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<title>07 November, 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>Beliefs in Conspiracy Theories and Online News Consumption during the onset of the COVID-19 pandemic</strong> -
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<div>
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Using an original survey covering 17 countries, this paper documents the prevalence of beliefs in theories related to the COVID-19 pandemic and characterizes the informational, demographic, and trust profiles of individuals who believe in conspiracy theories. There is considerable variation across countries in the level of conspiracy beliefs, with people in a set of countries like Romania, Poland, Greece, and Hungary being relatively more susceptible than respondents in northern Europe. We find several factors are correlated with conspiracy beliefs across countries. Relative to respondents who do not read news on social media, social media users tend to endorse more conspiracies, and this is the case for Facebook, Instagram, and YouTube users in particular. We also observe a link between distrust in medical experts or government and endorsement of conspiracy theories in most countries. In a subset of countries, we also find individuals with medium level of education and those who are younger to believe in a higher number of conspiracy theories.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/9zfg4/" target="_blank">Beliefs in Conspiracy Theories and Online News Consumption during the onset of the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Global Sensitivity Analysis of the Onset of Nasal Passage Infection by SARS-CoV-2 With Respect to Heterogeneity in Host Physiology and Host Cell-Virus Kinetic Interactions</strong> -
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<div>
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Throughout the COVID-19 pandemic, positive nasal swab tests have revealed dramatic population heterogeneity in viral titers spanning 6 orders-of-magnitude. Our goal here is to probe potential drivers of infection outcome sensitivity arising from (i) physiological heterogeneity between hosts and (ii) host-variant heterogeneity in the detailed kinetics of cell infection and viral replication. Toward this goal, we apply global sensitivity methods (Partial Rank Correlation Coefficient analysis and Latin Hypercube Sampling) to a physiologically faithful, stochastic, spatial model of inhaled SARS-CoV-2 exposure and infection in the human respiratory tract. We focus on the nasal passage as the primary origin of respiratory infection and site of clinical testing, and we simulate the spatial and dynamic progression of shed viral load and infected cells in the immediate 48 hours post infection. We impose immune evasion, i.e., suppressed immune protection, based on the preponderance of clinical evidence that nasal infections occur rapidly post exposure, largely independent of immune status. Global sensitivity methods provide the de-correlated outcome sensitivities to each source of within-host heterogeneity, including the dynamic progression of sensitivities at 12, 24, 36, and 48 hours post infection. The results reveal a dynamic rank-ordering of the drivers of outcome sensitivity in early infection, providing insights into the dramatic population-scale outcome diversity during the COVID-19 pandemic. While we focus on SARS-CoV-2, the model and methods are applicable to any inhaled virus in the immediate 48 hours post infection.
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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/10.1101/2023.11.04.565660v1" target="_blank">Global Sensitivity Analysis of the Onset of Nasal Passage Infection by SARS-CoV-2 With Respect to Heterogeneity in Host Physiology and Host Cell-Virus Kinetic Interactions</a>
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</div></li>
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<li><strong>Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants</strong> -
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<div>
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Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.
