niryuu/sni-each-converted huggingface dataset:
To explore longitudinal change patterns of key laboratory tests in patients with COVID-19, and to identify independent prognostic factors by examining the associations between laboratory findings and outcomes of patients. The multicenter study prospectively included 59 patients with COVID-19 treated at Jilin province from January 21, 2020 to May 5, 2020. Laboratory tests were included haematological, biochemical, and immunological tests. Laboratory findings, the characteristics of epidemiological and demographic data were extracted from electronic medical records. Eosinopenia was shown in 52.6% cases at onset, and the average value of eosinophil continued to significantly increase thereafter. Lymphopenia was found in 40.4% cases at onset, and the average value of lymphocyte was slowly elevated after day 5. Thrombocytopenia was shown in 12.3% cases at onset, and the average value of mean platelet volume was decreased sharply after day 7. The values of aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatinine kinase-muscle/brain activity, and cardiac troponin I, serum cardiac markers, were beyond the upper limit of RI from 6.1% to 30.6% at onset.
Output: Longitudinal analysis of laboratory findings during the process of recovery for patients with COVID-19
The prototype coronavirus mouse hepatitis virus (MHV) exhibits highly selective packaging of its genomic positive-stranded RNA into assembled virions, despite the presence in infected cells of a large excess of subgenomic viral mRNAs. One component of this selectivity is the MHV packaging signal (PS), an RNA structure found only in genomic RNA and not in subgenomic RNAs. It was previously shown that a major determinant of PS recognition is the second of the two RNA-binding domains of the viral nucleocapsid (N) protein. We have now found that PS recognition additionally depends upon a segment of the carboxy-terminal tail (domain N3) of the N protein. Since domain N3 is also the region of N protein that interacts with the membrane (M) protein, this finding suggests a mechanism by which selective genome packaging is accomplished, through the coupling of genome encapsidation to virion assembly.
Output: A key role for the carboxy-terminal tail of the murine coronavirus nucleocapsid protein in coordination of genome packaging
The genetic dissection of various human infectious diseases has led to the definition of inborn errors of human STAT1 immunity of four types, including (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria) and viruses (herpes viruses at least), due principally to the impairment of IFN-γ-mediated and IFN-α/β-mediated immunity, respectively. Clinical outcome depends on the extent to which the STAT1 defect decreases responsiveness to these cytokines. AD STAT1 deficiency selectively predisposes individuals to mycobacterial disease, owing to the impairment of IFN-γ-mediated immunity, as IFN-α/β-mediated immunity is maintained. Finally, AD gain of STAT1 activity is associated with autoimmunity, probably owing to an enhancement of IFN-α/β-mediated immunity. More surprisingly, it is also associated with chronic mucocutaneous candidiasis, through as yet undetermined mechanisms involving an inhibition of the development of IL-17producing T cells. Thus, germline mutations in human STAT1 define four distinct clinical disorders. Various combinations of viral, mycobacterial and fungal infections are therefore allelic at the human STAT1 locus. These experiments of Nature neatly highlight the clinical and immunological impact of the human genetic dissection of infectious phenotypes.
Output: Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes
The prevalence of antibodies to bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections was studied in 20 conventional and 20 organic dairy herds. The organic farms had produced 'certified' milk for at least 2 years. On two occasions, with a 1-year interval, 699 serum samples from 624 peri-parturient cows were tested by ELISA for antibodies to BCV and BRSV. Accompanying data relating to the sampled animals were collected in order to identify potential factors associated with increased antibody prevalence. The antibody prevalence was high at both sampling times with approximately 85% and 80% of animals positive for antibodies to BCV and to BRSV, respectively. Conventional herds had a significantly higher mean antibody prevalence to BCV and BRSV than the organically managed herds (P < 0.01). Animal age was significantly associated with increased antibody prevalence (P < 0.001). The findings of this study suggest that organic farm management may be effective in reducing the seroprevalence of these viruses relative to conventional farming methods.
