niryuu/sni-each-converted huggingface dataset:
Influenza has been well documented to significantly contribute to winter increase of mortality in the temperate countries, but its severity in the subtropics and tropics was not recognized until recently and geographical variations of disease burden in these regions remain poorly understood. In this study, we applied a standardized modeling strategy to the mortality and virology data from three Asian cities: subtropical Guangzhou and Hong Kong, and tropical Singapore, to estimate the disease burden of influenza in these cities. We found that influenza was associated with 10.6, 13.4 and 8.3 deaths per 100,000 population in Guangzhou, Hong Kong and Singapore, respectively. The annual rates of excess deaths in the elders were estimated highest in Guangzhou and lowest in Singapore. The excess death rate attributable to A/H1N1 subtype was found slightly higher than the rates attributable to A/H3N2 during the study period of 2004-2006 based on the data from Hong Kong and Guangzhou. Our study revealed a geographical variation in the disease burden of influenza in these subtropical and tropical cities. These results highlight a need to explore the determinants for severity of seasonal influenza.
Output: Influenza associated mortality in the subtropics and tropics: Results from three Asian cities
More than 60% of human infectious diseases are caused by pathogens shared with wild or domestic animals. Zoonotic disease organisms include those that are endemic in human populations or enzootic in animal populations with frequent cross-species transmission to people. Some of these diseases have only emerged recently. Together, these organisms are responsible for a substantial burden of disease, with endemic and enzootic zoonoses causing about a billion cases of illness in people and millions of deaths every year. Emerging zoonoses are a growing threat to global health and have caused hundreds of billions of US dollars of economic damage in the past 20 years. We aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources, and antimicrobial application change the dynamics of disease exposure to human beings. In view of present anthropogenic trends, a more eff ective approach to zoonotic disease prevention and control will require a broad view of medicine that emphasises evidence-based decision making and integrates ecological and evolutionary principles of animal, human, and environmental factors. This broad view is essential for the successful development of policies and practices that reduce probability of future zoonotic emergence, targeted surveillance and strategic prevention, and engagement of partners outside the medical community to help improve health outcomes and reduce disease threats.
Output: Zoonoses 1 Ecology of zoonoses: natural and unnatural histories
The genetic determinism of viral traits can generally be dissected using either forward or reverse genetics because the clonal reproduction of viruses does not require the use of approaches based on laboratory crosses. Nevertheless, we hypothesized that recombinant viruses could be analyzed as sexually reproducing organisms, using either a quantitative trait loci (QTL) approach or a locus-by-locus fixation index (F ST ). Locus-by-locus F ST analysis, and four different regressions and interval mapping algorithms of QTL analysis were applied to a phenotypic and genotypic dataset previously obtained from 47 artificial recombinant genomes generated between two begomovirus species. Both approaches assigned the determinant of within-host accumulation-previously identified using standard virology approaches-to a region including the 5' end of the replication-associated protein (Rep) gene and the upstream intergenic region. This study provides a proof of principle that QTL and population genetics tools can be extended to characterize the genetic determinants of viral traits.
Output: Mapping genetic determinants of viral traits with F ST and quantitative trait locus (QTL) approaches
Graphical Abstract Highlights d Temporal proteomic analysis quantifies host and viral dynamics during vaccinia infection d Host protein families are proteasomally degraded over the course of vaccinia infection d Vaccinia protein C6 targets HDAC5 for proteasomal degradation d HDAC5 is a host antiviral factor that restricts different families of DNA viruses SUMMARY Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor kB (NF-kB), and type I interferon (IFN) signaling. Here, we use highly multiplexed proteomics to quantify $9,000 cellular proteins and $80% of viral proteins at seven time points throughout VACV infection. A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes. Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection. In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1. By generating a proteinbased temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5. Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion.
