niryuu/sni-each-converted huggingface dataset:
Background: Nonspecific interstitial pneumonia (NSIP) is characterized by interstitial infiltration of T lymphocytes, and subpopulations of these cells may be associated with the progression of fibrosis. However, few studies evaluate the correlation of prognosis with this characteristic. Therefore, we performed morphological and quantitative analyses of T lymphocytes in patients with NSIP and evaluated the relationship between T lymphocytes and prognosis. Methods: Immunohistochemistry was used to detect the presence of CD4+ and CD8+ T lymphocytes in 55 biopsies of patients with NSIP to determine the numbers of these T cell subpopulations in lymphoid follicles as well as in perivascular, interstitial, and peribronchial anatomical compartments. The relationship between CD4+ and CD8+ T lymphocyte populations and prognosis was analyzed. Results: The mean age of 55 patients was 48.9 ± 10.5 years, and 36 (65 %) of patients were women. All patients were followed for a mean duration of 46 ± 25 months. Thirteen (23.6 %) patients died during follow-up. Perivascular CD4+ lymphocyte infiltration (HR, 0.939; 95 % CI, 0.883-0.999; p = 0.048) was an independent risk factor for survival. Perivascular infiltrates of CD4+ T lymphocytes correlated with survival time (r = 0.270, p = 0.046). Patients with improved forced vital capacity survived longer and had higher numbers of CD4+ T lymphocytes that infiltrated perivascular tissue. The densities of CD4+ and CD8+ T lymphocytes infiltrating other tissues were not significantly associated with survival time. Conclusions: Perivascular infiltration of CD4+ T lymphocytes in patients with NSIP correlated with prognosis. The underlying mechanisms are unknown and require further studies.
Output: Prognosis of nonspecific interstitial pneumonia correlates with perivascular CD4+ T lymphocyte infiltration of the lung
The envelope attachment glycoprotein (G) and fusion protein (F′) of Nipah virus (NiV) play a key role in viral entry and induction of neutralization antibody. In this study, recombinant baculoviruses, rBac-NF and rBac-NG, were generated to express F and G proteins of NiV. The expressions of recombinant G (rNG) and F (rNF) proteins in rBac-NF and rBac-NG-infected cells were confirmed by Western blot. Both rNG and rNF showed sensitive and specific antigenic reaction to rabbit serum anti-Nipah virus in indirect immunofluorescence detection and indirect ELISA. Immunization with rBac-NF and rBac-NG-infected insect cells elicited G and F protein-specific antibody responses in mice. Furthermore, the G and F protein-specific antibodies could neutralize the infectivity of the VSVΔG*F/G, the NiV F and G envelope glycoproteins of pseudotype recombinant Vesicular Stomatitis Virus expressing green fluorescence protein. The results demonstrated that the F and G proteins expressed by the recombinant baculoviruses could be safe diagnostic antigens for the surveillance and monitoring of NiV and could also be promising subunit vaccines for the prevention of NiV.
Output: Study of Fusion Protein and Attachment Glycoprotein of Nipah Virus Expressed in Recombinant Baculovirus
Background Although amoxicillin-clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis. We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1-19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin-clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897). Findings We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin-clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin-clavulanate group. The risk difference showed noninferiority (-0·3%, 95% CI -11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin-clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14 days [8-16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin-clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5). Interpretation By 21 days of treatment, azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance.
Output: Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial
The dynamics of H5N1 influenza virus pathogenesis are multifaceted and can be seen as an emergent property that cannot be comprehended without looking at the system as a whole. In past years, most of the high-throughput studies on H5N1-host interactions have focused on the host transcriptomic response, at the cellular or the lung tissue level. These studies pointed out that the dynamics and magnitude of the innate immune response and immune cell infiltration is critical to H5N1 pathogenesis. However, viral-host interactions are multidimensional and advances in technologies are creating new possibilities to systematically measure additional levels of 'omic data (e.g. proteomic, metabolomic, and RNA profiling) at each temporal and spatial scale (from the single cell to the organism) of the host response. Natural host genetic variation represents another dimension of the host response that determines pathogenesis. Systems biology models of H5N1 disease aim at understanding and predicting pathogenesis through integration of these different dimensions by using intensive computational modeling. In this review, we describe the importance of 'omic studies for providing a more comprehensive view of infection and mathematical models that are being developed to integrate these data. This review provides a roadmap for what needs to be done in the future and what computational strategies should be used to build a global model of H5N1 pathogenesis. It is time for systems biology of H5N1 pathogenesis to take center stage as the field moves towards a more comprehensive view of virushost interactions.