Output: Reduced likelihood of bovine coronavirus and bovine respiratory syncytial virus infection on organic compared to conventional dairy farms
Efforts to combat HIV, tuberculosis and malaria in sub-Saharan Africa in the past decade have underscored the inadequacy of laboratory systems in most African countries, as they were not equipped to perform vital testing for HIV care and prevention programmes. Laboratory testing is required for the diagnosis and management of these diseases and many other communicable and non-communicable diseases endemic to the African region. For many years, there had been steady neglect of national health laboratories in Africa, leading to a lack of trust in laboratory results and empiric treatment of patients. Early improvement efforts employed a vertical approach, creating national HIV-and AIDS-specific laboratories. This approach has proved inadequate, as it created competition for resources and did not improve the entire laboratory system in the countries. 1 It became clear that all laboratories in a country should be part of a fully-integrated laboratory network that can address both individual patient care needs and public health needs from the peripheral levels to the national level.
Output: Print) 2225-2002 in Africa in the Global Health Security era
Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)-neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra-and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in batspecies seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1-prevalence patterns in bat colonies and also provide useful information for public health officials.
Output: Ecological Factors Associated with European Bat Lyssavirus Seroprevalence in Spanish Bats
, the active isoform of X-box binding protein 1 (XBP-1), is a key regulator of UPR. Previously, we showed that a histone acetyltransferase (HAT), p300/CBP-associated factor (PCAF), binds to XBP-1S and functions as an activator of XBP-1S. Here, we identify general control nonderepressible 5 (GCN5), a HAT with 73% identity to PCAF, as a novel XBP-1S regulator. Both PCAF and GCN5 bind to the same domain of XBP-1S. Surprisingly, GCN5 potently blocks the XBP-1Smediated transcription, including cellular UPR genes and latent membrane protein 1 of Epstein-Barr virus. Unlike PCAF, GCN5 acetylates XBP-1S and enhances nuclear retention and protein stability of XBP-1S. However, such GCN5-mediated acetylation of XBP-1S shows no effects on XBP-1S activity. In addition, the HAT activity of GCN5 is not required for repression of XBP-1S target genes. We further demonstrate that GCN5 inhibits XBP-1S-mediated transcription by disrupting the PCAF-XBP-1S interaction and preventing the recruitment of XBP-1S to its target genes. Taken together, our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription. Oncotarget 272
Output: Oncotarget, Vol. 6, No. 1 GCN5 inhibits XBP-1S-mediated transcription by antagonizing PCAF action
Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.
Output: Host Cell Factors in Filovirus Entry: Novel Players, New Insights
Children and adults residing in densely populated urban centers around the world are at risk of seasonal influenza-like illness caused by respiratory viruses such as influenza virus, human metapneumovirus (hMPV), and respiratory syncytial virus (RSV). In a large metropolitan of Thailand's capital city Bangkok, most respiratory infections are rarely confirmed by molecular diagnostics. We therefore examined the frequency of RSV, hMPV, and influenza virus in 8,842 patients who presented influenza-like illness and sought medical care at a large hospital in Bangkok between 2016 and 2017. Using a multiplex real-time reverse-transcription polymerase chain reaction (RT-PCR), 30.5% (2,699/8,842) of nasopharyngeal (NP) swab samples tested positive for one or more of these viruses. Influenza virus comprised 17.3% (1,528/8,842), of which the majority were influenza A/H3N2. Such infection was most prevalent among adults and the elderly. RSV was identified in 11.4% (1,011/8,842) and were mostly ON1 and BA9 genotypes. Of the hMPV-positive samples (3.6%, 318/8,842), genotypes A2, B1, and B2 were detected. A small number of individuals experienced co-infections (1.8%, 155/8,842), most commonly between RSV and influenza A/H3N2. RSV and hMPV co-infections were also found, but mainly in young children. Viral respiratory tract infection peaked locally in the rainy season (June to September). These findings support the utility of rapid nucleic acid testing of RSV, hMPV, and influenza virus in patients with ILI. Agapov E, Sumino KC, Gaudreault-Keener M, Storch GA, Holtzman MJ. 2006. Genetic variability of human metapneumovirus infection: evidence of a shift in viral genotype without a change in illness.