Output: Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist
We investigated the antiviral activity of Arbidol, an antiviral chemical compound, against Coxsackie virus B5 (CVB 5 ) in vitro and in vivo. Arbidol not only prevented the cytopathic effect (CPE) of CVB 5 , as demonstrated in an MTT colorimetric assay, when added during or after viral infection, with a 50% inhibitory concentration (IC 50 ) from 2.66 to 6.62 lg/ml, but it also decreased the CVB 5 -RNA level in infected host cells, as shown in semi-quantitative RT-PCR. BALB/c mice were used as an animal model to test the Arbidol activity in vivo. Orally administered Arbidol at 50 mg/kg body weight/day (once a day) significantly reduced mean virus yields in the lungs and heart as well as mortality after infection for 6 days. Our results demonstrate that in vitro and in vivo infection with CVB 5 can be effectively treated by Arbidol.
Output: Antiviral activity of Arbidol against Coxsackie virus B5 in vitro and in vivo
This review details the molecular virology of the hepatitis E virus (HEV). While replicons and in vitro infection systems have recently become available, a lot of information on HEV has been generated through comparisons with better-studied positive-strand RNA viruses and through subgenomic expression of viral open reading frames. These models are now being verified with replicon and infection systems. We provide here the current knowledge on the HEV genome and its constituent proteins -ORF1, ORF2 and ORF3. Based on the available information, we also modify the existing model of the HEV life cycle.
Output: Molecular Virology of Hepatitis E Virus
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. *
Output: Rational monoclonal antibody development to emerging pathogens, biothreat agents and agents of foreign animal disease: The antigen scale
The fourth outbreak of the Coronaviruses, known as the 2019-nCoV, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a timevarying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dyamic transmission routes of this outbreak in mainland China over January 31 -February 19, 2020. Our results demonstrate that the influential interprovince routes from Hubei have become unidentifiable since February 4, whereas the self-transmission in each province was accelerating over February 4-15. From February 16, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in provinces with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of 2019-nCoV.
Output: How does the outbreak of 2019-nCoV spread in mainland China? A retrospective analysis of the dynamic transmission routes *
The entry of enveloped viruses into their host cells involves several successive steps, each one being amenable to therapeutic intervention. Entry inhibitors act by targeting viral and/or cellular components, through either the inhibition of protein-protein interactions within the viral envelope proteins or between viral proteins and host cell receptors, or through the inhibition of protein-lipid interactions. Interestingly, inhibitors that concentrate into/onto the membrane in order to target a protein involved in the entry process, such as arbidol or peptide inhibitors of the human immunodeficiency virus (HIV), could allow the use of doses compatible with therapeutic requirements. The efficacy of these drugs validates entry as a point of intervention in viral life cycles. Strategies based upon small molecule antiviral agents, peptides, proteins or nucleic acids, would most likely prove efficient in multidrug combinations, in order to inhibit several steps of virus life cycle and prevent disease progression.
Output: molecules Targeting Cell Entry of Enveloped Viruses as an Antiviral Strategy
Purpose: The recent Ebola epidemic that devastated West Africa has infected and killed more health care providers than any other outbreak in the history of this virus. An improved understanding of pathogen transmission and the institution of strategies to protect health care providers against infection are needed in infectious disease outbreaks. This review connects what is known about Ebola virus transmission with personal protective equipment (PPE) designed to arrest nosocomial transmission. Methods: Articles pertaining to filovirus transmission and PPE in filovirus outbreaks were reviewed and findings are presented. In addition, studies that evaluated PPE and donning and doffing strategies are presented. Findings: PPE is one step in a comprehensive infection prevention and control strategy that is required to protect health care providers. Given that the Ebola virus is primarily transmitted through direct contact of mucous membranes and cuts in the skin with infected patients and/or their bodily fluids, it is necessary to cover these potential portals of infection with PPE as part of a structured and instructed donning and doffing procedure. Implications: Current recommendations about PPE and the donning and doffing processes are based on anecdotal experience. However, the use of non-human viruses can help provide evidence-based guidelines on both PPE and donning and doffing processes.
Output: Personal Protective Equipment: Protecting Health Care Providers in an Ebola Outbreak
Coxsackie B3 virus (CVB3) is the most significant pathogen causing myocarditis in humans, and antiviral therapy would be most effective in the early stages of the disease. Here we provide evidence that BW001, a C-type CpG oligodeoxynucleotide, induces anti-CVB3 activity in human peripheral blood mononuclear cells (PBMCs). In parallel, we have demonstrated that BW001 induces human PBMCs to express mRNAs of multiple types of interferon (IFN), including IFN-a, IFN-b, IFN-o and IFN-g, and to express mRNAs of at least 11 subtypes of IFN-a. The induced IFNs may contribute to the anti-CVB3 activity. The results suggest that BW001 could be developed into a medication with the potential to treat CVB3 infectious diseases by inducing natural mixed IFNs.
