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186 lines
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<title>25 June, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>MOCHA: Advanced statistical modeling of scATAC-seq data enables functional genomic inference in large human disease cohorts</strong> -
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<div>
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Single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) has been increasingly used to study gene regulation. However, major analytical gaps limit its utility in studying gene regulatory programs in complex diseases. We developed MOCHA (Model-based single cell Open CHromatin Analysis) with major advances over existing analysis tools, including: 1) improved identification of sample-specific open chromatin, 2) proper handling of technical drop-out with zero-inflated methods, 3) mitigation of false positives in single cell analysis, 4) identification of alternative transcription-starting-site regulation, and 5) transcription factor-gene network construction from longitudinal scATAC-seq data. These advances provide a robust framework to study gene regulatory programs in human disease. We benchmarked MOCHA with four state-of-the-art tools to demonstrate its advances. We also constructed cross-sectional and longitudinal gene regulatory networks, identifying potential mechanisms of COVID-19 response. MOCHA provides researchers with a robust analytical tool for functional genomic inference from scATAC-seq data.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.23.544827v1" target="_blank">MOCHA: Advanced statistical modeling of scATAC-seq data enables functional genomic inference in large human disease cohorts</a>
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</div></li>
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<li><strong>PARP14 is a writer, reader and eraser of mono-ADP-ribosylation</strong> -
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<div>
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PARP14/BAL2 is a large multidomain enzyme involved in signaling pathways with relevance to cancer, inflammation, and infection. Inhibition of its mono-ADP-ribosylating PARP homology domain and its three ADP-ribosyl binding macro domains has been regarded as a potential means of therapeutic intervention. Macrodomains-2 and -3 are known to stably bind to ADP-ribosylated target proteins; but the function of macrodomain-1 has remained somewhat elusive. Here, we used biochemical assays of ADP-ribosylation levels to characterize PARP14 macrodomain-1 and the homologous macrodomain-1 of PARP9. Our results show that both macrodomains display an ADP-ribosyl glycohydrolase activity that is not directed toward specific protein side chains. PARP14 macrodomain-1 is unable to degrade poly(ADP-ribose), the enzymatic product of PARP1. The F926A mutation of PARP14 and the F244A mutation of PARP9 strongly reduced ADP-ribosyl glycohydrolase activity of the respective macrodomains, suggesting mechanistic homology to the Mac1 domain of the SARS-CoV-2 Nsp3 protein. This study adds two new enzymes to the previously known six human ADP-ribosyl glycohydrolases. Our results have key implications for how PARP14 and PARP9 will be studied and how their functions will be understood.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.24.546374v1" target="_blank">PARP14 is a writer, reader and eraser of mono-ADP-ribosylation</a>
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</div></li>
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<li><strong>Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states</strong> -
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<div>
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COVID-19 is associated with diverse neurological abnormalities, which predict poor outcome in patients. However, the mechanisms whereby infection-induced inflammation could affect complex neuropathologies in COVID-19 are unclear. We hypothesized that microglia, the resident immune cells of brain, are centrally involved in this process. To study this, we developed an autopsy platform allowing the integration of molecular anatomy-, protein- and mRNA data sets in post-mortem mirror blocks of brain and peripheral organ samples from COVID-19 cases. Nanoscale microscopy, single-cell RNA sequencing and analysis of inflammatory and metabolic signatures revealed distinct mechanisms of microglial dysfunction associated with cerebral SARS-CoV-2 infection. We observed focal loss of microglial P2Y12R at sites of virus-associated vascular inflammation together with dysregulated microglia-vascular-astrocyte interactions, Cx3Cr1-fractalkine axis deficits and mitochondrial failure in severely affected medullary autonomic nuclei and other brain areas. Microglial dysfunction occurs at sites of excessive synapse- and myelin phagocytosis and loss of glutamatergic terminals. While central and systemic viral load is strongly linked in individual patients, the regionally heterogenous microglial reactivity in the brain correlated with the extent of central and systemic inflammation related to IL-1 / IL-6 via virus-sensing pattern recognition receptors (PRRs) and inflammasome activation pathways. Thus, SARS-CoV-2-induced central and systemic inflammation might lead to a primarily glio-vascular failure in the brain, which could be a common contributor to diverse COVID-19-related neuropathologies.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.23.546214v1" target="_blank">Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states</a>
