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<title>28 February, 2024</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>The relationship between risk perception and information sources during the COVID-19 pandemic in Southeast Alaska</strong> -
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<div>
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Objective: We describe changes in consumption of different information sources during the first year of the COVID-19 pandemic across Southeast Alaska. Study Design: We administered two surveys in Southeast Alaska at two critical points during the COVID-19 pandemic (April-June 2020 and November 2020-February 2021) resulting in a convenience sample (n > 1000) of respondents over age 18. Methods: Using survey responses from the two time points, we calculated absolute and percent changes in reported usage of 11 different information sources and tested these changes using a two-proportion z-score. We used logistic regression to estimate the probability of consuming national news, local news, internet sources, social media, and talking with trusted individuals while controlling for demographic variables (age, sex, ethnicity group), risk perceptions, and time. Results: We found no strong relationships between risk perceptions and the probability of consuming various information sources. Males were significantly less likely to consume national sources, local sources, and use social media. Respondents 65 years and older were significantly more likely to consume national sources and local sources and were significantly less likely to consume social media. Conclusions: Different demographic groups use various information sources differently in Southeast Alaska. This could result in uneven quality of, understanding of, and action upon public health messages.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/u4kvs/" target="_blank">The relationship between risk perception and information sources during the COVID-19 pandemic in Southeast Alaska</a>
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</div></li>
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<li><strong>TISSUE-SPECIFIC METABOLOMIC REPROGRAMMING DETERMINES THE DISEASE PATHOPHYSIOLOGY OF SARS-COV-2 VARIANTS IN HAMSTER MODEL</strong> -
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<div>
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Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between organs and specific SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed increased viremia in diverse tissues of delta-infected GSH compared to the omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute 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/10.1101/2024.02.25.581989v1" target="_blank">TISSUE-SPECIFIC METABOLOMIC REPROGRAMMING DETERMINES THE DISEASE PATHOPHYSIOLOGY OF SARS-COV-2 VARIANTS IN HAMSTER MODEL</a>
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</div></li>
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<li><strong>RAMEN Unveils Clinical Variable Networks for COVID-19 Severity and Long COVID Using Absorbing Random Walks and Genetic Algorithms</strong> -
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<div>
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The COVID-19 pandemic has significantly altered global socioeconomic structures and individual lives. Understanding the disease mechanisms and facilitating diagnosis requires comprehending the complex interplay among clinical factors like demographics, symptoms, comorbidities, treatments, lab results, complications, and other metrics, and their relation to outcomes such as disease severity and long term outcomes (e.g. post-COVID-19 condition/long COVID). Conventional correlational methods struggle with indirect and directional connections among these factors, while standard graphical methods like Bayesian networks are computationally demanding for extensive clinical variables. In response, we introduced RAMEN, a methodology that integrates Genetic Algorithms with random walks for efficient Bayesian network inference, designed to map the intricate relationships among clinical variables. Applying RAMEN to the Biobanque quebecoise de la COVID-19 (BQC19) dataset, we identified critical markers for long COVID and varying disease severity. The Bayesian Network, corroborated by existing literature and supported through multi-omics analyses, highlights significant clinical variables linked to COVID-19 outcomes. RAMEN’s ability to accurately map these connections contributes substantially to developing early and effective diagnostics for severe COVID-19 and long COVID.