Output: A CpG oligodeoxynucleotide inducing anti-coxsackie B3 virus activity in human peripheral blood mononuclear cells
Evidence demonstrating that human rhinovirus (HRV) disease is not exclusively limited to the upper airways and may cause lower respiratory complications, together with the frequency of HRV infections and the increasing number of immunocompromised patients underline the need for rapid and accurate diagnosis of HRV infections. In this study, we developed the first quantitative real-time nucleic acid sequence-based amplification assay with an internal control using molecular beacon probes for selective and sensitive detection of human rhinovirus serotypes. We described a simple method to accurately quantify RNA target by computing the time to positivity (TTP) values for HRV RNA. Quantification capacity was assessed by plotting these TTP values against the starting number of target molecules. By using this simple method, we have significantly increased the diagnostic accuracy, precision, and trueness of real-time NASBA assay. Specificity of the method was verified in both in silico and experimental studies. Moreover, for assessment of clinical reactivity of the assay, NASBA has been validated on bronchoalveolar lavage (BAL) specimens. Our quantitative NASBA assay was found to be very specific, accurate, and precise with high repeatability and reproducibility.
Output: Development of a Quantitative Real-Time Nucleic Acid Sequence-Based Amplification Assay with an Internal Control Using Molecular Beacon Probes for Selective and Sensitive Detection of Human Rhinovirus Serotypes
Hantavirus structural proteins are believed to localize to intracellular membranes often identified as Golgi membranes, in virus-infected cells. After virus budding into the Golgi luminal space, virus-containing vesicles are transported to the plasma membrane via trafficking pathways that are not well defined. Using the New World hantavirus, Andes virus, we have investigated the role of various Rab proteins in the release of hantavirus particles from infected cells. Rabs 8 and 11 were found to colocalize with Andes virus proteins in virus infected cells and when expressed from cDNA, implicating the recycling endosome as an organelle important for hantavirus infection. Small interfering RNA-mediated downregulation of Rab11a alone or Rab11a and Rab11b together resulted in a decrease in infectious virus particle secretion from infected cells. Downregulation of Rab8a did not alter infectious virus release but reduction of both isoforms did. These data implicate the recycling endosome and the Rab proteins associated with vesicular transport to or from this intracellular organelle as an important pathway for hantavirus trafficking to the plasma membrane.
Output: Roles for the recycling endosome, Rab8, and Rab11 in hantavirus release from epithelial cells
Holy Birman cat Feline infectious peritonitis (FIP) α1-acid glycoprotein (AGP) CD4/CD8 ratio Th1 cytokines A B S T R A C T The aim of this study was to assess whether Holy Birman cats (HB) have a peculiar immune profile and a higher rate of infection by feline coronaviruses (FCoV). Leucocyte and lymphocyte subsets, antibody titers, α1-acid glycoprotein (AGP), globulin fractions, IL-4, IL-12 and IFN-γ in blood and fecal FCoV excretion were determined in HB (n = 75) and in cats from other breeds (n = 94). Significantly higher CD4/ CD8 ratio, IFN-γ concentration and IL12/IL4 ratio and significantly lower IL-4 concentration and proportion of shedders were found in HB than in other breeds. No other differences were found. In conclusion, this study did not provide evidence of peculiar immune profiles in HB, except for a prevalent Th1 profile, that may explain why in our caseload the rate of shedders was lower in HB than in other breeds.