Output: MOVING H5N1 STUDIES INTO THE ERA OF SYSTEMS BIOLOGY
Apart from the core (21 kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the À2/+1 reading frame. To date, no information is available on F1 protein of Indian isolates, and hence detection of antibodies for F1 protein in Indian patients assumes great relevance. Specific primers have been designed to amplify sequence coding for 120aa of truncated F1 (tF1). The amplified tF1 has been cloned in bacterial expression vector, pET21b for expression in Escherichia coli. Partially purified expressed protein has been subjected to western blot analysis using patients' sera. Three HCV positive sera employed in western analysis showed positive signals to tF1, while sera from uninfected individuals failed to give any signals. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Presence of antibodies against F1 protein of subtype 1c has been demonstrated, for the first time, in Indian patients. #
Output: Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients
This article presents experimental results that illustrate the unsteady characteristics of gas dispersion around a complex-shaped high-rise building for different incident wind directions. A series of wind tunnel experiments were conducted using a 1:30 scale model that represented the real structures under study. The objective of this paper is to study the behaviour of concentration fluctuations through transient analysis. Tracer gas was continuously released from a point source located at different positions, and a time series of fluctuating concentrations were recorded at a large number of points using fast flame ionization detectors. The experimental data were analysed to provide a comprehensive data set including variances and associated statistical quantities. Both the unsteady characteristics of the system and their potential practical impact are presented and discussed. Under crowd living conditions, the air pollutant exhausted from one household could probably re-enter into the neighbouring households, traveling with ambient airflow. Such pollutant dispersion process is defined as air cross-contamination in this study. The results indicate that the wind-induced cross-contamination around the studied type of high-rise building should not be overlooked, and the fluctuating concentrations should be paid attention to particularly during the evaluation of a potential contamination risk. This study can help deepen our understanding of the mechanisms of air cross-contamination, and will be useful for implementing optimization strategies to improve the built environments in metropolitan cities such as Hong Kong.
Output: Analysis of concentration fluctuations in gas dispersion around high-rise building for different incident wind directions
Very limited evidence has been reported on host T cell responses to the pandemic H1N1 swine-origin influenza A virus (S-OIV) infection in humans. Therefore, we investigated the proportions of peripheral T cell subsets and analyzed the relationship of T helper subset changes with T cell activation during this infection. We found that these S-OIV-infected patients exhibited rapid lymphopenia, T cell activation and preferential loss of Th17 subset at the early stage of acute infection. Statistical analysis indicated that CD4 depletion and loss of Th17 cells, rather than Th1 or Treg cells, were correlated with CD4 T cell activation. More importantly, upregulated IFN-α likely contributed to the functional loss of Th17 cells. Thus, rapidly generalized lymphopenia, preferential loss of Th17 population and T cell activation presented as characteristics of the early immune response in S-OIV-infected patients. These findings, therefore, may be helpful for an earlier diagnosis and further studies of immune pathogenesis of S-OIV infection.
Output: Preferential loss of Th17 cells is associated with CD4 T cell activation in patients with 2009 pandemic H1N1 swine-origin influenza A infection
. MOG 35-55 -specific T cell responses in J␣18 Ϫ/Ϫ mice treated with CEACAM1-Fc fusion protein or with AgB10. J␣18 Ϫ/Ϫ mice were treated with CEACAM1-Fc fusion protein (A) or AgB10 (B) twice per week from the day of immunization with MOG 35-55. Eleven days after the immunization, draining lymph node cells were incubated with MOG 35-55. Supernatants were collected from the culture and measured for the concentration of IFN-␥ and IL-17 by ELISA. Data represent the mean Ϯ SEM of samples from one of two independent experiments (n ϭ 3 mice).
Output: Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Modulates Experimental Autoimmune Encephalomyelitis via an iNKT Cell-Dependent Mechanism
Background: Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population. A hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted. Results: One polymorphism in the 3'-untranslated region (3'-UTR) of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95% CI) of 0.42 (0.20~0.89) and 0.30 (0.09~0.97), respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR = 3.06, 95% CI: 1.25~7.50). The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14~0.98 and OR = 3.22, 95% CI: 1.13~9.18, respectively). Conclusion: SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.
