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<title>05 March, 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>Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</strong> -
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<div>
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Since the publication of the genome of SARS-CoV-2 - the causative agent of COVID-19 - in January 2020, many bioinformatic tools have been applied to annotate its proteins. Although efficient methods have been used, such as the identification of protein domains stored in Pfam, most of the proteins of this virus have no detectable homologous protein domains outside the viral taxa. As it is now well established that some viral proteins share similarities with proteins of their hosts, we decided to explore the hypothesis that this lack of homologies could be, at least in part, the result of the documented loss of sensitivity of Pfam Hidden Markov Models (HMMs) when searching for domains in “divergent organisms”. To improve the annotation of SARS-CoV-2 proteins, we used here the HHpred protein annotation tool and an available custom HH-suite database of HMMs specific to Homo sapiens proteins. To avoid “false positive predictions” as much as possible, we designed a robustness procedure to evaluate the HHpred results. In total, 6 robust similarities involving 6 distinct SARS-CoV-2 proteins were detected. Of these 6 similarities, 3 are already known and well documented, and one is in agreement with recent crystallographic results. We then examined carefully the two similarities that have not yet been reported in the literature. We first show that the C-terminal part of Spike S (the protein that binds the virion to the cell membrane by interacting with the host receptor, triggering infection) has similarities with the human prominin-1/CD133; after reviewing what is known about prominin-1/CD133, we suggest that the C-terminal part of Spike S could both improve the docking of Spike S to ACE2 (the main cell entry receptor for SARS-CoV-2) and be involved in the delivery of virions to regions where ACE2 is located in cells. Secondly, we show that the SARS-CoV-2 ORF3a protein shares similarities with human G protein-coupled receptors (GPCRs) belonging mainly to the “Rhodopsin family”. We conclude that the approach described here (or similar approaches) opens up new avenues of research to better understand SARS-CoV-2 and could be used to complement virus annotations, particularly for less-studied viruses.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.06.543855v2" target="_blank">Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus</a>
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</div></li>
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<li><strong>Engineering customized viral receptors for various coronaviruses</strong> -
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<div>
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Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus amplification for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as amplification of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.
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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/10.1101/2024.03.03.583237v1" target="_blank">Engineering customized viral receptors for various coronaviruses</a>
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</div></li>
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<li><strong>Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection</strong> -
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<div>
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A highly transmissible SARS-CoV-2 variant JN.1 is rapidly spreading throughout the nation, becoming the predominant strain in China and worldwide. However, the current immunity against the circulating JN.1 at population level has yet to be fully evaluated. We recruited representative cohorts with stratified age groups and diverse combinations of vaccination and/or infection in recent months, and promptly assessed humoral immunity for these subjects predominantly exhibiting hybrid immunity. We report that at 11 months following BA.5-wave breakthrough infection (BTI), these vaccinated individuals generally showed above-the-threshold yet low level of neutralizing activity against JN.1, with slightly greater potency observed in children and adolescents compared to adults and seniors. Meanwhile, XBB/EG.5-wave reinfection post-BTI significantly boosted the neutralizing antibodies against Omicron variants, including JN.1 in both adults (13.4- fold increase) and seniors (24.9-fold increase). To better understand respiratory mucosal protection against JN.1 over an extended period of months post-BTI, we profiled the humoral immunity in bronchoalveolar lavage samples obtained from vaccinated subjects with or without BTI, and revealed increased potency of neutralizing activity against the BA.5 and JN.1 variants in the respiratory mucosa through natural infection. Notably, at 11 months post-BTI, memory B cell responses against prototype and JN.1 were detectable in both blood and respiratory mucosa, displaying distinct memory features in the circulation and airway compartments. XBB/EG.5-wave reinfection drove the expansion of JN.1-specific B cells, along with the back-boosting of B cells responding to the ancestral viral strain, suggesting the involvement of immune imprinting. Together, this study indicates heterogeneous hybrid immunity over 11 months post-BTI, and underscores the vulnerability of individuals, particularly high-risk seniors, to JN.1 breakthrough infection. An additional booster with XBB-containing vaccine may greatly alleviate the onward transmission of immune-evasive SARS-CoV-2 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/10.1101/2024.03.02.583082v1" target="_blank">Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection</a>
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</div></li>
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<li><strong>B cell maturation restored ancestral germlines to control Omicron BA.2.86</strong> -
