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190 lines
45 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>05 May, 2022</title>
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div.column{display: inline-block; vertical-align: top; width: 50%;}
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Establishment of regional genomic surveillance networks in lower and lower-middle income countries</strong> -
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This is a position letter that represents the stance of the members of the UNESCO-TWAS Advisory Committee on COVID-19, who come from various countries in the Global South. It addresses the disparity in SARS-CoV-2 genomic data between different countries of the global North and South. It discusses possible causes of the problem and suggests establishing national genomic surveillance networks.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/2dq39/" target="_blank">Establishment of regional genomic surveillance networks in lower and lower-middle income countries</a>
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</div></li>
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<li><strong>Adsorption of Pulmonary and Exogeneous Surfactants on SARS-CoV-2 Spike Protein</strong> -
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<div>
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COVID-19 is transmitted by inhaling SARS-CoV-2 virions, which are enveloped by a lipid bilayer decorated by a crown of Spike protein protrusions. In the respiratory tract, virions interact with surfactant films composed of phospholipids and cholesterol that coat lung airways. Here, we explore by using coarse-grained molecular dynamics simulations the physico-chemical mechanisms of surfactant adsorption on Spike proteins. With examples of zwitterionic dipalmitoyl phosphatidyl choline, cholesterol, and anionic sodium dodecyl sulfate, we show that surfactants form micellar aggregates that selectively adhere to the specific regions of S1 domain of the Spike protein that are responsible for binding with ACE2 receptors and virus transmission into the cells. We find high cholesterol adsorption and preferential affinity of anionic surfactants to Arginine and Lysine residues within S1 receptor binding motif. These findings have important implications for informing the search for extraneous therapeutic surfactants for curing and preventing COVID-19 by SARS-CoV-2 and its variants.
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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/10.1101/2022.05.04.490631v1" target="_blank">Adsorption of Pulmonary and Exogeneous Surfactants on SARS-CoV-2 Spike Protein</a>
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</div></li>
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<li><strong>Socio-ecological resilience relates to lower internalizing symptoms among adolescents during the strictest period of COVID-19 lockdown in Perú</strong> -
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<div>
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The COVID-19 pandemic has touched the lives of adolescents around the world. This short-term longitudinal, observational study followed 1,334 adolescents (11 - 17 yo) to investigate whether social-ecological resilience relates to intra- and inter-personal resources and/or the caregiver relationship relates to changes in internalizing symptoms during five stressful weeks of COVID-19 lockdown in Perú. In this work, we contextualize social-ecological resilience in relation to culturally-relevant personal and caregiver resources that youth can use to adapt to stressful situations. We found that adolescents who reported higher levels of personal, caregiver, and overall resilience had lower levels of anxiety and depressive symptoms at week six. We also find that personal, caregiver, and overall resilience moderated the change in anxiety symptoms from week 6 to week 11 of lockdown in 2020. Our findings underscore the importance of social-ecological resilience related to both intra/interpersonal resources and the caregiver relationship for minimizing the harmful impacts of COVID-19 on adolescent internalizing symptoms.
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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://psyarxiv.com/q9hcr/" target="_blank">Socio-ecological resilience relates to lower internalizing symptoms among adolescents during the strictest period of COVID-19 lockdown in Perú</a>
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</div></li>
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<li><strong>SARS-CoV-2 variants do not evolve to promote further escape from MHC-I recognition</strong> -
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SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that VOCs retain similar MHC-I downregulation capacity compared to the ancestral virus. However, VOCs exhibit a greater ability to suppress type I IFN than the ancestral virus. Although VOCs possess unique mutations within the ORF8 gene, which suppresses MHC-I expression, none of these mutations enhanced the ability of ORF8 to suppress MHC-I expression. Notably, MHC-I upregulation was strongly inhibited after the ancestral SARS-CoV-2 infection in vivo. Collectively, our data suggest that the ancestral SARS-CoV-2 already possesses an intrinsically potent MHC-I evasion capacity, and that further adaptation by the variants was not observed.
