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194 lines
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<title>08 May, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The Coviral Portal: Multi-Cohort Viral Loads and Antigen-Test Virtual Trials for COVID-19</strong> -
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Background. Regulatory approval of new over-the-counter tests for infectious agents such as SARS-CoV-2 has historically required that clinical trials include diverse groups of specific patient populations, making the approval process slow and expensive. Showing that populations do not differ in their viral loads—the key factor determining test performance—could expedite the evaluation of new tests. Methods. 46,726 RT-qPCR-positive SARS-CoV-2 viral loads were annotated with patient demographics and health status. Real-world performance of two commercially available antigen tests was evaluated over a wide range of viral loads. An open-access web portal was created allowing comparisons of viral-load distributions across patient groups and application of antigen-test performance characteristics to patient distributions to predict antigen-test performance on these groups. Findings. In several cases distributions were surprisingly similar where a difference was expected (e.g. smokers vs. non-smokers); in other cases there was a difference that was the opposite direction from expectations (e.g. higher in patients who identified as White vs. Black). Sensitivity and specificity of antigen tests for detecting contagiousness were similar across most groups. The portal is at https://arnaoutlab.org/coviral/. Conclusions. In silico analyses of large-scale, real-world clinical data repositories can serve as a timely evidence-based proxy for dedicated trials of antigen tests for specific populations. Free availability of richly annotated data facilitates large-scale hypothesis generation and testing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289582v1" target="_blank">The Coviral Portal: Multi-Cohort Viral Loads and Antigen-Test Virtual Trials for COVID-19</a>
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</div></li>
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<li><strong>Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19</strong> -
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Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with a novel airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Methods: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Results: Forty patients (32M:8F, age:22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. Conclusions: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established.
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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/10.1101/2023.05.05.23289594v1" target="_blank">Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19</a>
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<li><strong>A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic</strong> -
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Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/n3dyf/" target="_blank">A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic</a>
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<li><strong>A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic</strong> -
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The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/m4gpq/" target="_blank">A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic</a>
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<li><strong>An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique</strong> -
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<div>
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A novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 ( PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.04.539453v1" target="_blank">An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique</a>
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<li><strong>Paired associated SARS-CoV-2 spike variable positions: a network analysis approach to emerging variants</strong> -
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Amino acids in variable positions of proteins may be correlated, with potential structural and functional implications. Here, we apply exact tests of independence in R x C contingency tables to examine noise-free associations between variable positions of the SARS-CoV-2 spike protein, using as a paradigm sequences from Greece deposited in GISAID (N=6,683/1,078 full-length) for the period February 29, 2020 to April 26, 2021 that essentially covers the first three pandemic waves. We examine the fate and complexity of these associations by network analysis, using associated positions (exact p[≤]0.001 and Average Product Correction [≥]2) as links and the corresponding positions as nodes . We found a temporal linear increase of positional differences and a gradual expansion of the number of position associations over time, represented by a temporally evolving intricate web, resulting in a non-random complex network of 69 nodes and 252 links. Overconnected nodes corresponded to the most adapted variant positions in the population, suggesting a direct relation between network degree and position functional importance. Modular analysis revealed 25 k-cliques comprising three to 11 nodes. At different k-clique resolutions, one to four communities were formed, capturing epistatic associations of circulating variants (Alpha, Beta, B.1.1.318), but also Delta, which dominated the evolutionary landscape later in the pandemic. Cliques of aminoacidic positional associations tended to occur in single sequences, enabling the recognition of epistatic positions in real-world virus populations. Our findings provide a novel way of understanding epistatic relationships in viral proteins with potential applications in the design of virus control procedures.