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<div>
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The unceasing interplay between SARS-CoV-2 and the human immune system has led to a continuous maturation of the virus and B cell response providing an opportunity to track their evolution in real time. We longitudinally analyzed the functional activity of almost 1,000 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people, and from individuals with hybrid and super hybrid immunity (SH), developed after three mRNA vaccine doses and two breakthrough infections. The most potent neutralization and Fc functions against highly mutated variants, including BA.2.86, were found in the SH cohort. Despite different priming, epitope mapping revealed a convergent maturation of the functional antibody response. Neutralization was mainly driven by Class 1/2 nAbs while Fc functions were induced by Class 3/4 antibodies. Remarkably, broad neutralization was mediated by restored IGHV3-53/3-66 B cell germlines which, after heterogenous exposure to SARS-CoV-2 S proteins, increased their level of somatic hypermutations. Our study shows the resilience of the human immune system which restored previously expanded germlines and activated naive B cells to broaden the antibody repertoire of antibodies to control future SARS-CoV-2 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/10.1101/2024.03.03.583187v1" target="_blank">B cell maturation restored ancestral germlines to control Omicron BA.2.86</a>
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</div></li>
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<li><strong>Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated</strong> -
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<div>
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Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. This study analyses the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-{gamma}) in both CD4+ and CD8+ T-cells. In conclusion, the AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
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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/10.1101/2024.03.01.582987v1" target="_blank">Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated</a>
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</div></li>
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<li><strong>Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</strong> -
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<div>
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Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10 -3 and 1.1x10 -3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.25.568670v2" target="_blank">Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</a>
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</div></li>
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<li><strong>The Effect of Analytical Thinking on Irrational Behaviors in Times of COVID-19: the Mediating Role of Misinformation Beliefs</strong> -
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<div>
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The present study was to investigate the influence of analytical thinking on irrational behaviors evoked by COVID-19 (including excessive epidemic prevention and hoarding behavior) and the mediating role of misinformation beliefs related to COVID-19 (including social and pseudoscientific beliefs) in a public health crisis. 1968 Chinese participants completed the Analytical Thinking Test, Misinformation Beliefs Questionnaire and Irrational Behavior Questionnaire online. The results showed that (1) Analytical thinking had a negative prediction on both excessive epidemic prevention and hoarding behavior; (2) misinformation beliefs, even social misinformation beliefs, partly mediated the relationship between the analytical thinking and irrational behaviors. These findings provide some useful references for effectively reducing people’s irrational behaviors during a public health crisis.
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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/tfjsv/" target="_blank">The Effect of Analytical Thinking on Irrational Behaviors in Times of COVID-19: the Mediating Role of Misinformation Beliefs</a>
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<li><strong>A Descriptive Study of Patient Quality Care via Telehealth During COVID-19</strong> -
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<div>
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The COVID-19 pandemic has seen a rise in reported symptoms of anxiety or depressive disorders, difficulty sleeping or eating, and an increase in alcohol and substance use primarily resulting from isolation and job loss. Social distancing guidelines created the perfect opportunity for mental healthcare organizations across all mental health care settings and levels of care to connect with individuals and families suffering from mental abnormalities virtually; however, widespread adoption of telehealth programs by mental health practitioners continues to fall short. This study uses a non-experimental descriptive survey design to answer descriptive questions on how participants rated their experience with telehealth as a standalone service delivery method in private practice settings. When patients experience quality care, they are more likely to return for future services and refer others. Quality experiences do correlate with positive financial performance, and this study describes how patients are rating their experience. The survey in this study contained Likert Scale questions, and the researcher used cross-tabulation and pivot tables to describe how participants responded to the survey. Results from this study are intended to provide insight into telehealth acceptance and effectiveness. This study also provides a foundation for further research to discover participant perceptions and examine participant responses as it relates to telehealth as a standalone mode of treatment in a private practice setting.