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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/10.1101/2023.11.03.565292v1" target="_blank">Integrated longitudinal multi-omics study identifies immune programs associated with COVID-19 severity and mortality in 1152 hospitalized participants</a>
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</div></li>
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<li><strong>Dynamic gene expression analysis reveals distinct severity phases of immune and cellular dysregulation in COVID-19</strong> -
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Background: COVID-19 patients experience dynamic changes in immune and cellular function over time with potential clinical implications. However, there is insufficient research investigating, on a gene expression level, the mechanisms that become activated or suppressed over time as patients deteriorate or recover, which can inform use of repurposed and novel drugs as therapies. Objective: To investigate longitudinal changes in gene expression profiles throughout the COVID-19 disease timeline. Methods: Three-hundred whole blood samples from 128 adult patients were collected during hospitalization from COVID-19, with up to five samples per patient. Transcriptome sequencing (RNA-Seq), differential gene expression analysis and pathway enrichment was performed. Drug-gene set enrichment analysis was used to identify FDA-approved medications that could inhibit critical genes and proteins at each disease phase. Prognostic gene-expression signatures were generated using machine learning to distinguish 3 disease stages. Results: Samples were longitudinally grouped by clinical criteria and gene expression into six disease phases: Mild, Moderate, Severe, Critical, Recovery, and Discharge. Distinct mechanisms with differing trajectories during COVID-19 hospitalization were apparent. Antiviral responses peaked early in COVID-19, while heme metabolism pathways became active much later during disease. Adaptive immune dysfunction, inflammation, and metabolic derangements were most pronounced during phases with higher disease severity, while hemostatic abnormalities were elevated early and persisted throughout the disease course. Drug-gene set enrichment analysis predicted repurposed medications for potential use, including platelet inhibitors in early disease, antidiabetic medications for patients with increased disease severity, and dasatinib throughout the disease course. Disease phases could be categorized using specific gene signatures for prognosis and treatment selection. Disease phases were also highly correlated to previously developed sepsis endotypes, indicating that severity and disease timing were significant contributors to heterogeneity observed in sepsis and COVID-19. Conclusions: Higher temporal resolution of longitudinal mechanisms in COVID-19 revealed multiple immune and cellular changes that were activated at different phases of COVID-19. Understanding how a patient's gene expression profile changes over time can permit more accurate risk stratification of patients and provide time-dependent personalized treatments with repurposed medications. This creates an opportunity for timely intervention before patients transition to a more severe phase, potentially accelerating patients to recovery.
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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/10.1101/2023.11.04.565404v1" target="_blank">Dynamic gene expression analysis reveals distinct severity phases of immune and cellular dysregulation in COVID-19</a>
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<li><strong>Supply Chain Resilience and Medicine Availability in Saudi Arabian Pharmacies: A Case Study in Jeddah</strong> -
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This article investigates the critical issue of supply chain resilience and its impact on medicine availability in Saudi Arabian pharmacies, focusing on a case study in Jeddah. During the COVID-19 pandemic, pharmacies in Jeddah experienced significant supply chain disruptions, leading to challenges in maintaining medicine availability. The study explores the resilience measures implemented by these pharmacies during the crisis and offers practical recommendations to enhance supply chain resilience. These recommendations include regulatory adjustments, the adoption of advanced technology, and strategic approaches to ensure uninterrupted access to essential medicines. This research underscores the crucial role of resilient supply chains in the context of public health and emphasizes the need for proactive measures to safeguard medicine availability in Saudi Arabian pharmacies and similar healthcare settings.
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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://osf.io/f47xh/" target="_blank">Supply Chain Resilience and Medicine Availability in Saudi Arabian Pharmacies: A Case Study in Jeddah</a>
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</div></li>
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<li><strong>Zheln.com: A protocol for a universal living overview of health-related systematic reviews</strong> -
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<div>
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BACKGROUND Objectives. 1. Identify and monitor most of published systematic reviews. 2. Tag the identified systematic records with medical specialties. 3. Select or crowdfund reviews for further appraisal. 4. Critically appraise and replicate the selected systematic reviews. 5. Disseminate practice implications of positively appraised reviews to both the public and evidence-based practitioners in health care and other fields associated with intervention into a human life, such as education, business, policy, or ecology. METHODS Eligibility criteria. Record eligibility is assessed by checking the record title and, if the title failed, abstract against the ‘true positive criteria’ for systematic reviews taken from the publication by Shojania & Bero, 2001 (PMID 11525102). The record/study flow is as follows: All eligible records are amenable for tagging, selection, and crowdfunding process; Only those eligible records that have been selected or crowdfunded are subject to critical appraisal; For all records that have been selected, all relevant reports are collected; Reports are grouped into studies; Only for the studies appraised positively, practical implications are summarized and disseminated. COVID-19 publications are not selected. Crowdfunding an appraisal of any eligible record is possible for any individual or organization. Information sources. MEDLINE via PubMed. Adding other search sources, such as Scopus, OSF, and medRxiv, is planned in the future when more appraisers become available. The Replicated Version of the PubMed Systematic Review Subset Query Zheln Edition (DOI 10.17605/OSF.IO/Z3JU7) will be used. The searches are run daily. Risk of bias. Critical appraisal will feature: Duplication assessment; Replication; Assessment against the MECIR conduct standards; ROB-ME assessment; GRADE assessment. Synthesis of results. No across-studies synthesis is planned. Within-studies, I will formulate explicit practice-relevant statements based on the extracted health outcomes and quality-of-conduct assessment. Also, the process of each critical appraisal is video-recorded and published on YouTube daily. OTHER Funding. The review is crowdfunded; the details are available from the Zheln website (https://zheln.com). Crowd funders had no role in the design of the protocol. They will be able to request critical appraisal and additional critical appraisal (with new data provided) of any eligible record but will not influence the review process otherwise. Registration. The project is hosted on GitHub. Also, there is an umbrella Open Science Framework project that links repositories and preprints (DOI 10.17605/OSF.IO/EJKFC). The protocol for this overview of systematic reviews has been submitted for registration in PROSPERO.