Output: Distributed under Creative Commons CC-BY 4.0 Respiratory syncytial virus, human metapneumovirus, and influenza virus infection in Bangkok, 2016-2017
A B S T R A C T Neonatal calf diarrhea remains one of the most important problems faced by livestock, causing great economic losses. This study investigated the prevalence of Salmonella and Escherichia coli, especially enterotoxigenic E. coli (ETEC), in diarrheic calves. Fecal samples were collected from 127 diarrheic calves up to 3 months of age at 12 farms from different governorates in Egypt. 119 bacterial isolates (93.7%) were recovered and the prevalences of Salmonella and E. coli in diarrheic calves were 18.1% and 75.6%, respectively. Serotyping of Salmonella isolates revealed that S. Enteritidis and S. Typhimurium were the most prevalent serotypes, representing 60.9% and 30.4%, respectively, while S. Dublin was 8.7%. Serogrouping of E. coli isolates showed that 10 O-serogroups were obtained where O26 and O103 were the most prevalent (17.7% of each). Salmonella serotypes showed positive results with PCR test using oligonucleotide primer amplifying 521 bp fragment of invA gene of Salmonella while 70% of E. coli serogroups possessed ETEC virulent gene (K99). The in-vitro antibiotic sensitivity test indicated that Salmonella serotypes showed high sensitivity against enrofloxacin, spectinomycin and neomycin while E. coli isolates showed high sensitivities against marbofloxacin, spectinomycin and neomycin only. © 2016 Beni-Suef University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
Output: Prevalence of Salmonella and E. coli in neonatal diarrheic calves-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Dendritic cells (DCs) are recognized as highly potent antigen-presenting cells that are able to stimulate cytotoxic T lymphocyte (CTL) responses with antitumor activity. Consequently, DCs have been explored as cellular vaccines in cancer immunotherapy. To that end, DCs are modified with tumor antigens to enable presentation of antigen-derived peptides to CTLs. In this review we discuss the use of viral vectors for in situ modification of DCs, focusing on their clinical applications as anticancer vaccines. Among the viral vectors discussed are those derived from viruses belonging to the families of the Poxviridae, Adenoviridae, Retroviridae, Togaviridae, Paramyxoviridae, and Rhabdoviridae. We will further shed light on how the combination of viral vector-based vaccination with T-cell supporting strategies will bring this strategy to the next level. Since their discovery in 1973, it was clear that dendritic cells (DCs) stood out above the immune cell pack (1, 2). They are morphologically distinct from all other immune cell types and are gifted with an unparalleled capacity to take up, process and present self and foreign antigens to both CD4 + and CD8 + T cells. DCs are critical intermediaries between the innate and adaptive immune systems, as they stimulate, regulate, and shape both immunity and tolerance in all its disguises. Ralph Steinmann, who discovered these cells, was awarded the Nobel Prize for Medicine in 2011, because the discovery of DCs changed medicine (3). Dendritic cells in both humans and mice represent a population of at least four different subtypes with distinct phenotypical and functional characteristics (4-7). These subsets are: plasmacytoid DCs (pDCs), two subsets of conventional DCs (cDC1 and cDC2), and inflammatory DCs. The latter represent a monocyte-derived subset that appears during inflammatory responses (Table 1) . Recently, additional types of human blood DCs, monocytes, and progenitors were revealed using single cell RNA-sequencing. The group of Prof. Nir Hacohen identified pDCs next to cDC progenitor-derived cDC1 (Clec9A + ) and two types of CD1c + cDC2, of which one can also be derived from CD14 + DCs. Furthermore they found a CD141 − CD1c − CD11c + DC subset derived from CD16 + monocytes and an AXL + Siglec6 + subset (8). Future research will have to unravel a possible murine representative for the human cDC2 and AXL + Siglec6 + DC subset. Also, Langerhans cells have been considered an important DC subset for vaccination as they are localized in the epidermis (HLA-DR + CD11c + CD1a + CD207 + ). However, recent evidence suggests that they are related to macrophages, another antigen-presenting cell (APC) type with potential antitumor activity (9).