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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/xyre8/" target="_blank">A Descriptive Study of Patient Quality Care via Telehealth During COVID-19</a>
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</div></li>
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<li><strong>Promoting Daily Well-being in Adolescents using mHealth</strong> -
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<div>
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Adolescents are at increased risk for developing mental health problems. The Grow It! app is an mHealth intervention aimed at preventing mental health problems through improving coping by cognitive behavioral therapy (CBT)-inspired challenges as well as self-monitoring of emotions through Experience Sampling Methods (ESM). Yet, little is known about daily changes in well-being and coping during a stressful period, like the COVID-19 pandemic. The current study aimed to elucidate daily changes in positive and negative affect, and adaptive coping, and to better understand the within-person’s mechanisms of the Grow It! app. The sample consisted of 12-25-year old Dutch adolescents in two independent cohorts (cohort 1: N = 476, Mage=16.24, 76.1% female, 88.7% Dutch; cohort 2: N = 814, Mage=18.45, 82.8% female, 97.2% Dutch). ESM were used to measure daily positive and negative affect and coping (cohort 1: 42 days, 210 assessments per person; cohort 2: 21 days, 105 assessments). The results showed that, on average, adolescents decreased in daily positive affect and adaptive coping, and increased in their experienced negative affect. A positive relation between adaptive coping and positive affect was found, although independent of the CBT-based challenges. Latent class analysis identified two heterogeneous trajectories for both positive and negative affect, indicating that the majority of participants with low to moderate-risk on developing mental health problems were likely to benefit from the Grow It! app.
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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/pdgh9/" target="_blank">Promoting Daily Well-being in Adolescents using mHealth</a>
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<li><strong>Prospective, directional associations between Social Media Intensity, Loneliness, and Anxiety among Peruvian Adolescents during the COVID-19 Pandemic</strong> -
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The impact of social media on adolescent mental health is an area of intense interest and controversy, especially since the COVID-19 pandemic has increased youth’s reliance on online communications. Current evidence, mostly from cross-sectional studies in the Global North, is mixed. Thus, the aim of this study was to investigate the relationship between social media and mental health in adolescents in Perú across 15 months of COVID-19 lockdowns. In this observational study, we first examined associations between social media intensity (SMI), feelings of loneliness, and anxiety at the beginning of the pandemic (May 2020) in 1603 early adolescents (10 – 14 years). Hypotheses of a positive association between all outcomes, particularly for girls, were derived from exploring one half of the sample (n =807), preregistered, and then confirmed in the second half of the sample (n = 806). In May 2020, SMI was associated with more frequent loneliness for girls, and SMI was associated with more frequent anxiety for both sexes. In a longitudinal follow up (n = 455) we then investigated prospective and directional associations across three waves (May 2020, November 2020, and July 2021). Longitudinal analyses revealed a more complex pattern. Across 15 months of COVID-19 in Perú, feelings of loneliness in girls were associated with an increase in SMI. In contrast, higher SMI among girls was associated with an increase in feelings of anxiety. We did not find the reverse relationships. Our findings with early adolescents in low-and middle-income urban settings in Latin America, an underrepresented population, underscore the importance of longitudinal research and contribute to understanding these important issues globally.