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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/10.1101/2022.05.04.490614v1" target="_blank">SARS-CoV-2 variants do not evolve to promote further escape from MHC-I recognition</a>
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</div></li>
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<li><strong>Correcting COVID-19 Vaccine Misinformation in Ten Countries</strong> -
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<div>
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What can be done to reduce misperceptions about COVID-19 vaccines? We present results from experiments conducted simultaneously on YouGov samples in ten countries (N = 10,600), which reveal that factual corrections consistently reduce false belief about the vaccines. Globally, exposure to corrections increases belief accuracy by .16 on a 4-point scale, while exposure to misinformation decreases belief accuracy by .09 on the same scale. Neither misinformation nor factual corrections affect intent-to-vaccinate or vaccine attitudes. We find modest evidence that the effects of fact- checks endure, with 39% of the original correction effect in the direction of greater accuracy still detectable two weeks after initial exposure. These findings illustrate both the possibilities and limitations of factual corrections. Across ten highly diverse populations, exposure to factual information reliably reduces belief in falsehoods about vaccines, but has minimal influence on subsequent behaviors and attitudes.
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<div class="article-link article-html- link">
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🖺 Full Text HTML: <a href="https://osf.io/4stbm/" target="_blank">Correcting COVID-19 Vaccine Misinformation in Ten Countries</a>
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</div></li>
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<li><strong>Healthcare workers’ mental health and wellbeing during the COVID-19 pandemic: Longitudinal analysis of interview and social media data</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemic has shed light on the fractures of healthcare systems around the world, particularly in relation to the healthcare workforce. Frontline staff, in particular, have been exposed to unprecedented strain and delivering care during the pandemic has impacted their safety, mental health and wellbeing. The aim of this paper was to explore the experiences of HCWs delivering care in the UK during the COVID-19 pandemic to understand their wellbeing needs, experiences and strategies used to maintain wellbeing (at individual and organizational levels). We analysed 94 telephone interviews with HCWs and 2000 tweets about HCWs mental health taking place during the first year of the COVID-19 pandemic. Results were grouped under six themes: redeployment; wellbeing support and coping strategies; mental health effects; organisational support; social network and public support. These findings demonstrate a need for open conversations, where staff9s wellbeing needs and strategies can be shared and encouraged, rather than implementing solely top-down psychological interventions. At the macro level, findings also highlighted the impact on HCWs9 wellbeing of public and government support, as well as the need for ensuring protection through PPE, testing, and/or vaccines for frontline workers.
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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/10.1101/2022.04.29.22274481v2" target="_blank">Healthcare workers’ mental health and wellbeing during the COVID-19 pandemic: Longitudinal analysis of interview and social media data</a>
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</div></li>
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<li><strong>Analysis of immunization time, amplitude, and adverse events of seven different vaccines against SARS-CoV-2 across four different countries.</strong> -
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Background: Scarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI. Methods: A multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed. Results: We recruited 1867 subjects [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p<0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p<0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with SARS-CoV-2, Gam-COVID-Vac and ChAdOx1-S (p<0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naive SARS-CoV-2 subjects with age and sex (p<0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p<0.01). mRNA-1273 had a higher number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p<0.001). Conclusions: The magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response is positively correlated with AEs in patients previously exposed to SARS-CoV-2.
