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<title>05 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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<li><strong>Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.
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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/10.1101/2024.04.03.24305293v1" target="_blank">Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.</a>
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</div></li>
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<li><strong>The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence</strong> -
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<div>
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A randomized survey experiment (N=2,868) was conducted at the onset of the COVID-19 pandemic to examine the effects of information provision on individuals’ cooperation with social distancing measures. Employing a 2 × 2 factorial design, the study examined the influence of social comparison and a powerful messenger. Using an online sample of approximately 3,000 Japanese respondents, it was found that participants demonstrated greater cooperation with social distancing measures when they perceived that they had spent a relatively <em>long</em> time outside the home compared with prevailing social norms in the previous week. Conversely, individuals who spent a relatively <em>short</em> time outside the home, exhibited the opposite effect. However, these results were observed solely in conjunction with the influence of a powerful messenger. The study also explored heterogeneous responses based on personality traits. In conclusion, the results highlight the challenges of changing behavior through informational interventions, emphasizing the role of both the characteristics of the sender and recipient of the information.
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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/rsbmz/" target="_blank">The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence</a>
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</div></li>
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<li><strong>Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19</strong> -
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<div>
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The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.
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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/10.1101/2024.04.03.587929v1" target="_blank">Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19</a>
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</div></li>
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<li><strong>Within-host genetic diversity of SARS-CoV-2 across animal species</strong> -
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<div>
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Infectious disease transmission to different host species makes eradication very challenging and expands the diversity of evolutionary trajectories taken by the pathogen. Since the beginning of the ongoing COVID-19 pandemic, SARS-CoV-2 has been transmitted from humans to many different animal species, and viral variants of concern could potentially evolve in a non-human animal. Previously, using available whole genome consensus sequences of SARS-CoV-2 from four commonly sampled animals (mink, deer, cat, and dog) we inferred similar numbers of transmission events from humans to each animal species but a relatively high number of transmission events from mink back to humans (Naderi et al., 2023). Using a genome-wide association study (GWAS), we identified 26 single nucleotide variants (SNVs) that tend to occur in deer – more than any other animal – suggesting a high rate of viral adaptation to deer. Here we quantify intra-host SARS-CoV-2 across animal species and show that deer harbor more intra-host SNVs (iSNVs) than other animals, providing a larger pool of genetic diversity for natural selection to act upon. Within-host diversity is particularly high in deer lymph nodes compared to nasopharyngeal samples, suggesting tissue-specific differences in viral population sizes or selective pressures. Neither mixed infections involving more than one viral lineage nor large changes in the strength of selection are likely to explain the higher intra-host diversity within deer. Rather, deer are more likely to contain larger viral population sizes, to be infected for longer periods of time, or to be systematically sampled at later stages of infections. Combined with extensive deer-to-deer transmission, the high levels of within-deer viral diversity help explain the apparent rapid adaptation of SARS-CoV-2 to deer.
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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/10.1101/2024.04.03.587973v1" target="_blank">Within-host genetic diversity of SARS-CoV-2 across animal species</a>
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</div></li>
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<li><strong>Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology</strong> -
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<div>
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Background: Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to people's health, which is a high-risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. Methods: We used a bioinformatics and systems biology approach to investigate the relationship between GC and COVID-19. The gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. Results: A total of 209 shared DEGs were identified to explore the linkages between COVID-19 and GC. Functional analyses showed that Immune-related pathway collectively participated in the development and progression of COVID-19 and GC. In addition, there are selected 10 hub genes including CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, and IFIT2. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. This study also provides insight into the diseases most associated with mutual DEGs, which may provide new ideas for research on the treatment of COVID-19. Conclusions: This research has the possibility to be contributed to effective therapeutic in COVID-19 and GC.
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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/10.1101/2024.04.03.587916v1" target="_blank">Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology</a>
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</div></li>
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<li><strong>Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19</strong> -
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<div>
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The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CLpro), and papain-like protease (PLpro) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CLpro inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CLpro from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms. Through the application of a structure-based drug design (SBDD) approach, we discovered a series of novel potent non-covalent PLpro inhibitors with remarkable in vitro potency and in vivo PK properties. The co-crystal structures of PLpro with leads revealed that the residues E164 and Q269 around the S2 site are critical for improving the inhibitor's potency. The lead compound GZNL-P36 not only inhibited SARS-CoV-2 and its variants at the cellular level with EC50 ranging from 58.2 nM to 306.2 nM, but also inhibited HCoV-NL63 and HCoV-229E with EC50 of 81.6 nM and 2.66 M, respectively. Oral administration of the compound resulted in significantly improved survival and notable reductions in lung viral loads and lesions in SARS-CoV-2 infection mouse model, consistent with RNA-seq data analysis. Our results indicate that PLpro inhibitor is a promising SARS-CoV-2 therapy.
