niryuu/sni-each-converted huggingface dataset:
Background: Mathematical and statistical models are used to project the future time course of infectious disease epidemics and the expected future burden on health care systems and economies. Influenza is a particularly important disease in this context because it causes annual epidemics and occasional pandemics. In order to forecast health care utilization during epidemics-and the effects of hospitalizations and deaths on the contact network and, in turn, on transmission dynamics-modellers must make assumptions about the lengths of time between infection, visiting a physician, being admitted to hospital, leaving hospital, and death. More reliable forecasts could be be made if the distributions of times between these types of events ("delay distributions") were known. Methods: We estimated delay distributions in the province of Ontario, Canada, between 2006 and 2010. To do so, we used encrypted health insurance numbers to link 1.34 billion health care billing records to 4.27 million hospital inpatient stays. Because the four year period we studied included three typical influenza seasons and the 2009 influenza pandemic, we were able to compare the delay distributions in non-pandemic and pandemic settings. We also estimated conditional probabilities such as the probability of hospitalization within the year if diagnosed with influenza. Results: In non-pandemic [pandemic] years, delay distribution medians (inter-quartile ranges) were: Service to Admission 6.3 days (0.1-17.6 days) [2.4 days (-0.3-13.6 days)], Admission to Discharge 3 days (1.4-5.9 days) [2.6 days (1.2-5.1 days)], Admission to Death 5.3 days (2.1-11 days) [6 days (2.6-13.1 days)]. (Service date is defined as the date, within the year, of the first health care billing that included a diagnostic code for influenza-like-illness.) Among individuals diagnosed with either pneumonia or influenza in a given year, 19% [16%] were hospitalized within the year and 3% [2%] died in hospital. Among all individuals who were hospitalized, 10% [12%] were diagnosed with pneumonia or influenza during the year and 5% [5%] died in hospital. Conclusion: Our empirical delay distributions and conditional probabilities should help facilitate more accurate forecasts in the future, including improved predictions of hospital bed demands during influenza outbreaks, and the expected effects of hospitalizations on epidemic dynamics.
Output: Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada
The field of viral molecular biology has reached a precipice for which pioneering studies on the structure of viral RNAs are beginning to bridge the gap. It has become clear that viral genomic RNAs are not simply carriers of hereditary information, but rather are active players in many critical stages during replication. Indeed, functions such as cap-independent translation initiation mechanisms are, in some cases, primarily driven by RNA structural determinants. Other stages including reverse transcription initiation in retroviruses, nuclear export and viral packaging are specifically dependent on the proper 3-dimensional folding of multiple RNA domains to recruit necessary viral and host factors required for activity. Furthermore, a large-scale conformational change within the 5 -untranslated region of HIV-1 has been proposed to regulate the temporal switch between viral protein synthesis and packaging. These RNA-dependent functions are necessary for replication of many human disease-causing viruses such as severe acute respiratory syndrome (SARS)-associated coronavirus, West Nile virus, and HIV-1. The potential for antiviral development is currently hindered by a poor understanding of RNA-driven molecular mechanisms, resulting from a lack of structural information on large RNAs and ribonucleoprotein complexes. Herein, we describe the recent progress that has been made on characterizing these large RNAs and provide brief descriptions of the techniques that will be at the forefront of future advances. Ongoing and future work will contribute to a more complete understanding of the lifecycles of retroviruses and RNA viruses and potentially lead to novel antiviral strategies.
Output: Progress and outlook in structural biology of large viral RNAs
The ecological success of social insects is based on division of labour, not only between queens 20 and workers, but also among workers. Whether a worker tends the brood or forages is strongly 21 influenced by age, fertility and nutritional status, with brood carers being younger, more fecund 22 and corpulent. Here, we experimentally disentangle behaviour from age and fertility 23 in Temnothorax longispinosus ant workers and analyse how these parameters are linked to 24 whole-body gene expression. Our transcriptome analysis reveals four times more genes 25 associated with behaviour than with age and only few fertility-associated genes. Brood carers 26 exhibited an upregulation of genes involved in lipid biosynthesis, whereas foragers invested in 27 metabolism. Additional simulations revealed that the experimental disassociation of co-varying 28 factors reduces transcriptomic noise, potentially explaining discrepancies between 29 transcriptomic studies on worker behaviour in other social insects. Our study highlights the 30 influence of nutritional status on task choice in ant workers. 31 32 33 34 35 36 author/funder. All rights reserved. No reuse allowed without permission.