Output: The Journey of in vivo Virus Engineered Dendritic Cells From Bench to Bedside: A Bumpy Road
The bacteria involved in tonsil disease have been well studied, but we cannot say the same for the viruses. The method to detect virus make this approach difficult to study. Epstein -Barr Virus (EBV) infection usually occurs in early childhood and can persist in palatine and pharyngeal tonsil lymphocytes. EBV has been closely associated with the undifferentiated form of nasopharyngeal carcinoma (NPC) in its effect. Nevertheless, the presence of EBV in non-neoplastic lymphoid tissue of the nasopharynx and tonsil has rarely been investigated. Our objective was to study the frequency of EBV in tonsils and adenoids and to define the correlation between EBV and adenoid hyperplasia. In this study, we looked for EBV in adenoid and tonsil tissue of 165 patients (2 and 15 years old ) by in situ hybridization (ISH) for EBER 1/2 RNA. Resection of the adenoids was done for relief of upper respiratory tract obstruction, and the tonsils were resected because of recurrent tonsillitis and/or hyperplasia with upper airway obstruction. We divided the adenoid samples in two groups: one group 12 -24 months old (average 18 months old) and the second group, 25 months to 15 years old. Tonsils were obtained from 85 patients, 3 -13 years old (mean age 5.6 years) who underwent surgery due to recurrent tonsillitis or hyperplasia. EBV was demonstrated in lymphoid cells of 11 (34.3%) out of 32 adenoids for the first group and 36 (72%) out of 48 children of the second group. EBV was found in the respiratory epithelial cells of adenoid in one case. Children under 24 months of age can be infected by EBV, and this virus might be responsible for obstructive hyperplasia. Tonsils are less affected by EBV than the adenoids, suggesting that the EBV is more attracted to the adenoid tissue than the tonsillar tissue. D
Output: The EBV action in tonsils and adenoids
Aim: Bile salt export pump (BSEP) have been confirmed to play an important role for bile acid canalicular export in the treatment of cholestasis. In this study, we investigated the stimulatory effect of emodin on BSEP signaling pathway in cholestasis. Methods: Cell and animal experiments were given different concentrations of emodin. The BSEP upstream molecule farnesoid X receptor was down-regulated by small interfering RNA (siRNA) technology or guggulsterones and up-regulated by lentivirus or GW4064. Real-time PCR and Western blotting was employed to detect the mRNA and protein levels of BSEP in LO2 cell, rat primary hepatocytes and liver tissue. Immunohistochemistry (IHC) was used to examine the expression of BSEP in liver tissues. Rat liver function and pathological changes of liver tissue were performed by biochemical test and hematoxylin and eosin (HE) staining. Results: Emodin could increase the mRNA and protein expression of BSEP and FXR. When down-regulating farnesoid X receptor expression with the siRNA or inhibitor guggulsterones, and up-regulating farnesoid X receptor expression with the lentivirus or agonist GW4064, emodin could increase the mRNA level of BSEP and FXR and the protein level of BSEP, FXR1, and FXR2. Emodin also had a notable effect on rat primary hepatocytes experiment, rat pathological manifestation, BSEP, FXR1, and FXR2 positive staining in liver tissues and the test of liver function. Conclusion: Emodin has a protective effect and a rescue activity on cholestasis via stimulating FXR/BSEP pathways in promoting the canalicular export of accumulated bile.
Output: Emodin Rescues Intrahepatic Cholestasis via Stimulating FXR/BSEP Pathway in Promoting the Canalicular Export of Accumulated Bile
Oligonucleotide microarrays have been applied to microbial surveillance and discovery where highly multiplexed assays are required to address a wide range of genetic targets. Although printing density continues to increase, the design of comprehensive microbial probe sets remains a daunting challenge, particularly in virology where rapid sequence evolution and database expansion confound static solutions. Here, we present a strategy for probe design based on protein sequences that is responsive to the unique problems posed in virus detection and discovery. The method uses the Protein Families database (Pfam) and motif finding algorithms to identify oligonucleotide probes in conserved amino acid regions and untranslated sequences. In silico testing using an experimentally derived thermodynamic model indicated near complete coverage of the viral sequence database.
Output: Comprehensive viral oligonucleotide probe design using conserved protein regions
Objective: To optimize clinical laboratory diagnosis of COVID-19 from suspect cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody. Methods: By reinterpreting the data in the article "Diagnostic Value of Combined Detection of Serum 2019 novel coronavirus IgM and IgG Antibodies in novel coronavirusin Infection", the positive likelihood ratio of IgM and IgG antibody in diagnosis of COVID-19 (nucleic acid positive patients) was calculated, and the posterior probability of IgM and IgG antibodies and their tandem detection to diagnose was finally calculated. Results: The positive likelihood ratios of single IgM and IgG antibody were 18.50 and 12.65 respectively, and the posterior probabilities were 90.18% and 86.26% respectively. However, the posterior probability of the two antibodies tandem detection is 99.15%, which can give clinicians quantitative confidence in the diagnosis of COVID-19 from suspected cases. According to the results of this study, combining the advantages and disadvantages of nucleic acid detection and antibody detection, the clinical pathway for clinicians to diagnose COVID-19 is found. Conclusion: For suspected cases, IgM and IgG antibody tests should be firstly done at the same time. If the antibody tests are all positive, COVID-19 can be confirmed. If not, nucleic acid detection (one or more times) is performed, and in extreme cases, high-throughput viral genome sequencing is performed.