Output: Relationship between rate of infection and markers of inflammation/ immunity in Holy Birman cats with feline coronavirus
Aims: Vinegar-baked Radix Bupleuri (VBRB) potentiates the activity of anticancer drugs in the liver by increasing their hepatic distribution. However, this phenomenon may be associated with drug transporters. We investigated the effect of saikosaponin b2 (SSb2; the main component of VBRB) on the activity and expression of different drug transporters in both normal cells and those that overexpress the transporter. Main methods: The activities of transporters were analyzed by concentration of their cellular substrates. Concentrations of colchicine (substrate of Pgp and MRP1) and cisplatin (substrate of OCT2 and MRP2) were determined by high-performance liquid chromatography (HPLC). The concentration of rhodamine B was determined by flow cytometry. The expression of transporter gene and protein were determined by qRT-PCR and Western blotting analysis. Key findings: SSb2 increased colchicine efflux in HEK293 cells by primarily increasing Mrp1 activity, independent of gene and protein expression. SSb2 enhanced Mrp2 function and increased cisplatin efflux in BRL3A cells by upregulating Mrp2 gene expression, with a marginal effect on Pgp in normal cells. SSb2 increased OCT2 activity in OCT2-HEK293 cells by increasing the expression of OCT2 protein and mRNA; however, SSb2 inhibited MRP2 activity in MRP2-HEK293 cells by decreasing MRP2 protein expression, and decreased Pgp and MRP1 activity in Pgp-and MRP1-HEK293 cells. Significance: SSb2 might potentially be the key active component of VBRB that enhances the hepatotargeting of anticancer drugs through the inhibition of multidrug resistance-associated drug transporters (Pgp, MRP1, and MRP2) in an environment-dependent manner.
Output: Saikosaponin b2 enhances the hepatotargeting effect of anticancer drugs through inhibition of multidrug resistance-associated drug transporters
A novel binding site for angiotensins II and III that is unmasked by parachloromercuribenzoate has been reported in rat, mouse and human brains. Initial studies of this binding site indicate that it is not expressed in the adrenal, liver or kidney of the rat and mouse. To determine if this binding site occurs in other mouse tissues, 8 tissues were assayed for expression of this binding site by radioligand binding assay and compared with the expression of this binding site in the forebrain. Particulate fractions of homogenates of testis, epididymis, seminal vesicles, heart, spleen, pancreas, lung, skeletal muscle, and forebrain were incubated with 125 I-sarcosine 1 , isoleucine 8 angiotensin II in the presence or absence of 0.3 mM parachloromercuribenzoate plus 10 µM losartan and 10 µM PD123319 (to saturate AT 1 and AT 2 receptors). Specific (3 µM angiotensin II displaceable) high affinity binding occurred in the testis N forebrainN epididymisN spleen N pancreas N lung when parachloromercuribenzoate was present. Binding could not be reliably observed in heart, skeletal muscle and seminal vesicles. High affinity binding of 125 I-sarcosine 1 , isoleucine 8 angiotensin II was observed in the absence of parachloromercuribenzoate in the pancreas on occasion. This suggests that this novel angiotensin binding site may have a functional role in these tissues.
Output: Distribution of a novel binding site for angiotensins II and III in mouse tissues
Background: Identifying the bacteria and viruses present in a complex sample is useful in disease diagnostics, product safety, environmental characterization, and research. Array-based methods have proven utility to detect in a single assay at a reasonable cost any microbe from the thousands that have been sequenced. We designed a pan-Microbial Detection Array (MDA) to detect all known viruses (including phages), bacteria and plasmids and developed a novel statistical analysis method to identify mixtures of organisms from complex samples hybridized to the array. The array has broader coverage of bacterial and viral targets and is based on more recent sequence data and more probes per target than other microbial detection/discovery arrays in the literature. Family-specific probes were selected for all sequenced viral and bacterial complete genomes, segments, and plasmids. Probes were designed to tolerate some sequence variation to enable detection of divergent species with homology to sequenced organisms, and to have no significant matches to the human genome sequence. Results: In blinded testing on spiked samples with single or multiple viruses, the MDA was able to correctly identify species or strains. In clinical fecal, serum, and respiratory samples, the MDA was able to detect and characterize multiple viruses, phage, and bacteria in a sample to the family and species level, as confirmed by PCR. The MDA can be used to identify the suite of viruses and bacteria present in complex samples.