Output: Gene expression is stronger associated with behaviour than 1 with age and fertility in ant workers 2
C Springer Science+Business Media, LLC 2011 Johnston SL, Martin RJ (2005) Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma pathogenesis? Am J Respir Crit Care Med 172:1078-1089 Kazor CE, Mitchell PM, Lee AM, Stokes LN, Loesche WJ, Dewhirst FE, Paster BJ (2003) Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients. J Clin Microbiol 41:558-563 Keatings VM, Collins PD, Scott DM, Barnes PJ (1996) Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 153:530-534 Kirby AC, Coles MC, Kaye PM (2009) Alveolar macrophages transport pathogens to lung draining lymph nodes. J Immunol 183:1983 Kistler A, Avila PC, Rouskin S et al (2007) Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity. J Infect Dis 196:817-825 Knowles MR, Durie PR (2002) What is cystic fibrosis? N Engl J Med 347:439-442 Kobashi Y, Fukuda M, Yoshida K, Miyashita N, Niki Y, Oka M (2006) Chronic necrotizing pulmonary aspergillosis as a complication of pulmonary Mycobacterium avium complex disease. Respirology 11:809-813 Korting HC, Lukacs A, Braun-Falco O (1988) Microbial flora and odor of the healthy human skin. Hautarzt 39:564-568 Koziel H, Kim S, Reardon C, Li X, Garland R, Pinkston P, Kornfeld H (1999) Enhanced in vivo human immunodeficiency virus-1 replication in the lungs of human immunodeficiency virus-infected persons with Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 160:
Output: The Human Lung Microbiome The Human Lung Lung Microbiome Overview
Over the life course, we are invariably faced with some form of adversity. The process of positively adapting to adverse events is known as 'resilience'. Despite the acknowledgement of 2 common components of resilience, that is, adversity and positive adaptation, no consensus operational definition has been agreed. Resilience operationalisations have been reviewed in a cross-sectional context; however, a review of longitudinal methods of operationalising resilience has not been conducted. The present study conducts a systematic review across Scopus and Web of Science capturing studies of ageing that posited operational definitions of resilience in longitudinal studies of ageing. Thirty-six studies met inclusion criteria. Non-acute events, for example, cancer, were the most common form of adversity identified and psychological components, for example, the absence of depression, the most common forms of positive adaptation. Of the included studies, 4 used psychometrically driven methods, that is, repeated administration of established resilience metrics, 9 used definition-driven methods, that is, a priori establishment of resilience components and criteria, and 23 used datadriven methods, that is, techniques that identify resilient individuals using latent variable models. Acknowledging the strengths and limitations of each operationalisation is integral to the appropriate application of these methods to life course and longitudinal resilience research.
Output: Operationalising resilience in longitudinal studies: a systematic review of methodological approaches
Interferons (IFNs) are generally considered antiviral cytokines, yet the newly discovered IFN-l4 is linked with the failure to clear hepatitis C virus (HCV) infection either spontaneously or in response to treatment. IFN-l4 can be generated only by individuals who carry the IFNL4-DG allele (rs368234815), which is the strongest known host factor for predicting clearance of HCV. The ancestral IFNL4-DG allele is the major variant in Africans while the minor variant in Asians, suggesting very strong negative genetic selection for this allelemost likely driven by an infectious agent other than HCV. IFN-l4 most closely resembles IFN-l3, but these proteins share only 29% amino-acid identity, and, in contrast to IFN-l3, IFN-l4 is only weakly secreted. Nevertheless, IFN-l4 signals through the IFN-l receptor complex and induces expression of IFN-stimulated genes via the Janus kinase-signal transducer and activator of transcription signaling pathway. Although the IFNL4-DG variant is strongly associated with the failure to clear HCV infection, HCV-infected patients who carry this allele have lower baseline HCV RNA levels in the absence of treatment. Resolving the paradoxical functions of IFN-l4, which appears to induce antiviral activity yet impair effective clearance of HCV, may yield critical new insights into the immunologic response to HCV infection and IFN biology.