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</div></li>
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<li><strong>Germline-encoded specificities and the predictability of the B cell response</strong> -
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<div>
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Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors, the precursors to antibodies, are encoded by particular immunoglobulin alleles. This raises the possibility that the presence of particular germline alleles in the B cell repertoire is a major determinant of the quality of the antibody response. Alternatively, initial differences in germline alleles’ propensities to form high-affinity receptors might be overcome by chance events during affinity maturation. We first investigate these scenarios in simulations: when germline-encoded fitness differences are large relative to the rate and effect size variation of somatic mutations, the same germline alleles persistently dominate the response of different individuals. In contrast, if germline-encoded advantages can be easily overcome by subsequent mutations, allele usage becomes increasingly divergent over time, a pattern we then observe in mice experimentally infected with influenza virus. We investigated whether affinity maturation might nonetheless strongly select for particular amino acid motifs across diverse genetic backgrounds, but we found no evidence of convergence to similar CDR3 sequences or amino acid substitutions. These results suggest that although germline-encoded specificities can lead to similar immune responses between individuals, diverse evolutionary routes to high affinity limit the genetic predictability of responses to infection and vaccination.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.16.508315v3" target="_blank">Germline-encoded specificities and the predictability of the B cell response</a>
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</div></li>
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<li><strong>Optimal Non-Pharmaceutical Interventions Considering Limited Healthcare System Capacity and Economic Costs in the Republic of Korea</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Due to the relatively low severity and fatality rates of the omicron variant of COVID-19, strict non-pharmaceutical interventions (NPIs) with high economic costs may not be necessary. We develop a mathematical model of the COVID-19 outbreak in Korea that considers NPIs, variants, medical capacity, and economic costs. Using optimal control theory, we propose an optimal strategy for the omicron period. To suggest a realistic strategy, we consider limited hospital beds for severe cases and incorporate it as a penalty term in the objective functional using a logistic function. This transforms the constrained problem into an unconstrained one. Given that the solution to the optimal control problem is continuous, we propose the adoption of a sub-optimal control as a more practically implementable alternative. Our study demonstrates how to strategically balance the trade-off between minimizing the economic cost for NPIs and ensuring that the number of severe cases in hospitals is manageable.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.24.23290452v2" target="_blank">Optimal Non-Pharmaceutical Interventions Considering Limited Healthcare System Capacity and Economic Costs in the Republic of Korea</a>
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</div></li>
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<li><strong>Psycho-social factors associated with mental resilience in the Corona lockdown</strong> -
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<div>
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The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. While increases in stress-related symptomatology and other adverse psycho-social outcomes as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. In order to gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (March 22nd to April 19th) in a convenience sample of N=15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p<0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p<0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/4z62t/" target="_blank">Psycho-social factors associated with mental resilience in the Corona lockdown</a>
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</div></li>
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<li><strong>PCR data accurately predict infectious virus: a characterization of SARS-CoV-2 in non-human primates</strong> -
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<div>
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Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. Here, we compare total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates using bespoke statistical models. On out-of-sample data, our best models predict subgenomic RNA from total RNA with 91% accuracy, and they predict culture positivity with 85% accuracy. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors, including exposure conditions and host traits, influence culture predictions for total RNA quantities spanning twelve orders of magnitude. Our model framework can be adapted to compare any assays, in any host species, and for any virus, to support laboratory analyses, medical decisions, and public health guidelines.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.23.546114v1" target="_blank">PCR data accurately predict infectious virus: a characterization of SARS-CoV-2 in non-human primates</a>