Output: A microbial detection array (MDA) for viral and bacterial detection
Bovine coronaviruses (BCoVs) isolated in Japan consist of four genetic groups, as determined by phylogenetic analysis using the polymorphic region (aa 456-592) of the S glycoprotein gene. Japanese field isolates of BCoV, reference Kakegawa strain, and vaccine strain 66/H were analyzed for their antigenic properties by indirect immunofluorescence and neutralization testing. There were no significant differences observed among these BCoVs in direct immunofluorescence tests. However, antigenic differences were observed between BCoVs in the neutralization tests, although there was no clear indication of a distinct serotype. A monoclonal antibody, 4H4, against the Kakegawa strain belonging to group 1 lacked significant neutralizing activity for viruses of groups 2, 3, and 4. Therefore, we speculate that the genetic differences between these groups may have altered their antigenicity. Analysis of mutant viruses resistant to neutralization by 4H4 revealed that the antigenic site of the Kakegawa strain maps to amino acid position 284 of the S glycoprotein. This site is not homologous to a known antigenic site (aa 528) of the Quebec strain belonging to group 1, and it is not located in the conformational domain comprising domain I (aa 351-403) and domain II (aa 517-621). This amino acid constitutes a neutralization epitope of BCoV, which is distinct from aa 528 of the Quebec strain. These results indicate antigenic evolution of BCoV between the genetic groups circulating in Japan.
Output: Antigenic variation among recent Japanese isolates of bovine coronaviruses belonging to phylogenetically distinct genetic groups
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. Enteric protozoal infection is the commonest cause of diarrhoea in HIV-seropositive persons (table) and is associated with apoptosis, occasional crypt abscesses, and much more severe villus atrophy than that seen with HIV infection alone. 18 Malabsorption and maldigestion increase bowel frequency. However, symptoms persist despite
Output: Gastrointestinal manifestations of HIV infection Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications
The complement system plays a crucial role in host defense against pathogen infections and in the recognition and removal of damaged or altered selfcomponents. Complement system activation can be initiated by three different pathways-classical, alternative, and lectin pathways-resulting in a proteolytic cascade, which culminates in multiple biological processes including opsonization and phagocytosis of intruders, inflammation, cell lysis, and removal of immune complexes and apoptotic cells. Furthermore, it also functions as a link between the innate and adaptive immune responses. The lectin pathway (LP) activation is mediated by serine proteases, termed mannan-binding lectin (MBL)associated serine proteases (MASPs), which are associated with the pattern recognition molecules (PRMs) that recognize carbohydrates or acetylated compounds on surfaces of pathogens or apoptotic cells. These result in the proteolysis of complement C2 and C4 generating C3 convertase (C4b2a), which carries forward the activation cascade of complements, culminating in the elimination of foreign molecules. This chapter presents an overview of the complement system focusing on the characterization of MASPs and its genes, as well as its functions in the immune response.
Output: 8 Serine Proteases in the Lectin Pathway of the Complement System
Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and antiinflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.
Output: Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model
The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the characteristic and risk factors of the illness severity. We extracted data regarding 47 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University between February 1 and February 18, 2020. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society (ATS) guidelines for communityacquired pneumonia (CAP). The median age was 64.91 years, 26 cases (55.31%) were male of which, and 70.83% were severe cases. Severe patients had higher APACHE II (9.92 vs 4.74) and SOFA (3.0 vs 1.0) scores on admission, as well as the higher PSI (86.13 vs 61.39), Curb-65 (1.14 vs 0.48) and CT semiquantitative scores (5.0 vs 2.0) when compared with nonsevere patients. Among all univariable parameters, APACHE II, SOFA, lymphocytes, CRP, LDH, AST, cTnI, BNP, et al were significantly independent risk factors of COVID-19 severity. Among which, LDH was most positively related both with APACHE II (R = 0.682) and SOFA (R = 0.790) scores, as well as PSI (R = 0.465) and CT (R = 0.837) scores. To assess the diagnostic value of these selected parameters, LDH (0.9727) had maximum sensitivity (100.00%) and specificity (86.67%), with the cutoff value of 283. As a protective factor, lymphocyte counts less than 1.045 x 10 9 /L showed a good accuracy for identification of severe patients with AUC = 0.9845 (95%CI 0.959-1.01), the maximum specificity (91.30%) and sensitivity (95.24%). In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocyte cells and its subsets, including CD3 + , CD4 + and CD8 + T cells (P < 0.01).