Output: Optimize Clinical Laboratory Diagnosis of COVID-19 from Suspect Cases by Likelihood Ratio of SARS-CoV-2 IgM and IgG antibody
DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines.
Output: vaccines Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines
We investigate the effects of delaying the time to recovery (delayed recovery) and of nonuniform transmission on the propagation of diseases on structured populations. Through a mean-field approximation and large-scale numerical simulations, we find that postponing the transition from the infectious to the recovered states can largely reduce the epidemic threshold, therefore promoting the outbreak of epidemics. On the other hand, if we consider nonuniform transmission among individuals, the epidemic threshold increases, thus inhibiting the spreading process. When both mechanisms are at work, the latter might prevail, hence resulting in an increase of the epidemic threshold with respect to the standard case, in which both ingredients are absent. Our findings are of interest for a better understanding of how diseases propagate on structured populations and to a further design of efficient immunization strategies.
Output: Physica A Effects of delayed recovery and nonuniform transmission on the spreading of diseases in complex networks
Infectious bronchitis is considered to be one of the most devastating diseases in poultry. Control of its spread is typically attempted through biosecurity measures and extensive vaccination. However, the remarkable genetic and antigenic variability of the virus, which originate from both mutations and recombination events, represents an unsolved challenge for this disease. The present study reports on the emergence and spread of recombinant clusters detected in Italy and Spain between 2012 and 2014. A total of 36 Spanish and Italian infectious bronchitis virus (IBV) field strains were investigated and genetically characterized using phylogenetic, molecular, recombination and selection pressure analyses of the complete S1 gene. Based on the partial S1 sequencing, 27 IBV strains originating from Spain and nine from Italy were initially classified as being closely related to the Guandong/Xindadi (XDN) genotype. Phylogenetic analysis of the complete S1 gene revealed that the XDN strains formed a homogeneous clade with the Spanish IBV isolates within the QX genotype, whereas there was higher variability within the Italian strains. Recombination analysis determined that these strains belonged to four groups, which originated from independent recombination events between the QX and 793B IBV genotypes. Our data support the hypothesis of two different scenarios: firstly, in Spain, the large and homogeneous clade probably originated from a single offspring of the recombinant founder, which became dominant and spread throughout the country. Secondly, the nine Italian recombinants, which are characterized by three different recombination patterns, probably represent less fitted strains, because they were less viable with respect to their recombinant parents. ARTICLE HISTORY
Output: A novel variant of the infectious bronchitis virus resulting from recombination events in Italy and Spain
Porcine reproductive and respiratory syndrome (PRRS) is a disease of domestic swine characterized by exceptionally high clinical variability. This study addresses the question of whether clinical variability in PRRS results from (a) genetic variation among viral isolates and/or (b) variation in management practices among farms on which isolates are found. Genetic data (open reading frame 5 gene sequences) and data on farm characteristics and associated clinical disease signs were collected for 62 PRRS virus (PRRSV) field isolates, representing 52 farms. Clinical disease signs were interrelated Ð confirming that a true reproductive syndrome exists (involving abortions, infertility in sows, deaths of sows and preweaning mortality). Pairs of farms experiencing deaths in their sow populations also tended to share viral isolates which were more similar to one another than expected by chance alone. This implies that sow death (one of the more-severe manifestations of PRRS) is under genetic influence. Large herd size was a significant risk factor for the death of sows and for respiratory disease in nursery pigs. All-in±allout management practices in the nursery were protective against reproductive signs in the sow herd. All-in±all-out management practices in the finishing stages of production were protective against respiratory disease in nursery pigs Ð but were paradoxically associated with an increased risk of infertility in sows. These results suggest that farm-management practices can also influence which PRRS clinical signs are manifested during an outbreak. In general, signs associated with PRRS appear to result from a combination of genetic factors and herd-management characteristics. The relative contributions of these two influences differ depending on the specific clinical sign in question. # : S 0 1 6 7 -5 8 7 7 ( 9 9 ) 0 0 1 0 4 -X