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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/10.1101/2024.04.03.587743v1" target="_blank">Discovery of orally bioavailable SARS-CoV-2 papain-like protease inhibitor as a potential treatment for COVID-19</a>
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</div></li>
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<li><strong>Comparative analysis of serological assays and sero-surveillance for SARS-CoV-2 exposure in US cattle</strong> -
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<div>
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Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose a significant threat to public health globally. Notably, SARS-CoV-2 demonstrates a unique capacity to infect various non-human animal species, documented in captive and free-living animals. However, experimental studies revealed low susceptibility of domestic cattle (Bos taurus) to ancestral B.1 lineage SARS-CoV-2 infection, with limited viral replication and seroconversion. Despite the emergence of viral variants with potentially altered host tropism, recent experimental findings indicate greater permissiveness of cattle to SARS-CoV-2 Delta variant infection compared to other variants, though with limited seroconversion and no clear evidence of transmission. While some studies detected SARS-CoV-2 antibodies in cattle in Italy and Germany, there is no evidence of natural SARS-CoV-2 infection in cattle from the United States or elsewhere. Since serological tests have inherent problems of false positives and negatives, we conducted a comprehensive assessment of multiple serological assays on over 600 cattle serum samples, including pre-pandemic and pandemic cattle sera. We found that SARS-CoV-2 pseudovirus neutralization assays with a luciferase reporter system can produce false positive results, and care must be taken to interpret serological diagnosis using these assays. We found no serological evidence of natural SARS-CoV-2 infection or transmission among cattle in the USA. Hence, it is critical to develop more reliable serological assays tailored to accurately detect SARS-CoV-2 antibodies in cattle populations and rigorously evaluate diagnostic tools. This study underscores the importance of robust evaluation when employing serological assays for SARS-CoV-2 detection in cattle populations.
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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/10.1101/2024.04.03.587933v1" target="_blank">Comparative analysis of serological assays and sero-surveillance for SARS-CoV-2 exposure in US cattle</a>
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</div></li>
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<li><strong>Visualization Guardrails: Designing Interventions Against Cherry-Picking in Interactive Data Explorers</strong> -
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<div>
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The growing popularity of interactive time series exploration platforms has made visualizing data of public interest more accessible to general audiences. At the same time, the democratized access to professional-looking explorers with preloaded data enables the creation of convincing visualizations with carefully cherry-picked items. Prior research shows that people use data explorers to create and share charts that support their potentially biased or misleading views on public health or economic policy and that such charts have, for example, contributed to the spread of COVID-19 misinformation. Interventions against misinformation have focused on post hoc approaches such as fact-checking or removing misleading content, which are known to be challenging to execute. In this work, we explore whether we can use visualization design to impede cherry-picking—one of the most common methods employed by deceptive charts created on data exploration platforms. We describe a design space of guardrails—interventions against cherry-picking in time series explorers. Using our design space, we create a prototype data explorer with four types of guardrails and conduct two crowd-sourced experiments. In the first experiment, we challenge participants to create cherry-picked charts. We then use these charts in a second experiment to evaluate the guardrails’ impact on the perception of cherry-picking. We find evidence that guardrails—particularly superimposing relevant primary data—are successful at encouraging skepticism in a subset of experimental conditions but come with limitations. Based on our findings, we propose recommendations for developing effective guardrails for visualizations.
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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/4j9nr/" target="_blank">Visualization Guardrails: Designing Interventions Against Cherry-Picking in Interactive Data Explorers</a>
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</div></li>
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<li><strong>Misleading Beyond Visual Tricks: How People Actually Lie with Charts</strong> -
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<div>
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Data visualizations can empower an audience to make informed decisions. At the same time, deceptive representations of data can lead to inaccurate interpretations while still providing an illusion of data-driven insights. Existing research on misleading visualizations primarily focuses on examples of charts and techniques previously reported to be deceptive. These approaches do not necessarily describe how charts mislead the general population in practice. We instead present an analysis of data visualizations found in a real-world discourse of a significant global event—Twitter posts with visualizations related to the COVID-19 pandemic. Our work shows that, contrary to conventional wisdom, violations of visualization design guidelines are not the dominant way people mislead with charts. Specifically, they do not disproportionately lead to reasoning errors in posters’ arguments. Through a series of examples, we present common reasoning errors and discuss how even faithfully plotted data visualizations can be used to support misinformation online.