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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/8bvjc/" target="_blank">Prospective, directional associations between Social Media Intensity, Loneliness, and Anxiety among Peruvian Adolescents during the COVID-19 Pandemic</a>
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<li><strong>Public Health Communication Reduces COVID-19 Misinformation Sharing and Boosts Self-Efficacy</strong> -
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During pandemics, circulation of misinformation has optimal conditions as information spreads fast while uncertainty is high. While health authorities play a key role in providing advice for protective behaviors, little is known on how health authorities can mitigate the spread of misinformation on social media. In two experiments in Denmark, we assess the effect of an accuracy nudge and two video interventions from the Danish Health Authorities used in a real-world public health campaign circulated on social media in Denmark during the COVID-19 pandemic. Our findings show that providing citizens with elaborate, actionable and concrete advice decrease misinformation sharing by boosting citizens’ sense of self-efficacy. Furthermore, while accuracy nudges may less effective during times with high uncertainty, public health authorities can provide citizens with competences through scaleable video interventions on social media.
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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/8wdfp/" target="_blank">Public Health Communication Reduces COVID-19 Misinformation Sharing and Boosts Self-Efficacy</a>
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<li><strong>How did UK social distancing restrictions affect the lives of women experiencing intimate partner violence during the COVID-19 pandemic? A qualitative exploration of survivor views</strong> -
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Background: An increase of domestic abuse cases was reported at the start of the COVID-19 pandemic, with many people living with abuse facing additional barriers to seeking support. Available evidence suggests women are overrepresented in the reported cases of intimate partner violence (IPV) and we aimed to learn more about how their lives were impacted by social distancing restrictions. Methods: We conducted a qualitative interview study, using reflexive thematic analysis. Interviews were conducted between April 2021 and March 2022. 18 women in the UK with past experiences of IPV provided informed consent and participated in this study. Results: We identified five themes related to the experiences of COVID-19 lockdown restrictions on the lives of the participants. Firstly, lockdown meant being confined to a place where abuse was escalating in frequency and intensity. Participants described fear, isolation, and loss of control during the early stages of the pandemic from the combination of abuse and pandemic-related changes to daily life. However, psychosocial wellbeing and identity underwent a transformation when abuse ended during lockdown, with many participants using the word “freedom” when reflecting on their experience of living through the COVID-19 pandemic. We identified key barriers that prevented access to support for IPV, including “cancelled” services and missed opportunities to intervene during interactions in lockdown with frontline workers. Paradoxically, some participants found other forms of support were more readily available, such as provision of online psychological support and social groups. Conclusions: In this study, we explored the views of female survivors of IPV in the UK during the COVID-19 pandemic. Our results highlight the importance of combined public awareness campaigns and community intervention points for victims to safely seek help during social distancing restrictions. Having the time and space to reflect on healing after escaping abuse was described by women in our study as a benefit from their lives in lockdown, which is a factor that could be incorporated into future initiatives developed to support people subjected to violence and abuse.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/d8rvk/" target="_blank">How did UK social distancing restrictions affect the lives of women experiencing intimate partner violence during the COVID-19 pandemic? A qualitative exploration of survivor views</a>
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<li><strong>Impacts of Inequality and Poverty on COVID-19 in Indonesia</strong> -
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Purpose: The purpose of this study was to investigate how inequality and poverty contributed to COVID-19 cases and mortality using panel regression. Design/methodology/approach: The data cover semiannual observations during the COVID-19 period spanning from 2019 to 2022 in 34 provinces in Indonesia. This study split samples into high- and low-inequality provinces and apply the fixed effect panel regression on COVID-19 cases and mortality. Findings: The results suggest that the effect of inequality on the spread of COVID-19 was greater in low-inequality provinces. Whereas poverty and unemployment positively influenced the total cases in high-inequality provinces. The variable of unmet health facility had a negative impact on COVID-19 cases, but education positively influenced COVID-19 cases. There were identical results for all the variables when looking at COVID-19 mortality, except for unemployment. Unemployment showed a positively significant influence on COVID-19 mortalities in all samples, whereas it only influenced COVID-19 cases in high-inequality provinces. Originality/value: the most crucial outcome of this study concerns the distinctive implications for different types of inequality and their impact on COVID-19.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/39ayz/" target="_blank">Impacts of Inequality and Poverty on COVID-19 in Indonesia</a>