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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/10.1101/2023.05.04.539462v1" target="_blank">Paired associated SARS-CoV-2 spike variable positions: a network analysis approach to emerging variants</a>
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<li><strong>The plasma metabolome of long COVID-19 patients two years after infection</strong> -
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Background: One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as long COVID) which has emerged as a consequence of the SARS-CoV-2 epidemic. The World Health Organization (WHO) recognized long COVID as a distinct clinical entity in 2021. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. This has put a tremendous strain on still-overstretched healthcare systems around the world. Methods: In this study, our goal was to assess the plasma metabolome in a total of 108 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin concentrations were measured in long COVID patients by immunoenzymatic assay. Results: The comparison of paired COVID-19/post-COVID-19 samples revealed 53 metabolites that were statistically different (FDR < 0.05). Compared to controls, 29 metabolites remained dysregulated even after two years. Notably, glucose, kynurenine, and certain acylcarnitines continued to exhibit altered concentrations similar to the COVID-19 phase, while sphingomyelins and long saturated and monounsaturated LysoPCs, phenylalanine, butyric acid, and propionic acid levels normalized. Post-COVID-19 patients displayed a heterogeneous metabolic profile, with some showing no symptoms while others exhibiting a variable number of symptoms. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, sarcosine, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Conclusions: Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289456v1" target="_blank">The plasma metabolome of long COVID-19 patients two years after infection</a>
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<li><strong>COVID-19 vaccination at a hospital in Paris: spatial analyses and inverse equity hypothesis</strong> -
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Background: Vaccination against SARS-CoV-2 has been deployed in France since January 2021. Evidence was beginning to show that the most vulnerable populations were the most affected by COVID-19. Without specific action for different population subgroups, the inverse equity hypothesis postulates that people in the least deprived neighbourhoods will be the first to benefit. Methods: We performed a spatial analysis using primary data from the vaccination centre of the Avicenne Hospital in Bobigny (Seine-Saint-Denis, France) from January 8th to September 30th, 2021. We used secondary data to calculate the social deprivation index. We performed flow analysis, k-means aggregation, and mapping. Results: During the period, 32,712 people were vaccinated at the study centre. Vaccination flow to the hospital shows that people living in the least disadvantaged areas were the first to be vaccinated. The number of people immunized according to the level of social deprivation then scales out with slightly more access to the vaccination centre for the most advantaged. The furthest have travelled more than 100 kilometres, and more than 1h45 of transport time to get to this vaccination centre. Access times are, on average, 50 minutes in February to 30 minutes in May 2021. Conclusion: The study confirms the inverse equity hypothesis and shows that vaccination preparedness strategies must take equity issues into account. Public health interventions should be implemented according to proportionate universalism and use community health, health mediation, and outreach activities for more equity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289561v1" target="_blank">COVID-19 vaccination at a hospital in Paris: spatial analyses and inverse equity hypothesis</a>
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<li><strong>COVID-19 risk variant associations with chromatin remodelling, DNA maintenance and surfactant genes are infection dependent in the lung</strong> -
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During viral infection the structure of host chromatin is modified. It is generally assumed that these chromatin modifications will affect variant-gene mapping, and therefore gene expression. What is not clear is how limitations imposed by host germline risk affect the expression changes that occur with infection induced chromatin remodelling. Critically, this lack of information extends to how germline variants associated with severe SARS-CoV-2 impact on tissue-specific gene expression changes in response to infection-induced chromatin conformation changes. Here we combined temporal chromatin conformation data from SARS-CoV-2 stimulated cells with a lung spatial-eQTL gene expression analysis to contextualise the functional effects and contributions of germline risk on the severe phenotypes observed in SARS-CoV-2. We identify changes in lung-specific SARS-CoV-2 risk variant-gene mapping across the infection time course. Our results provide evidence for infection-induced chromatin remodelling that impacts the regulation of genes associated with the severity of SARS-CoV-2 infection. The gene targets we identified are functionally involved in host chromatin modifications and