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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/ky6th/" target="_blank">Misleading Beyond Visual Tricks: How People Actually Lie with Charts</a>
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</div></li>
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<li><strong>Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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A substantial proportion of acute SARSCoV2 infection cases exhibit gastrointestinal symptoms, yet the genetic determinants of these extrapulmonary manifestations are poorly understood. Using survey data from 239,866 individuals who tested positively for SARSCoV2, we conducted a multi-ancestry GWAS of 80,289 cases of diarrhea occurring during acute COVID19 infection (33.5%). Six loci (CYP7A1, LZFTl1/CCR9, TEME182, NALCN, LFNG, GCKR) met genomewide significance in a trans-ancestral analysis. The top significant GWAS hit mapped to the CYP7A1 locus, which plays an etiologic role in bile acid metabolism and is in high LD (r2= 0.93) with the SDCBP gene, which was previously implicated in antigen processing and presentation in the COVID-19 context. Another association was observed with variants in the LZTFL1/CCR9 region, which is a known locus for COVID19 susceptibility and severity. PheWAS showed a shared association across three of the six SNPs with irritable bowel syndrome (IBS) and its subtypes. Mendelian randomization showed that genetic liability to IBS-diarrhea increased (OR=1.40,95%,CI[1.33,1.47]), and liability to IBS-constipation decreased (OR=0.86, 95%CI[0.79,0.94]) the relative odds of experiencing COVID19+ diarrhea. Our genetic findings provide etiological insights into the extrapulmonary manifestations of acute SARSCoV2 infection.
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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/10.1101/2024.04.03.24305274v1" target="_blank">Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes</a>
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</div></li>
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<li><strong>Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Abstract: Objectives: This study aimed to assess the safety and preliminary efficacy of MiSaver stem cells in enhancing left ventricular ejection function and functional activity among patients with acute myocardial infarction (AMI). Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with heart attacks and strokes accounting for a significant portion of deaths. Recovery of left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is crucial for prognosis, as patients with poor LVEF recovery face increased risks of sudden cardiac arrest events and mortality. Stem cell therapy offers regenerative potential for cardiovascular diseases, yet accessibility remains limited. This study investigates the safety and efficacy of MiSaver, a prefabricated stem cell investigational product, in recent AMI patients, aiming to enhance accessibility and patient outcomes. Methods: Patients who were admitted for AMI within 7 days and had reduced LVEF (≤45%) were eligible for the study. MiSaver were matched for blood group and administered in participants in cohorts of five, each receiving escalating dosages (0.5x10^7, 1.6x10^7, and 5.0x10^7 cells/kg, respectively). Patients were assessed for symptoms of graft-versus-host disease (GVHD) and treatment-related adverse events (AE). LVEF measured by echocardiographic on admission, at 6 months, and at 12 months after treatment. Patients functional activity status evalution ( using the New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classification systems. Results: Out of the initially planned 15 participants, eleven were enrolled in the study. The trial was halted prematurely due to challenges associated with the COVID-19 pandemic and impractical transportation logistics. During the 12-month follow-up period, no study-related adverse events or signs of graft-versus-host disease were reported. At 12 months post-treatment, both the low and middle dose groups, as well as participant 11, showed improved left ventricular ejection fraction (LVEF), accompanied by enhanced Canadian Cardiovascular Society (CCS) class grades compared to baseline. Conclusion: Intravenous infusion of MiSaver stem cells in AMI patients demonstrated safety and tolerability for low and middle dosage groups, suggesting potential for improving left ventricular function following AMI. However, further research with larger cohorts and controlled placebos is necessary to confirm these findings and address trial limitations encountered.
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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/10.1101/2024.04.01.24305125v2" target="_blank">Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study</a>
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</div></li>
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<li><strong>Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. We estimated overall PASC incidence using a computable phenotype. We also measured the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.98, 95% confidence interval [CI] 0.95-1.01). However, it had a protective effect on cognitive (RR = 0.90, 95% CI 0.84-0.96) and fatigue (RR = 0.95, 95% CI 0.91-0.98) symptom clusters, which suggests that the etiology of these symptoms may be more closely related to viral load than that of respiratory symptoms.