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</div></li>
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<li><strong>A benchmark study of data normalisation methods for PTR-TOF-MS exhaled breath metabolomics</strong> -
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<div>
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Background: Volatilomics is the branch of metabolomics dedicated to the analysis of volatile organic compounds (VOCs) in exhaled breath for medical diagnostic or therapeutic monitoring purposes. Real-time mass spectrometry technologies such as proton transfer reaction mass spectrometry (PTR-MS) are commonly used, and data normalisation is an important step to discard unwanted variation from non-biological sources, as batch effects and loss of sensitivity over time may be observed. As normalisation methods for real-time breath analysis have been poorly investigated, we aimed to benchmark known metabolomic data normalisation methods and apply them to PTR-MS data analysis. Methods: We compared seven normalisation methods, five statistically based and two using multiple standard metabolites, on two datasets from clinical trials for COVID-19 diagnosis in patients from the emergency department or intensive care unit. We evaluated different means of feature selection to select the standard metabolites, as well as the use of multiple repeat measurements of ambient air to train the normalisation methods. Results: We show that the normalisation tools can correct for time-dependent drift. The methods that provided the best corrections for both cohorts were Probabilistic Quotient Normalisation and Normalisation using Optimal Selection of Multiple Internal Standards. Normalisation also improved the diagnostic performance of the machine learning models, significantly increasing sensitivity, specificity and area under the ROC curve for the diagnosis of COVID-19. Conclusions: Our results highlight the importance of adding an appropriate normalisation step during the processing of PTR-MS data, which allows significant improvements in the predictive performance of statistical models.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.22.546053v1" target="_blank">A benchmark study of data normalisation methods for PTR-TOF-MS exhaled breath metabolomics</a>
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</div></li>
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<li><strong>Effective vaccination strategies to control COVID-19 outbreak: A modeling study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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OBJECTIVES Three years following the start of the COVID-19 pandemic, the World Health Organization (WHO) declared COVID-19 a global health emergency of international concern. As immunity levels in the population acquired through past infections and vaccinations have been decreasing, booster vaccinations have become necessary to control new outbreaks. This study aimed to determine the most suitable vaccination strategy to control the COVID-19 surge. METHODS A mathematical model was developed to simultaneously consider the immunity levels induced by vaccines and infections, and employed to analyze the possibility of future resurgence and control using vaccines and antivirals. RESULTS As of May 11, 2023, a peak in resurgence is predicted to occur around mid-October of the same year if the current epidemic trend continues without additional vaccinations. In the best scenario, the peak number of severely hospitalized patients can be reduced by 43% (480) compared to the scenario without vaccine intervention (849). Depending on the outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing the said peak varies from May to August 2023. CONCLUSIONS Our results indicate that if the epidemic continues, the best timing for vaccinations must be earlier than specified by the current plan in Korea. Further monitoring of outbreak trends is crucial for determining the optimal timing of vaccinations to manage future surges.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.18.23291573v2" target="_blank">Effective vaccination strategies to control COVID-19 outbreak: A modeling study</a>
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</div></li>
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<li><strong>Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation</strong> -
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Background: Social determinants of health are non-medical factors that influence health outcomes (SDOH). There is a wealth of SDOH information available via electronic health records, clinical reports, and social media, usually in free text format, which poses a significant challenge and necessitates the use of natural language processing (NLP) techniques to extract key information. Objective: The objective of this research is to advance the automatic extraction of SDOH from clinical texts. Setting and Data: The case reports of COVID-19 patients from the published literature are curated to create a corpus. A portion of the data is annotated by experts to create gold labels, and active learning is used for corpus re-annotation. Methods: A named entity recognition (NER) framework is developed and tested to extract SDOH along with a few prominent clinical entities (diseases, treatments, diagnosis) from the free texts. Results: The proposed NER implementation achieves an accuracy (F1-score) of 92.98% on our test set and generalizes well on benchmark data. A careful analysis of case examples demonstrates the superiority of the proposed approach in correctly classifying the named entities. Conclusions: NLP can be used to extract key information, such as SDOH from free texts. A more accurate understanding of SDOH is needed to further improve healthcare outcomes.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.30.22282946v5" target="_blank">Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation</a>