Output: IFN-l4: The Paradoxical New Member of the Interferon Lambda Family
Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses and Mycoplasma pneumoniae. Infectious agents including M. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak of M. pneumoniae infection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.
Output: Prescription Surveillance and Polymerase Chain Reaction Testing to Identify Pathogens during Outbreaks of Infection
ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity. Here, we map the endogenous in vivo ISGylome in the liver following Listeria monocytogenes infection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics. Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome. The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy. Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes. Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7. Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver.
Output: The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection
Background. Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. Methods. Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction-based assays. Results. BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples ( ). We observed a significant association between the presence of respiratory symptoms and positive viral P ! .001 detection in the lower respiratory tract ( ). Conversely, acute rejection was not associated with the presence P p .012 of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20-0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection. Lung transplant recipients are exposed to respiratory viruses circulating year-round in the community [1] [2] [3] [4] [5] [6] . In the general population, most of these infections lead to self-limited upper respiratory tract diseases, but protracted respiratory viral infection and lower respiratory tract complications are more likely in lung transplant recipients. This is related to specific risk factors, including direct exposure of the graft to airborne viruses, impaired mucociliary clearance, poor cough re-
Output: Respiratory Viruses and Acute Rejection • CID
Infectious disease occurs when a person is infected by a pathogen from another person or an animal. It is a problem that causes harm at both individual and macro scales. The Korea Center for Disease Control (KCDC) operates a surveillance system to minimize infectious disease contagions. However, in this system, it is difficult to immediately act against infectious disease because of missing and delayed reports. Moreover, infectious disease trends are not known, which means prediction is not easy. This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. The results show that the DNN and LSTM models perform better than ARIMA. When predicting chickenpox, the top-10 DNN and LSTM models improved average performance by 24% and 19%, respectively. The DNN model performed stably and the LSTM model was more accurate when infectious disease was spreading. We believe that this study's models can help eliminate reporting delays in existing surveillance systems and, therefore, minimize costs to society.
Output: Predicting Infectious Disease Using Deep Learning and Big Data
Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for addressing influenza pandemics. MDCK-33016PF cells are used in propagation of a cell-based seasonal influenza vaccine (Optaflu Ò ); but, like most continuous cell lines, can grow in immunocompromised mice to produce tumors. It is, therefore, essential that no residual cells remain within the vaccine, that cell lysates or DNA are not oncogenic, and that the cell substrate does not contain oncogenic viruses or oncogenic DNA. Multiple, redundant processes ensure the safety of influenza vaccines produced in MDCK-33016PF cells. The probability of a residual cell being present in a dose of vaccine is approximately 1 in 10 34 . Residual MDCK-DNA is 10 ng per dose and the ß-propiolactone used to inactivate influenza virus results in reduction of detectable DNA to less than 200 base pairs (bp). Degenerate PCR and specific PCR confirm exclusion of oncogenic viruses. The manufacturing process has been validated for its capacity to remove and inactivate viruses. We conclude that the theoretical risks arising from manufacturing seasonal influenza vaccine using MDCK-33016PF cells are reduced to levels that are effectively zero by the multiple, orthogonal processes used during production.
Output: Validation of the safety of MDCK cells as a substrate for the production of a cell-derived influenza vaccine
Collagen is one of the most abundant and important proteins in the human body. Human collagen type III (hCOL3A1) belongs to the fibril-forming collagens and is widely distributed in extensible connective tissue like skin, internal organs, or the vascular system. It plays key roles in wound healing, collagen fibrillogenesis, and normal cardiovascular development in human. The charged residues are considered to be an important characteristic of hCOL3A1, especially for collagen binding and recognition. Here we found that a triple helix fragment of hCOL3A1, Gly489-Gly510, contained multiple charged residues, as well as representative Glu-Lys-Gly and Glu-Arg-Gly charged triplets. We solved the crystal structure of this new fragment to a high-resolution of 1.50 Å and identified some important conformations of this new triple-helix region, including strong hydrogen bonds in interchain and interhelical interactions in addition to obvious flexible bending for the triple helix. We also found that the synthetic collagen peptides around this region exhibited potent activities through integrin-mediated peptide-membrane interaction. We then developed a method to produce a recombinant protein consisting of 16 tandem repeats of the triple-helix fragment of hCOL3A1 with strong activity without cytotoxicity. These results provide a strong base for further functional studies of human collagen type III and the method developed in this study can be applied to produce hCOL3A1-derived proteins or other tandem-repeat proteins with membrane adhesion activity.