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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://osf.io/preprints/metaarxiv/y2nrb/" target="_blank">Zheln.com: A protocol for a universal living overview of health-related systematic reviews</a>
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</div></li>
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<li><strong>Not Causal or Descriptive But Some Secret, Other Thing: Entropy as a Criterion for Causal Learning</strong> -
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While many classify studies as either descriptive or causal, I argue that causality is a continuous construct, and different inference modes–experimental, observational and mechanistic–can at best provide only partial causal information. To discriminate between the relative value of different inference modes, I employ statistical entropy as a possible yardstick for evaluating research designs as different operations on causal graphs. Rather than dichotomize studies as either causal or descriptive, the concept of entropy instead emphasizes the relative causal knowledge gained from a given research finding. I employ this theory to clarify why and when researchers relied on divergent modes of inference to determine the efficacy of vaccines over the course of the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/a492b/" target="_blank">Not Causal or Descriptive But Some Secret, Other Thing: Entropy as a Criterion for Causal Learning</a>
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<li><strong>Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19</strong> -
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Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans’ experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars, who completed a total of four assessments: one every two months for a total duration of six months. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/xf3zb/" target="_blank">Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19</a>
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<li><strong>Associations among anxiety, risk perception, preventive behaviors, and personality in Japanese older adults aged 78 to 99 years during the COVID-19 pandemic</strong> -
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<div>
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Background and Objectives: To deepen the understanding of processes underlying older adults’ behavior during the COVID-19 pandemic, we investigated associations among affective (anxiety about the coronavirus), cognitive (perceived risk of infection and fatality), and behavioral (engagement in preventive behaviors) variables. We also examined how these variables were predicted by personality traits measured before the pandemic. Research Design and Methods: Older adults (N = 1,727; 78–99 years old) were recruited from an ongoing longitudinal cohort study started in 2010. They responded to a questionnaire sent in August 2020, which included four items measuring COVID-19 anxiety, infection risk perception, fatality risk perception, and engagement in preventive behaviors. Big Five personality traits were measured years ago when the participants had first participated in the study. Results: Most participants felt anxious, engaged in preventive behaviors, and overestimated infection and fatality risks. Older age was associated with low anxiety, a low perception of infection risk, a high perception of fatality risk, and a little engagement in preventive behaviors. Women were more susceptible to the pandemic than men were, demonstrated by higher scores on all four items. Partial correlation analysis controlling for age and sex demonstrated positive associations among all four items except for infection risk perception and preventive behaviors. Anxiety and perceived infection risk were positively predicted by neuroticism and conscientiousness, respectively. Engagement in preventive behaviors was positively predicted by extraversion, openness to experience, and conscientiousness. Discussion and Implications: We highlighted the critical distinction between infection and fatality risk perceptions and demonstrated the need to consider each individual’s attributes.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/vzgcp/" target="_blank">Associations among anxiety, risk perception, preventive behaviors, and personality in Japanese older adults aged 78 to 99 years during the COVID-19 pandemic</a>
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<li><strong>Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution</strong> -