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</div></li>
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<li><strong>Enhanced real-time mass spectrometry breath analysis for the diagnosis of COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Although rapid screening for and diagnosis of COVID-19 are still urgently needed, most current testing methods are either long, costly, and/or poorly specific. The objective of the present study was to determine whether or not artificial-intelligence-enhanced real-time MS breath analysis is a reliable, safe, rapid means of screening ambulatory patients for COVID-19. Methods: In two prospective, open, interventional studies in a single university hospital, we used real-time, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of exhaled breath from adults requiring screening for COVID-19. Artificial intelligence and machine learning techniques were used to build mathematical models based on breath analysis data either alone or combined with patient metadata. Results: We obtained breath samples from 173 participants, of whom 67 had proven COVID-19. After using machine learning algorithms to process breath analysis data and further enhancing the model using patient metadata, our method was able to differentiate between COVID-19-positive and -negative participants with a sensitivity of 98%, a specificity of 74%, a negative predictive value of 98%, a positive predictive value of 72%, and an area under the receiver operating characteristic curve of 0.961. The predictive performance was similar for asymptomatic, weakly symptomatic and symptomatic participants and was not biased by the COVID-19 vaccination status. Conclusions: Real-time, non-invasive, artificial-intelligence-enhanced mass spectrometry breath analysis might be a reliable, safe, rapid, cost-effective, high-throughput method for COVID-19 screening.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.21.23291712v1" target="_blank">Enhanced real-time mass spectrometry breath analysis for the diagnosis of COVID-19</a>
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<li><strong>Association between post-infection COVID-19 vaccination and symptom severity of post COVID-19 condition among patients on Bonaire, Caribbean Netherlands: a retrospective cohort study</strong> -
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Objectives: In this retrospective cohort study, we aimed to investigate symptom severity change following COVID-19 vaccination among post COVID-19 condition (PCC) patients on Bonaire. Methods: Symptomatic cases who tested positive for SARS-CoV-2 between the start of the pandemic and 1 October 2021, were unrecovered on the interview day, and unvaccinated prior to infection were identified from the national case registry. Patients were interviewed by telephone between 15 November and 4 December 2021 about sociodemographic factors, pre-pandemic health, COVID-19 symptoms and vaccination status. We compared symptom severity change between the acute and post-acute disease phase (>4 weeks after disease onset) of 14 symptoms on a five-point Likert scale for 36 PCC patients having received at least one dose of the BNT162 (BioNTech/Pfizer) vaccine and 11 patients who remained unvaccinated, using separate multiple linear regression models. Results: Most common post-acute symptoms included fatigue (81%), reduced physical endurance (79%), and reduced muscle strength (64%). Post-infection vaccination was significantly associated with reduced severity of heart palpitations, after adjusting for acute phase severity and duration of illness (β 0.60, 95% CI 0.18, 1.02). We did not find a statistically significant association with symptom severity change for other, more prevalent symptoms. Conclusions: Larger prospective studies are needed to confirm our observation in a small study population that post-infection COVID-19 vaccination was associated with reduced severity of heart palpitations among those with this symptom self-attributed to SARS-CoV-2 infection.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.20.23291649v1" target="_blank">Association between post-infection COVID-19 vaccination and symptom severity of post COVID-19 condition among patients on Bonaire, Caribbean Netherlands: a retrospective cohort study</a>
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<li><strong>Evaluating the buffering role of perceived social support and coping resources against the adult mental health impacts of COVID-19 psychosocial stress: a cross-sectional study in South Africa</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objectives: Growing evidence has highlighted the global mental health impacts of the COVID-19 pandemic and lockdown, particularly in societies with pre-existing socioeconomic adversities and public health concerns. Despite the sudden and prolonged nature of many psychosocial stressors during the pandemic, recent studies have shown that communities utilized several coping mechanisms to buffer the mental health consequences of COVID-related stress. This paper examines the extent to which coping resources and social support buffered against the mental health effects of COVID-19 psychosocial stress among adults in South Africa. Materials & Methods: Adult participants (n=117) completed an online survey during the second