maintenance and the expression of these genes is amplified by SARS-CoV-2-induced epigenetic remodelling. The effect of this remodelling includes transcriptional changes to gene targets such as SMARCA4, NCOR1, DNMT1, DNMT3a, DAXX, and PIAS4, all critical components of epigenetic control mechanisms and SARS-CoV-2 antiviral activity, along with several genes involved in surfactant metabolism. We show how severe-phenotype-associated eQTLs form and break in an infection time-course-dependent manner that mimics positive feedback loops connecting germline variation with the process of viral infection and replication. Our results provide a novel bridge between existing COVID-19 epigenetic research and demonstrate the critical role of epigenomics in understanding SARS-CoV-2-risk-associated gene regulation in the lung.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289478v1" target="_blank">COVID-19 risk variant associations with chromatin remodelling, DNA maintenance and surfactant genes are infection dependent in the lung</a>
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<li><strong>Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023</strong> -
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IMPORTANCE Several pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed. OBJECTIVE To analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA). DESIGN, SETTINGS, AND PARTICIPANTS This cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases. EXPOSURES Demographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination. MAIN OUTCOMES AND MEASURES Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy. RESULTS Among 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI ≥6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment. CONCLUSIONS AND RELEVANCE Among veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289479v1" target="_blank">Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023</a>
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<li><strong>Comprehensive Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome.</strong> -
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Wastewater is a discarded human by-product but analyzing it may help us understand the health of communities. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. We conducted a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Over 450 distinct pathogenic viruses were detected. Sequencing reads of established pathogens and emerging viruses correlated to clinical data sets. Viral communities were tightly organized by space and time. Finally, the most abundant human viruses yielded sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289441v1" target="_blank">Comprehensive Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome.</a>
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<li><strong>Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography</strong> -
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Since emergence of the initial SARS-CoV-2 omicron BA.1, BA.2 and BA.5 variants, omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5 omicron. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.02.23289412v1" target="_blank">Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography</a>
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<li><strong>Excess Mortality Resulting from COVID-19 in Turkey during 2020-2021: Regional and Time-Based Analysis</strong> -
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Turkey experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This study assessed the impact of the COVID-19 pandemic in Turkey, using the TURKSTAT data which became available on February 23, 2023. We applied a quasi-Poisson model to estimate excess mortality during 2020-2021, comparing excess mortality by time periods and socioeconomic factors (SEGE grades). During 2020-2021, Turkey experienced 72,886 excess deaths in 2020 (P-score 16.8%) and 125,540 in 2021 (P-score 28.5%). Excess all-cause mortality varied across SEGE levels, with notable social disparities in pandemic deaths as the highest rates were observed in SEGE 6, the lowest socioeconomic group. An additional 80 excess deaths per 100,000 people were recorded in 2020 and 143 in 2021. This study highlights the importance of a comprehensive approach to address the diverse impacts of the pandemic on health and well-being while considering socioeconomic disparities, and potential areas for improvement in data collection and reporting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.04.23289498v1" target="_blank">Excess Mortality Resulting from COVID-19 in Turkey during 2020-2021: Regional and Time-Based Analysis</a>
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<li><strong>Improved access to diabetic retinopathy screening through primary care-based teleophthalmology during the COVID-19 pandemic</strong> -