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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/10.1101/2022.03.11.22272153v2" target="_blank">Analysis of immunization time, amplitude, and adverse events of seven different vaccines against SARS-CoV-2 across four different countries.</a>
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</div></li>
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<li><strong>Excess all-cause mortality across counties in the United States, March 2020 to December 2021</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Official Covid-19 death tallies have underestimated the mortality impact of the Covid-19 pandemic in the United States. Excess mortality, which compares observed deaths to deaths expected in the absence of the pandemic, is a useful measure for assessing the total effect of the pandemic on mortality levels. In the present study, we produce county- level estimates of excess mortality for 3,127 counties between March 2020 and December 2021. We fit two hierarchical linear models to county-level death rates from January 2015 to December 2019 and predict expected deaths for each month during the pandemic. We compare these estimates with the observed numbers of deaths to obtain excess deaths for each county-month. An estimated 936,911 excess deaths occurred during 2020 and 2021, of which 171,168 were not assigned to Covid-19 on death certificates. Urban counties in the Far West, Great Lakes, Mideast, and New England experienced a substantial urban mortality disadvantage in 2020, whereas rural counties in these regions had higher mortality in 2021. In the Southeast, Southwest, Rocky Mountain, and Plains regions, there was a rural mortality disadvantage in 2020, which was exacerbated in 2021. The proportion of excess deaths assigned to Covid-19 was lower in 2020 (76.3%) than in 2021 (87.0%), suggesting fewer Covid-19 deaths went unassigned later in the pandemic. However, in rural areas and in the Southeast and Southwest a large share of excess deaths were still not assigned to Covid-19 during 2021.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.23.22274192v2" target="_blank">Excess all-cause mortality across counties in the United States, March 2020 to December 2021</a>
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</div></li>
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<li><strong>Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein</strong> -
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<div>
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The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC I and MHC II epitopes by ELIspot and cytolytic assays to a conserved MHC I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against 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/10.1101/2021.11.21.469172v3" target="_blank">Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein</a>
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</div></li>
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<li><strong>Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium</strong> -
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Introduction: Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes. Methods: The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA’s 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys. Results: The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi’s sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate. Conclusion: IeDEA’s approach for site survey development approach has broad relevance for HIV research networks and other priority health conditions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.25.22274292v2" target="_blank">Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium</a>
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<li><strong>Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population</strong> -
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Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS- CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post- booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively. Results: After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre- vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naive individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (β=-0.94, p=0.001) and malignancy (β=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p=0.004); (β=-0.66, p=0.014)], diabetes mellitus [(β=-0.57, p=0.032); (β=-0.44, p=0.028)], and systemic steroid use [(β=-0.066, p=0.032); (β=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (β =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001). Conclusion: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.03.22273355v2" target="_blank">Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Social activity promotes resilience against loneliness in depressed individuals: A study over 14-days of physical isolation during the COVID-19 pandemic in Australia</strong> -
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Loneliness is a subjectively perceived state of social isolation that is associated with negative emotional, cognitive, and physical health outcomes. Physical distancing and shelter-in-place public health responses designed to curb COVID-19 transmission has led to concerns over elevated risk of loneliness. Given that physical isolation does not necessitate social isolation in the age of digital communication, this study investigated the relationship between the frequency of social interaction and loneliness over a two-week period in people engaging in physical distancing, and examined whether this relationship was moderated by physical isolation level, age, or depression. A self-selected sample of N = 469 individuals across Australia who were engaged in physically distanced living completed daily surveys for 14-days during April to June of 2020. Multilevel modelling showed that more frequent social interaction with close, but not intermediate or distant contacts, was uniquely associated with lower loneliness. In addition, being younger, more depressed, more anxious, or having a mental health condition diagnosis (past or present) were also independently associated with higher loneliness. Critically, depression was the only significant moderator of the relationship between social interaction and loneliness over time, where more frequent social interaction with close contacts buffered against loneliness over time in high depression individuals only. The findings suggest that encouraging social activity with close contacts may promote resilience against loneliness in individuals with elevated depression symptoms.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/ejdmp/" target="_blank">Social activity promotes resilience against loneliness in depressed individuals: A study over 14-days of physical isolation during the COVID-19 pandemic in Australia</a>