and third waves of the COVID-19 pandemic in South Africa (January-July 2021), which assessed experiences of stress, coping resources, social support, and four mental health outcomes: depression, anxiety, post-traumatic stress disorder, and bipolar disorder. Moderation analyses examined the potential buffering role of coping resources and social support against the mental health effects of COVID-19 stress. Results: Adults reported elevated rates of psychiatric symptoms. Coping resources buffered against the poor mental health effects of COVID-19 psychosocial stress, whereas perceived social support did not significantly moderate the association between COVID-19 stress and adult mental health. Discussion: These results suggest that adults in our sample utilized a variety of coping resources to protect their mental health against psychosocial stress experienced during the COVID-19 lockdown and pandemic in South Africa. Additionally, existing mental health conditions and strained social relationships may have attenuated the potential stress-buffering effect of perceived social support on adult mental health.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.20.23291688v1" target="_blank">Evaluating the buffering role of perceived social support and coping resources against the adult mental health impacts of COVID-19 psychosocial stress: a cross-sectional study in South Africa</a>
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<li><strong>Covid-19 Excess Mortality in China: A Regional Comparison</strong> -
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Estimates of Covid-19 excess mortality are often considered to reflect the true death toll of the pandemic. As such, information on excess mortality is urgently needed to better understand the impact of the pandemic and prepare for future crises. This study estimated Covid-19 excess mortality at the provincial, regional, and national levels in China and investigated its associated regional disparities. The analyses were based on population and death rates data published by the national and provincial bureaus of statistics in China. The results suggest that excess deaths in China were over 1 million during each year of the pandemic, totaling to over 4 million by the end of 2022, at an excess death rate of 15.4%. This rate was likely comparable to that of the Organization for Economic Cooperation and Development (OECD), but higher than the US rate. Striking disparities were discovered among the 31 provinces with excess death rates ranging from negative rates in two eastern provinces to over 30% in three inland provinces. Rates in western China were over twice as high as those in eastern China. Variations with each individual regions were the largest in the central region and the smallest in the Northeast, which was the hardest hit with excess death rate of over 23%. The regional disparities in excess mortality rates seem to reflect pre-existing regional inequalities in socio-economic development in China. Such findings suggest that China has far to go to mitigate regional inequalities, achieve sustainability, and prepare for the next major crises.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.15.23291443v2" target="_blank">Covid-19 Excess Mortality in China: A Regional Comparison</a>
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<li><strong>The Lived Experiences of Post-Pandemic Working Students on Face-to-Face Learning Modality</strong> -
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The COVID-19 pandemic has caused widespread disruptions in educational institutions, presenting a challenging routine for working students who juggle employment and academic pursuits. This study aims to uncover the lived experiences of post-pandemic working students in the context of face-to-face learning. A descriptive phenomenological approach was employed to explore and capture their experiences. Purposive sampling was utilized to collect data from seven working students who met the inclusion criteria. The data analysis followed Braun and Clarke’s (2006) method, involving the extraction of codes, categories, and themes from the responses obtained through semi-structured interviews. As a result of the analysis, six major themes emerged: (1) financial struggles, (2) personal objectives, (3) time and schedule adjustments, (4) struggles with utilizing physical and social skills, (5) paying off debt, and (6) futurism. The findings indicate that working students require time to adapt and overcome the challenges and difficulties presented in the post-pandemic period. Therefore, it is crucial to provide them with support and measures to ensure that their studies and employment are not compromised.
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🖺 Full Text HTML: <a href="https://edarxiv.org/p23s5/" target="_blank">The Lived Experiences of Post-Pandemic Working Students on Face-to-Face Learning Modality</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Probiotic and Colchicine in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Colchicine 0.5 MG; Dietary Supplement: Probiotic Formula; Other: Standard protocol<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: manual therapy; Other: breathing exercise and prone position alone<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 capsule; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C); Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: control group; Biological: Placebo group<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: sensory re-education training; Other: traditional treatment<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Investigate the Safety, Immunogenicity of a Bivalent mRNA Vaccine RQ3025 as a Booster Dose in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: RQ3025<br/><b>Sponsors</b>: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation</strong> - <b>Conditions</b>: COVID-19; Hematopoietic Stem Cell Transplantation<br/><b>Intervention</b>: Biological: COVID Convalescent Plasma<br/><b>Sponsor</b>: Institute of Hematology & Blood Diseases Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cupping Therapy on Immune System in Post Covid -19</strong> - <b>Condition</b>: Covid-19 Patients<br/><b>Interventions</b>: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection.</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Drug: Remdesivir<br/><b>Sponsors</b>: University of Derby; University of Exeter; Peninsula Clinical Trials Unit; University Hospitals of Derby and Burton NHS Foundation Trust<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 DNA Vaccine (ICCOV)<br/><b>Sponsors</b>: Immuno Cure 3 Limited; The University of Hong Kong<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NC Testing in LC & POTS: A Pilot Study</strong> - <b>Conditions</b>: Postural Orthostatic Tachycardia Syndrome; Post Acute Sequelae of SARS CoV 2 Infection<br/><b>Intervention</b>: Other: IV normal saline (1 Litre)<br/><b>Sponsor</b>: University of Calgary<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Investigate Efficacy, Pharmacodynamics, and Safety of BC 007 in Participants With Long COVID</strong> - <b>Condition</b>: Long Covid<br/><b>Intervention</b>: Drug: BC 007 or matching placebo<br/><b>Sponsor</b>: Berlin Cures GmbH<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II/III Study to Evaluate the Immunogenicity and Safety and Efficacy of SWIM816 Vaccines for SARS-CoV-2</strong> - <b>Conditions</b>: Immunogenicity; Safety<br/><b>Interventions</b>: Biological: Phase II:SWIM816;SARS-Cov-2;; Biological: Phase II:SW-BIC-213;SARS-Cov-2;; Biological: PhaseIII:SWIM816;SARS-Cov-2;; Biological: PhaseIII:Pfizer(Pfizer Bivalent vaccine);SARS-Cov-2；<br/><b>Sponsor</b>: Stemirna Therapeutics<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About the Study Medicine Called Nirmatrelvir/Ritonavir in People Who Are Healthy Volunteers Co-administered the Medicine Rosuvastatin</strong> - <b>Conditions</b>: Pharmacokinetics; Healthy Volunteers<br/><b>Interventions</b>: Drug: Rosuvastatin; Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection</strong> - The severity of the SARS-CoV-2 pandemic and the recurring (re)emergence of viruses prompted the development of new therapeutic approaches that target viral and host factors crucial for viral infection. Among them, host peptidases cathepsins B and L have been described as essential enzymes during SARS-CoV-2 entry. In this study, we evaluated the effect of potent selective cathepsin inhibitors as antiviral agents. We demonstrated that selective cathepsin B inhibitors, such as the antimicrobial…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 protein ORF8 limits expression levels of Spike antigen and facilitates immune evasion of infected host cells</strong> - Recovery from COVID-19 depends on the ability of the host to effectively neutralize virions and infected cells, a process largely driven by antibody-mediated immunity. However, with the newly emerging variants that evade Spike-targeting antibodies, re-infections and breakthrough infections are increasingly common. A full characterization of SARS-CoV-2 mechanisms counteracting antibody-mediated immunity is therefore needed. Here, we report that ORF8 is a virally encoded SARS-CoV-2 factor that…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Jingfang granules ameliorate inflammation and immune disorders in mice exposed to low temperature and high humidity by restoring the dysregulation of gut microbiota and fecal metabolites</strong> - The dramatic changes in global climate on human health have been extremely severe. The immune disorder caused by low temperature and high humidity (LTHH) have become a severe public health issue. Clinically, Jingfang granule (JF) has the effect of dispelling cold and eliminating dampness, and is widely used in the treatment of cold caused by wind and cold, autoimmune diseases, and COVID-19 with cold-dampness stagnating in the lung pattern. Our study aims to elucidate the effect of JF on…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>VANGL2 inhibits antiviral IFN-I signaling by targeting TBK1 for autophagic degradation</strong> - Stringent control of type I interferon (IFN-I) signaling is critical to potent innate immune responses against viral infection, yet the underlying molecular mechanisms are still elusive. Here, we found that Van Gogh-like 2 (VANGL2) acts as an IFN-inducible negative feedback regulator to suppress IFN-I signaling during vesicular stomatitis virus (VSV) infection. Mechanistically, VANGL2 interacted with TBK1 and promoted the selective autophagic degradation of TBK1 via K48-linked polyubiquitination…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mpropred: A machine learning (ML) driven Web-App for bioactivity prediction of SARS-CoV-2 main protease (Mpro) antagonists</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged in 2019 and still requiring treatments with fast clinical translatability. Frequent occurrence of mutations in spike glycoprotein of SARS-CoV-2 led the consideration of an alternative therapeutic target to combat the ongoing pandemic. The main protease (Mpro) is such an attractive drug target due to its importance in maturating several polyproteins during the replication process. In