Output: Characterization by high-resolution crystal structure analysis of a triple-helix region of human collagen type III with potent cell adhesion activity
Background: Public health systems in Canada have undergone significant policy renewal over the last decade in response to threats to the public's health, such as severe acute respiratory syndrome. There is limited research on how public health policies have been implemented or what has influenced their implementation. This paper explores policy implementation in two exemplar public health programs -chronic disease prevention and sexually-transmitted infection prevention -in Ontario, Canada. It examines public health service providers' , managers' and senior managements' perspectives on the process of implementation of the Ontario Public Health Standards 2008 and factors influencing implementation. Methods: Public health staff from six health units representing rural, remote, large and small urban settings were included. We conducted 21 focus groups and 18 interviews between 2010 (manager and staff focus groups) and 2011 (senior management interviews) involving 133 participants. Research assistants coded transcripts and researchers reviewed these; the research team discussed and resolved discrepancies. To facilitate a breadth of perspectives, several team members helped interpret the findings. An integrated knowledge translation approach was used, reflected by the inclusion of academics as well as decision-makers on the team and as co-authors. Results: Front line service providers often were unaware of the new policies but managers and senior management incorporated them in operational and program planning. Some participants were involved in policy development or provided feedback prior to their launch. Implementation was influenced by many factors that aligned with Greenhalgh and colleagues' empirically-based Diffusion of Innovations in Service Organizations Framework. Factors and related components that were most clearly linked to the OPHS policy implementation were: attributes of the innovation itself; adoption by individuals; diffusion and dissemination; the outer contextinterorganizational networks and collaboration; the inner settingimplementation processes and routinization; and, linkage at the design and implementation stage. Conclusions: Multiple factors influenced public health policy implementation. Results provide empirical support for components of Greenhalgh et al's framework and suggest two additional componentsthe role of external organizational collaborations and partnerships as well as planning processes in influencing implementation. These are important to consider by government and public health organizations when promoting new or revised public health policies as they evolve over time. A successful policy implementation process in Ontario has helped to move public health towards the new vision.
Output: Moving towards a new vision: implementation of a public health policy intervention
The novel coronavirus disease was first reported in Wuhan, China in December 2019 and is now pandemic all over the world. Previous study has reported several COVID-19 cases with conjunctivitis. However, the complete profiling of COVID-19 related ocular symptoms and diseases are still missing. We aim to investigate the ocular manifestations and clinical characteristics of COVID-19 patients. Methods: A total of five hundred and thirty-four patients were recruited at Mobile Cabin Hospital and Tongji Hospital. We collected information on demographic characteristics, exposure history, ocular symptoms, systemic concomitant symptoms, eye drop medication, eye protections, radiologic findings, and SARS-CoV-2 detection in nasopharyngeal swabs by RT-PCR from questionnaires and electronic medical records.
Output: Ocular manifestations and clinical characteristics of 534 cases of COVID-19 in China: A cross-sectional study
The exported cases of 2019 novel coronavirus infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number-the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.
Output: Clinical Medicine Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases
The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses."