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<li><strong>Spatiotemporal landscape of SARS-CoV-2 pulmonary infection reveals Slamf9+Spp1+ macrophages promoting viral clearance and inflammation resolution</strong> -
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While SARS-CoV-2 pathogenesis has been intensively investigated, the host mechanisms of viral clearance and inflammation resolution are still elusive because of the ethical limitation of human studies based on COVID-19 convalescents. Here we infected Syrian hamsters by authentic SARS-CoV-2 and built an ideal model to simulate the natural recovery process of SARS-CoV-2 infection from severe pneumonia. We developed and applied a spatial transcriptomic sequencing technique with subcellular resolution and tissue-scale extensibility, i.e., Stereo-seq, together with single- cell RNA sequencing (scRNA-seq), to the entire lung lobes of 45 hamsters and obtained an elaborate map of the pulmonary spatiotemporal changes from acute infection, severe pneumonia to the late viral clearance and inflammation resolution. While SARS-CoV-2 infection caused massive damages to the hamster lungs, including naive T cell infection and deaths related to lymphopenia, we identified a group of monocyte-derived proliferating Slamf9+Spp1+ macrophages, which were SARS-CoV-2 infection-inducible and cell death-resistant, recruiting neutrophils to clear viruses together. After viral clearance, the Slamf9+Spp1+ macrophages differentiated into Trem2+ and Fbp1+ macrophages, both responsible for inflammation resolution and replenishment of alveolar macrophages. The existence of this specific macrophage subpopulation and its descendants were validated by RNAscope in hamsters, immunofluorescence in hACE2 mice, and public human autopsy scRNA-seq data of COVID-19 patients. The spatiotemporal landscape of SARS-CoV-2 infection in hamster lungs and the identification of Slamf9+Spp1+ macrophages that is pivotal to viral clearance and inflammation resolution are important to better understand the critical molecular and cellular players of COVID-19 host defense and also develop potential interventions of COVID-19 immunopathology.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.03.490381v1" target="_blank">Spatiotemporal landscape of SARS-CoV-2 pulmonary infection reveals Slamf9+Spp1+ macrophages promoting viral clearance and inflammation resolution</a>
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<li><strong>Protection from Omicron and other VOCs by Bivalent S-Trimer COVID-19 Vaccine</strong> -
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The Omicron variant of SARS-COV-2 (GISAID GRA clade [B.1.1.529, BA.1 and BA.2]) is now the single dominant Variant of Concern (VOC). The high number of mutations in the Omicron Spike (S) protein promotes humoral immunological escape. Although a third homologous boost with S, derived from the ancestral strain, was able to increase neutralizing antibody titers and breadth including to Omicron, the magnitude of virus neutralization could benefit from further optimization. Moreover, combining SARS-COV-2 strains as additional valences may address the current antigenicity range occupied by VOCs. Using Trimer-TagTM platform we have previously demonstrated phase 3 efficacy and safety of a prototypic vaccine SCB-2019 in the SPECTRA trial and have submitted applications for licensure. Here, we successfully generated a bivalent vaccine candidate including both Ancestor and Omicron variant S-proteins. Preclinical studies demonstrate this SARS- CoV-2 bivalent S-Trimer subunit vaccine elicits high titers of neutralizing antibodies against all VOCs, with markedly enhanced Omicron specific neutralizing antibody responses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.03.490428v1" target="_blank">Protection from Omicron and other VOCs by Bivalent S-Trimer COVID-19 Vaccine</a>
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<li><strong>Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta</strong> -
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The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 to 0.51; P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 to 0.24; P<.0001)).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274602v1" target="_blank">Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta</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>Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2<br/><b>Sponsors</b>: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E; Biological: mRNA-1273<br/><b>Sponsor</b>: Sinocelltech 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 First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AmnioPul-02<br/><b>Sponsor</b>: Amniotics AB<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 COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<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>Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology Co., 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 COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<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>The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Chinese herbal medicine<br/><b>Sponsor</b>: <br/>
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Hong Kong Baptist University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-based Exercise Program in Patients With the Post-COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Home- based physical training<br/><b>Sponsor</b>: University of Sao Paulo<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>Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo<br/><b>Sponsor</b>: Shaperon<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>Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics)</strong> - <b>Conditions</b>: COVID-19; Post Intensive Care Syndrome<br/><b>Interventions</b>: <br/>