Output: BMC Infectious Diseases Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study
High ventilation rate is shown to be effective for reducing cross-infection risk of airborne diseases in hospitals and isolation rooms. Natural ventilation can deliver much higher ventilation rate than mechanical ventilation in an energy-efficient manner. This paper reports a field measurement of naturally ventilated hospital wards in Hong Kong and presents a possibility of using natural ventilation for infection control in hospital wards. Our measurements showed that natural ventilation could achieve high ventilation rates especially when both the windows and the doors were open in a ward. The highest ventilation rate recorded in our study was 69.0 ACH. The airflow pattern and the airflow direction were found to be unstable in some measurements with large openings. Mechanical fans were installed in a ward window to create a negative pressure difference. Measurements showed that the negative pressure difference was negligible with large openings but the overall airflow was controlled in the expected direction. When all the openings were closed and the exhaust fans were turned on, a reasonable negative pressure was created although the air temperature was uncontrolled. The high ventilation rate provided by natural ventilation can reduce cross-infection of airborne diseases, and thus it is recommended for consideration of use in appropriate hospital wards for infection control. Our results also demonstrated a possibility of converting an existing ward using natural ventilation to a temporary isolation room through installing mechanical exhaust fans.
Output: Natural ventilation for reducing airborne infection in hospitals
The primary objective of this randomized controlled challenge study was to investigate the effect of ampicillin on ultrasonographic (US) lung consolidation after experimental challenge with Pasteurella multocida in preweaned dairy calves. The secondary objectives were to determine whether ampicillin affected respiratory score, gross consolidation, or the detection of P. multocida in lung tissue at postmortem exam (PME). Holstein bull calves (n = 39) were transported to the University of Wisconsin-Madison School of Veterinary Medicine isolation facility at the mean (±SD) age of 52 ± 6 d. After a 7-d acclimation period, 30 calves were inoculated intratracheally with 10 10 cfu of ampicillinsensitive P. multocida. Lung US and respiratory scoring were performed 2, 6, 12, and 24 h post-challenge, then US once daily and respiratory scoring twice daily until d 14. Calves were randomized to receive ampicillin [n = 17, treatment (TX), 6.6 mg/kg i.m. once daily for 3 d] or placebo [n = 11, control (CON), saline, equal volume, i.m. once daily for 3 d] when ≥1 cm 2 of lung consolidation was observed and ≥6 h had elapsed since challenge. Lung lesions ≥1 cm 2 were considered positive for consolidation. Calves were respiratory score positive if ≥2 in 2 or more categories based on the Wisconsin respiratory health score chart. Area under the curve (AUC) was calculated for US score and respiratory score as a proxy for time with consolidation and clinical respiratory disease, respectively. Gross lung lesions and pathogens were quantified following PME. At the time of first treatment, consolidation had developed in 28/30 calves (TX, n = 17; CON, n = 11) and 6% (1 out of 17) of TX and 9% (1 out of 11) of CON calves had a positive respiratory score. The TX calves had a significantly lower median (interquartile range given in parentheses) AUC for US score [TX: 23 (20, 29), CON: 47 (33, 53)], whereas mean AUC for respiratory score was not different between groups (TX: 93 ± 28, CON: 96 ± 17). On d 14, 70% (12 out of 17) of TX and 100% (11 out of 11) of CON calves had lung consolidation, and 24% (4 out of 17) of TX and 27% (3 out of 11) of CON calves had clinical respiratory disease. On PME, median consolidation was 10% (6, 15) for TX and 10% (2, 28) for CON calves. Lung cultures were positive for P. multocida in 77% (13 out of 17) of TX and 91% (10 out of 11) of CON calves. Lung health benefited from a 3-d ampicillin therapy, but benefits were short-lived. Treatment failures might be due to incomplete resolution of the initial lung infection. Future studies are needed to optimize TX strategies to improve long-term lung health.
Output: Effect of antibiotic treatment in preweaned Holstein calves after experimental bacterial challenge with Pasteurella multocida
There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.