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BACKGROUND Eye diseases worldwide, including within the United States, are underdiagnosed and undertreated1. A multitude of factors contribute to this deficiency in eye care including, but not limited to, availability of specialists, transportation and mobility barriers, financial burden, lack of education, and poor patient-physician communication and understanding2,3,4. Teleophthalmology, a paradigm of care delivery in which ocular images are interpreted remotely by an eye specialist, has increased in interest since the COVID-19 pandemic, may offer improved access to necessary eye care5. The need for improved access through teleophthalmology is particularly critical for diabetic retinopathy (DR), the leading cause of new cases of blindness among adults aged 20 to 60 affecting more than 100 million patients worldwide6,7. DR arises when elevated levels of blood sugar resulting from either type 1 or 2 diabetes mellitus damage the blood vessels that supply oxygen and nutrients to the retina, the light-sensing part of the eye. The risk of developing DR is directly related to the length of time that a patient has diabetes and usually does not appear for approximately five years after a type 1 diabetes diagnosis, although it may already be present when type 2 diabetes is diagnosed8. In the absence of glycemic control and/or ophthalmic treatment, the disease may progress through three stages of non-proliferative retinopathy (mild, moderate, severe) before proliferative retinopathy develops. Diabetic macular edema can occur with any stage of retinopathy. If DR is diagnosed early, vision loss may be mitigated or prevented9. An annual fundus examination to screen for DR is critical, however, only about half of all patients with diabetes receive proper screening and less than 40% of patients with a high risk of vision loss ever undergo treatment10,11. In 2010, primary care providers (PCPs) delivered clinical care to approximately 90% of individuals with type 2 diabetes, and the proportion has increased over time12. The importance of primary care practitioners ensuring that their diabetic patients receive recommended eye care is reflected in the Healthcare Effectiveness Data and Information Set (HEDIS). This comprehensive set of quality performance measures across six domains of care guide the primary care of chronic medical conditions like diabetes mellitus and includes assessment of whether a diabetic patient receives diabetic eye screening at least every two years13. Attainment of these quality measures is increasingly important for health-system quality ratings and value-based reimbursement models. Practices are increasingly turning to teleophthalmology programs to aid in this goal of care5,14. Traditionally, DR is diagnosed by an eye specialist via an annual in-person fundoscopic examination. However, with appropriate training, non-ophthalmic clinicians and clinical personnel are able to use a fundus camera to take retinal photos that can then be evaluated by an ophthalmologist typically via a store-and-forward model. DR can be determined with high sensitivity and specificity from fundus photography, and a referral for further ophthalmic evaluation or treatment is made for those patients with retinopathy15. Primary care-based teleophthalmology programs have improved the accessibility and cost-effectiveness of DR screening in both rural and urban settings worldwide and are currently being applied to DR screening more commonly than any other ocular pathology16, 17,18. The ongoing COVID-19 pandemic has exacerbated existing barriers and increased the likelihood of ophthalmic appointment postponement or cancellation rendering teleophthalmology services even more critical to DR screening programs19, 20. The prevalence of diabetes in California is more than 40% above the United States national average21. As a means to improve the ophthalmic health of our patients, the Stanford Teleophthalmology Automated Testing and Universal Screening (STATUS) program was developed as a multi-site teleophthalmology DR screening collaboration between the Byers Eye Institute of Stanford (BEIS) and five affiliated primary care clinics throughout the San Francisco Bay Area. The program was initiated two to six months (depending on the site) prior to the onset of the COVID-19 pandemic in the United States and continued to provide remote eye examinations to patients throughout 2020 and 2021. The goal of the program was to evaluate whether the use of teleophthalmology could increase the percentage of patients screened for DR in collaboration with regional primary care clinics. Here, we examine the ability of the 18-month teleophthalmology program to improve and maintain access to DR eye care prior to and during the COVID-19 pandemic. METHODS Clinic Sites Non-mydriatic fundus cameras were deployed at an academic-affiliated primary care site in Santa Clara, CA in September 2019, and in four additional affiliated primary care sites in Los Gatos, Oakland, Hayward, and Pleasanton, CA beginning in February 2020. The primary care sites ranged from 20 miles (25-minute drive) to 42 miles (45-minute drive) away from the BEIS. Store-and-forward teleophthalmology screening for diabetic retinopathy continued at all five locations throughout the study period which ended April 2021. In order to determine whether the teleophthalmology program impacted the adherence rate to annual diabetic eye exams, HEDIS measures at two primary care sites (Pinole, CA and San Pablo, CA) in the same healthcare system that did not deploy the teleophthalmology system were also assessed. The study was approved by the Institutional Review Board at Stanford University. Patient Image Collection and Assessment Patients 18 years or older with type 1 or type 2 diabetes mellitus without a prior DR diagnosis or a DR exam in the past 12 months were offered the opportunity to have fundus photographs taken at the