Output: Lactate dehydrogenase, a Risk Factor of Severe COVID-19 Patients: A Retrospective and Observational Study
We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have antiinflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium-(DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E 2 , nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis.
Output: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages
Background: The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD. Methods: We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. Results: A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ 2 = 28.52, p = 0.001). Conclusion: Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case.
Output: Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana
Turkey coronavirus (TCoV) infection induces the production of protective antibodies against the sequent exposure of TCoV. Serological tests to determine TCoV-specifi c antibodies are critical to evaluate previous exposure to TCoV in the turkey fl ocks and differentiate serotypes from different isolates or strains. A specifi c virus neutralization assay using embryonated turkey eggs and immunofl uorescent antibody assay for determining TCoV-specifi c neutralizing antibodies is described in this chapter. Virus neutralization titer of turkey serum from turkeys infected with TCoV is the dilution of serum that can inhibit TCoV infection in 50 % of embryonated turkey eggs. Virus neutralization assay for TCoV is useful to monitor the immune status of turkey fl ocks infected with TCoV for the control of the disease.
Output: Chapter 3 Virus Neutralization Assay for Turkey Coronavirus Infection
Metagenomics is helping to expand the known diversity of viruses, especially of those with poorly studied hosts in remote areas. the Neotropical region harbors a considerable diversity of avian species that may play a role as both host and short-distance vectors of unknown viruses. Viral metagenomics of cloacal swabs from 50 Neotropical birds collected in French Guiana revealed the presence of four complete astrovirus genomes. they constitute an early diverging novel monophyletic clade within the Avastrovirus phylogeny, representing a putative new astrovirus species (provisionally designated as Avastrovirus 5) according to the International Committee on Taxonomy of Viruses (ICTV) classification criteria. their genomic organization shares some characteristics with Avastrovirus but also with Mamastrovirus. The pan-astrovirus RT-PCR analysis of the cloacal samples of 406 wild Neotropical birds showed a community-level prevalence of 4.9% (5.1% in passerines, the highest described so far in this order of birds). By screening birds of a remote region, we expanded the known host range of astroviruses to the avian families Cardinalidae, Conopophagidae, Furnariidae, thamnophilidae, Turdidae and Tyrannidae. Our results provide important first insights into the unexplored viral communities, the ecology, epidemiology and features of host-pathogen interactions that shape the evolution of avastroviruses in a remote Neotropical rainforest. The last decades have witnessed a broadening of the global diversity of viruses thanks to rapidly evolving random amplification sequencing technology. Next Generation Sequencing (NGS) has revolutionized our knowledge by not only uncovering the diversity of viruses at an unprecedented rate, but also by allowing to gain insight into their ecology and distribution, helping to disentangle the network that connects viruses with their hosts and the geographical scenario in which such interactions take place 1 . However, deciphering the global virome and its structure becomes challenging not just because of the technical difficulties associated with the screening of diverse viruses, but because their many hosts are often understudied, particularly those from remote areas. The Neotropical region is one such example; being among the most biodiverse realms on Earth, Neotropical rainforests are candidates to host and conserve relevant parts of the virosphere diversity 2 . However, the knowledge of Neotropical viral diversity and their hosts is in its infancy. Given that zoonotic viruses are considered the most probable causative agents of emerging diseases 3 and that mammal and avian species are their main hosts 4,5 , the study of the wildlife viral diversity and their ecological context in these remote areas will provide important information for public and animal health to prevent potential new emerging viral epidemics 2,6 . For example, the great diversity of the Neotropical fauna harbors the risk of emergence of new infections in domestic animals and
Output: A novel group of avian astroviruses from Neotropical passerine birds broaden the diversity and host range of Astroviridae
New possibilities for the design of coronavirus vaccines have been opened up with the elucidation of the structure of the receptorbinding domain (RBD) of severe acute respiratory syndrome (SARS) spike protein. The RBD of the SARS spike protein is responsible for virus attachment to its receptor, angiotensinconverting enzyme-2 (ACE2), on human cells. The RBD of the human epidemic strain differs from that of the animal virus by just two amino acids. Harrison and colleagues determined the complex of the interacting segments of these proteins, which consists of residues 19-615 of the peptidase domain of human ACE2 and residues 323-502 of the RBD, to 2.9-Å resolution. The ACE2 peptidase domain comprises two lobes that close during substrate binding, and the spike RBD contacts the tip of one lobe when ACE2 is either open or closed. The RBD has a five-stranded, antiparallel β-sheet core, and an extended-loop subdomain that lies along one edge of the core. A two-stranded β-sheet in this loop forms a concave surface that cradles the N-terminal helix of ACE2, and ridges along either side of the loop interact with structural features of ACE2. This loop (residues 424-494) was named the receptor-binding motif (RBM) and makes the only contacts with ACE2, producing a 1,700 Å 2 interface that is consistent with the high binding affinity of these proteins (K d ~10 -8 ). The detailed analysis of the contacts between these two proteins provides useful information for rational vaccine design. REFERENCE Li, F. et al. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor.