Output: Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus
ECP (eosinophil cationic protein) is a major component of eosinophil granule proteins, and is used as a clinical biomarker for asthma and allergic inflammatory disease. ECP has been implicated in damage to the cell membrane of many tissue types, but the mechanism is not well known. In the present study, mECP-eGFP-6H, a recombinant fusion protein containing mature ECP (mECP), enhanced green fluorescence protein (eGFP) and a His 6 tag (6H), has been expressed, purified and added to GH3 neuroendocrine cells to study the internalization ability of ECP. We found that mECP-eGFP-6H entered into GH3 neuroendocrine cells and inhibited the growth of the cells with an IC 50 of 0.8 µM. By yeast two-hybrid screening and immunoprecipitation, we have identified a specific protein-protein interaction between mECP and CPE (carboxypeptidase E), a well characterized metal-loprotease. Further in vivo yeast two-hybrid screening has also revealed that residues 318-387 located in a region of unknown function in mature CPE are indispensable for association with mECP. In addition, the uptake of mECP-eGFP-6H is suppressed by dominant-negative expression of the recycling defect mutant pre-pro-HA-CPE S471A,E472A in GH3 cells, suggesting that the entry of mECP-eGFP-6H is associated with the recycling of CPE in GH3 cells. Taken together, we have demonstrated that CPE possesses a novel function to facilitate the entry of ECP to neuroendocrine cells, and such an endocytotic process allows the cytotoxic ECP to inhibit growth of the target cells.
Output: Membrane-bound carboxypeptidase E facilitates the entry of eosinophil cationic protein into neuroendocrine cells
The viral dissemination in a patient with avian influenza A subtype H5N1 infection was retrospectively studied by the immunohistochemical localization of viral nucleoprotein antigen. The pathology was marked by diffuse alveolar damage, lymphoid depletion, and reactive hemophagocytic syndrome. Besides the lung and the upper respiratory tract, viral antigen was detected in the small and large intestinal epithelial cells, hematopoietic cells in the bone marrow, glial cells and neurons of the brain, and lymphocytes. The results confirmed that H5N1 virus disseminated to multiple organs beyond the respiratory system. However, specific pathological changes were noted in the respiratory system only, and productive viral replication confirmed by culture was noted only in the lung. More postmortem studies are needed to elucidate the pathogenesis of this highly fatal zoonotic disease.
Output: Systemic infection of avian influenza A virus H5N1 subtype in humans ☆
Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model.
Output: A study of the virulence in mice of high copying fidelity variants of human enterovirus 71
To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G 1 phase. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into S phase, failed to normalize virus production. Infection by influenza A virus triggered redistribution of cyclin D3 from the nucleus to the cytoplasm, followed by its proteasomal degradation. When overexpressed in HEK 293T cells, cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection.
Output: Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection
Research has shown that obesity appears to spread through social ties. However, the association between other characteristics of social networks and obesity is unclear. This study aimed to identify the association between social network characteristics and body mass index (BMI, kg/m 2 ) in an elderly Korean population. : This cross-sectional study analyzed data from 657 Koreans (273 men, 384 women) aged 60 years or older who participated in the Korean Social Life, Health, and Aging Project. Network size is a count of the number of friends. Density of communication network is the number of connections in the social network reported as a fraction of the total links possible in the personal (ego-centric) network. Average frequency of communication (or meeting) measures how often network members communicate (or meet) each other. The association of each social network measure with BMI was investigated by multiple linear regression analysis. Results: After adjusting for potential confounders, the men with lower density (<0.71) and higher network size (4-6) had the higher BMI (β=1.089, p=0.037) compared to the men with higher density (>0.83) and lower size (1-2), but not in the women (p=0.393). The lowest tertile of communication frequency was associated with higher BMI in the women (β=0.885, p=0.049), but not in the men (p=0.140). Our study suggests that social network structure (network size and density) and activation (communication frequency and meeting frequency) are associated with obesity among the elderly. There may also be gender differences in this association.