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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/10.1101/2024.01.20.24301525v2" target="_blank">Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia</a>
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</div></li>
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<li><strong>Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Abstract: Objectives: This study aimed to assess the safety and preliminary efficacy of MiSaver stem cells in enhancing left ventricular ejection function and functional activity among patients with acute myocardial infarction (AMI). Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with heart attacks and strokes accounting for a significant portion of deaths. Recovery of left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is crucial for prognosis, as patients with poor LVEF recovery face increased risks of sudden cardiac arrest events and mortality. Stem cell therapy offers regenerative potential for cardiovascular diseases, yet accessibility remains limited. This study investigates the safety and efficacy of MiSaver, a prefabricated stem cell investigational product, in recent AMI patients, aiming to enhance accessibility and patient outcomes. Methods: Patients admitted for AMI with reduced LVEF (≤45%) were eligible. MiSaver stem cells, matched for blood group, were administered to participants in cohorts of five, with escalating dosages (0.5x10^7, 1.6x10^7, and 5.0x10^7 cells/kg) 2-5 days post-AMI onset. Echocardiographic assessments were conducted upon admission, at 6 months, and at 12 months post-treatment. Results: Out of the initially planned 15 participants, eleven were enrolled in the study. The trial was halted prematurely due to challenges associated with the COVID-19 pandemic and impractical transportation logistics. During the 12-month follow-up period, no study-related adverse events or signs of graft-versus-host disease were reported. At 12 months post-treatment, both the low and middle dose groups, as well as participant 11, showed improved left ventricular ejection fraction (LVEF), accompanied by enhanced Canadian Cardiovascular Society (CCS) class grades compared to baseline. Conclusion: Intravenous infusion of MiSaver stem cells in AMI patients demonstrated safety and tolerability for low and middle dosage groups, suggesting potential for improving left ventricular function following AMI. However, further research with larger cohorts and controlled placebos is necessary to confirm these findings and address trial limitations encountered.
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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/10.1101/2024.04.01.24305125v1" target="_blank">Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study</a>
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</div></li>
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<li><strong>Disease diagnostics using machine learning of immune receptors</strong> -
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<div>
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Clinical diagnosis typically incorporates physical examination, patient history, and various laboratory tests and imaging studies, but makes limited use of the human system’s own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis (Mal-ID), an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences. Human-interpretable features of the model recapitulate known immune responses to SARS-CoV-2, Influenza, and HIV, highlight antigen-specific receptors, and reveal distinct characteristics of Systemic Lupus Erythematosus and Type-1 Diabetes autoreactivity. This analysis framework has broad potential for scientific and clinical interpretation of human immune responses.
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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/10.1101/2022.04.26.489314v5" target="_blank">Disease diagnostics using machine learning of immune receptors</a>
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<li><strong>How Long is the Worst Part of the COVID-19 Mortality Surge?</strong> -
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Objectives: Define and quantify the critical surge period of existing on-line COVID-19 mortality data; this could be instrumental to decision makers to determine how long health controls should be in place, and how long to expect the public health system to be in great stress. Create and share on-line, open-source software to continuously monitor critical surge periods in various communities as the data set grows. Test the critical surge period computational method on hierarchical data sets of various communities: a) globally; b) countrywide (states in the US); and c) statewide (counties/towns in the US states). Study Design: This was an open-source, on-line, COVID-19 data analytics development with support for web-browsers on any current mobile device. Methods: On-line, timely data for COVID-19 mortality was automatically retrieved by a developed application using the programming Python language and Jupyter electronic notebooks. An on-line, version-controlled code repository was created for the application and also used for providing an open execution environment for the research community. The data was fitted to a modified sigmoid function via an automated non- linear least-squares method. Three optimal parameters were computed and the critical times for the maximum and minimum curvatures of the function were used to obtain the critical surge period. The goodness of the fit was measured by a standard coefficient of determination, and alternatively, by direct pointwise relative error. Results: The software developed (a Python package) is called covid-surge (repository URL: htttps://github.com/dpploy/covid-surge) and available for download from PyPI on-line (URL: https://pypi.org/project/covid-surge/). Using covid-surge, the critical surge period was computed for the communities with the most evolved COVID-19 outbreak. At the time of this writing, the critical surge period was calculated for all countries with fully evolved mortality (12 out of 188) and found to be in average 23 days with 3 days of standard deviation. Similarly, for all states/districts in the US (20 out of 56), the computed average was 25 days with 3 days of standard deviation. Likewise, for the same states in the US, counties/towns that had fully evolved mortality surge (91 total out of 981 that had death cases) had the overall average of the surge period equal to 23 days with a standard deviation of 3 days. The accuracy of these results can be reproduced on-line using the software provided. In addition, forward results using newer data can also be generated by the research community using covid-surge. Conclusions: The surge period for hierarchical data including 12 countries, 20 US states, and 91 US counties/towns is remarkably similar: a 24-day period with 3-day standard deviation for all communities across many countries and the US. All of these communities were under similar COVID-19 controls, including social distancing, improved hygiene, and isolation which helps explain the constancy of the surge period. That is, these communities experienced nearly the same amount of time during the most stressful period of the mortality surge. Although the extent to which epidemic controls are applied can vary from community to community, this study shows that the variability of the surge period is small. As the COVID-19 sweeps over the continents, additional data will be available for fully-evolved communities and a later comparison can be made with covid-surge on-line. This study suggests that communities not yet fully affected by the COVID-19 mortality may expect a period of high stress on their public health system of about 30 days (lower bound). That is, health care organizations should plan to operate at full capacity for a minimum of 30 days.