Output: STRUCTURE WATCH Spikes point the way
In this study, respiratory viral pathogens were screened using real-time RT-PCR in 86 broiler chicken flocks suffering from respiratory diseases problems in 4 Egyptian governorates between January 2012 and February 2014. The mortality rates in the investigated flocks ranged from 1 to 47%. Results showed that mixed infection represented 66.3% of the examined flocks. Mixed infectious bronchitis (IBV) and avian influenza (AI)-H9N2 viruses were the most common infection (41.7%). Lack of AI-H9N2 vaccination and high rates of mixed infections in which AI-H9N2 is involved indicate an early AI-H9N2 infection with a potential immunosuppressive effect that predisposes for other viral infections. High pathogenic AI-H5N1 and virulent Newcastle disease virus (vNDV) infections were also detected (26.7% and 8.1%, respectively). Interestingly, co-infection of AI-H9N2 with either AIV-H5N1 or vNDV rarely resulted in high mortality. Partial cell-mediated immunity against similar internal AI genes, as well as virus interference between AI and vNDV, could be an explanation for this. Highly prevalent IBV and AI-H9N2 were isolated and were molecularly characterized based on S1 gene hypervariable region 3 (HVR3) and hemagglutinin gene (HA) sequences, respectively. IBV strains were related to the variant group of IBV with multiple mutations in HVR3. Though AI-H9N2 viruses showed low rate of evolution in comparison to recent strains, few amino acid substitutions indicative of antibody selection pressure were observed in the HA gene. In conclusion, mixed viral infections, especially with IBV and AI-H9N2 viruses, are the predominant etiology of respiratory disease problems in broiler chickens in Egypt. Further investigations of the role of AI, IBV, and ND viruses' co-infections and interference in terms of altering the severity of clinical signs and lesions and/or generating novel reassortants within each virus are needed.
Output: Prevalence of avian respiratory viruses in broiler flocks in Egypt
Purpose: To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on protection of patients and staff. Methods: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including protection of patients and staff. Results: Key recommendations include: (1) prepare infection control and occupational health policies for clinical risks relating to potential disease transmission; (2) decrease clinical risks and provide adequate facilities through advanced planning to maximise capacity by increasing essential equipment, drugs, supplies and encouraging staff availability; (3) create robust systems to maintain staff confidence and safety by minimising non-clinical risks and maintaining or escalating essential services; (4) prepare formal reassurance plans for legal protection; (5) provide assistance to staff working outside their normal domains. Conclusions: Judicious planning and adoption of protocols for protection of patients and staff are necessary to optimise outcomes during a pandemic.