Output: Social Network Characteristics and Body Mass Index in an Elderly Korean Population
Avipoxviruses are divided into three clades: canarypox-like viruses, fowlpox-like viruses, and psittacinepox-like viruses. Several molecular clock and demographic models available in the BEAST package were compared on three avipoxvirus genes (P4b, cnpv186 and DNA polymerase genes), which enabled to determine that avipoxviruses evolved at a rate of 2-8 Â 10 À5 substitution/site/year, in the range of poxviruses previously reported evolution rates. In addition, the date of mean time of divergence of avipoxviruses from a common ancestor was extrapolated to be about 10,000-30,000 years ago, at the same period as modern poxvirus species. Our findings will facilitate epidemiological investigations on avipoxviruses' spread, origin and circulation.
Output: Time scale evolution of avipoxviruses-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Elucidating antiviral CD8 T lymphocyte responses to SARS-CoV-2 may shed light on the heterogeneity of clinical outcomes and inform vaccine or therapeutic approaches. To facilitate the evaluation of antiviral CD8 T cell responses to SARS-CoV-2, we generated a publicly accessible database of epitopes predicted to bind any class I HLA protein across the entire SARS-CoV-2 proteome. While a subset of epitopes from earlier betacoronaviruses, such as SARS-CoV (SARS), have been validated experimentally, validation systems are often biased toward specific HLA haplotypes (notably HLA-A*02:01) that only account for a fraction of the haplotypes of individuals affected by the SARS-CoV-2 pandemic. To enable evaluation of epitopes across individuals with a variety of HLA haplotypes, we computed the predicted binding affinities between 9-mer peptides derived from the annotated SARS-CoV-2 peptidome across 9,360 MHC class I HLA-A, -B, and -C alleles. There were 6,748 unique combinations of peptides and HLA alleles (pMHCs) with a predicted binding affinity of less than 500nM, including 1,103 unique peptides and 1,022 HLA alleles, spanning 11 annotated superfamilies. These peptides were derived from all 11 proteins spanning the SARS-CoV-2 peptidome, including peptides that have previously been validated experimentally. We also show evidence that these previously
Output: Prediction of SARS-CoV-2 epitopes across 9360 HLA class I alleles
The conditions of a rapid, indirect-enzyme linked immunosorbent assay for Infectious Bronchitis Virus (IBV) antibodies have been established. Optimal sensitivity was obtained using 10 ~g/ml protein concentration of the Mass 41 strain purified from infected allantoic fluid. Specificity was demonstrated with Newcastle Disease Virus (NDV) antigen-antibody system. Negligible crossreactions were observed. After bromelain or lipase treatment IBV had an ELISA reactivity similar to untreated particles suggesting that peripheral constituents of IBV play a minor role when whole virus is adsorbed on solid phase. The method offers a simple and specific antibody assay which could be used for the laboratory diagnosis of avian infectious bronchitis,
Output: Archives of Virology Antigen Requirements and Specificity of a Mieroplate Enzyme-Linked Immunosorbent Assay (ELISA) for Deteetin 9 Infectious Bronchitis Viral Antibodies in Ehieken Serum
Immunomodulation of natural polysaccharides has been the hot topic of research in recent years. In order to explore the immunomodulatory effect of Houttuynia cordata Thunb., the water extract was studied and a polysaccharide HCP-2 with molecular weight of 60,000 Da was isolated by chromatography using DEAE Sepharose CL-6B and Sephacryl S-400 HR columns. The structure characterization of HCP-2 was performed by Fourier transform infrared spectroscopy (FTIR), acidic hydrolysis, PMP derivation, HPLC analysis and nuclear magnetic resonance spectra (NMR). HCP-2 was elucidated as a pectic polysaccharide with a linear chain of 1,4-linked ␣-d-galacturonic acid residues in which part of the 6-carboxyl groups were methyl esterified and part of 2-hydroxyl groups were acetylated. The bioactivity assays showed that HCP-2 could increase the secretions of interleukin-1␤ (IL-1␤), tumor necrosis factor-␣ (TNF-␣), macrophage inhibitory protein-1␣ (MIP-1␣), macrophage inhibitory protein-1␤ (MIP-1␤), and RANTES (regulated on activation, normal T cell expressed and secreted) in human peripheral blood mononuclear cells (PBMCs), which play critical roles in the innate immune system and shape the adaptive immunity. Our results implied that HCP-2 could be an immune enhancer.