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<li><strong>Is resisting Covid-19 vaccination a “problem”? A critical policy inquiry of vaccine mandates for healthcare workers</strong> -
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As the COVID-19 global vaccination campaign was launched in December of 2020, vaccination became mandatory for many healthcare workers (HCWs) worldwide. Large minorities resisted the policy, and the responses of authorities to this resistance led to damaged professional reputations, job losses, and suspension or termination of practice licenses. The joint effect of dismissals, early retirements, career changes, and vaccine injuries disabling some compliant HCWs from adequate performance, has exacerbated existing crises within health systems. Nevertheless, the position of leading health authorities has been that the benefits of a fully vaccinated healthcare labour force - protecting health systems, vulnerable patient populations, and even HCWs themselves – achieved through mandates, if necessary, outweigh its potential harms. Informed by critical policy and discourse traditions, we examine the expert literature on vaccine mandates for HCWs. We find that this literature neglects evidence countering claims about the safety and effectiveness of COVID-19 vaccines, dismisses the science supporting the contextual nature of microbial virulence, miscalculates patient and system-level harms of vaccination policies, and ignores or legitimizes the coercive elements built into their design. We discuss the implications of our findings for the sustainability of health systems, for patient care, and for the well-being of HCWs, and suggest directions for ethical clinical and policy practice.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/z7usq/" target="_blank">Is resisting Covid-19 vaccination a “problem”? A critical policy inquiry of vaccine mandates for healthcare workers</a>
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<li><strong>Genotypic-phenotypic landscape computation based on first principle and deep learning</strong> -
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The relationship between genotype and fitness is fundamental to evolution, but quantitatively mapping genotypes to fitness has remained challenging. We propose the Phenotypic-Embedding theorem (P-E theorem) that bridges genotype-phenotype through an encoder-decoder deep learning framework. Inspired by this, we proposed a more general first principle for correlating genotype-phenotype, and the Phenotypic-Embedding theorem provides a computable basis for the application of first principle. As an application example of the P-E theorem, we developed the Co-attention based Transformer model to bridge Genotype and Fitness (CoT2G-F) model, a Transformer-based pre-train foundation model with downstream supervised fine-tuning (SFT) that can accurately simulate the neutral evolution of viruses and predict immune escape mutations. Accordingly, following the calculation path of the P-E theorem, we accurately obtained the basic reproduction number (R) of SARS-CoV-2 from first principles, quantitatively linked immune escape to viral fitness, and plotted the genotype-fitness landscape. The theoretical system we established provides a general and interpretable method to construct genotype-phenotype landscapes, providing a new paradigm for studying theoretical and computational biology.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.09.527693v3" target="_blank">Genotypic-phenotypic landscape computation based on first principle and deep learning</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>Phase 3 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</b>: Novavax <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>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma 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>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>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>Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <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>Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <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>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation & Development <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What kind of a problem is loneliness? Representations of connectedness and participation from a study of telepresence technologies in the UK</strong> - Loneliness is represented in UK policy as a public health problem with consequences in terms of individual suffering, population burden and service use. However, loneliness is historically and culturally produced; manifestations of loneliness and social isolation also require social and cultural analysis. We explored meanings of loneliness and social isolation in the UK 2020-2022 and considered what the solutions of telepresence technologies reveal about the problems they are used to address….</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>Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease</strong> - Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary…</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>Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention</strong> - The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies…</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>Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice</strong> - CONCLUSION: Our results indicate significant immunogenicity and neutralization efficacy induced by PastoCovac Plus and Sinopharm, but not by Noora and SpikoGen. This suggests the need for additional comparative assessment of the potency and efficacy of these four vaccines in vaccinated subjects.