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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/10.1101/2023.01.24.525413v2" target="_blank">RAMEN Unveils Clinical Variable Networks for COVID-19 Severity and Long COVID Using Absorbing Random Walks and Genetic Algorithms</a>
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</div></li>
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<li><strong>End-user feedback of rapid diagnostics in rural Kenya</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Underserved communities in low-resource countries are disproportionately impacted by communicable diseases when compared to those in developed countries. These communities have limited access to life saving diagnostic laboratory tests making it difficult to treat communicable diseases like SARS-CoV-2 and Human Immunodeficiency Virus (HIV). Rapid diagnostic tests, like the COVID-19 antigen (Ag) test, play a crucial role in underserved communities by enabling fast and inexpensive diagnosis in low-resource settings. Unfortunately, these rapid test platforms often lack the accuracy and precision of their laboratory-based analogs, resulting in a need for improved rapid diagnostics. The World Health Organization’s (WHO) ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable to end-users) criteria are often referenced in the development of diagnostic tests. In this work, we aim to provide guidance to the “user-friendly” component of ASSURED through end-user surveys taken in rural Kenya. In these surveys, we examine the user-friendliness of two of the most commonly used rapid diagnostic tests, the COVID-19 Ag test and pregnancy test, by assessing participants’ familiarity with the tests, their opinion of test appearance, and the perceived complexity of the operator’s workflow. We also examine community acceptance and desire for a self-test for the highly stigmatized HIV. We intend these results to help guide developers of future rapid diagnostic tests intended for low-resource communities.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.23.24302446v1" target="_blank">End-user feedback of rapid diagnostics in rural Kenya</a>
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</div></li>
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<li><strong>Telemedicine’s Impact on Diabetes Care during the COVID-19 Pandemic: A Cohort Study in a Large Integrated Healthcare System</strong> -
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Introduction To examine if patients exposed to primary care telemedicine (telephone or video) early in the COVID-19 pandemic had higher rates of downstream HbA1c measurement and improved HbA1c levels in the second year of the pandemic. Research Design and Methods In a cohort of 242, 848 Kaiser Permanente Northern California patients with diabetes, we examined associations between early-pandemic patient-initiated telemedicine visit and downstream HbA1c monitoring and results during the second year of the pandemic. Results Adjusted HbA1c measurement rates were significantly higher among patients with telemedicine exposure in the early-pandemic prior year than those with no visits in the prior year (91.0% testing for patients with video visits, 90.5% for telephone visits, visits, 86.7% for no visits, p < 0.05). Among those with HbA1c measured, the rates of having an HbA1c < 8% in the second year of the COVID-19 pandemic were also statistically significantly higher among patients with telemedicine exposure in the early-pandemic prior year than those with no visits in the prior year (68.5% with HbA1c< 8% for video visits, 67.3% for telephone visits, 66.6% for no visits, p < 0.05). Conclusions Access to telephone and video telemedicine throughout the early COVID-19 pandemic was associated with patients9 continued engagement in recommended diabetes care. Although our study analyzed telemedicine use during a pandemic, telemedicine visits may continue to support ongoing health care access and positive clinical outcomes.
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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/10.1101/2024.02.25.24303335v1" target="_blank">Telemedicine’s Impact on Diabetes Care during the COVID-19 Pandemic: A Cohort Study in a Large Integrated Healthcare System</a>
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</div></li>
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<li><strong>Risk of Adverse Events Following Monovalent Third or Booster Dose of COVID-19 mRNA Vaccination in U.S. Adults Ages 18 Years and Older</strong> -
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Background The U.S. FDA authorized the monovalent third primary series or booster doses of COVID-19 mRNA vaccines in August 2021 for persons 18 years and older. Monitoring of outcomes following updated authorizations is critical to evaluate vaccine safety and can provide early detection of rare adverse events (AEs) not identified in pre-licensure trials. Methods We evaluated the risk of 17 AEs following third doses of COVID-19 mRNA vaccines from August 2021 through early 2022 among adults aged 18-64 years in three commercial databases (Optum, Carelon Research, CVS Health) and adults aged >65 years in Medicare Fee-For-Service. We compared observed AE incidence rates to historical (expected) rates prior to the pandemic, estimated incidence rate ratios (IRRs) for the Medicare database and pooled IRR across the three commercial databases. Analyses were also stratified by prior history of COVID-19 diagnosis. Estimates exceeding a pre-defined threshold were considered statistical signals. Results Four AEs met the threshold for statistical signals for BNT162b2 and mRNA-1273 vaccines including Bells Palsy and pulmonary embolism in Medicare, and anaphylaxis and myocarditis/pericarditis in commercial databases. Nine AEs and three AEs signaled among adults with and without prior COVID-19 diagnosis, respectively. Conclusions This early monitoring study identified statistical signals for AEs following third doses of COVID-19 mRNA vaccination. Since this method is intended for screening purposes and generates crude results, results do not establish a causal association between the vaccines and AEs. FDAs public health assessment remains consistent that the benefits of COVID-19 vaccination outweigh the risks of vaccination.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.20.24303089v1" target="_blank">Risk of Adverse Events Following Monovalent Third or Booster Dose of COVID-19 mRNA Vaccination in U.S. Adults Ages 18 Years and Older</a>