Output: Structural characterization and immunomodulatory effect of a polysaccharide HCP-2 from Houttuynia cordata
Any infectious diseases have been reported in sub-Saharan countries over the past decade due to the inefficiency of health structures to anticipate outbreaks. In a poorly-infrastructure country such as the Democratic Republic of Congo (DRC), with inadequate health staff and laboratories, it is difficult to respond rapidly to an epidemic, especially in rural areas. As the DRC's health system has three levels (peripheral, regional and national), from the production of health data at the peripheral level to the national level that makes the decision, meantime the disease can spread to many people. Lack of communication between health centres of the same health zone and Health zones of the same Health Provincial Division does not contribute to the regional response. This article, an extended version of [1], proposes a well elaborated solution track to deal with this problem by using an agent-centric approach to study by simulation how to improve the process. A new experiment is described by arranging twentyeight health zones of Kinshasa to show how their collaboration can provide unique health data source for all stakeholders and help reducing disease propagation. It concerns also 47 health centres, 1 medical laboratory, 1 Provincial Health Division and 4 Rapid Riposte Teams. The simulation data, provided by Provincial Health Division of Kinshasa, concerned cholera outbreak from January to December 2017. The interaction between these agents demonstrated that Health Zone Agent can automatically alert his neighbours whenever he encountered a confirmed case of an outbreak. This action can reduce disease propagation as population will be provided with prevention measures. These interactions between agents have provided models to propose to the current system in order to find out the best that can help reducing decision time. Access to health care is a major concern in developing countries. The Democratic Republic of Congo ranks among the poorest countries according to its HDI 1 [2]. Despite its millions of hectares of arable land, this vast country of Central Africa is 1 Human Development Index.
Output: A Multiagent-Based Model for Epidemic Disease Monitoring in DR Congo
As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2α in A549 cells were detected; the levels of IFNβ, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication in vitro, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.
Output: Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT- dependent suppression of viral RNA replication
Recombination in the family Coronaviridae has been well documented and is thought to be a contributing factor in the emergence and evolution of different coronaviral genotypes as well as different species of coronavirus. However, there are limited data available on the frequency and extent of recombination in coronaviruses in nature and particularly for the avian gamma-coronaviruses where only recently the emergence of a turkey coronavirus has been attributed solely to recombination. In this study, the full-length genomes of eight avian gamma-coronavirus infectious bronchitis virus (IBV) isolates were sequenced and along with other full-length IBV genomes available from GenBank were analyzed for recombination. Evidence of recombination was found in every sequence analyzed and was distributed throughout the entire genome. Areas that have the highest occurrence of recombination are located in regions of the genome that code for nonstructural proteins 2, 3 and 16, and the structural spike glycoprotein. The extent of the recombination observed, suggests that this may be one of the principal mechanisms for generating genetic and antigenic diversity within IBV. These data indicate that reticulate evolutionary change due to recombination in IBV, likely plays a major role in the origin and adaptation of the virus leading to new genetic types and strains of the virus.
Output: Recombination in Avian Gamma-Coronavirus Infectious Bronchitis Virus
The COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. We collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level.
Output: Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study
For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, 0vR 0 v1 and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring R 0 and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer R 0 , but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, k) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both R 0 and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for R 0 is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in R 0 is detectable. In addition, by allowing for superspreading events, inference of k shifts the threshold above which a transmission chain should be considered anomalously large for a given value of R 0 (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.
Output: Inference of R 0 and Transmission Heterogeneity from the Size Distribution of Stuttering Chains
Background: Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. Objective: We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. Methods: We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. Results: Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were viruspositive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF 25%-75% ), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. Conclusion: Urban children with asthma with high-symptom respiratory viral infections have reduced FEF 25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virusnegative illnesses.
Output: Impact of community respiratory viral infections in urban children with asthma
The filoviruses Ebolavirus and Marburgvirus are among the deadliest viral pathogens known to infect humans, causing emerging diseases with fatality rates of up to 90% during some outbreaks. The replication cycles of these viruses are comprised of numerous complex molecular processes and interactions with their human host, with one key feature being the means by which nascent virions exit host cells to spread to new cells and ultimately to a new host. This review focuses on our current knowledge of filovirus egress and the viral and host factors and processes that are involved. Within the virus, these factors consist of the major matrix protein, viral protein 40 (VP40), which is necessary and sufficient for viral particle release, and nucleocapsid and glycoprotein that interact with VP40 to promote egress. In the host cell, some proteins are hijacked by filoviruses in order to enhance virion budding capacity that include members of the family of E3 ubiquitin ligase and the endosomal sorting complexes required for transport (ESCRT) pathway, while others such as tetherin inhibit viral egress. An understanding of these molecular interactions that modulate viral particle egress provides an important opportunity to identify new targets for the development of antivirals to prevent and treat filovirus infections.