Output: Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research
Background: Both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are important viral pathogens causing respiratory tract infection (RTI) in the pediatric population. However, the clinical manifestations of RSV and hMPV infections are similar. Therefore, a reliable and rapid diagnostic tool is needed for diagnostic performance. Methods: In order to optimize diagnosis efficiency of RTI, the aim of this study is to establish a rapid and advanced method for simultaneous detecting RSV and hMPV in nasopharyngeal aspirates specimens from patients. We designed a one-step triplex real-time RT-PCR (qRT-PCR) protocol using TaqMan probes for detecting RSV and hMPV. The plasmid clones containing RSV nucleoprotein gene and hMPV fusion gene were established as reference standards. We used virus culture supernatants from 86 known pediatric RTI patient to test the specificity and sensitivity of our assay. Then we used total 222 nasopharyngeal aspirates specimens from pediatric patients hospitalized with respiratory symptoms to evaluate our assay. Results: Our one-step triplex qRT-PCR assay showed 100% sensitivity and specificity in testing RSV and hMPV in 86 known virus culture supernatants, with excellent linearity (R 2 > 0.99) and reliable reproducibility (CV lower than 1.04%). This assay has a wide dynamic range 10 2 -10 9 copies/reaction (limit of detection; LOD = 100 copies/reaction). A total of 222 patients hospitalized with respiratory symptoms were enrolled for clinical evaluation. In these samples, our qRT-PCR assay detected 68 RSV positive and 18 hMPV positive cases. However, standard virus culture only detected 8 RSV positive cases and 0 hMPV cases. Based on this improved triplex qRT-PCR assay, we found that RSV infection was associated with severe inflammation by chest X-ray and occurrence of pneumonia which were not observed previously. In summary, we have developed a highly specific and sensitive one-step triplex qRT-PCR assay to detect hMPV and RSV simultaneously. This assay offers a valuable tool for routine diagnosis.
Output: Simultaneous detection of respiratory syncytial virus and human metapneumovirus by one-step multiplex real-time RT-PCR in patients with respiratory symptoms
Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be associated with ischemic heart disease, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathy. In this study, we investigated the relationship between Kawasaki disease and insertion/deletion polymorphism of ACE gene. Fifty five Kawasaki disease patients and 43 healthy children were enrolled. ACE genotype was evaluated from each of the subjects' DNA fragments through polymerase chain reaction (PCR). Frequencies of ACE genotypes (DD, ID, II) were 12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group respectively, indicating low rate of DD and high rate of ID genotype among Kawasaki patients (p<0.01). Comparing allelic (I, D) frequencies, I allele was more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05). In Kawasaki group, both genotype and allelic frequencies were not statistically different between those with coronary dilatations and those without. ACE gene I/D polymorphism is thought to be associated with Kawasaki disease but not with the development of coronary dilatations.
Output: Address for correspondence Insertion/Deletion Polymorphism of Angiotensin Converting Enzyme Gene in Kawasaki Disease
High salt intake has been related to the development to chronic kidney disease (CKD) as well as hypertension. In its early stages, symptoms of CKD are usually not apparent, especially those that are induced in a "silent" manner in normotensive individuals, thereby providing a need for some kind of urinary biomarker to detect injury at an early stage. Because traditional renal biomarkers such as serum creatinine are insensitive, it is difficult to detect kidney injury induced by a high-salt diet, especially in normotensive individuals. Recently, several new biomarkers for damage of renal tubular epithelia such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) have been identified. Previously, we found a novel renal biomarker, urinary vanin-1, in several animal models with renal tubular injury. However, there are few studies about early biomarkers of the progression to CKD associated with a high-salt diet. This review presents some new insights about these novel biomarkers for CKD in normotensives and hypertensives under a high salt intake. Interestingly, our recent reports using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) fed a high-salt diet revealed that urinary vanin-1 and NGAL are earlier biomarkers of renal tubular damage in SHR and WKY, whereas urinary Kim-1 is only useful as a biomarker of salt-induced renal injury in SHR. Clinical studies will be needed to clarify these findings.
Output: Molecular Sciences Biomarkers for Chronic Kidney Disease Associated with High Salt Intake
Activation of autoreactive T cells is a necessary-but not sufficient-step in the development of T cell mediated autoimmunity. Autoreactive T cells can be activated by viral and bacterial peptides that meet the structural requirements for MHC molecule binding and T cell receptor recognition. Due to the degenerate nature of MHC class 11 molecule binding motifs and a certain degree of flexibility in T cell receptor recognition, such microbial peptides have been found to be quite distinct in their primary sequence from the self-peptide they mimic.