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</div></li>
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<li><strong>The Impact on Well-Being of Cognitive Bias about Infectious Diseases</strong> -
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We investigate the relationship between bias about infectious disease and well-being. First, we empirically establish the existence and the causes of bias, specifically during the COVID-19 pandemic. After that we investigate theoretically the effects of bias on well-being. In order to do this, we present a behavioral-epidemiological differential equation model derived from an agent-based model that combines rational choice behavior with infectious disease dynamics. In addition the model is evaluated normatively by an axiomatically characterized model of an ethical, impartial, eudaimonistic and individualist observer. These assumptions imply a new proof for the utilitarian principle. The result is that while increased fear improves purely epidemiological outcomes, the social welfare outcome shows mixed results; which shows that it is not enough to take only epidemiological measures into account when generating policy recommendations. Finally, we draw some practical consequences from the model, argue, as it pertains to the topic, for protective rights against psychological control by the state, and give some outlooks for future research.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.25.24303338v1" target="_blank">The Impact on Well-Being of Cognitive Bias about Infectious Diseases</a>
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<li><strong>Beyond Borders: Spatial Disparities in the Mortality Burden of the Covid-19 pandemic across 569 European Regions (2020-2021)</strong> -
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This article presents a detailed analysis of the global mortality burden of the COVID-19 pandemic across 569 regions in 25 European countries. We produce sex-specific excess mortality and present our results using Age-Standardised Years of Life Lost (ASYLL) in 2020 and 2021, as well as the cumulative impact over the two pandemic years. Employing a robust forecasting approach that considers regional diversity and provides confidence intervals, we find notable losses in 362 regions in 2020 (440 regions in 2021). Conversely, only seven regions experienced gains in 2020 (four regions in 2021). Most importantly, we estimate that eight regions suffered losses exceeding 20 years of life per 1,000 population in 2020, whereas this number increased to 75 regions in 2021. The contiguity of the regions investigated in our study also reveals the changing geographical patterns of the pandemic. While the highest excess mortality values were concentrated in the early COVID-19 outbreak areas during the initial pandemic year, a clear East-West gradient appeared in 2021, with regions of Slovakia, Hungary, and Latvia experiencing the highest losses. This research underscores the importance of regional analyses for a nuanced comprehension of the pandemic9s impact.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.12.18.23300149v2" target="_blank">Beyond Borders: Spatial Disparities in the Mortality Burden of the Covid-19 pandemic across 569 European Regions (2020-2021)</a>
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</div></li>
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<li><strong>Respiratory symptoms after coalmine fire and pandemic: a longitudinal analysis of the Hazelwood Health Study adult cohort</strong> -
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Background Extreme but discrete fine particle <2.5μm (PM<sub>2.5</sub>) exposure is associated with higher prevalence of respiratory symptoms. It is unknown whether these effects abate, persist, or worsen over time, nor whether COVID-19 exacerbates PM<sub>2.5</sub> effects. Methods We analysed longitudinal survey data from a cohort residing near a 2014 coalmine fire in regional Australia. A 2016/2017 survey included n=4,056 participants, of whom n=612 were followed-up in 2022. Items include questions about 7 respiratory symptoms, history of COVID-19, and time-location diaries that were combined with geospatial models of fire-related PM<sub>2.5</sub>. Associations were examined using logistic and mixed-effects logistic regressions. Results PM<sub>2.5</sub> exposure predicted higher prevalence of chronic cough and current wheeze 2-3 years post-fire. At the 2022 follow-up, PM<sub>2.5</sub> exposure was associated with worsening prevalence of chronic cough and possibly current wheeze. While were no detectable interaction effects between PM<sub>2.5</sub> and COVID-19, participants with a history of COVID-19 exhibited more significant associations between PM<sub>2.5</sub> exposure and respiratory symptoms. Discussion Short-term but extreme PM<sub>2.5</sub> may increase the long-term prevalence of chronic cough, while COVID-19 may exacerbate the effect on other respiratory symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.23.23294510v2" target="_blank">Respiratory symptoms after coalmine fire and pandemic: a longitudinal analysis of the Hazelwood Health Study adult cohort</a>
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<li><strong>Career Navigator: An online platform to streamline professional development and career education for graduate bioscientists</strong> -
