155 lines
32 KiB
HTML
155 lines
32 KiB
HTML
|
<!DOCTYPE html>
|
|||
|
|
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
|||
|
|
<meta charset="utf-8"/>
|
|||
|
|
<meta content="pandoc" name="generator"/>
|
|||
|
|
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
|||
|
|
<title>25 March, 2024</title>
|
|||
|
|
<style>
|
|||
|
|
code{white-space: pre-wrap;}
|
|||
|
|
span.smallcaps{font-variant: small-caps;}
|
|||
|
|
span.underline{text-decoration: underline;}
|
|||
|
|
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
|||
|
|
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
|
|||
|
|
ul.task-list{list-style: none;}
|
|||
|
|
</style>
|
|||
|
|
<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>
|
|||
|
|
<body>
|
|||
|
|
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
|||
|
|
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><a href="#from-preprints">From Preprints</a></li>
|
|||
|
|
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
|||
|
|
<li><a href="#from-pubmed">From PubMed</a></li>
|
|||
|
|
<li><a href="#from-patent-search">From Patent Search</a></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><strong>A human commons cell atlas reveals cell type specificity for OAS1 isoforms</strong> -
|
|||
|
|
<div>
|
|||
|
|
We describe an open source Human Commons Cell Atlas comprising 2.9 million cells across 27 tissues that can be easily updated and that is structured to facilitate custom analyses. To showcase the flexibility of the atlas, we demonstrate that it can be used to study isoforms of genes at cell resolution. In particular, we study cell type specificity of isoforms of OAS1, which has been shown to offer SARS-CoV-2 protection in certain individuals that display higher expression of the p46 isoform. Using our commons cell atlas we localize the OAS1 p44b isoform to the testis, and find that it is specific to round and elongating spermatids. By virtue of enabling customized analyses via a modular and dynamic atlas structure, the commons cell atlas should be useful for exploratory analyses that are intractable within the rigid framework of current gene-centric cell atlases.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.23.586412v1" target="_blank">A human commons cell atlas reveals cell type specificity for OAS1 isoforms</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Do abortion bans somehow save pregnant people’s lives? A cautionary research note on trends in maternal death post-Dobbs</strong> -
|
|||
|
|
<div>
|
|||
|
|
The National Center for Health Statistics’ published provisional monthly estimates of maternal death (12-month ending counts) appear to demonstrate that the end of federal protection for abortion rights in June 2022 was associated with an immediate and dramatic decline in maternal deaths. In this research note we investigate this apparent association by comparing the 12-month ending counts with monthly counts of maternal death. We decompose change in the 12-month ending counts into change due to months leaving the sum and change due to the current month entering the sum and conclude that the rapid decline in the 12-month ending counts is driven by events in 2021, specifically the shock to maternal deaths during the Delta and Omicron waves of the COVID-19 pandemic. Actual monthly final and provisional maternal deaths from the National Vital Statistics Surveillance System did not decline after June 2022. We caution that any analysis of change in maternal deaths should exercise extreme caution when using summed measures in general and the 12-month ending counts in particular.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/jtkqe/" target="_blank">Do abortion bans somehow save pregnant people’s lives? A cautionary research note on trends in maternal death post-Dobbs</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Online Data Collection in Applied Linguistics</strong> -
|
|||
|
|
<div>
|
|||
|
|
During the height of the COVID-19 pandemic, researchers became resourceful and many transitioned to online methods for remote data collection, suddenly bringing many platforms and methods to prominence in new experimental contexts. As in-person data collection resumed, online data collection remained as these methods have proven particularly useful in the field of applied linguistics and especially Second Language Acquisition (SLA), which often requires researchers to recruit participants who are inherently difficult to find (e.g., individuals proficient in less-commonly taught languages or living in a context far from the researcher’s university). In this chapter, we highlight factors that researchers should consider when implementing online research along with a high-level troubleshooting guide. We cover recruitment, enhancing participant performance, implementation, and deployment. Within these topics, we highlight important technological, procedural, and participant privacy recommendations for visual, aural, and oral online data collection designs specially tailored for applied linguists.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/pxfc4/" target="_blank">Online Data Collection in Applied Linguistics</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Identification of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro) for the Development of COVID-19 Antivirals</strong> -
|
|||
|
|
<div>
|
|||
|
|
Coronaviruses such as SARS-CoV-2 encode a conserved papain-like protease (PLpro) that is crucial for viral replication and immune evasion, making it a prime target for antiviral drug development. In this study, three surface pockets on SARS-CoV-2 PLpro that may function as sites for allosteric inhibition were computationally identified. To evaluate the effects of these pockets on proteolytic activity, 52 residues were separately mutated to alanine. In Pocket 1, located between the Ubl and thumb domains, the introduction of alanine at T10, D12, T54, Y72, or Y83 reduced PLpro activity to <12% of that of WT. In Pocket 2, situated at the interface of the thumb, fingers, and palm domains, Q237A, S239A, H275A, and S278A inactivated PLpro. Finally, introducing alanine at five residues in Pocket 3, between the fingers and palm domains, inactivated PLpro: S212, Y213, Y251, K254, and Y305. Pocket 1 has a higher druggability score than Pockets 2 and 3. MD simulations showed that interactions within and between domains play critical roles in PLpro activity and thermal stability. The essential residues in Pockets 1 and 2 participate in a combination of intra- and inter-domain interactions. By contrast, the essential residues in Pocket 3 predominantly participate in inter-domain interactions. The most promising targets for therapeutic development are Pockets 1 and 3, which have the highest druggability score and the largest number of essential residues, respectively. Non-competitive inhibitors targeting these pockets may be antiviral agents against COVID-19 and related coronaviruses.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.540953v3" target="_blank">Identification of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro) for the Development of COVID-19 Antivirals</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Neural networks built from enzymatic reactions can operate as linear and nonlinear classifiers</strong> -
|
|||
|
|
<div>
|
|||
|
|
The engineering of molecular programs capable of processing patterns of multi-input biomarkers holds great potential in applications ranging from in vitro diagnostics (e.g., viral detection, including COVID-19) to therapeutic interventions (e.g., discriminating cancer cells from normal cells). For this reason, mechanisms to design molecular networks for pattern recognition are highly sought after. In this work, we explore how enzymatic networks can be used for both linear and nonlinear classification tasks. By leveraging steady-state analysis and showing global stability, we demonstrate that these networks can function as molecular perceptrons, fundamental units of artificial neural networks-capable of processing multiple inputs associated with positive and negative weights to achieve linear classification. Furthermore, by composing orthogonal enzymatic reactions, we show that multi-layer networks can be constructed to achieve nonlinear classification.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.23.586372v1" target="_blank">Neural networks built from enzymatic reactions can operate as linear and nonlinear classifiers</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Neutralisation sensitivity of the SARS-CoV-2 BA.2.87.1 variant</strong> -
|
|||
|
|
<div>
|
|||
|
|
Against the backdrop of the rapid global takeover and dominance of BA.1/BA.2 and subsequently BA.2.86 lineages, the emergence of a highly divergent SARS-CoV-2 variant warrants characterization and close monitoring. Recently, another such BA.2 descendent, designated BA.2.87.1, was detected in South Africa. Here, we show using spike-pseudotyped viruses that BA.2.87.1 is less resistant to neutralisation by prevailing antibody responses in Sweden than other currently circulating variants such as JN.1. Further we show that a monovalent XBB.1.5-adapted booster enhanced neutralising antibody titers to BA.2.87.1 by almost 4-fold. While BA.2.87.1 may not outcompete other currently-circulating lineages, the repeated emergence and transmission of highly diverged variants suggests that another large antigenic shift, similar to the replacement by Omicron, may be likely in the future.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.21.586176v1" target="_blank">Neutralisation sensitivity of the SARS-CoV-2 BA.2.87.1 variant</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Design of Antigen-Specific Antibody CDRH3 Sequences Using AI and Germline-Based Templates</strong> -
|
|||
|
|
<div>
|
|||
|
|
Antibody-antigen specificity is engendered and refined through a number of complex B cell processes, including germline gene recombination and somatic hypermutation. Here, we present an AI-based technology for de novo generation of antigen-specific antibody CDRH3 sequences using germline-based templates, and validate this technology through the generation of antibodies against SARS-CoV-2. AI-based processes that mimic the outcome, but bypass the complexity of natural antibody generation, can be efficient and effective alternatives to traditional experimental approaches for antibody discovery.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.22.586241v1" target="_blank">Design of Antigen-Specific Antibody CDRH3 Sequences Using AI and Germline-Based Templates</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>The influence of COVID-19 fear beliefs on the relationships between positive mood and loss-of-control eating: a ten-day diary study</strong> -
|
|||
|
|
<div>
|
|||
|
|
Loss-of-control eating (LOCE) is driven by mood, and prevalence increased following onset of coronavirus 2019 (COVID-19). COVID-19 is associated with many stressors, including fear of illness, which could potentiate a relationship between mood and LOCE. Additionally, daily protective strategies to prevent contagion may be associated with LOCE, in line with ego depletion theory. Adults (N = 108) completed a 10-day diary study regarding LOCE, positive and negative mood, and protective behaviors. Participants rated COVID fear beliefs at a baseline assessment, hypothesized to predict LOCE directly between-subjects and have a cross-level interactive effect within-subjects. Data were analyzed with a multilevel model. Negative mood was associated with LOCE at both levels, although protective behaviors evinced no significant associations. Positive mood lacked significant direct association with LOCE, although there was an interactive effect such that there was an inverse association at low fear beliefs. Directions for future research and clinical implications are discussed.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/ta659/" target="_blank">The influence of COVID-19 fear beliefs on the relationships between positive mood and loss-of-control eating: a ten-day diary study</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants</strong> -
|
|||
|
|
<div>
|
|||
|
|
Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. We characterized the memory B-cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, and compared the immunogenicity with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one-month after a monovalent, BA.1 or BA.5 bivalent fourth dose COVID-19 vaccine. RBD-specific Bmem were quantified with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. All recipients had slightly increased WH1 RBD-specific Bmem numbers. Recognition of Omicron subvariants was not enhanced following monovalent vaccination, while both bivalent vaccines significantly increased WH1 RBD-specific Bmem cross-recognition of all Omicron subvariants tested by flow cytometry. Thus, Omicron-based bivalent vaccines can improve recognition of descendent Omicron subvariants by pre-existing, WH1-specific Bmem, beyond that of a conventional, monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.20.585861v1" target="_blank">Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Power users: Technology and Canadian sex workers during COVID-19</strong> -
|
|||
|
|
<div>
|
|||
|
|
The transition from physical to online advertising by sex workers in Canada has been well documented. However, few studies use rigorous sampling methods. This study considers how a technically sophisticated group of advertisers from a large Canadian sex work classifieds site used multiple online resources to promote or provide services during the COVID-19 pandemic. Advertisers qualified for the study if they used a URL as part of their contact information and were actively advertising between August 23 and September 22, 2022. A random sample of 1000 qualifying advertisers were selected of which 783 had accessible contact URLs. Themes were identified in downloaded website texts using grounded theory analysis. Ad metadata was used to identify demographic and behavioral distinctions between the sample and other advertisers. Almost all sampled advertisers (99%) provided in person services and most (70%) provided online services. The sample advertised more frequently, were more affluent and were more likely to be Anglophone, White, trans-female, or provide BDSM services. Themes of security, health, identity, and social networks were identified. Advertisers emphasized physical, emotional, and financial security. Most workers did not work in isolation and many participated in extensive social networks.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/u5kd2/" target="_blank">Power users: Technology and Canadian sex workers during COVID-19</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Predictive validity of the simplified Radiographic Assessment of Lung Edema score for the mortality in critically ill COVID-19 patients with the B.1.617.2 (Delta) variant in Vietnam: a single-centre, cross-sectional study</strong> -
|
|||
|
|
<div>
|
|||
|
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
|
Background Evaluating the prognosis of COVID-19 patients who may be at risk of mortality using the simple chest X-ray (CXR) severity scoring systems provides valuable insights for treatment decisions. This study aimed to assess how well the simplified Radiographic Assessment of Lung Edema (RALE) score could predict the death of critically ill COVID-19 patients in Vietnam. Methods From July 30 to October 15, 2021, we conducted a cross-sectional study on critically ill COVID-19 adult patients at an intensive care centre in Vietnam. We calculated the areas under the receiver operator characteristic (ROC) curve (AUROC) to determine how well the simplified RALE score could predict hospital mortality. In a frontal CXR, the simplified RALE score assigns a score to each lung, ranging from 0 to 4. The overall severity score is the sum of points from both lungs, with a maximum possible score of 8. We also utilized ROC curve analysis to find the best cut-off value for this score. Finally, we utilized logistic regression to identify the association of simplified RALE score with hospital mortality. Results Of 105 patients, 40.0% were men, the median age was 61.0 years (Q1-Q3: 52.0-71.0), and 79.0% of patients died in the hospital. Most patients exhibited bilateral lung opacities on their admission CXRs (99.0%; 100/102), with the highest occurrence of opacity distribution spanning three (18.3%; 19/104) to four quadrants of the lungs (74.0%; 77/104) and a high median simplified RALE score of 8.0 (Q1-Q3: 6.0-8.0). The simplified RALE score (AUROC: 0.747 [95% CI: 0.617-0.877]; cut-off value >=5.5; sensitivity: 93.9%; specificity: 45.5%; PAUROC <0.001) demonstrated a good discriminatory ability in predicting hospital mortality. After adjusting for confounding factors such as age, gender, Charlson Comorbidity Index, serum interleukin-6 level upon admission, and admission severity scoring systems, the simplified RALE score of >=5.5 (adjusted OR: 18.437; 95% CI: 3.215-105.741; p =0.001) was independently associated with an increased risk of hospital mortality. Conclusions This study focused on a highly selected cohort of critically ill COVID-19 patients with a high simplified RALE score and a high mortality rate. Beyond its good discriminatory ability in predicting hospital mortality, the simplified RALE score also emerged as an independent predictor of hospital mortality.
|
|||
|
|
</p>
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.20.24304599v1" target="_blank">Predictive validity of the simplified Radiographic Assessment of Lung Edema score for the mortality in critically ill COVID-19 patients with the B.1.617.2 (Delta) variant in Vietnam: a single-centre, cross-sectional study</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Greater Role of Cognitive Impairment Over Fatigue in Post-COVID-19 Quality of Life: A Post-Hoc Analysis of a Randomized Controlled Trial</strong> -
|
|||
|
|
<div>
|
|||
|
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
|
Background Post COVID-19 Condition (PCC) is a common and debilitating condition with significant reports of fatigue and psychosocial impairment globally. The extent to which cognitive symptoms and fatigue contribute to reduced quality of life in affected individuals remains clear. Methods This is a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial that evaluated the effect of vortioxetine on cognitive function in adults with PCC. The post-hoc analysis herein aimed to determine the overall effect of baseline cognitive function [as measured by the Digit Symbol Substitution Test (DSST)] and baseline fatigue severity [as measured by the Fatigue Severity Scale (FSS)] on baseline health-related quality of life (HRQoL) [as measured by the 5-item World Health Organisation Well-Being Index (WHO-5)]. Results A total of 200 participants were enrolled in the primary trial. Due to missing baseline data, our statistical analysis included baseline measures of 147 individuals. Our generalized linear model analysis revealed a significant positive correlation between DSST-measured objective cognitive function and self-reported WHO-5-measured HRQoL (beta; = 0.069, 95% CI [0.006, 0.131], p = 0.032). In contrast, our analysis revealed a significant negative correlation between FSS and WHO-5 scores (beta; = -0.016, 95% CI [-0.021, -0.011], p < 0.001). The beta-coefficient ratio (beta;DSST / beta;FSS = 0.069 / 0.016) is calculated as 4.313. Conclusions Overall, we observed that increased cognitive function was associated with increased HRQoL at baseline in adults with PCC. Moreover, we observed that increased severity of fatigue symptoms was associated with decreased HRQoL at baseline in adults with PCC. Furthermore, we observed that an improvement in cognitive function would have a four-fold greater impact on HRQoL than the effect generated by improvement in fatigue.