Output: Activation of autoreactive T cells by peptides from human pathogens
Clinical characteristics of novel coronavirus disease (COVID-19) have been described in numerous studies but yielded varying results. We aimed to conduct a systematic review on scientific literatures and to synthesize critical data on clinical traits of COVID-19 from its initial outbreak to pandemic. Systematic searches were conducted to identify retrospective observational study that contained clinical characteristics on COVID-19 through multiple databases. Two reviewers independently evaluated eligible publications. Data on clinical characteristics of COVID-19 were extracted and analyzed. RESULTS -two retrospective studies demonstrating the clinical characteristics of COVID-19 were included. A total of 3470 COVID-19 patients were synthesized to the final analysis in an unbiased manner. The most common symptom was fever (2878 [83.0%]), and 63.4% of the patients presented fever as onset symptom. There were 2528 [88.2%] of 2866 cases had abnormal lung findings on chest CT scan. Laboratory findings showed that 1498 [62.8%] of 2387 cases had lymphopenia, and 1354 [64.8%] of 2091 cases had an increased level of C-reactive protein (CRP). A total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall case fatality rate (CFR) was 3.7%. Compared to patients admitted outside of Hubei, China, those from Hubei had a significant higher ICU admission rate (21.9% vs. 2.5%, p<0.001). Also, CFR attributed to COVID-19 was significantly higher in Hubei than that of non-Hubei admissions (10.4% vs. 0.6%, p<0.001). This large patient-based systematic review presents a more precise profiling of the COVID-19 from its outbreak to current pandemic. Dynamic evolvements of COVID-19 are needed to be characterized in future studies.
Output: Clinical Characteristics of Coronavirus Disease 2019 (COVID-19): An Updated Systematic Review
Background: Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings. Methods: From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC] b 40%), intermediate (40-79%), and high (≥80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models. Results: From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%-79% (HR = 0.46, 95% C.I. 0.41-0.52, p b 0.001) and ≥ 80% (HR = 0.91, 95% C.I. 0.85-0.98, p = 0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group. Conclusions: Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings.
Output: Drug adherence and the incidence of coronary heart disease-and stroke-specific mortality among 218,047 patients newly prescribed an antihypertensive medication: A five-year cohort study
Individual-based epidemiology models are used to study the effects of public health interventions and changes in individual behavior to the dynamics of infectious diseases [1] . A detailed description of the individual-based model used in simulating the outbreaks in this study is presented in [2] . The individual-based model is made up of a dynamic social contact network and a disease transmission model. The social contact network which is a synthetic representation of a particular geographical region is generated using United States Census data. The structure of the underlying network is important since interactions between agents influences how disease propagates during epidemic simulations. In this initial study, neither changes in individual behavior nor intervention strategies are explored. However, in later studies to better understand the implications of specific intervention strategies, we would forecast disease dynamics given that effective measures have been introduced to control the spread of an outbreak. The construction of the dynamic social contact network requires two steps. In step 1 a synthetic population is created. Individuals in the synthetic population are tagged to realistic demographics while preserving the confidentiality of the original data sets. Each individual is assigned to a household using a decision tree based on demographic information (such as number of people in a household, number of children etc.) from data provided in SF3 and PUMA (Public Use Microdata Area) census files. Households are placed in realistic geographical regions. The synthetic population is statistically identical to the census aggregated at the block level. More information can be found in [3], [4] and [5]. Step 2 assigns a daily activity list with specified durations (start and end times) to each household based on several thousand responses to an activity or time-use survey. The activity templates which vary by region given factors such as the geographical location and age composition of the population, are created based on the National
Output: A Simulation Optimization Approach to Epidemic Forecasting Supporting Information Individual-based Model