Output: Chapter 6. Protection of patients and staff during a pandemic
Objective This study was conducted to investigate the viral and bacterial etiology and epidemiology of patients with acute febrile respiratory syndrome (AFRS) in Qinghai using a commercial routine multiplex-ligation-nucleic acid amplification test (NAT)-based assay. Methods A total of 445 nasopharyngeal swabs specimens from patients with AFRS were analyzed using the RespiFinderSmart22kit (PathoFinder BV, Netherlands) and the LightCycler 480 real-time PCR system. Among the 225 (225/445, 51%) positive specimens, 329 positive pathogens were detected, including 298 (90.58%) viruses and 31 (9%) bacteria. The most commonly detected pathogens were influenza virus (IFV; 37.39%; 123/329), adenovirus (AdV; 17.02%; 56/329), human coronaviruses (HCoVs; 10.94%; 36/329), rhinovirus/enterovirus (RV/EV; 10.03%; 33/329), parainfluenza viruses (PIVs; 8.51%; 28/329), and Mycoplasma pneumoniae (M. pneu; 8.51%; 28/329), respectively. Among the co-infected cases (17.53%; 78/445), IFV/AdV and IFV/M. pneu were the most common co-infections. Most of the respiratory viruses were detected in summer and fall. Conclusion In our study, IFV-A was the most common respiratory pathogen among 22 detected pathogens, followed by AdV, HCoV, RV/EV, PIV, and M. pneu. Bacteria appeared less frequently than viruses, and co-infection was the most common phenomenon among viral pathogens. Pathogens were distributed among different age groups and respiratory viruses were generally active in July, September, and November. Enhanced surveillance and early detection can be useful in the diagnosis, treatment, and prevention of AFRS, as well as for guiding the development of appropriate public health strategies.
Output: Original Article Viral and Bacterial Etiology of Acute Febrile Respiratory Syndrome among Patients in Qinghai, China *
Loop-mediated isothermal amplifi cation (LAMP) is an established nucleic acid amplifi cation method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. This technology has been developed into commercially available detection kits for a variety of pathogens including bacteria and viruses. The current focus on LAMP methodology is as a diagnostic system to be employed in resource-limited laboratories in developing countries, where many fatal tropical diseases are endemic. The combination of LAMP and novel microfl uidic technologies such as Lab-on-a-chip may facilitate the realization of genetic point-of-care testing systems to be used by both developed and developing countries in the near future. This review will describe the historical, current, and future developments of such technologies.
Output: Loop-mediated isothermal amplifi cation (LAMP): a rapid, accurate, and cost-effective diagnostic method for infectious diseases
Background: Oxygen exists in two gaseous and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. Methods: Cyclooctaoxygen sodium was synthesized in vitro from atmospheric oxygen, or catalase effectgenerated oxygen, under catalysis of cytosine nucleosides and either ninhydrin or eukaryotic low-molecular weight RNA. Thin-layer chromatographic mobility shift assays were applied on specific nucleic acids and the cyclooctaoxygen sodium complex. Results: We report the first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes. The cationic cyclooctaoxygen sodium complex is shown to bind to nucleic acids (RNA and DNA), to associate with single-stranded DNA and spermine phosphate, and to be essentially non-toxic to cultured mammalian cells at 0.1-1.0 mM concentration. Conclusions: We postulate that cyclooctaoxygen is formed in most eukaryotic cells in vivo from dihydrogen peroxide in a catalase reaction catalyzed by cytidine and RNA. A molecular biological model is deduced for a first epigenetic shell of eukaryotic in vivo DNA. This model incorporates an epigenetic explanation for the interactions of the essential micronutrient selenium (as selenite) with eukaryotic in vivo DNA. General significance: Since the sperminium phosphate/cyclooctaoxygen sodium complex is calculated to cover the active regions (2.6%) of bovine lymphocyte interphase genome, and 12.4% of murine enterocyte mitotic chromatin, we propose that the sperminium phosphate/cyclooctaoxygen sodium complex coverage of nucleic acids is essential to eukaryotic gene regulation and promoted proto-eukaryotic evolution.
Output: A new oxygen modification cyclooctaoxygen binds to nucleic acids as sodium crown complex
The spike gene of porcine epidemic diarrhea virus (PEDV) was sequenced from 55 South China field strains isolated from pigs with symptoms of diarrhea. The sequences were compared within the set of field strains as well as with reference strains available in GenBank. Within the 55 South China PEDV field strains, the deduced amino acid sequence identities ranged from 93.8% to 99.9 % and ranged from 90.7% to 99.5% when compared with the foreign reference strains in GenBank. Our phylogenetic analysis showed that 10 of the 55 South China PEDV strains belonged to G1b and 45 belonged to G2b.
Output: Sequence analysis of the spike gene of Porcine epidemic diarrhea virus isolated from South China during 2011-2015