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Measures to control the COVID-19 pandemic such as antiviral therapy and vaccination have been challenged by ongoing virus evolution under antiviral and immune pressures. Understanding viral evolutionary dynamics is crucial for responding to SARS-CoV-2, and preparing for the next pandemic, by informing prediction of virus adaptation, public health strategies, and design of broadly effective therapies. Whole-genome sequencing (WGS) of SARS-CoV-2 during the pandemic enabled fine-grained studies of virus evolution in the human population. Serial passaging in vitro offers a controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage. Nine virus lineages, including four "variants of concern" and three former "variants under investigation" as designated by the World Health Organisation, were chosen to investigate intra- and inter-lineage evolution through long-term serial passaging in Vero E6 cells. Viruses were sampled over at least 33 passages (range 33-100) and analysed using WGS to examine evolutionary dynamics and identify key mutations with implications for virus fitness, transmissibility, and immune evasion. All passages continued to replicate in culture, despite regular accumulation of mutations. There was evidence of convergent acquisition of mutations both across passage lines and compared with contemporaneous SARS CoV-2 clinical sequences from population studies. Some of these convergent mutations are hypothesised to be important in proliferation of SARS-CoV-2 lineages, such as by evading host immune responses (e.g. S:A67V, S:H655Y). Given these mutations arose in vitro, in the absence of a multicellular host immune response, this suggests virus genome mutation resulted from stochastic events, rather than immune-driven mutation. There was a regular gain and loss of low-frequency variants during serial passaging, but some became fixed in subsequent multiple passages, suggesting either a benefit of the mutation in vitro, or at least a lack of deleterious effect. Our findings reveal valuable insights into the evolution of SARS-CoV-2 by quantitatively investigating evolutionary dynamics of the virus over the greatest number of serial passages to date. Knowledge of these evolutionary trends will be useful for public health and the development of antiviral and vaccine measures to reduce the effects of SARS CoV-2 infection on the human population.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.02.565396v1" target="_blank">Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution</a>
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<li><strong>Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2</strong> -
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Bulk RNA sequencing (RNA-seq) of blood is typically used for gene expression analysis in biomedical research but is still rarely used in clinical practice. In this study, we argue that RNA-seq should be considered a routine diagnostic tool, as it offers not only insights into aberrant gene expression and splicing but also delivers additional readouts on immune cell type composition as well as B-cell and T-cell receptor (BCR/TCR) repertoires. We demonstrate that RNA-seq offers vital insights into a patient's immune status via integrative analysis of RNA-seq data from patients infected with various SARS-CoV-2 variants (in total 240 samples with up to 200 million reads sequencing depth). We compare the results of computational cell-type deconvolution methods (e.g., MCP-counter, xCell, EPIC, quanTIseq) to complete blood count data, the current gold standard in clinical practice. We observe varying levels of lymphocyte depletion and significant differences in neutrophil levels between SARS-CoV-2 variants. Additionally, we identify B and T cell receptor (BCR/TCR) sequences using the tools MiXCR and TRUST4 to show that - combined with sequence alignments and pBLAST - they could be used to classify a patient's disease. Finally, we investigated the sequencing depth required for such analyses and concluded that 10 million reads per sample is sufficient. In conclusion, our study reveals that computational cell-type deconvolution and BCR/TCR methods using bulk RNA-seq analyses can supplement missing CBC data and offer insights into immune responses, disease severity, and pathogen-specific immunity, all achievable with a sequencing depth of 10 million reads per sample.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.03.564190v1" target="_blank">Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2</a>
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<li><strong>Voltage-gated T-type calcium channel blockers reduce apoptotic body-mediated SARS-CoV-2 cell-to-cell spread and subsequent cytokine storm</strong> -
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SARS-CoV-2 typically utilises host angiotensin-converting enzyme 2 (ACE2) as a cellular surface receptor and host serine protease TMPRSS2 for the proteolytic activation of viral spike protein enabling viral entry. Although macrophages express low levels of ACE2, they are often found positive for SARS-CoV-2 in autopsied lungs from COVID-19 patients. As viral-induced macrophage inflammation and overwhelming cytokine release are key immunopathological events that drives exacerbated tissue damage in severe COVID-19 patients, insights into the entry of SARS-CoV-2 into macrophages are therefore critical to understand COVID-19 pathogenesis and devise novel COVID-19 therapies. Mounting evidence suggest that COVID-19 pathogenesis is associated with apoptosis, a type of programmed cell death that often leads to the release of numerous large extracellular vesicles (EVs) called apoptotic bodies (ApoBDs). Here, we showed that ApoBDs derived from SARS-CoV-2-infected cells carry viral antigens and infectious virions. Human monocyte-derived macrophages readily efferocytosed SARS-CoV-2-induced ApoBDs, resulting in SARS-CoV-2 entry and pro-inflammatory responses. To target this novel ApoBD-mediated viral entry process, we screened for ApoBD formation inhibitors and discovered that T-type voltage-gated calcium channel (T-channel) blockers