Background: False negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike. Objective: To develop multivariate models to determine clinical characteristics that contribute to false negative results of SARS-CoV-2 nucleic acid detection, and use them to predict false negative results as well as time windows for testing positive. Design: Retrospective Cohort Study (Ethics number of Tongji Hospital Measurements: Clinical information on CT imaging reports, blood routine tests, and clinic symptoms were collected. A multivariate logistic regression was used to explain and predict false negative testing results of SARS-CoV-2 detection. A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive. Results: Of the 1,324 outpatients who diagnosed of COVID-19, 633 patients tested positive in their first SARS-CoV-2 nucleic acid test (47.8%), with a mean age of 51 years (SD=14.9); the rest, which had a mean age of 47 years (SD=15.4), tested negative in the first test. "Ground glass opacity" in a CT imaging report was associated with a lower chance of false negatives (aOR, 0.56), and reduced the length of time window for testing positive by 26%. "Consolidation" was associated with a higher chance of false negatives (aOR, 1.57), and extended the length of time window for testing positive by 44%. In blood routine tests, basophils (aOR, 1.28) and eosinophils (aOR, 1.29) were associated with a higher chance of false negatives, and were found to extend the time window for testing positive by 23% and 41%, respectively. Age and gender also affected the significantly. Limitation: Data were generated in a large single-center study. Testing outcome and positive window of SARS-CoV-2 detection for COVID-19 patients were associated with CT imaging results, blood routine tests, and clinical symptoms. Taking into account relevant information in CT imaging reports, blood routine tests, and clinical symptoms helped reduce a false negative testing outcome. The predictive AFT model, what we believe to be one of the first statistical models for predicting time window of SARS-CoV-2 detection, could help clinicians improve the accuracy and efficiency of the diagnosis, and hence, optimizes the timing of nucleic acid detection and alleviates the shortage of nucleic acid detection kits around the world. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Output: Analysis and Prediction of COVID-19 Patients' False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen: A Retrospective Study Running Title: Prediction of False Negative Results for SARS-CoV-2 Detection
Production of large quantities of viral vectors is crucial for the success of gene therapy in the clinic. There is a need for higher titers of herpes simplex virus-1 (HSV-1) vectors both for therapeutic use as well as in the manufacturing of clinical grade adenoassociated virus (AAV) vectors. HSV-1 yield increased when primary human fibroblasts were treated with anti-inflammatory drugs like dexamethasone or valproic acid. In our search for compounds that would increase HSV-1 yield, we investigated another anti-inflammatory compound, aurintricarboxylic acid (ATA). Although ATA has been previously shown to have antiviral effects, we find that low (micromolar) concentrations of ATA increased HSV-1 vector production yields. Our results showing the use of ATA to increase HSV-1 titers have important implications for the production of certain HSV-1 vectors as well as recombinant AAV vectors.
Output: Aurintricarboxylic acid increases yield of HSV-1 vectors
A new coronavirus (severe acute respiratory syndrome coronavirus [SARS-CoV]) has been identified to be the etiological agent of severe acute respiratory syndrome. Given the highly contagious and acute nature of the disease, there is an urgent need for the development of diagnostic assays that can detect SARS-CoV infection. A total of 81 sera, including 67 from convalescent patients and seven pairs from two time points of infection, were analyzed, and all showed immunoreactivity towards the nucleocapsid protein (N). Sera from some of the patients also showed immunoreactivity to U274 (59 of 81 [73%]), a protein that is unique to SARS-CoV. In addition, all of the convalescent-phase sera showed immunoreactivity to the spike (S) protein when analyzed by an immunofluorescence method utilizing mammalian cells stably expressing S. However, samples from the acute phase (2 to 9 days after the onset of illness) did not react with S, suggesting that antibodies to N may appear earlier than antibodies to S. Alternatively, this could be due to the difference in the sensitivities of the two methods. The immunoreactivities to these recombinant viral proteins are highly specific, as sera from 100 healthy donors did not react with any of them. These results suggest that recombinant N, S, and U274 proteins may be used as antigens for the development of serological assays for SARS-CoV.
