon idella kidney (CIK) cells gradually increased from 6 h after infection with GCRV. The nuclear translocation of p65, which acts in the NF-κB signaling pathway, was also increased by GCRV infection. The overexpression of IL-17AF1, IL-17AF2, or IL-17AF3 also promoted the nuclear translocation of p65 and the levels of phospho-IκBα in CIK cells, and reduced the expression of the viral structural protein VP7. An NF-κB signal inhibitor abolished the inhibition of GCRV infection by IL-17 proteins. These results suggested that the NF-κB signaling pathway was activated by the overexpression of IL-17 proteins, resulting in the inhibition of viral infection. In conclusion, in this study, we demonstrated that IL-17AF1, IL-17AF2, and IL-17AF3 acted as immune cytokines, exerting an antiviral effect by activating the NF-κB signaling pathway.
Output: Interleukin-17 suppresses grass carp reovirus infection in Ctenopharyngodon idellus kidney cells by activating NF-κB signaling
Objectives: To improve diagnosis as part of laboratory surveillance in Taiwan, influenza-like illness (ILI) surveillance was conducted using a new multiplex PCR assay (FilmArray) and the results compared to those of conventional methods The study was performed during the winter months. Methods: Throat swabs from patients with an ILI presenting to physicians in sentinel practices were collected during the 2016-2017 influenza season. Results: A total of 52 samples tested positive by FilmArray Respiratory Panel. Forty percent were influenza A virus, and subtype H3N2 virus was the major epidemic strain. However, nearly 60% of ILI cases seen at sentinel sites were caused by non-influenza pathogens. The results of the FilmArray assay and cell culture were identical, and this assay was more sensitive than a rapid influenza diagnostic test. Genetic analyses revealed new influenza A H3N2 variants belonging to a novel subclade 3C.2a2. Conclusions: The FilmArray assay facilitates urgent testing and laboratory surveillance for common viral and bacterial respiratory pathogens. This study demonstrated the use of a highly sensitive assay using clinical samples that is feasible for application worldwide. This may lead to an increased rate of diagnosis of viral infections and to improved patient outcomes, and in particular to a reduction in the overuse of antibiotics and antivirals.
Output: Surveillance of upper respiratory infections using a new multiplex PCR assay compared to conventional methods during the influenza season in Taiwan
Rotavirus and Coronavirus are two main causes of severe diarrhea in human infants and many animal species worldwide. Calves up to 3 months old can be affected by these viruses. The importance of these viruses in cattle industry is due to substantial economic loss, treatment costs, and reduced growth rates in beef and dairy calves. Mixed infections caused by Rotavirus and Coronavirus can lead to severe form of diarrhea. In present casecontrol study, 261 samples of healthy and diarrheic calves from farms around Mashhad were collected. These samples were tested by antigen-capture enzyme-linked immunosorbent assay (Bio-X diagnosis kit). The results showed that the prevalence of Rotavirus and Coronavirus infection in diarrheic calves is 26.98% and 3.17%, respectively. Also, there was no significant relationship between infection with Rotavirus, Coronavirus, and diarrhea in the studied population.
Output: Evaluation of relationship between Rotavirus and Coronavirus infections with calf diarrhea by capture ELISA
Epidemic outbreaks are a special case of supply chain (SC) risks which is distinctively characterized by a long-term disruption existence, disruption propagations (i.e., the ripple effect), and high uncertainty. We present the results of a simulation study that opens some new research tensions on the impact of COVID-19 (SARS-CoV-2) on the global SCs. First, we articulate the specific features that frame epidemic outbreaks as a unique type of SC disruption risks. Second, we demonstrate how simulation-based methodology can be used to examine and predict the impacts of epidemic outbreaks on the SC performance using the example of coronavirus COVID-19 and anyLogistix simulation and optimization software. We offer an analysis for observing and predicting both short-term and long-term impacts of epidemic outbreaks on the SCs along with managerial insights. A set of sensitivity experiments for different scenarios allows illustrating the model's behavior and its value for decision-makers. The major observation from the simulation experiments is that the timing of the closing and opening of the facilities at different echelons might become a major factor that determines the epidemic outbreak impact on the SC performance rather than an upstream disruption duration or the speed of epidemic propagation. Other important factors are lead-time, speed of epidemic propagation, and the upstream and downstream disruption durations in the SC. The outcomes of this research can be used by decisionmakers to predict the operative and long-term impacts of epidemic outbreaks on the SCs and develop pandemic SC plans. Our approach can also help to identify the successful and wrong elements of risk mitigation/preparedness and recovery policies in case of epidemic outbreaks. The paper is concluded by summarizing the most important insights and outlining future research agenda.
Output: Predicting the impacts of epidemic outbreaks on global supply chains: A simulation-based analysis on the coronavirus outbreak (COVID-19/SARS-CoV-2) case
Ethnopharmacological relevance: Scutellaria baicalensis: Georgi (Labiatae) is a well-known traditional Chinese medicine to treat inflammation, cardiovascular diseases, respiratory and gastrointestinal infections, etc. The present study was to understand the metabolism of the root of Scutellaria baicalensis (a.k.a. Huangqin in Chinese) in the gastrointestinal tract and the correlation between the metabolites and their respective pharmacological activities. Materials and methods: The water extract of the root of Scutellaria baicalensis (WESB) was incubated with simulated gastric and intestinal juices, and human fecal microflora for 24 h at 37 1C. The HPLC-DAD analysis was used to monitor the in vitro metabolic process and identify its metabolites by comparing their absorption spectrum and retention time with those of chemical references. The in vitro anticomplementary and antimicrobial activity was evaluated with hemolysis assay, agar disc-diffusion method and MIC value, respectively. Results: Main constituents of WESB remain unchanged during the incubation with simulated gastric juice (pH¼ 1.5) and intestinal juice (pH¼6.8), whereas four flavones, baicalin, wogonoside, oroxyloside and norwogonoside were metabolized into their respective aglycons by human intestinal bacteria. All four metabolites were demonstrated to have higher anticomplementary and antimicrobial activity than those of WESB. The anticomplementary active metabolites were identified to be baicalein, oroxylin A and norwogonin, among them, norwogonin is the most active compound. Conclusion: The presence of intestinal bacteria is demonstrated to play an important role in the gastrointestinal metabolism of WESB, and the pharmacological effects of Scutellaria baicalensis may be dependent on the intestinal bacteria metabolism.
Output: Simulated gastrointestinal tract metabolism and pharmacological activities of water extract of Scutellaria baicalensis roots