Output: viruses Host and Viral Proteins Modulating Ebola and Marburg Virus Egress
The affinity of a panel of neutralizing monoclonal IgGs and their Fab fragments has been measured for the first time with an enveloped type A influenza virus, by surface plasmon resonance (SPR) and the BIAlite'" instrument. Equilibrium constants could be calculated for four of the five mAbs tested. These were in the nanomolar range. The ranking order was very similar to that obtained with an affinity ELISA, (an equilibrium system) but as others have found, affinities were 2-lo-fold lower as measured by SPR (a flow system). No data were obtained with mAb HC58 although it had one of the highest affinities using an ELISA format, and was 2%fold higher than another mAb (HCIO) which gave good data by SPR. This may relate to the orientation of its binding on the virion surface. The K d,J ,<I' of the Fabs was only 3-lo-fold higher compared to their IgGs. Fab from the lowest affinity IgG (HClO) could not be measured, possibly because it fell below the threshold for detection.
Output: Determination of affinities of a panel whole enveloped (influenza A) virions resonance of IgGs and Fabs for using surface plasmon
Background: Human rhinoviruses (HRVs) are a well-recognized cause of long-term care home (LTCH) outbreaks of respiratory illness. However, there are limited data on the molecular epidemiology of the HRV types involved. Objectives: To determine whether a large respiratory outbreak in a LTCH was caused by a single type of HRV, and to describe the clinical impact of the outbreak. Study design: Nasopharyngeal swabs were collected from residents with one or more of the following: fever, cough, rhinitis, or congestion. Specimens were interrogated by multiplex PCR using the ResPlex II assay. Samples positive for HRV were then submitted for genotyping by partial sequence analysis of the 5 untranslated (UTR) and viral protein (VP) 1 capsid regions. Results: Of 71 screened, 56 residents were positive for a HRV during an outbreak that lasted 5.5 weeks; 27 healthcare workers also had respiratory symptoms. Three residents were transferred to hospital and 2 died. Seven units in two wings of the LTCH were affected, resulting in 3152.5 resident unit closure days. Three different HRV genotypes were identified, although HRV-A1 dominated. Conclusions: This large outbreak of HRVs among residents and healthcare workers in a LTCH was associated with substantial resident and staff morbidity as well as significant unit closures. Multiple types of HRV were implicated but an HRV-A1 type dominated, warranting further investigation into viral determinants for virulence and transmission.
Output: Co-circulation of multiple genotypes of human rhinovirus during a large outbreak of respiratory illness in a veterans' long-term care home
Background Ethnic minorities in Europe such as the Chinese may need a special strategy with regard to risk communication about emerging infectious diseases. To engage them in precautionary actions, it is important to know their information sources, knowledge, and health beliefs. Purpose This study's purpose is to study the use of information sources, knowledge, and health beliefs related to SARS and avian flu of Chinese people in the UK and The Netherlands, and to make comparisons with the general population in these countries. Method Results of a self-administered questionnaire among 300 British/Dutch Chinese were compared to data obtained from a computer-assisted phone survey among the general population (n=800). Results British/Dutch Chinese got most information about emerging diseases from family and friends, followed by Chinese media and British/Dutch TV. They had less confidence than general groups in their doctor, government agencies, and consumer/patient interest groups. Their knowledge of SARS was high. They had a lower perceived threat than general populations with regard to SARS and avian flu due to a lower perceived severity. They had higher selfefficacy beliefs regarding SARS and avian flu. Conclusion In case of new outbreaks of SARS/avian flu in China, local authorities in the UK and The Netherlands can best reach Chinese people through informal networks and British/Dutch TV, while trying to improve confidence in information from the government. In communications, the severity of the disease rather than the susceptibility appears to need most attention.
Output: Sources of Information and Health Beliefs Related to SARS and Avian Influenza among Chinese Communities in the United Kingdom and The Netherlands, Compared to the General Population in these Countries