Output: Associations between genetics, farm characteristics and clinical disease in field outbreaks of porcine reproductive and respiratory syndrome virus
J o u r n a l P r e -p r o o f Highlights • As of 10 March 2020, Italy has reported 9,172 COVID-19 cases with 463 deaths. • We reported real-time reproductive numbers (R(t))and case fatality rate in in selected European countries (Italy, France, Germany, and Spain) by 9 March 2020. • The R(t) was greater than 2 in the selected European countries, indicating the outbreak will continue. Objectives: As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective was to report real-time effective reproduction numbers (R(t)) case fatality rate (CFR). Methods: Data were mainly obtained from WHO website, up to 9 March 2020. R(t) was estimated by exponential growth rate (EG) and time dependent (TD) methods. "R0" package in R was employed to estimate R(t) by fitting the existing epidemic curve. Both naïve CFR (nCFR) and adjust CFR (aCFR) were estimated. : In EG method, R(t) was 3.27 [3.17-3.38] for Italy, 6.32 [5.72-6.99] for France, 6.07 [5.51-6.69] for Germany, 5.08 [4.51-5.74] for Spain. With TD method, the R value for March 9 was 3.10 J o u r n a l P r e -p r o o f [2.21-4.11] for Italy, 6.56 [2.04-12.26] for France, 4.43 [1.83-7.92] for Germany, and 3.95 [0-10.19] for Spain. Conclusions: This study provides important findings on an early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority J o u r n a l P r e -p r o o f disease 2019 in China. N Engl J Med. 2020; 9. Kucharski AJ, Edmunds WJ. Case fatality rate for Ebola virus disease in west Africa. Lancet. 2014;384(9950):1260. J o u r n a l P r e -p r o o f
Output: Journal Pre-proof Monitoring Transmissibility and Mortality of COVID-19 in Europe TITLE PAGE Monitoring Transmissibility and Mortality of COVID-19 in Europe
To investigate the factors associated with death and describe the gestational outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case-control study (deaths and recovered) in hospitalized pregnant women with laboratory-confirmed influenza A (H1N1)pdm09 with severe acute respiratory illness (SARI) in the state of São Paulo from June 9 to December 1, 2009. All cases were evaluated, and four controls that were matched by the epidemiological week of hospitalization of the case were randomly selected for each case. Cases and controls were selected from the National Disease Notification System-SINAN Influenza-web. The hospital records from 126 hospitals were evaluated, and home interviews were conducted using standardized forms. A total of 48 cases and 185 controls were investigated. Having had a previous health visit to a healthcare provider for an influenza episode before hospital admission was a risk factor for death (adjusted OR (OR adj ) of 7.93, 95% CI 2.19-28.69). Although not significant in the multiple analysis (OR adj of 2.13, 95% CI 0.91-5.00), the 3 rd trimester deserves attention, with an OR = 2.22, 95% CI 1.13-4.37 in the univariate analysis. Antiviral treatment was a protective factor when administered within 48 hours of symptom onset (OR adj = 0.16, 95% CI 0.05-0.50) and from 48 to 72 hours (OR adj = 0.09, 95% CI 0.01-0.87). There was a higher proportion of fetal deaths and preterm births among cases (p = 0.001) and live births with low weight (p = 0.019), compared to control subjects who gave birth during hospitalization. After discharge, control subjects had a favorable neonatal outcome. Early antiviral treatment during the presence of a flu-like illness is an important factor in reducing mortality from influenza in pregnant women and unfavorable neonatal outcomes. It is important to monitor pregnant women, particularly in the 3 rd trimester of gestation, with influenza illness for diagnosis and early treatment.