</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 Therapeutic Strategies and Drugs That Target Vascular Permeability in Severe Infectious Diseases</strong> - Severe infection pathogenicity is induced by processes such as pathogen exposure, immune cell activation, inflammatory cytokine production, and vascular hyperpermeability. Highly effective drugs, such as antipathogenic agents, steroids, and antibodies that suppress cytokine function, have been developed to treat the first three processes. However, these drugs cannot completely suppress severe infectious diseases, such as coronavirus disease 2019 (COVID-19). Therefore, developing novel drugs 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>Preliminary report on therapeutic potential of coal-derived carbon quantum dots against SARS-CoV-2 virus</strong> - Due to the pandemic of COVID-19 and subsequent emerging of new mutant strains, there has been a worldwide hunt for therapeutic and protective agents for its inhibition. In this short communication, for the first time, we report the coal-derived carbon quantum dot (CQD) for the possible therapeutic application against SARS-CoV-2. The synthesized C1-CQD is observed to be safe towards the normal cell line at highest dose, while effectively inhibiting growth of SARS-CoV2 (>95%) with IC(50) value of…</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 Membrane protein regulates the function of Spike by inhibiting its plasma membrane localization and enzymatic activity of Furin</strong> - The presence of a multibasic cleavage site in the Spike protein of SARS-CoV-2 makes it prone to be cleaved by Furin at the S1/S2 junction (aa. 685-686), which enhances the usage of TMPRSS2 to promote cell-cell fusion to form syncytia. Syncytia may contribute to pathology by facilitating viral dissemination, cytopathicity, immune evasion, and inflammation. However, the role of other SARS-CoV-2 encoding viral proteins in syncytia formation remains largely unknown. Here, we report that SARS-CoV-2 M…</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>Role of telerehabilitation in the rehabilitation of children with cerebral palsy during COVID-19: A review</strong> - Individuals with cerebral palsy (CP) have limited mobility and are unable to actively participate in tasks that are part of their daily living. Thus, continuous therapeutic sessions are required to keep such individuals active and engaged in the environment. Due to the coronavirus disease of 2019 (COVID-19) lockdowns, rehabilitation for children with CP was inhibited which consequently put them at risk of losing their functional gains which were obtained through previous in-person therapies. 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>Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies to protect individuals at high risk of COVID-19 are critical but are currently a largely unmet need. We evaluated the oral antiviral drug ensitrelvir, which specifically targets the SARS-CoV-2 3CL protease, for its efficacy as a pre-exposure prophylactic treatment. Aged BALB/c mice were subcutaneously treated…</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>Priming congruence and COVID-19 vaccination intention: a mediation analysis</strong> - CONCLUSIONS: Implications of these results are discussed in light of the socially situated cognition perspective and the congruence of (a) a societal context of communication toward the vaccine and the unvaccinated, (b) the participant’s degree of adherence to that communication, (c) the theme of priming, whether or not related to feeling connected to others. Implications of materialism priming are discussed, and the effect of commitment on intention to get vaccinated.</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 subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice</strong> - Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed 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>Nudging Public Health Behaviors to Prevent COVID-19: A Systematic Review</strong> - Many countries have implemented strict preventive measures and mandatory policies to curb virus transmission during the COVID-19 pandemic. Some have adopted softer approaches, such as nudge-based intervention, to influence public health behavior. This systematic review, conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines, aims to determine if the nudge-based intervention can effectively influence people’s preventive behavior during 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>Imatinib treatment improves hyperglycaemic dysregulation in severe COVID-19: a secondary analysis of blood biomarkers in a randomised controlled trial</strong> - SARS-CoV-2 can induce insulin resistance, which is, among others, mediated by adipose tissue dysfunction and reduced angiotensin-converting enzyme 2 (ACE2) enzymatic activity. In SARS-CoV-2-infected mice, the tyrosine kinase inhibitor imatinib attenuates inflammation and improves insulin sensitivity. Here, we report the effects of imatinib on incident hyperglycaemia, circulating levels of glucoregulatory proteins, longitudinal insulin sensitivity and ACE-2 enzymatic activity in 385 hospitalized…</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>IFN-gamma decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3beta signaling pathway</strong> - Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8^(+) T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8^(+) T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8^(+) T cells from 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>Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters</strong> - CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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