Output: Profiles of Antibody Responses against Severe Acute Respiratory Syndrome Coronavirus Recombinant Proteins and Their Potential Use as Diagnostic Markers
Background: Treatments for autoimmune diseases aim to dampen autoreactivity while preserving normal immune function. In CD4 + T cells, the transcription factor Oct1/Pou2f1 is a dispensable transcription factor for T cell development and response to primary infection, but promotes expression of target genes, including Il2 and Ifng, under conditions of antigen reencounter. As a result, they are more strongly expressed upon secondary stimulation. Such repeated antigen encounters occur in memory recall responses, in autoimmunity where self-antigen can be recognized multiple times, and in chronic infection where foreign antigen is persistent. Based on these previous findings, we hypothesized that Oct1 loss would protect animals from autoimmunity but maintain normal responses to pathogens in the CNS. Objective: We used a conditional mouse Oct1 (Pou2f1) allele and a CD4-Cre driver to determine the effect of T cellspecific Oct1 loss on autoimmune-and viral-induced neuroinflammation using an autoantigen-driven EAE model of autoimmunity and a JHMV model of viral infection. Results: Oct1 conditional deletion mitigated clinical scores and reduced infiltrating T cells and cytokine production in the EAE model. Consistently, Oct1-deficient CD4 + T cells stimulated in vitro showed increased expression of markers associated with T cell anergy, particularly in the absence of co-stimulatory signals. In contrast, anti-viral T cell effector functions are intact in the absence of Oct1, with no changes in neuroinflammation, infiltrating T cells or cytokine production. Conclusion: Our findings uncover a significant difference between the effect of Oct1 loss on autoimmune and antipathogen responses, which potentially could be exploited for therapeutic benefit.
Output: T cell-selective deletion of Oct1 protects animals from autoimmune neuroinflammation while maintaining neurotropic pathogen response
The mechanism of systemic spread of H5N1 virus in patients with avian influenza is unknown. Here, H5N1 nucleoprotein and hemagglutinin were identified by immunohistochemistry in the nucleus and cytoplasm of neutrophils in the placental blood of a pregnant woman. Viral RNA was detected in neutrophils by in situ hybridization and enhanced realtime polymerase chain reaction. Therefore, neutrophils may serve as a vehicle for viral replication and transportation in avian influenza. Human avian influenza (H5N1) infection possesses a great potential threat to human health. However, the pathogenesis of this emerging disease is poorly understood. A previous study demonstrated that extrapulmonary organs, including the placenta, trachea, intestine, and brain, can be infected with human avian influenza H5N1 virus [1] . This virus has been detected in serum [2], but the exact means of viral spread beyond the respiratory system is unclear. In the present study, we investigated organs obtained at autopsy from an H5N1 virus-infected pregnant woman and from her fetus in an attempt to study the mechanism of systemic dissemination of H5N1 virus. Neutrophils were abundant in the placenta, and therefore, we evaluated blood cells in the
Output: Neutrophils May Be a Vehicle for Viral Replication and Dissemination in Human H5N1 Avian Influenza
Background: Google Flu Trends was developed to estimate US influenza-like illness (ILI) rates from internet searches; however ILI does not necessarily correlate with actual influenza virus infections. Findings: Influenza activity data from 2003-04 through 2007-08 were obtained from three US surveillance systems: Google Flu Trends, CDC Outpatient ILI Surveillance Network (CDC ILI Surveillance), and US Influenza Virologic Surveillance System (CDC Virus Surveillance). Pearson's correlation coefficients with 95% confidence intervals (95% CI) were calculated to compare surveillance data. An analysis was performed to investigate outlier observations and determine the extent to which they affected the correlations between surveillance data. Pearson's correlation coefficient describing Google Flu Trends and CDC Virus Surveillance over the study period was 0.72 (95% CI: 0.64, 0.79). The correlation between CDC ILI Surveillance and CDC Virus Surveillance over the same period was 0.85 (95% CI: 0.81, 0.89). Most of the outlier observations in both comparisons were from the 2003-04 influenza season. Exclusion of the outlier observations did not substantially improve the correlation between Google Flu Trends and CDC Virus Surveillance (0.82; 95% CI: 0.76, 0.87) or CDC ILI Surveillance and CDC Virus Surveillance (0.86; 95%CI: 0.82, 0.90). Conclusions: This analysis demonstrates that while Google Flu Trends is highly correlated with rates of ILI, it has a lower correlation with surveillance for laboratory-confirmed influenza. Most of the outlier observations occurred during the 2003-04 influenza season that was characterized by early and intense influenza activity, which potentially altered health care seeking behavior, physician testing practices, and internet search behavior.
Output: Monitoring Influenza Activity in the United States: A Comparison of Traditional Surveillance Systems with Google Flu Trends