Output: Author Contributions
Exhaust air heat recovery is of great significance for building energy conservation. Since passive heat recovery systems use temperature or enthalpy difference between outdoor air and indoor air to drive the system, the temperature of fresh air supply cannot meet indoor requirements and the exhaust heat is not fully recovered. In this study, a solar-driven exhaust air thermoelectric heat pump recovery (SDEATHP) system is tested and evaluated for its ability to recover thermal energy from exhaust air to cool or heat fresh air. An experimental platform was established to test its performance. Results show that the SDEATHP system can obtain higher fresh air supply temperature in winter and lower fresh air supply temperature in summer. The system requires only 3.12 W of power for the fans, and the average relative cooling coefficient in summer and the average relative heating coefficient can reach 50.6 and 57.9, respectively. The optimal operating current and voltage of TE modules and photovoltaic system is analyzed, and then the number and types of electrical connections for the TE modules in SDEATHP system are discussed. The SDEATHP system provides a new method for building energy recovery and fresh air supply.
Output: Experimental study and performance analysis of solar-driven exhaust air thermoelectric heat pump recovery system
The outbreak of coronavirus disease 2019 which originated in Wuhan, China, constitutes a public health emergency of international concern with a very high risk of spread and impact at the global level. We developed data-driven susceptible-exposed-infectious-quarantine-recovered (SEIQR) models to simulate the epidemic with the interventions of social distancing and epicenter lockdown. Population migration data combined with officially reported data were used to estimate model parameters, and then calculated the daily exported infected individuals by estimating the daily infected ratio and daily susceptible population size. As of Jan 01, 2020, the estimated initial number of latently infected individuals was 380.1 (95%-CI: 379.8~381.0). With 30 days of substantial social distancing, the reproductive number in Wuhan and Hubei was reduced from 2.2 (95%-CI: 1.4~3.9) to 1.58 (95%-CI: 1.34~2.07), and in other provinces from 2.56 (95%-CI: 2.43~2.63) to 1.65 (95%-CI: 1.56~1.76). We found that earlier intervention of social distancing could significantly limit the epidemic in mainland China. The number of infections could be reduced up to 98.9%, and the number of deaths could be reduced by up to 99.3% as of Feb 23, 2020. However, earlier epicenter lockdown would partially neutralize this favorable effect. Because it would cause in situ deteriorating, which overwhelms the improvement out of the epicenter. To minimize the epidemic size and death, stepwise implementation of social distancing in the epicenter city first, then in the province, and later the whole nation without the epicenter lockdown would be practical and cost-effective.
Output: The impact of social distancing and epicenter lockdown on the COVID-19 epidemic in mainland China: A data-driven SEIQR model study
The spread of infectious disease epidemics is mediated by human travel. Yet human mobility patterns vary substantially between countries and regions. Quantifying the frequency of travel and length of journeys in well-defined population is therefore critical for predicting the likely speed and pattern of spread of emerging infectious diseases, such as a new influenza pandemic. Here we present the results of a large population survey undertaken in 2007 in two areas of China: Shenzhen city in Guangdong province, and Huangshan city in Anhui province. In each area, 10,000 randomly selected individuals were interviewed, and data on regular and occasional journeys collected. Travel behaviour was examined as a function of age, sex, economic status and home location. Women and children were generally found to travel shorter distances than men. Travel patterns in the economically developed Shenzhen region are shown to resemble those in developed and economically advanced middle income countries with a significant fraction of the population commuting over distances in excess of 50 km. Conversely, in the less developed rural region of Anhui, travel was much more local, with very few journeys over 30 km. Travel patterns in both populations were well-fitted by a gravity model with a lognormal kernel function. The results provide the first quantitative information on human travel patterns in modern China, and suggest that a pandemic emerging in a less developed area of rural China might spread geographically sufficiently slowly for containment to be feasible, while spatial spread in the more economically developed areas might be expected to be much more rapid, making containment more difficult.
Output: Travel Patterns in China
This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebocontrolled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.
Output: Treatment of Common Cold Patients with the Shi-Cha Capsule: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalation Trial
Newcastle disease virus (NDV) is a member of the Paramyxovirinae subfamily and can infect most species of birds. It has been a great threat for the poultry industry all around the world. In this report, we successfully produced infectious pseudotyped pNL4-3-Luc-R 2 E 2 (HIV-Luc) viruses with the HN and F envelope proteins of NDV. Further investigation revealed the cytoplasmic domains of HN and F, especially HN, plays a significant role in the infection efficiency of these pseudotyped HIV-Luc viruses. Replacement of, or direct fusion to the cytoplasmic domain of the HN protein by that of vesicular stomatitis virus G (VSV-G) could greatly enhance or destroy the infective potential of HN and F-pseudotyped (NDVpseudotyped) HIV-Luc virus. We further established a novel neutralization assay to evaluate neutralizing antibodies against NDV with the NDV-pseudotyped HIV-Luc viruses. Comparative neutralization data indicate that the results determined by using the NDV-pseudotyped HIV-Luc viruses are as reliable as those by the conventional virus-neutralization assay (VN test) with native NDV. Moreover, the results show that the novel neutralization assay is more sensitive than the VN test.