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🖺 Full Text HTML: <a href="https://osf.io/z59uy/" target="_blank">How Long is the Worst Part of the COVID-19 Mortality Surge?</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>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD)</strong> - <b>Conditions</b>: Post-Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program <br/><b>Sponsors</b>: University of Minnesota <br/><b>Recruiting</b></p></li>
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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>SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the surface angiotensin-converting enzyme 2 (ACE2) receptor as the site of entry into host cardiac, respiratory, intestinal, renal, and nervous system cells. Predisposing risk factors such as cardiovascular disease increase the risk of developing severe disease. Hypertension is characterized by the stimulation of the renin-angiotensin-aldosterone system…</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>Ipsilateral and contralateral coadministration of influenza and COVID-19 vaccines produce similar antibody responses</strong> - BACKGROUND: World Health Organisation (WHO) and USA Centers for Disease Control and Prevention (U.S. CDC) recommendations now allow simultaneous administration of COVID-19 and other vaccines. We compared antibody responses after coadministration of influenza and bivalent COVID-19 vaccines in the same (ipsilateral) arm vs. different (contralateral) arms.</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 the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide</strong> - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-β). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and…</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>TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency</strong> - INTRODUCTION: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition.</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>Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19</strong> - CONCLUSIONS: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.</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>Quercetin inhibition of porcine intestinal alpha coronavirus in vitro and in vivo</strong> - CONCLUSIONS: Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.</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>Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques</strong> - CONCLUSIONS: We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A rigorous theoretical and numerical analysis of a nonlinear reaction-diffusion epidemic model pertaining dynamics of COVID-19</strong> - The spatial movement of the human population from one region to another and the existence of super-spreaders are the main factors that enhanced the disease incidence. Super-spreaders refer to the individuals having transmitting ability to multiple pathogens. In this article, an epidemic model with spatial and temporal effects is formulated to analyze the impact of some preventing measures of COVID-19. The model is developed using six nonlinear partial differential equations. The infectious…</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 randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV)</strong> - CONCLUSION: Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.</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 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling</strong> - Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since its emergence in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse…</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>Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19?</strong> - The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and…</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>In vitro suppression of porcine epidemic diarrhea virus by Panax notoginseng saponins: assessing antiviral potential</strong> - Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity…</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 death domain-associated protein suppresses porcine epidemic diarrhea virus replication by interacting with signal transducer and activator of transcription 1 and inducing downstream ISG15 expression</strong> - Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute enteric disease in piglets and severely threatens the pig industry all over the world. Death domain-associated protein (DAXX) is a classical chaperone protein involved in multiple biological processes, such as cell apoptosis, transcriptional regulation, DNA damage repair, and host innate immunity. However, whether DAXX functions in the anti-PEDV innate immune responses remains unclear. In this study, we found 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>Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots</strong> - CONCLUSION: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.</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>Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection</strong> - CONCLUSION: Both LNP-Trap and LNP-Trim formulations were able to safely and effectively inhibit SARS-CoV-2 pseudoviral infection in airway epithelial cells. These studies provide proof-of-principle for a localized treatment approach for SARS-CoV-2 in the upper airway.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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