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Other: Aerobic Exercise Training; Other: Home Plan<br/><b>Sponsor</b>: Riphah International University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of JT001 (VV116) Compared With Paxlovid</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Paxlovid<br/><b>Sponsor</b>: <br/>
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Vigonvita Life Sciences<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>Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Drug: EXOFLO<br/><b>Sponsor</b>: Direct Biologics, LLC<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>High Frequency Percussive Ventilation in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Acute Respiratory Failure<br/><b>Intervention</b>: <br/>
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Device: High frequency Percussive ventilation<br/><b>Sponsor</b>: University Magna Graecia<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>Knowledge Mobilization Activities to Support Decision-Making by Youth, Parents and Adults: Study Protocol</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Plain Language Recommendation (PLR); Other: Standard Language Version (SLV)<br/><b>Sponsors</b>: McMaster University; Western University; The Hospital for Sick Children; University of Alberta<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>Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings</strong> - <b>Conditions</b>: Covid19; Diabetes Mellitus<br/><b>Intervention</b>: Device: continuous glucose monitoring<br/><b>Sponsor</b>: Tanureet K Arora<br/><b>Completed</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>25 (S)-Hydroxycholesterol acts as a possible dual enzymatic inhibitor of SARS-CoV-2 M<sup>pro</sup> and RdRp-: an insight from molecular docking and dynamics simulation approaches</strong> - The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (M^(pro)) of the virus mediate viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an <em>in silico</em> perspective</strong> - During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential Inhibitors of SARS-CoV-2 from <em>Neocarya macrophylla</em> (Sabine) Prance ex F. White: Chemoinformatic and Molecular Modeling Studies for Three Key Targets</strong> - CONCLUSION: The findings of this study have shown that N. macrophylla contains potential leads for SARS-CoV-2 inhibition and thus, should be studied further for development as therapeutic agents against COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IL-25 blockade augments antiviral immunity during respiratory virus infection</strong> - IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal…</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>Megakaryocytes in pulmonary diseases</strong> - Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are…</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>Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study</strong> - CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.</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>Artificial Neural Network-Based Study Predicts GS-441524 as a Potential Inhibitor of SARS-CoV-2 Activator Protein Furin: a Polypharmacology Approach</strong> - Furin, a pro-protein convertase, plays a significant role as a biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS-CoV-2, furin has become the center of attraction for researchers as the spike protein contains a polybasic furin cleavage site. In…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as “variant of concern” due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of an At-home Metal Corrosion Laboratory Experiment for STEM Outreach in Biomaterials During the Covid-19 Pandemic</strong> - Due to the coronavirus disease 2019 (COVID-19) pandemic, many universities and outreach programs have switched to online learning platforms, which inhibits students from completing formative hands-on experiments. To address this, we developed a series of at-home experiments for undergraduate engineering students and adapted one of these experiments for outreach purposes. This experiment was well received by middle school students in the Young Eisner Scholars (YES) Program and resulted in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building integrated, adaptive and responsive healthcare systems - lessons from paramedicine in Ontario, Canada</strong> - CONCLUSIONS: The findings of this study add to the discourse on governing health systems towards being more integrated, adaptive and responsive to population needs. Governance strategies include: supporting networks of local organizational relationships; considering the role of a functionally flexible health workforce; promoting a shared vision and framework for collaboration; and enabling distributed, local control and experimentation.</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 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants</strong> - As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension…</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>Computational study on the affinity of potential drugs to SARS-CoV-2 main protease</strong> - Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using Molecular and Quantum Mechanics as well as Molecular Docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the Docking…</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>Pirfenidone ameliorates early pulmonary fibrosis in LPS-induced acute respiratory distress syndrome by inhibiting endothelial-to-mesenchymal transition via the Hedgehog signaling pathway</strong> - Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases….</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>2’- and 3’-Ribose Modifications of Nucleotide Analogues Establish the Structural Basis to Inhibit the Viral Replication of SARS-CoV-2</strong> - Inhibition of RNA-dependent RNA polymerase (RdRp) by nucleotide analogues with ribose modification provides a promising antiviral strategy for the treatment of SARS-CoV-2. Previous works have shown that remdesivir carrying 1’-substitution can act as a “delayed chain terminator”, while nucleotide analogues with 2’-methyl group substitution could immediately terminate the chain extension. However, how the inhibition can be established by the 3’-ribose modification as well as other 2’-ribose…</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 second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era</strong> - Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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