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Graduate professional development is a highly dynamic enterprise that prepares graduate students for personal and career success in a variety of fields, including the biosciences. National policies, funding awards, and institutional programs have generated myriad tools and services for graduate bioscience students, including new learning resources, events, connections to prospective employers, and opportunities to strengthen academic and professional portfolios. These interventions are welcome and have done much to enhance graduate bioscience training, but they may also be overwhelming for trainees. To streamline professional development and career education information for the bioscience graduate students at our institution, we tested a model where we built a centralized web portal of career development resources. Here we present our strategy and best practices for website design. We show data that students preferred a centralized online portal over other forms of resource communication; that programming, paired communication and environmental factors (e.g. remote learning and work as in the COVID-19 pandemic) combined to increase sustained engagement with the site; and that harnessing website analytics is an effective way to measure site utilization and generate insights on programming and resource development. This data, in turn, fits into broader priorities to evaluate interventions in graduate bioscience education.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.22.580689v1" target="_blank">Career Navigator: An online platform to streamline professional development and career education for graduate bioscientists</a>
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<li><strong>Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing</strong> -
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Protein nanoparticles are effective platforms for antigen presentation and targeting effector immune cells in vaccine development. Encapsulins are a class of protein-based microbial nanocompartments that self-assemble into icosahedral structures with external diameters ranging from 24 to 42 nm. Encapsulins from Mxyococcus xanthus were designed to package bacterial RNA when produced in E. coli and were shown to have immunogenic and self-adjuvanting properties enhanced by this RNA. We genetically incorporated a 20-mer peptide derived from a mutant strain of the SARS-CoV-2 receptor binding domain (RBD) into the encapsulin protomeric coat protein for presentation on the exterior surface of the particle. This immunogen elicited conformationally-relevant humoral responses to the SARS-CoV-2 RBD. Immunological recognition was enhanced when the same peptide was presented in a heterologous prime/boost vaccination strategy using the engineered encapsulin and a previously reported variant of the PP7 virus-like particle, leading to the development of a selective antibody response against a SARS-CoV-2 RBD point mutant. While generating epitope-focused antibody responses is an interplay between inherent vaccine properties and B/T cells, here we demonstrate the use of orthogonal nanoparticles to fine-tune the control of epitope focusing.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.24.581861v1" target="_blank">Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing</a>
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<li><strong>Biochemical characterization of naturally occurring mutations in SARS-CoV-2 RNA-dependent RNA polymerase</strong> -
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Since the emergence of SARS-CoV-2, mutations in all subunits of the RNA-dependent RNA polymerase (RdRp) of the virus have been repeatedly reported. Although RdRp represents a primary target for antiviral drugs, experimental studies exploring the phenotypic effect of these mutations have been limited. This study focuses on the phenotypic effects of substitutions in the three RdRp subunits: nsp7, nsp8, and nsp12, selected based on their occurrence rate and potential impact. We employed nano-differential scanning fluorimetry and microscale thermophoresis to examine the impact of these mutations on protein stability and RdRp complex assembly. We observed diverse impacts; notably, a single mutation in nsp8 significantly increased its stability as evidenced by a 13 [deg]C increase in melting temperature, whereas certain mutations in nsp7 and nsp8 reduced their binding affinity to nsp12 during RdRp complex formation. Using a fluorometric enzymatic assay, we assessed the overall effect on RNA polymerase activity. We found that most of the examined mutations altered the polymerase activity, often as a direct result of changes in stability or affinity to the other components of the RdRp complex. Intriguingly, a combination of nsp8 A21V and nsp12 P323L mutations resulted in a 50% increase in polymerase activity. Additionally, some of the examined substitutions in the RdRp subunits notably influenced the sensitivity of RdRp to Remdesivir, highlighting their potential implications for therapeutic strategies. To our knowledge, this is the first biochemical study to demonstrate the impact of amino acid mutations across all components constituting the RdRp complex in emerging SARS-CoV-2 subvariants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.24.581855v1" target="_blank">Biochemical characterization of naturally occurring mutations in SARS-CoV-2 RNA-dependent RNA polymerase</a>
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<li><strong>Emotional Contagion in Scandinavia during the COVID-19 Public Health Crisis</strong> -
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In this article we present the findings of social media analysis of the spread of misinformation in the wake of the COVID-19 pandemic and outline how analyses of the psychological properties of a text can be used to optimize strategic messaging online. Our data used Twitter data, collected during the COVID-19 pandemic and analyzed using a suite of AI based analytical tools, which provided data for further empirical analysis. The analysis yielded insights related to the differences in the dynamics of the spread of misinformation within (and outside of) Scandinavian countries. Analysing this data enabled us to explore three hypotheses: (1) Misinformation will be associated with specific moral signatures, which will differ between Scandinavian and non-Scandinavian samples, (2) Levels of engagement will be associated with specific themes and moral concerns, which will differ between Scandinavian and non-Scandinavian samples, and (3) Within Scandinavia, similar unique signatures will be discernible at the country level, with Sweden driving significant differences. These specific results provide guidance for healthcare professionals responsible for communicating information and crafting messages that are more resonant with their target population and more generally demonstrate the ability for social media analysis to be useful in strategic decision making when going beyond focusing on engagement metrics or sentiment alone.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/9e5f7/" target="_blank">Emotional Contagion in Scandinavia during the COVID-19 Public Health Crisis</a>
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<li><strong>Leveraging Social Media Data for Unobtrusive Measurement of Academics’ Well-Being</strong> -
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Understanding and promoting researchers’ well-being is crucial for successful research outcomes and a thriving scientific community. Traditional well-being assessments can be resource-intensive, prompting the computational analysis of academic social networks as a promising alternative. It has been shown that sentiment analysis of social media text data can be used to infer well-being in the general population, but it is not known whether this approach is transferable to the specific subgroup of researchers. This proof-of-concept study addresses this research question by assessing the potential of scholarly communication in social media to provide insights into researchers’ emotional well-being using sentiment analysis. Therefore, we derived researchers’ emotional well-being from a dataset of more than 13 Million tweets from almost 16,000 psychology researchers, and utilized survey data from the COVID-19 pandemic for external validation of our results. Our aim was to confirm two hypotheses: lower well-being during the pandemic (H1) and a stronger impact on female researchers (H2). Using structural break analysis, the impact of the pandemic was found to be statistically significant for positive sentiments. A differential effect by gender was observed descriptively, but did not reach statistical significance. Results suggest that sentiment analysis of researchers’ tweets can provide insights into their well-being, but to a limited extent than in the general population. Exploratory analysis of cognitive well-being revealed that some, but not all PERMA+4 dimensions are prevalent in researchers’ social media posts. We discuss promising expansions of our approach and highlight practical implications for policymakers.
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🖺 Full Text HTML: <a href="https://osf.io/957h8/" target="_blank">Leveraging Social Media Data for Unobtrusive Measurement of Academics’ Well-Being</a>
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<li><strong>Deep plasma proteomics with data-independent acquisition: A fastlane towards biomarkers identification.</strong> -
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Plasma proteomic is a precious tool in human disease research, but requires extensive sample preparation in order to perform in-depth analysis and biomarker discovery using traditional Data-Dependent Acquisition (DDA). Here, we highlight the efficacy of combining moderate plasma prefractionation and Data-Independent Acquisition (DIA) to significantly improve proteome coverage and depth, while remaining cost- and time-efficient. Using human plasma collected from a 20-patient COVID-19 cohort, our method utilises commonly available solutions for depletion, sample preparation, and fractionation, followed by 3 LC-MS/MS injections for a 360-minutes DIA run time. DIA-NN software was then used for precursor identification, and the QFeatures R package was used for protein aggregation. We detect 1,321 proteins on average per patient, and 2,031 unique proteins across the cohort. Filtering precursors present in under 25% of patients, we still detect 1,230 average proteins and 1,590 unique proteins, indicating robust protein identification. Differential analysis further demonstrates the applicability of this method for plasma proteomic research and clinical biomarker identification. In summary, this study introduces a streamlined, cost- and time-effective approach to deep plasma proteome analysis, expanding its utility beyond classical research environments and enabling larger-scale multi-omics investigations in clinical settings.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.23.581160v1" target="_blank">Deep plasma proteomics with data-independent acquisition: A fastlane towards biomarkers identification.</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>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation & Development <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>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <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>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit 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>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <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>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <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>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <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>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <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>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto 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>Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood.</strong> - <b>Conditions</b>: Covid-19 <br/><b>Interventions</b>: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) <br/><b>Sponsors</b>: Vachira Phuket 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>UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH <br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploring Retrograde Trafficking: Mechanisms and Consequences in Cancer and Disease</strong> - Retrograde trafficking (RT) orchestrates the intracellular movement of cargo from the plasma membrane, endosomes, Golgi or endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) in an inward/ER-directed manner. RT works as the opposing movement to anterograde trafficking (outward secretion), and the two work together to maintain cellular homeostasis. This is achieved through maintaining cell polarity, retrieving proteins responsible for anterograde trafficking and redirecting proteins…</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>Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study</strong> - One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50%…</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>Pan-viral propagation blockade by inhibiting host cell PNPT1</strong> - Successful viral propagation within infected cells necessitates the viruses’ ability to overcome the cellular integrated stress response (ISR), triggered during viral infection, which in turn inhibits general protein translation. In our study, we unveil a shared tactic employed by viruses to suppress ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus, and hepatovirus within their respective host cells induces…</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>Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes</strong> - Viruses utilize cell surface glycans and plasma membrane receptors to attain an adequate attachment strength for initiating cellular entry. We show that SARS-CoV-2 particles bind to endogenous ACE2 receptors and added sialylated gangliosides in near-native membranes. This was explored using supported membrane bilayers (SMBs) that were formed using plasma membrane vesicles having endogenous ACE2 and GD1a gangliosides reconstituted in lipid vesicles. The virus binding rate to the SMBs is…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Viral RNA Replication Suppression of SARS-CoV-2: Atomistic Insights into Inhibition Mechanisms of RdRp Machinery by ddhCTP</strong> - The nonstructural protein 12, known as RNA-dependent RNA polymerase (RdRp), is essential for both replication and repair of the viral genome. The RdRp of SARS-CoV-2 has been used as a promising candidate for drug development since the inception of the COVID-19 spread. In this work, we performed an in silico investigation on the insertion of the naturally modified pyrimidine nucleobase ddhCTP into the SARS-CoV-2 RdRp active site, in a comparative analysis with the natural one (CTP). 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>NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway</strong> - Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor…</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>Nsp1 facilitates SARS-CoV-2 replication through calcineurin-NFAT signaling</strong> - SARS-CoV-2, the causative agent of COVID-19, has been intensely studied in search of effective antiviral treatments. The immunosuppressant cyclosporine A (CsA) has been suggested to be a pan-coronavirus inhibitor, yet its underlying mechanism remained largely unknown. Here, we found that non-structural protein 1 (Nsp1) of SARS-CoV-2 usurped CsA-suppressed nuclear factor of activated T cells (NFAT) signaling to drive the expression of cellular DEAD-box helicase 5 (DDX5), which facilitates viral…</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>Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes</strong> - CONCLUSIONS: Our data demonstrate that strains, which harbor covR/S mutations, interfere with IL-18 and IL-8 responses in monocytic cells by utilizing the caspase-8 axis. Future experiments aim to identify the underlying mechanism and consequences for NSTI 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>Methyl rosmarinate is an allosteric inhibitor of SARS-cov-2 3 C L protease as a potential candidate against SARS-cov-2 infection</strong> - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been ongoing for more than three years and urgently needs to be addressed. Traditional Chinese medicine (TCM) prescriptions have played an important role in the clinical treatment of patients with COVID-19 in China. However, it is difficult to uncover the potential molecular mechanisms of the active ingredients in these TCM prescriptions. In this paper, we developed a new…</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>Human transferrin receptor can mediate SARS-CoV-2 infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron…</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>Polyvalent Nanobody Structure Designed for Boosting SARS-CoV-2 Inhibition</strong> - Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections. Our polyvalent Nb structure, called “PNS”, is achieved by first conjugating single-stranded DNA (ssDNA) and the receptor-binding domain (RBD)-targeting Nb with retained…</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 Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19</strong> - We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including transmembrane protease serine 2 (TMPRSS2), matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have…</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>Antimicrobial and Virus Adsorption Properties of Y-Zeolite Exchanged with Silver and Zinc Cations</strong> - The antimicrobial activity of silver and zinc exchanged cations in Y-zeolite (Ag/CBV-600, Zn/CBV-600) is evaluated against Staphylococcus aureus (gram (+)) and Escherichia coli (gram (-)) bacteria along with their adsorption capacity for viruses: brome mosaic virus (BMV), cowpea chlorotic mottle virus (CCMV), and the bacteriophage MS2. The physicochemical properties of synthesized nanomaterials are characterized by inductively coupled plasma optical emission spectroscopy (ICP-OES), UV-Vis…</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>Diphenyl ethers from the cultured lichen mycobiont of <em>Graphis handelii</em> Zahlbr</strong> - CONCLUSION: A new compound, handelone (1) was isolated from the cultured mycobiont of Graphis handelii. From these compounds, four new derivatives were prepared. Compound 1 showed good activity against M^(pro) with an IC(50) value of 5.2 μM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.</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>Sialic Acid Conjugate-Modified Cationic Liposomal Paclitaxel for Targeted Therapy of Lung Metastasis in Breast Cancer: What a Difference the Cation Content Makes</strong> - Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these…</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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