the present study, we used a…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, characterization and identification of inhibitory activity on the main protease of COVID-19 by molecular docking strategy of (4-oxo-piperidinium ethylene acetal) trioxonitrate</strong> - In this investigation a single crystal of (4-oxo-piperidinium ethylene acetal) trioxonitrate (4-OPEAN) was synthesized by modifying the mechanism of gradual evaporation at ambient temperature. The operational groupings are found in the complex material in the elaborate substance, according to the infrared spectrum. Single crystal X-ray diffraction suggests, (4-OPEAN) with the chemical formula (C(7)H(12)NO(2))NO(3) belongs to the orthorhombic space group Pnma and is centrosymmetric in three…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial</strong> - BACKGROUND: Activation of the TREM-1 pathway is associated with outcome in life threatening COVID-19. Data suggest that modulation of this pathway with nangibotide, a TREM-1 modulator may improve survival in TREM-1 activated patients (identified using the biomarker sTREM-1).</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reconsideration of interferon treatment for viral diseases: Lessons from SARS, MERS, and COVID-19</strong> - Periodic pandemics of coronavirus (CoV)-related pneumonia have been a major challenging issue since the outbreak of severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012. The ongoing pandemic of CoV disease (COVID-19) poses a substantial threat to public health. As for the treatment options, only limited antiviral agents have been approved hitherto, and clinicians mainly focus on currently available drugs including the conventional antiviral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two Novel Adenovirus Vectors Mediated Differential Antibody Responses via Interferon-α and Natural Killer Cells</strong> - Recombinant adenovirus vectors have been widely used in vaccine development. To overcome the preexisting immunity of human adenovirus type 5 (Ad5) in populations, a range of chimpanzee or rare human adenovirus vectors have been generated. However, these novel adenovirus vectors mediate the diverse immune responses in the hosts. In this study, we explored the immune mechanism of differential antibody responses to SARS-CoV-2 S protein in mice immunized by our previously developed two novel simian…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 nsp13 Restricts Episomal DNA Transcription without Affecting Chromosomal DNA</strong> - Nonstructural protein 13 (nsp13), the helicase of SARS-CoV-2, has been shown to possess multiple functions that are essential for viral replication, and is considered an attractive target for the development of novel antivirals. We were initially interested in the interplay between nsp13 and interferon (IFN) signaling, and found that nsp13 inhibited reporter signal in an IFN-β promoter assay. Surprisingly, the ectopic expression of different components of the RIG-I/MDA5 pathway, which were used…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 hijacks p38β/MAPK11 to promote virus replication</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, drastically modifies infected cells to optimize virus replication. One such modification is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammatory cytokine production, a hallmark of severe COVID-19. We previously demonstrated that inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduced…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Accelerating drug target inhibitor discovery with a deep generative foundation model</strong> - Inhibitor discovery for emerging drug-target proteins is challenging, especially when target structure or active molecules are unknown. Here, we experimentally validate the broad utility of a deep generative framework trained at-scale on protein sequences, small molecules, and their mutual interactions-unbiased toward any specific target. We performed a protein sequence-conditioned sampling on the generative foundation model to design small-molecule inhibitors for two dissimilar targets: the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ARF6 is a host factor for SARS-CoV-2 infection <em>in vitro</em></strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Irreversible Inactivation of SARS-CoV-2 by Lectin Engagement with Two Glycan Clusters on the Spike Protein</strong> - Host cell infection by SARS-CoV-2, similar to that by HIV-1, is driven by a conformationally metastable and highly glycosylated surface entry protein complex, and infection by these viruses has been shown to be inhibited by the mannose-specific lectins cyanovirin-N (CV-N) and griffithsin (GRFT). We discovered in this study that CV-N not only inhibits SARS-CoV-2 infection but also leads to irreversibly inactivated pseudovirus particles. The irreversibility effect was revealed by the observation…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Viral evasion of the interferon response at a glance</strong> - Re-emerging and new viral pathogens have caused significant morbidity and mortality around the world, as evidenced by the recent monkeypox, Ebola and Zika virus outbreaks and the ongoing COVID-19 pandemic. Successful viral infection relies on tactical viral strategies to derail or antagonize host innate immune defenses, in particular the production of type I interferons (IFNs) by infected cells. Viruses can thwart intracellular sensing systems that elicit IFN gene expression (that is, RIG-I-like…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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