end of their primary care visit. Fundus imaging was performed by a trained medical assistant using the CenterVue DRS fundus camera (Hillrom Inc., Chicago, IL) at the Santa Clara primary clinic site and the TopCon NW400 fundus camera (Welch Allyn Inc., Skaneateles Falls, NY) at the Los Gatos, Oakland, Hayward, and Pleasanton primary care clinics. If medical assistants deemed the image quality to be poor, they repeated image acquisition and did so up to 4 times. The fundus images were forwarded to vitreoretinal specialists at BEIS who evaluated the images within one week. These fundus images were classified as ungradable (such as when opacity, blurring, or decentration impaired visualization of the fundus), or gradable if quality was sufficient for grading of DR. Images of adequate quality had a DR grade assigned in accordance with the International Clinical Diabetic Retinopathy Disease Severity Scale with moderate and severe categories combined on teleophthalmology evaluation (no diabetic retinopathy/mild non-proliferative diabetic retinopathy/moderate to severe non-proliferative diabetic retinopathy/proliferative diabetic retinopathy)22. Patient images were also assessed for the presence of macular edema or other fundus abnormalities. Patients with images of insufficient quality from one or both eyes were recommended to have the images retaken or present for an in-person eye examination. Diagnosis and stage of DR was determined by the eye with more advanced retinopathy. Those with referral-warranted disease were referred for an in-person exam at BEIS or their local ophthalmologist. A subset of patients (N=26) voluntarily presented for a second teleophthalmology screening one year after their first examination. Patient Data Patient files containing information on labs, orders, clinical notes, and patient information were retrieved from The STAnford Research Repository (STARR), an institutional resource for working with clinical data for research purposes. Data was managed and analyzed using Python (version 3.9.0) with Pandas (version 1.3.0). Patients who underwent fundus imaging without a documented assessment by BEIS specialists were excluded (N = 23). For all patients who were seen at BEIS after a referral for in-person examination, data was manually collected from the electronic health record. For analyses comparing patients prior to and during the COVID-19 pandemic, March 16th, 2020, was used as the start of the pandemic since on that date legal stay-at-home orders were announced in Alameda, Contra Costa, Marin, San Francisco, San Mateo, and Santa Clara counties. Longitudinal HEDIS data were only available for three of the teleophthalmology primary care sites and the two non-teleophthalmology comparison sites; two teleophthalmology primary care sites did not have structured HEDIS data available for analysis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289435v1" target="_blank">Improved access to diabetic retinopathy screening through primary care-based teleophthalmology during the COVID-19 pandemic</a>
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<li><strong>Mode Connections For Clinical Incremental Learning: Lessons From The COVID-19 Pandemic</strong> -
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Dynamic distribution shifts caused by evolving diseases and demographic changes require domain-incremental adaptation of clinical deep learning models. However, this process of adaptation is often accompanied by catastrophic forgetting, and even the most sophisticated methods are not good enough for clinical applications. This paper studies incremental learning from the perspective of mode connections, that is, the low-loss paths connecting the minimisers of neural architectures (modes or trained weights) in the parameter space. The paper argues for learning the low-loss paths originating from an existing mode and exploring the learned paths to find an acceptable mode for the new domain. The learned paths, and hence the new domain mode, are a function of the existing mode. As a result, unlike traditional incremental learning, the proposed approach is able to exploit information from a deployed model without changing its weights. Pre-COVID and COVID-19 data collected in Oxford University hospitals are used as a case study to demonstrate the need for domain-incremental learning and the advantages of the proposed approach.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289583v1" target="_blank">Mode Connections For Clinical Incremental Learning: Lessons From The COVID-19 Pandemic</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>Long COVID-19 Syndrome Lifestyle Intervention Study</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: Low carbohydrate diet intervention<br/><b>Sponsor</b>: University of Southern California<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>Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: mHealth Outreach; Other: Care Coordination<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<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 Coping and Resilience Intervention for Adolescents</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents<br/><b>Sponsor</b>: Taipei Medical University<br/><b>Enrolling by invitation</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>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>: Sars-CoV-2 Infection<br/><b>Interventions</b>: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>: Alvea Holdings, LLC<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>Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19</strong> - <b>Conditions</b>: GERD; Post COVID-19 Condition; Diaphragm Issues<br/><b>Interventions</b>: Other: modified diaphragmatic training; Other: standard diaphragmatic training<br/><b>Sponsor</b>: Indonesia 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>COVID-19 Vaccination Detoxification in LDL-C</strong> - <b>Conditions</b>: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Atorvastatin Calcium Tablets<br/><b>Sponsor</b>: Yang I. Pachankis<br/><b>Active, not 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>The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants</strong> - <b>Condition</b>: COVID-19 (Coronavirus Disease 2019)<br/><b>Interventions</b>: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10<br/><b>Sponsor</b>: Guangdong Raynovent Biotech 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>Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints</strong> - <b>Conditions</b>: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired<br/><b>Intervention</b>: Device: RehaCom<br/><b>Sponsor</b>: Erasmus Medical Center<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>Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome.</strong> - <b>Condition</b>: Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: RehabCovid_Telematic; Behavioral: RehabCovid_ImmersiveVR; Behavioral: Control_Condition<br/><b>Sponsors</b>: Consorci Sanitari de Terrassa; University of Barcelona; Universitat de Girona; Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment; Politecnic University of Catalonia; Corporación Fisiogestión<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 in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ALG-097558; Drug: Placebo; Drug: Midazolam; Drug: Itraconazole; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation<br/><b>Sponsor</b>: Aligos 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>Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition<br/><b>Interventions</b>: Device: Immunoadsorption; Device: Sham-apheresis<br/><b>Sponsor</b>: University Medical Center Mainz<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>Digital Mental Health Care for COVID-19 High-Risk Populations - Phase 2</strong> - <b>Conditions</b>: Stigma, Social; Help-Seeking Behavior<br/><b>Interventions</b>: Other: Adjusted Content Intervention; Other: Non-Adjusted Intervention Video<br/><b>Sponsors</b>: Research Foundation for Mental Hygiene, Inc.; Columbia 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 of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2; Influenza<br/><b>Interventions</b>: Biological: Fluarix; Biological: mRNA-1083.1; Biological: mRNA-1083.2; Biological: mRNA-1083.3; Biological: mRNA-1010.4; Biological: mRNA-1283.222; Biological: mRNA-1273.222; Biological: mRNA-1010; Biological: Fluzone HD<br/><b>Sponsor</b>: ModernaTX, 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>Efficacy of an Smartphone App Intervention Based on Self-compassion for Mental Health Among University Students</strong> - <b>Condition</b>: Mental Health Issue<br/><b>Interventions</b>: Behavioral: mHealth Intervention Based on Self-Compassion; Behavioral: Psychoeducation Intervention<br/><b>Sponsors</b>: Federal University of Health Science of Porto Alegre; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.<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>Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2</strong> - <b>Conditions</b>: Long COVID; Insulin Resistance; Insulin Sensitivity<br/><b>Interventions</b>: Procedure: Adipose Tissue Biopsy; Diagnostic Test: Steady State Plasma Glucose (SSPG) Test<br/><b>Sponsor</b>: Stanford University<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Critical role of TLR activation in viral replication, persistence, and pathogenicity of Theiler’s virus</strong> - Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections in the central nervous system and induces chronic inflammatory demyelinating disease in susceptible mice. TMEV infects dendritic cells, macrophages, B cells, and glial cells. The state of TLR activation in the host plays a critical role in initial viral replication and persistence. The further activation of TLRs enhances viral replication and persistence, leading to the pathogenicity of TMEV-induced…</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>Increased inflammatory cytokines and oxidative stress enhanced antibody production in breast and prostate cancer patients with COVID-19 related depression</strong> - Cancer management is highly dependent on the immune status of the patient. During the COVID-19 pandemic, a large number of people suffered from anxiety and depression, especially cancer patients. The effect of depression on breast cancer (BC) and prostate cancer (PC) patients, during the pandemic has been analyzed in this study. Levels of proinflammatory cytokines (IFN-γ, TNF-α, and IL-6) and oxidative stress markers malondialdehyde (MDA) and carbonyl content (CC) were estimated in patients’…</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>“Super” SERPINs-A stabilizing force against fibrinolysis in thromboinflammatory conditions</strong> - The superfamily of serine protease inhibitors (SERPINs) are a class of inhibitors that utilise a dynamic conformational change to trap and inhibit their target enzymes. Their powerful nature lends itself well to regulation of complex physiological enzymatic cascades, such as the haemostatic, inflammatory and complement pathways. The SERPINs α2-antiplasmin, plasminogen-activator inhibitor-1, plasminogen-activator inhibitor-2, protease nexin-1, and C1-inhibitor play crucial inhibitory roles 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>A Developmental Pathway From Early Behavioral Inhibition to Young Adults’ Anxiety During the COVID-19 Pandemic</strong> - CONCLUSION: This study identifies a developmental pathway from toddlerhood BI to young adults’ elevated anxiety during the COVID-19 pandemic. Findings have implications for early identification of individuals at risk for dysregulated worry and the prevention of anxiety during stressful life events in young adulthood.Reprinted from J Am Acad Child Adolesc Psychiatry, 60, Zeytinoglu et al., A Developmental Pathway From Early Behavioral Inhibition to Young Adults’ Anxiety During the COVID-19…</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>Deficient Radiation Transcription Response in COVID-19 Patients</strong> - CONCLUSIONS: SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19.</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>Application of single-cell RNA sequencing on human testicular samples: a comprehensive review</strong> - So far there has been no comprehensive review using systematic literature search strategies to show the application of single-cell RNA sequencing (scRNA-seq) in the human testis of the whole life cycle (from embryos to aging males). Here, we summarized the application of scRNA-seq analyses on various human testicular biological samples. A systematic search was conducted in PubMed and Gene Expression Omnibus (GEO), focusing on English researches published after 2009. Articles related to GEO…</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><em>In silico</em> study of potential SARS-CoV-2 antagonist from <em>Clitoria ternatea</em></strong> - CONCLUSION: From these results, it was concluded that C. ternatea possess potential therapeutic properties against COVID-19.</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>Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses</strong> - Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11’,13’-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4…</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>Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway</strong> - Porcine epidemic diarrhea virus (PEDV) is an entero-pathogenic coronavirus, which belongs to the genus Alphacoronavirus in the family Coronaviridae, causing lethal watery diarrhea in piglets. Previous studies have shown that PEDV has developed an antagonistic mechanism by which it evades the antiviral activities of interferon (IFN), such as the sole accessory protein open reading frame 3 (ORF3) being found to inhibit IFN-β promoter activities, but how this mechanism used by PEDV ORF3 inhibits…</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>Development and validation of an LC-MS/MS method for quantification of favipiravir in human plasma</strong> - Favipiravir (FVP) is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, first trialled for the treatment of influenza infection. It has been shown to be effective against a number of RNA virus families including arenaviruses, flaviviruses and enteroviruses. Most recently, FVP has been investigated as a potential therapeutic for severe acute respiratory syndrome coronavirus 2 infection. A liquid chromatography tandem mass spectrometry method for 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>Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2</strong> - Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus’s multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1)….</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>Myeloperoxidase inhibition may protect against endothelial glycocalyx shedding induced by COVID-19 plasma</strong> - CONCLUSIONS: Neutrophil MPO may increase EG shedding in COVID-19, and inhibiting MPO activity may protect against EG degradation. Further research is needed to evaluate the utility of MPO inhibitors as potential therapeutics against severe COVID-19.</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>Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation</strong> - Severe COVID-19 is characterized by an increase in the number and changes in the function of innate immune cells including neutrophils. However, it is not known how the metabolome of immune cells changes in patients with COVID-19. To address these questions, we analyzed the metabolome of neutrophils from patients with severe or mild COVID-19 and healthy controls. We identified widespread dysregulation of neutrophil metabolism with disease progression including in amino acid, redox, and central…</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>Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients</strong> - Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying…</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 anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids</strong> - The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar…</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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