Output: Package of NDV-Pseudotyped HIV-Luc Virus and Its Application in the Neutralization Assay for NDV Infection
Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse models: db/db mice and angiotensin II-infused mice. A disintegrin and metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane. The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in pancreatic islets and ␤-cells. Dynamics of ADAM17-mediated ACE2 shedding were investigated in 832/13 insulinoma cells. Within a wide range of ACE2 expression levels, including the level observed in mouse pancreatic islets, overexpression of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels. We provide a mathematical description of shed and cellular ACE2 activities as a function of the ADAM17 activity. The effect of ADAM17 on the cellular ACE2 content was relatively modest with an absolute control strength value less than 0.25 and approaching 0 at low ADAM17 activities. Although we found that ADAM17 and ACE2 are both expressed in pancreatic islets, the ␤-cell is not the major cell type expressing ACE2 in islets. During diabetes progression in 8-, 12-, and 15-week-old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not decreased over time nor significantly decreased compared with nondiabetic db/m mice. Levels of ADAM17 mRNA and ADAM17 activity were also not significantly changed. Inhibiting basal ADAM17 activity in mouse islets failed to affect ACE2 levels. We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does not deplete ACE2 from pancreatic islets in diabetic db/db mice. (Endocrinology 156: 4411-4425, 2015 ) Endocrinology, December 2015, 156(12):4411-4425 press.endocrine.org/journal/endo 4411 Pedersen et al ACE2 and ADAM17 in Pancreatic Islets Endocrinology, December 2015, 156(12):4411-4425 Pedersen et al ACE2 and ADAM17 in Pancreatic Islets Endocrinology, December 2015, 156(12):4411-4425 Pedersen et al ACE2 and ADAM17 in Pancreatic Islets Endocrinology, December 2015, 156(12):4411-4425 Pedersen et al ACE2 and ADAM17 in Pancreatic Islets Endocrinology, December 2015, 156(12):4411-4425
Output: Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice
Viral diseases are a major cause of morbidity and mortality and result in a significant public health burden. T lymphocytes first identified in the chordate lineage and constitute a highly sophisticated branch of adaptive immune system. Apart from B cells, it is the only cell type that exhibits antigenic specificities; achieved by gene rearrangement. T cells are unique with respect to diversity of their subsets, which have distinct effector specificities, proliferative abilities, memory generation, and life span. T cells are impactful in viral infections by virtue of their capability to combat intracellular pathogens. The effector functions of T cells are mediated through cytokines/chemokines and by direct cytotoxicity of infected cells. T cell response can be beneficial or detrimental to host; prognosis depending on qualitative and quantitative differences in the response. Persistent viral infections are associated with functionally suboptimal, exhausted T cell responses, which are unable to clear virus. Specific subsets such as regulatory T cells (Tregs) dampen antiviral responses; thereby favouring viral persistence. However, Tregs protect the host from immunopathology by limiting perpetual inflammation. Certain other subsets such as Th17 cells may contribute to autoimmune component of viral infections. The importance of T cells is highlighted by the fact that modern vaccination and therapeutic approaches focus on modulating T cell frequencies and effector functions. This chapter emphasises the understanding how T cells influence outcomes of viral infections, modern vaccination and therapeutic strategies with thrust on T cell biology. Achanta Jagadeesh, A. M. V. N. Prathyusha, G. Mohana Sheela and Pallaval Veera Bramhachari contributed equally with all other contributors. 140 Adaptive immune system · T cell responses · Viral infections · Therapeutic strategies 9.1
Output: 9 T Cells in Viral Infections: The Myriad Flavours of Antiviral Immunity
containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease. Keywords: germanium biotite, immune enhancement, porcine reproductive and respiratory syndrome virus 136 Bock-Gie Jung et al.
Output: Veterinary Science pISSN 1229-845X, eISSN 1976-555X
Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (−)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.
Output: molecules Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies