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165 lines
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<title>10 April, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Psychological distance to science as a predictor of science skepticism across domains</strong> -
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<div>
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The current paper presents and tests psychological distance to science (PSYDISC) as a domain-general predictor of science skepticism. Drawing on the concept of psychological distance, PSYDISC reflects the extent to which individuals perceive science as a tangible undertaking conducted by people similar to oneself (social), with effects in the here (spatial) and now (temporal), and as useful and applicable in the real world (hypothetical distance). In six studies (2 preregistered; total N = 1,630) and two countries, we developed and established the factor structure and validity of a scale measuring PSYDISC. Crucially, higher PSYDISC predicted skepticism beyond established predictors, across science domains. A final study showed that PSYDISC shapes real-world behavior (COVID-19 vaccination uptake). The current work thus provides a novel tool to predict science skepticism, as well as a construct that can help to further develop a unifying framework to understand science skepticism across domains.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/avtgu/" target="_blank">Psychological distance to science as a predictor of science skepticism across domains</a>
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</div></li>
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<li><strong>GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</strong> -
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<div>
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Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
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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/10.1101/2023.12.05.570076v3" target="_blank">GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</a>
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</div></li>
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<li><strong>Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy</strong> -
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<div>
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Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
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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/10.1101/2023.12.31.573251v3" target="_blank">Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy</a>
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</div></li>
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<li><strong>Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling</strong> -
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<div>
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RHIM is a protein motif in cell death proteins that assembles higher-order signaling complexes and triggers regulated cell death, which in itself limits virus spread and additionally triggers inflammation for mounting immune responses. A few DNA viruses employ viral RHIMs mimicking host RHIMs. However, these viral RHIMs counteract host cell death by interacting with host RHIM proteins and blocking complex formation to alleviate antiviral defenses. Whether RNA viruses operate such viral RHIMs remains unknown. RHIM-protein signaling promotes lung damage and cytokine storm in respiratory RNA virus infections, arguing the presence of viral RHIMs. Here, we report the novel viral RHIMs in Nsp13 and Nsp14 of SARS-CoV-2 and other bat RNA viruses, providing the basis for bats as the hosts for their evolution. Nsp13 promoted cell death in bat and human cells, however, viral RHIM of Nsp13 is more critical for human cell death than bat cells, suggesting species-specific regulation. The conformation of RNA-binding channel in Nsp13 is critical for cell death in bat and human cells. Nsp13 showed RHIM-dependent interactions with ZBP1 and RIPK3 and promoted the formation of large insoluble complexes of ZBP1 and RIPK3. Also, Nsp13 promoted ZBP1-RIPK3 signaling-mediated cell death dependent on intracellular RNA ligands. Intriguingly, the SARS-CoV-2 genome consists of bona fide Z-RNA-forming segments. These SARS-CoV-2 Z-RNA segments promoted Nsp13-dependent cell death, further revealing Nsp13’s association with Z-RNA sensing and ZBP1-RIPK3 signaling. Our findings reveal the functional viral RHIMs of bat-originated RNA viruses regulating host cell death associated with Z-RNA sensing and ZBP1-RIPK3 signaling activation. These observations allow the understanding of mechanisms of cellular damage and cytokine storm in SARS-CoV-2 and other bat-originated RNA virus infections.
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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/10.1101/2023.08.23.554434v2" target="_blank">Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling</a>
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</div></li>
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<li><strong>Turn `noise’ to signal: accurately rectify millions of erroneous short reads through graph learning on edit distances</strong> -
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<div>
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Although the per-base erring rate of NGS is very low at 0.1% to 0.5%, the percentage/probability of erroneous reads in a short-read sequencing dataset can be as high as 10% to 15% or in the number of millions. Correction of these wrongly sequenced reads to retrieve their huge missing value will improve many downstream applications. As current methods correct only some of the errors at the cost of introducing many new errors, we solve this problem by turning erroneous reads into their original states, without bringing up any non-existing reads to keep the data integrity. The novelty of our method is originated in a computable rule translated from PCR erring mechanism that: a rare read is erroneous if it has a neighbouring read of high abundance. With this principle, we construct a graph to link every pair of reads of tiny edit distances to detect a solid part of erroneous reads; then we consider them as training data to learn the erring mechanisms to identify possibly remaining hard-case errors between pairs of high-abundance reads. Compared with state-of-the-art methods on tens of datasets of UMI-based ground truth, our method has made a remarkably better performance under 19 metrics including two entropy metrics that measure noise levels in a dataset. Case studies found that our method can make substantial impact on genome abundance quantification, isoform identification, SNP profiling, and genome editing efficiency estimation. For example, the abundance level of the reference genome of SARS-CoV-2 can be increased by 12% and that of Monkeypox can be boosted by 52.12% after error correction. Moreover, the number of distinct isomiRs is decreased by 31.56%, unveiling there are so many previously identified isomiRs that are actually sequencing errors.
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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/10.1101/2024.04.05.588226v1" target="_blank">Turn `noise’ to signal: accurately rectify millions of erroneous short reads through graph learning on edit distances</a>
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</div></li>
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<li><strong>Pathway Circuit Mapping for Drug Repurposing: CoV-DrugX Tool Sheds Light on Therapeutic Opportunities</strong> -
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The fight against new diseases like COVID-19 demands creative ways to find and reuse existing drugs. This article examines how scientists are rethinking drug use by focusing on cellular pathways as a guide to finding new treatments. A key part of this effort is the CoV-DrugX Pathway Circuit Tool, a new online program developed by Kamal Rawal’s team. This tool uses pathway information and links between genes and drugs to predict how drugs might interact with these pathways, helping researchers quickly find existing drugs that could be repurposed to treat COVID-19. By combining data from various sources, the CoV-DrugX Tool offers a systematic and affordable way to identify drugs that target important pathways involved in COVID-19. However, there are still challenges, such as limited data and the possibility of inaccurate predictions. Despite these limitations, the CoV-DrugX Pathway Circuit Tool is a major step forward in drug discovery. It gives researchers a powerful tool to speed up finding potential treatments during health crises. In the future, this tool could be adapted for other infectious diseases, using its focus on pathways to address urgent medical needs beyond COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/f74yg/" target="_blank">Pathway Circuit Mapping for Drug Repurposing: CoV-DrugX Tool Sheds Light on Therapeutic Opportunities</a>
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</div></li>
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<li><strong>Cheating in the wake of COVID-19: How dangerous is ad-hoc online testing for academic integrity?</strong> -
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Worldwide, higher education institutions made quick and often unprepared shifts from on-site to online examination in 2020 due to the COVID-19 health crisis. This development sparked an ongoing debate on whether this development made it easier for students to cheat. We investigated whether students indeed cheated more often in online than in on-site exams and whether the use of online exams was also associated with higher rates of other behaviors deemed as academic dishonesty. To answer our research questions, we questioned 1,608 German students from a wide variety of higher education institutions about their behavior during the summer semester of 2020. The participating students reported that they cheated more frequently in online than in on-site exams. Effects on other measures of academic dishonesty were more negligible. These results speak for the notion that the swift application of ad-hoc online testing during 2020 has led to negative consequences for academic integrity.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/6xmzh/" target="_blank">Cheating in the wake of COVID-19: How dangerous is ad-hoc online testing for academic integrity?</a>
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<li><strong>Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work</strong> -
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<div>
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This paper presents the findings from a detailed study investigating UK undergraduate students’ experience of practical science in their post-16 studies during the COVID-19 pandemic. It also examines the perceived confidence and preparedness of the students in relation to areas of practical science skills at the start of their degree courses. The study employed an exploratory sequential mixed methods design, with the findings from focus groups with students at the end of their post-16 studies used to support the development of a comprehensive skills audit and quantitative survey for incoming undergraduate students. Survey data were collected in September and October 2021 from 275 students commencing Biosciences, Chemistry, Physics and Natural Science degrees at two universities in England. The research is important because although almost all students had the opportunity to undertake practical work as part of their post-16 studies during the COVID-19 pandemic, there was considerable variation in students’ experiences. The data indicate that students’ self-efficacy in relation to practical science was impacted by the closures of post-16 education establishments, ongoing social distancing and the removal of the assessment criteria for students to have ‘routinely and consistently’ undertaken each of the practical assessment requirements. The research presents important considerations which are relevant for educators supporting students’ transition from post-16 to Higher Education.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/gx2jh/" target="_blank">Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work</a>
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</div></li>
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<li><strong>Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain</strong> -
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<div>
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Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg relative to a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.
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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/10.1101/2024.04.05.588051v1" target="_blank">Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain</a>
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<li><strong>Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology</strong> -
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<div>
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The use of metagenomic next-generation sequencing technology to obtain complete viral genome sequences directly from clinical samples with low viral load remains challenging–especially in the case of respiratory viruses–due to the low copy number of viral versus host genomes. To overcome this limitation, target capture sequencing for the enrichment of specific genomes has been developed and applied for direct genome sequencing of viruses. However, as the efficiency of enrichment varies depending on the probes, the type of clinical sample, etc., validation is essential before target capture sequencing can be applied to clinical diagnostics. Here we evaluated the utility of target capture sequencing with a comprehensive viral probe panel for clinical respiratory specimens collected from patients diagnosed with SARS-CoV-2 or influenza type A. We focused on clinical specimens containing low copy numbers of viral genomes. Target capture sequencing yielded approximately 180- and 2000-fold higher read counts of SARS-CoV-2 and influenza A virus, respectively, than metagenomic sequencing when the RNA extracted from specimens contained 59.3 copies/L of SARS-CoV-2 or 544 copies/L of influenza A virus, respectively. In addition, the target capture sequencing identified sequence reads in all SARS-CoV-2- or influenza type A-positive specimens with <26 RNA copies/L, some of which also yielded >70% of the full-length genomes of SARS-CoV-2 or influenza A virus. Furthermore, the target capture sequencing using comprehensive probes identified co-infections with viruses other than SARS-CoV-2, suggesting that this approach will not only detect a wide range of viruses, but also contribute to epidemiological studies.
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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/10.1101/2024.04.05.588295v1" target="_blank">Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology</a>
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<li><strong>Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor-antigen recognition</strong> -
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Understanding the mechanisms of T-cell antigen recognition that underpin adaptive immune responses is critical for the development of vaccines, immunotherapies, and treatments against autoimmune diseases. Despite extensive research efforts, the accurate identification of T cell receptor (TCR)-antigen binding pairs remains a significant challenge due to the vast diversity and cross-reactivity of TCRs. Here, we propose a deep-learning framework termed Epitope-anchored Contrastive Transfer Learning (EPACT) tailored to paired human CD8+ TCRs from single-cell sequencing data. Harnessing the pre-trained representations and the contrastive co-embedding space, EPACT demonstrates state-of-the-art model generalizability in predicting TCR binding specificity for unseen epitopes and distinct TCR repertoires, offering potential values for practical outcomes in real-world scenarios. The contrastive learning paradigm achieves highly precise predictions for immunodominant epitopes and facilitates interpretable analysis of epitope-specific T cells. The TCR binding strength predicted by EPACT aligns well with the surge in spike-specific immune responses targeting SARS-CoV-2 epitopes after vaccination. We further fine-tune EPACT on TCR-epitope structural data to decipher the residue-level interactions involved in T-cell antigen recognition. EPACT not only exhibits superior capabilities in quantifying inter-chain distance matrices and identifying contact residue pairs but also corroborates the presence of molecular mimicry across multiple tumor-associated antigens. Together, EPACT can serve as a useful AI approach with significant potential in practical applications and contribute toward the development of TCR-based diagnostics and immunotherapies.
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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/10.1101/2024.04.05.588255v1" target="_blank">Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor-antigen recognition</a>
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<li><strong>Adaptive and Maladaptive Pathways of COVID-19 Worry on Well-Being: A Cross-National Study</strong> -
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Objective: In a preregistered study, we examined whether worries about COVID-19 are simultaneously linked with enhanced well-being through social interaction and reduced well-being through depression symptoms. Method: In August 2020, census-matched participants from high and low prevalence regions in the United States and Italy (N = 857) completed assessments of COVID-19 worry, social interaction, depression symptoms, and well-being. Results: Worries about COVID-19 predicted both more social interaction and more depression (ps < .001). In multiple mediational analyses, an adaptive pathway of COVID-19 worry through social interaction was associated with higher well-being, whereas a maladaptive pathway through depression symptoms was associated with lower well-being. Further, a comparison of high and low COVID-19 prevalence regions replicated the mediational findings for social interaction, providing evidence against reverse causation and common method variance. Conclusion: Findings suggest that normative worries about acute stressors may both benefit and undermine well-being, depending on their impact on social behavior or depression symptoms.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/h8y4c/" target="_blank">Adaptive and Maladaptive Pathways of COVID-19 Worry on Well-Being: A Cross-National Study</a>
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<li><strong>Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11</strong> -
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Appropriate cellular recognition of viruses is essential for the generation of effective innate and adaptive antiviral immunity. Viral sensors and their signalling components thus provide a crucial first line of host defence. Many exhibit subcellular relocalisation upon activation, triggering expression of interferon and antiviral genes. To identify novel signalling factors we analysed protein relocalisation on a global scale during viral infection. CREB Regulated Transcription Coactivators-2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon a diversity of viral stimuli, in diverse cell types. This movement was depended on Mitochondrial Antiviral Signalling Protein (MAVS), cyclo-oxygenase proteins and protein kinase A. We identify a key effect of transcription stimulated by CRTC2/3 translocation as production of the pro-fibrogenic cytokine interleukin-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2.
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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/10.1101/2024.04.04.588067v1" target="_blank">Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11</a>
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<li><strong>Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera</strong> -
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Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.04.05.588359v1" target="_blank">Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera</a>
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<li><strong>Care-full Collectives and their Care Practices</strong> -
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In my dissertation, I examine different collectives and their practices through different applied theories of care and theorize on new organizational structures and rituals. This is a study of how people came together during the first wave of Covid-19, myself included. It studies these coming-togethers through different “do-ings” and “be–ings” and juxtaposes them with different theories of care. Theories that include Annemarie Mol’s “Logic of Care”, Ella Myers’ “Worldly things”, Jenna Grant’s “Repair as Care”, Sara Ahmed’s “Fragile Connections” and Lucy Suchman’s “Relocating Innovation”. These different theories come from places like medical anthropology, STS, queer theory, and more. I give an honest account of my journey through these collectives and these theories. I also start to propose an alternate way of organizing institutions for mutual aid through two tools - archetypes and axioms.
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🖺 Full Text HTML: <a href="https://osf.io/ds39u/" target="_blank">Care-full Collectives and their Care Practices</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>Detoxification From the Lipid Tract</strong> - <b>Conditions</b>: COVID-19 Vaccine Adverse Reaction <br/><b>Interventions</b>: Device: electroencephalogram biofeedback; Device: electrical brain stimulation; Device: ultra-low frequency transcranial magnetic stimulation; Drug: Sertraline Hydrochloride; Drug: Clonazepam; Drug: Alprazolam; Drug: Metoprolol; Drug: Olanzapine; Drug: Pravastatin Sodium 20 MG; Drug: Sacubitril Valsartan Sodium Hydrate <br/><b>Sponsors</b>: Pachankis, Yang I., M.D.; First Affiliated Hospital of Chongqing Medical University <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid-19 and Influenza Oral Vaccine Study</strong> - <b>Conditions</b>: covid19 Infection; Influenza, Human <br/><b>Interventions</b>: Biological: Covid-19 vaccine; Biological: Influenza vaccine <br/><b>Sponsors</b>: Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute Ltd <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of the Efficacy of Troxerutin in Preventing Thrombotic Events in COVID-19 Patients</strong> - <b>Conditions</b>: COVID 19 Associated Coagulopathy <br/><b>Interventions</b>: Drug: Troxerutin; Drug: Placebo; Drug: placebo + low molecular weight heparin; Drug: troxerutin + low molecular weight heparin <br/><b>Sponsors</b>: Westlake University; Shaoxing Central 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>A Study of an Investigational mRNA-1273.815 COVID-19 Vaccine in Previously Vaccinated Adults</strong> - <b>Conditions</b>: SARS-CoV-2 <br/><b>Interventions</b>: Biological: Investigational mRNA-1273.815; Biological: Licensed Spikevax Vaccine <br/><b>Sponsors</b>: ModernaTX, 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 Use of Isatidis Root and Forsythia Oral Liquid for the Treatment of Mild Cases of COVID-19: A Trial Clinical Study</strong> - <b>Conditions</b>: Treatment of Mild Cases of COVID-19 <br/><b>Interventions</b>: Drug: Langenlianqiao; Drug: LianhuaQingWen; Other: placebo control group <br/><b>Sponsors</b>: Central South 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>Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID</strong> - <b>Conditions</b>: Long COVID; Brain Fog; Cognitive Change <br/><b>Interventions</b>: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose <br/><b>Sponsors</b>: Taipei Veterans General Hospital, Taiwan <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>Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Guidebook; Other: Guidebook and Myofascial Reorganization® (RMF). <br/><b>Sponsors</b>: University of the State of Santa Catarina; Larissa Sinhorim <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>Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure</strong> - <b>Conditions</b>: Acute Respiratory Failure <br/><b>Interventions</b>: Behavioral: Standard of Care; Behavioral: Rehabilitation <br/><b>Sponsors</b>: Hospital Israelita Albert Einstein <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>Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands</strong> - CONCLUSION: Our study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti-PF4-inducing, FcɣRIIa-dependent platelet activation, suggesting an HIT-like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology (‘non-HIT like’) leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies.</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 surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model</strong> - INTRODUCTION: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins.</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>Elderberry interaction with pazopanib in a patient with soft‑tissue sarcoma: A case report and literature review</strong> - Elderberry flower extract is marketed as an herbal supplement with purported benefits in boosting the immune system. The use of elderberry increased during the coronavirus pandemic. However, the interaction of elderberry with cytotoxic medicines has remained elusive. Pazopanib is a multikinase inhibitor approved for patients diagnosed with soft-tissue sarcoma. The present study reported on the case of a middle-aged woman diagnosed with localized intermediate-grade sarcoma of the left sartorius…</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 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 that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown that…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and Repress Coronavirus Replication, Validating Mac1 as an Antiviral Target</strong> - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed. Here, we describe small-molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation-mediated innate immune responses. Three high-throughput screening hits had the same 2-amide-3-methylester thiophene scaffold. We studied the compound binding mode using X-ray crystallography, allowing us to design…</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>Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics</strong> - CONCLUSION: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating mAbs binding abilities to Omicron subvariant RBDs: implications for selecting effective mAb therapies</strong> - The ongoing evolution of the Omicron lineage of SARS-CoV-2 has led to the emergence of subvariants that pose challenges to antibody neutralization. Understanding the binding dynamics between the receptor-binding domains (RBD) of these subvariants spike and monoclonal antibodies (mAbs) is pivotal for elucidating the mechanisms of immune escape and for advancing the development of therapeutic antibodies. This study focused on the RBD regions of Omicron subvariants BA.2, BA.5, BF.7, and XBB.1.5,…</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>Discovery of components in honeysuckle for treating COVID-19 and diabetes based on molecular docking, network analysis and experimental validation</strong> - Molecular docking screening identified ochnaflavone, madreselvin B and hydnocarpin as key components for treating COVID-19 with diabetes in honeysuckle using 3 C-like protease (Mpro), angiotensin-converting enzyme 2 (ACE2), and dipeptidyl peptidase 4 (DPP4) as molecular docking targets, ACE2, DPP4, IL2, NFKB1, PLG, TBK1, TLR4 and TNF were the core targets, and multiple antiviral and anti-inflammatory signalling pathways were involved. Further, the levels of IL-1β and DPP4 in cell supernatant…</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>Swine acute diarrhea syndrome coronavirus Nsp1 suppresses IFN-lambda1 production by degrading IRF1 via ubiquitin-proteasome pathway</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an…</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>Swine acute diarrhea syndrome coronavirus nucleocapsid protein antagonizes the IFN response through inhibiting TRIM25 oligomerization and functional activation of RIG-I/TRIM25</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging Alpha-coronavirus, brings huge economic loss in swine industry. Interferons (IFNs) participate in a frontline antiviral defense mechanism triggering the activation of numerous downstream antiviral genes. Here, we demonstrated that TRIM25 overexpression significantly inhibited SADS-CoV replication, whereas TRIM25 deficiency markedly increased viral yield. We found that SADS-CoV N protein suppressed interferon-beta (IFN-β)…</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>Inhibition of influenza A virus and SARS-CoV-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor</strong> - Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into…</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>Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron</strong> - BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic…</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>Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health</strong> - The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called “gut-lung axis”. Perturbations in gut microbiota composition, termed dysbiosis, can 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>SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway</strong> - CONCLUSION: These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.</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>Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?</strong> - Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines’ rapidly waning immunity. Mounting…</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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