|
|||
|
|
</p>
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.20.24304411v1" target="_blank">Greater Role of Cognitive Impairment Over Fatigue in Post-COVID-19 Quality of Life: A Post-Hoc Analysis of a Randomized Controlled Trial</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Improved diagnosis of COVID-19 vaccine-associated myocarditis with cardiac scarring identified by cardiac magnetic resonance imaging.</strong> -
|
|||
|
|
<div>
|
|||
|
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
|
Aims Myocarditis is a rare but potentially serious complication of COVID-19 vaccination. Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging can identify cardiac scar, which may improve diagnostic accuracy and prognostication. We sought to define the incidence of long-term LGE post COVID-19 vaccine-associated myocarditis (C-VAM) and to establish the additive role of CMR in the diagnostic work up. Methods and Results Patients with Brighton Collaboration Criteria Level 1 (definite) or Level 2 (probable) C-VAM were prospectively recruited from the Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC) database to undergo CMR at least 6 months after diagnosis. As there were limited patients with access to baseline CMR, prior CMR results were not included in the initial case definition. The presence of LGE at follow-up CMR was then integrated into the diagnostic algorithm and the reclassification rate (definite vs. probable) was calculated. Sixty-seven patients with C-VAM (mean age 30 +/- 13 years, 72% male) underwent CMR evaluation. Median time from vaccination to CMR was 548 (range 398-603) days. Twenty patients (30%) had persistent LGE. At diagnosis, nine patients (13%) were classified as definite and 58 (87%) as probable myocarditis. With integration of CMR LGE data, 16 patients (28%) were reclassified from probable to definite myocarditis. Conclusion Persistent LGE on CMR occurs in one third of patients with C-VAM. Without CMR at the time of diagnosis, almost one third of patients are misclassified as probable rather than definite myocarditis, indicating a diagnostic strategy using echocardiography alone is insufficient.
|
|||
|
|
</p>
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.20.24304640v1" target="_blank">Improved diagnosis of COVID-19 vaccine-associated myocarditis with cardiac scarring identified by cardiac magnetic resonance imaging.</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2</strong> -
|
|||
|
|
<div>
|
|||
|
|
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also exhibiting functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.21.568093v2" target="_blank">Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids</strong> -
|
|||
|
|
<div>
|
|||
|
|
SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.20.585837v1" target="_blank">SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids</a>
|
|||
|
|
</div></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reducing Chronic Breathlessness in Adults by Following a Self-guided, Internet Based Supportive Intervention (SELF-BREATHE)</strong> - <b>Conditions</b>: Advanced Respiratory Disease; Chronic Breathlessness Due to Advanced Respiratory Disease; Chronic Obstructive Pulmonary Disease; Bronchiectasis; Interstitial Lung Disease; Lung Cancer; Asthma; Chronic Fibrotic Lung Disease Following SARS-CoV2 Infection <br/><b>Interventions</b>: Other: SELF-BREATHE <br/><b>Sponsors</b>: King’s College Hospital NHS Trust <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2</strong> - <b>Conditions</b>: Long COVID; PASC Post Acute Sequelae of COVID 19 <br/><b>Interventions</b>: Drug: Valacyclovir celecoxib dose 1; Drug: Valacyclovir celecoxib dose 2; Drug: Placebo <br/><b>Sponsors</b>: Bateman Horne Center <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supervised Computerized Active Program for People With Post-COVID Syndrome (SuperCAP Study)</strong> - <b>Conditions</b>: Post-COVID Condition <br/><b>Interventions</b>: Device: SuperCAP Program <br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Institut de Recerca de la SIDA IrsiCaixa; Germans Trias i Pujol Hospital <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Diagnostic Test: RNA Biomarker Blood Test <br/><b>Sponsors</b>: MaxWell Clinic, PLC <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman University <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
|||
|
|
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
|||
|
|
|
|||
|
|
|
|||
|
|
<script>AOS.init();</script></body></html>
|