can inhibit SARS-CoV-2-induced ApoBD formation. Mechanistically, T-channel blockers impaired the extracellular calcium influxes required for ApoBD biogenesis. Importantly, blockade of ApoBD formation by T-channel blockers were able to limit viral dissemination and virus-induced macrophage inflammation in vitro and in a pre-clinical mouse model of severe COVID-19. Our discovery of the ApoBD-efferocytosis-mediated viral entry reveals a novel route for SARS-CoV-2 infection and cytokine storm induction, expanding our understanding of COVID-19 pathogenesis and offering new therapeutic avenues for infectious diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.03.565419v1" target="_blank">Voltage-gated T-type calcium channel blockers reduce apoptotic body-mediated SARS-CoV-2 cell-to-cell spread and subsequent cytokine storm</a>
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<li><strong>Can a pan-coronavirus vaccine limit the threat of SARS-CoV-2 emerging variants and prevent any future pandemic?</strong> -
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During coronavirus disease 2019 (COVID-19) pandemic, the initial application of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines were deemed to be effective in preventing infection. However, the efficacy of these vaccines was then significantly reduced due to the emergence of SARS-CoV-2 variants that can evade host immune response. Moreover, waning of SARS-CoV-2 neutralizing antibodies (nAbs) level over time represents another challenge to control COVID-19 ongoing waves. The short-term immunity conferred by the currently available vaccines may lead to a never-ending cycle of SARS-CoV-2 variants emergence and ongoing waves of COVID-19. In addition, the presence of animal reservoir for coronaviruses is complicating efforts to eradicate these pathogens. As such, by employing different designs and approaches, broad-spectrum or pan-coronavirus vaccines may represent a potential tool to fight various emergent variants of SARS-CoV-2 through the generation of long-lasting and cross-reactive neutralizing antibodies. The production of these broad-spectrum neutralizing antibodies is currently explored through application of strategies like the use of pathogen conserved (consensus) epitopes, heterologous sequential immunization, and mosaic nanoparticle platform. But the big questions that need answers: Can these proposed broad-spectrum or pan-coronavirus vaccines be effective against the emergent variants for SARS-CoV-2? And can they prevent any future pandemic driven by coronaviruses?
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🖺 Full Text HTML: <a href="https://osf.io/q4u5d/" target="_blank">Can a pan-coronavirus vaccine limit the threat of SARS-CoV-2 emerging variants and prevent any future pandemic?</a>
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<li><strong>MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C)</strong> -
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Background: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus. Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018-December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5+-DM outbreak. Results: Sixty new anti-MDA5+, but not other MSAs surged between 2020-2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. Few (8/60) had a prior history of COVID-19, whereas 58% (35/60) had received anti-SARS-CoV-2 RNA vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. Conclusions: A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.03.23297727v1" target="_blank">MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C)</a>
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<li><strong>M3NetFlow: a novel multi-scale multi-hop multi-omics graph AI model for omics data integration and interpretation</strong> -
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The integration and interpretation of multi-omics data play a crucial role in systems biology for prioritizing vital molecular targets and deciphering core signaling pathways of complex diseases, such as cancer, COVID-19 and Alzheimer’s disease. However, it remains a challenge that has not been adequately addressed. Graph neural networks (GNN) have emerged as powerful artificial intelligence models for analyzing data with a graphical structure. Nevertheless, GNN models have not been sufficiently designed for integrative and interpretable multi-omics data analysis. In this study, we propose a novel multi-scale multi-hop multi-omics GNN model, M3NetFlow, to integrate and interpret multi-omics data to rank key targets and infer core signaling pathways. Specifically, we applied the M3NetFlow model to infer cell-line-specific core signaling networks explaining drug combination response. The evaluation and comparison results on drug combination prediction showed that the M3NetFlow model achieved significantly higher prediction accuracy than existing GNN models. Furthermore, M3NetFlow can predict key targets and infer essential signaling networks regulating drug combination response. It is critical for guiding the development of personalized precision medicine for patients with drug resistance. This model can be applied to general multi-omics data-driven research. Aside from that, we developed the visualization tool, NetFlowVis, the better analysis of targets and signaling pathways of drugs and drug combinations.
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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/10.1101/2023.06.15.545130v2" target="_blank">M3NetFlow: a novel multi-scale multi-hop multi-omics graph AI model for omics data integration and interpretation</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>Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting</strong> - <b>Conditions</b>: Post COVID-19 Condition (PCC) <br/><b>Interventions</b>: Device: RDX-19 <br/><b>Sponsors</b>: KNOWBio Inc.; NAMSA <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 PhaseⅡ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O)</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) 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>CPAP Therapy Through a Helmet or a Full Face Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study</strong> - <b>Conditions</b>: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia <br/><b>Interventions</b>: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate <br/><b>Sponsors</b>: I.M. Sechenov First Moscow State 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>Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Virus Diseases; COVID-19 <br/><b>Interventions</b>: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment <br/><b>Sponsors</b>: AVB Biotechnology <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 PhaseⅠ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O)</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) 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>SAFE Workplace Intervention for People With IDD</strong> - <b>Conditions</b>: Developement of Infectious Airborne Disease Prevention Workplace Curriclulm <br/><b>Interventions</b>: Behavioral: SAFE Employment Training <br/><b>Sponsors</b>: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research <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>Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms</strong> - <b>Conditions</b>: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame <br/><b>Interventions</b>: Behavioral: EMDR <br/><b>Sponsors</b>: University of Pisa <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>Lithium Long COVID Dose-finding Study</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Dietary Supplement: Lithium <br/><b>Sponsors</b>: State University of New York at Buffalo <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>Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Drug: GST-HG171 Tablets <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology 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>Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic</strong> - <b>Conditions</b>: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children <br/><b>Interventions</b>: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education <br/><b>Sponsors</b>: Chung Shan Medical 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>Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Liver Function</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Drug: GST-HG171 Tablets <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <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>Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19; Coronavirus <br/><b>Interventions</b>: Device: eBAM Cov Testing <br/><b>Sponsors</b>: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE <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>Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: EG-COVII <br/><b>Sponsors</b>: EyeGene Inc. <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>Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers</strong> - <b>Conditions</b>: Viral Infection COVID-19 <br/><b>Interventions</b>: Drug: Aterixen <br/><b>Sponsors</b>: Valenta Pharm JSC <br/><b>Not yet 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>Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer</strong> - CONCLUSIONS: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.</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>Broad spectrum post-entry inhibitors of coronavirus replication: Cardiotonic steroids and monensin</strong> - A small molecule screen identified several cardiotonic steroids (digitoxin and ouabain) and the ionophore monensin as potent inhibitors of HCoV-229E, HCoV-OC43, and SARS-CoV-2 replication with EC(50)s in the low nM range. Subsequent tests confirmed antiviral activity in primary cell models including human nasal epithelial cells and lung organoids. Addition of digitoxin, ouabain, or monensin strongly reduced viral gene expression as measured by both viral protein and RNA accumulation….</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>Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon</strong> - Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits viral replication both in vitro and in vivo. Moreover, lipin-2 also acts as a regulator of…</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>Saying no to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia</strong> - Nitric oxide (NO), a gaseous free radical produced from L-arginine catalyzed by NO synthase, functions as an important signaling molecule in the human body. Its antiviral activity was confirmed in the 1990s, and has been studied more extensively since the outbreak of the SARS pandemic in 2003. In the fight against the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, some recent studies have revealed the potential of NO in the treatment of coronavirus disease 2019…</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>Understanding psychology students’ perspective on video psychotherapy and their intention to offer it after graduation: a mixed-methods study</strong> - INTRODUCTION: Video psychotherapy (VPT) demonstrated strong clinical efficacy in the past, with patients and psychotherapists expressing satisfaction with its outcomes. Despite this, VPT only gained full recognition from the German healthcare system during the COVID-19 pandemic. As society increasingly relies on new media, it seems likely that VPT will become even more relevant. Previous studies surveyed practicing psychotherapists and patients about advantages and disadvantages of VPT. In…</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>Oral mucosa immunity: ultimate strategy to stop spreading of pandemic viruses</strong> - Global pandemics are most likely initiated via zoonotic transmission to humans in which respiratory viruses infect airways with relevance to mucosal systems. Out of the known pandemics, five were initiated by respiratory viruses including current ongoing coronavirus disease 2019 (COVID-19). Striking progress in vaccine development and therapeutics has helped ameliorate the mortality and morbidity by infectious agents. Yet, organism replication and virus spread through mucosal tissues cannot be…</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>Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation associated transcription factors</strong> - The novel coronavirus SARS-CoV-2, responsible for COVID-19, can trigger dysregulated immune responses known as cytokine release syndrome (CRS), leading to severe organ dysfunction and respiratory distress. Our study focuses on developing an improved cell-permeable nuclear import inhibitor, iCP-NI, capable of blocking the nuclear transport of inflammation-associated transcription factors (IATFs), specifically nuclear factor kappa B (NF-κB). By fusing advanced macromolecule transduction domains…</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>Hyperbaric Oxygen Treatment for Long COVID: From Molecular Mechanism to Clinical Practice</strong> - Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus…</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>The extracellular polysaccharide inhibit porcine epidemic diarrhea virus with extract and gene editing Lacticaseibacillus</strong> - Lacticaseibacillus is one of the predominant microorganisms in gut from human and animal, and the lacticaseibacillus have effective applications against the viral diarrhea of piglets in the farm. However, the function and the concrete cell single pathways of the active ingredient from lacticaseibacillus was not clear within anti-infection in the postbiotics research. Here, we compared the biological function of extracellular polysaccharides (EPS) purified from lacticaseibacillus casei (L. casei)…</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>Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story</strong> - Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatory…</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>Veratramine Inhibits Porcine Epidemic Diarrhea Virus Entry through Macropinocytosis by Suppressing PI3K/Akt Pathway</strong> - Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by α-coronavirus porcine epidemic diarrhea virus (PEDV). At present, no effective vaccine is available to prevent the disease. Therefore, research for novel antivirals is important. This study aimed to identify the antiviral mechanism of Veratramine (VAM), which actively inhibits PEDV replication with a 50% inhibitory concentration (IC(50)) of ∼ 5 µM. Upon VAM treatment, both PEDV-nucleocapsid (N) protein level and virus…</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>Promising role of Vitamin D and plant metabolites against COVID-19: Clinical trials review</strong> - Vitamin D possesses immunomodulatory qualities and is protective against respiratory infections. Additionally, it strengthens adaptive and cellular immunity and boosts the expression of genes involved in oxidation. Experts suggested taking vitamin D supplements to avoid and treat viral infection and also COVID-19, on the other hand, since the beginning of time, the use of plants as medicines have been vital to human wellbeing. The WHO estimates that 80 % of people worldwide use plants or herbs…</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>Plant-Derived Antioxidants for Management of COVID-19: A Comprehensive Review of Molecular Mechanisms</strong> - We aimed to review the literature to introduce some effective plant-derived antioxidants to prevent and treat COVID-19. Natural products from plants are excellent sources to be used for such discoveries. Among different plant-derived bioactive substances, components including luteolin, quercetin, glycyrrhizin, andrographolide, patchouli alcohol, baicalin, and baicalein were investigated for several viral infections as well as SARS-COV-2. The mechanisms of effects detected for these agents were…</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 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was…</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 novel cell-permeable peptide prevents protein SUMOylation and supports the mislocalization and aggregation of TDP-43</strong> - SUMOylation is a post-translational modification (PTM) that exerts a regulatory role in different cellular processes, including protein localization, aggregation, and biological activities. It consists of the dynamic formation of covalent isopeptide bonds between a family member of the Small Ubiquitin Like Modifiers (SUMOs) and the target proteins. Interestingly, it is a cellular mechanism implicated in several neurodegenerative pathologies and potentially it could become a new therapeutic…</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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