174 lines
48 KiB
HTML
174 lines
48 KiB
HTML
|
<!DOCTYPE html>
|
|||
|
|
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
|||
|
|
<meta charset="utf-8"/>
|
|||
|
|
<meta content="pandoc" name="generator"/>
|
|||
|
|
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
|||
|
|
<title>20 October, 2022</title>
|
|||
|
|
<style type="text/css">
|
|||
|
|
code{white-space: pre-wrap;}
|
|||
|
|
span.smallcaps{font-variant: small-caps;}
|
|||
|
|
span.underline{text-decoration: underline;}
|
|||
|
|
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
|||
|
|
</style>
|
|||
|
|
<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
|
|||
|
|
<body>
|
|||
|
|
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
|||
|
|
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><a href="#from-preprints">From Preprints</a></li>
|
|||
|
|
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
|||
|
|
<li><a href="#from-pubmed">From PubMed</a></li>
|
|||
|
|
<li><a href="#from-patent-search">From Patent Search</a></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><strong>Security Motives and Negative Affective Experiences During the Early Months of the COVID-19 Pandemic</strong> -
|
|||
|
|
<div>
|
|||
|
|
Objective: Self-regulation can help individuals cope during stressful events, but little is known about why and when this might occur. We examined if being more focused on prevention was linked to negative affective experiences during the COVID-19 pandemic. We also examined possible underlying mechanisms for this association, and whether social support buffered it. Design: Pre-registered longitudinal study, with surveys every two weeks over one month (N = 1,269). Main outcome measures: Regulatory focus and worry for health (T1), adherence to self isolation and preventive health behaviors (T2), negative affective experiences, positive affect, frequency of online interactions, and perceived social support (T3). Results: Prevention focus was associated with health worries at baseline and linked to greater adherence to preventive health behaviors (T2). Only adherence to self isolation was linked to more negative affective experiences (T3). Exploratory analyses showed that prevention focus was linked to more negative affective experiences (T3), but only for participants with fewer online interactions with their family and less perceived social support from family and friends. Conclusions: Prevention motives in threatening times can be a double-edged sword, with benefits for health behaviors and consequences for negative affective experiences. Having a strong social network during these times can alleviate these consequences.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/xwtmy/" target="_blank">Security Motives and Negative Affective Experiences During the Early Months of the COVID-19 Pandemic</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Education, Financial Stress, and Trajectory of Mental Health During the COVID-19 Pandemic</strong> -
|
|||
|
|
<div>
|
|||
|
|
Socioeconomic disparities in mental health have been reported during the COVID-19 pandemic. However, few studies have examined the mechanisms through which such disparities in mental health occurred. This pre-registered study aimed to examine socioeconomic disparities, as indexed by education levels, in the trajectory of mental health at the early stages of the COVID-19 pandemic and whether financial stress associated with the pandemic mediated socioeconomic disparities in mental health. Data were drawn from the Love in the Time of COVID project, of which we included four waves of data (N = 2,204) collected between March 27th and June 21st, 2020. Education was assessed at baseline, and mental health outcomes (i.e., eudaimonic well-being, positive affect, negative affect, depressive and anxious symptoms) and financial stress associated with the COVID-19 pandemic were assessed at each wave. Results indicated that there were educational disparities in eudaimonic well-being, negative affect, and depressive and anxiety symptoms at baseline, with those with lower education levels reporting poorer mental health. However, education did not amplify disparities in mental health outcomes over time, showing no associations with the rates of change in mental health outcomes. Financial stress mediated the associations between education and eudaimonic well-being, negative affect, and depressive and anxious symptoms at baseline, and there were no temporal variations in the mediation effects of financial stress. These results highlight persistent educational disparities in mental health at the early stages of the COVID-19 pandemic, and such educational disparities may be partially explained by financial stress associated with the COVID-19 pandemic.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/tvry4/" target="_blank">Education, Financial Stress, and Trajectory of Mental Health During the COVID-19 Pandemic</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Sexual Desire in the Time of COVID-19: How COVID-Related Stressors are Associated with Sexual Desire in Romantic Relationships</strong> -
|
|||
|
|
<div>
|
|||
|
|
The COVID-19 pandemic and the resulting social distancing measures have caused widespread social and economic disruptions, resulting in spikes in unemployment and financial instability, along with drastic changes to people’s ability to feel socially connected. Many of the changes resulting from the COVID-19 pandemic are risk factors for depressive symptoms, which are associated with lower levels of sexual desire. The current research (N = 4,993) examined whether responses to external stressors brought on by COVID-19 (i.e., financial concern, worry, loneliness, stress) were associated with sexual desire among a multi-national sample of people in relationships (Studies 1-2), and whether this association was, in part, due to reports of depressive symptoms (Study 2). In the period immediately following the onset of the pandemic, more financial concern (Study 1) and worry (Study 2) were associated with higher sexual desire, while other factors, like stress (Studies 1-2), were associated with lower desire. We also followed a subset of participants every two weeks during the initial stages of the pandemic and at times when people reported greater stress, loneliness, financial strain, or worry than their average, they reported greater depressive symptoms, which, was in turn, associated with lower sexual desire. Results suggest that the social isolation and stress resulting from the COVID-19 pandemic has mixed associations with sexual desire at the onset of the pandemic. But over time, when people report heightened COVID-related stressors, they tend to report lower sexual desire for their partner, in part because these stressors are associated with more depressive symptoms.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/nxkgp/" target="_blank">Sexual Desire in the Time of COVID-19: How COVID-Related Stressors are Associated with Sexual Desire in Romantic Relationships</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Having a Prevention Regulatory Focus Longitudinally Predicts Distress and Health-Protective Behaviors During the COVID-9 Pandemic</strong> -
|
|||
|
|
<div>
|
|||
|
|
Background: Past research has shown that regulatory focus shapes people’s health and well-being, with those who are focused on prevention (vs. promotion) being more motivated by safety and being less inclined to take risks. Purpose: In the current study, we tested if having a prevention (vs. promotion) focus before the COVID-19 pandemic outbreak predicted perceptions and health outcomes and threat over the course of the pandemic. Methods: Participants (N = 161, 51.6% women; Mage = 34.04, SD = 7.77) took part in a longitudinal study. Measures were assessed before the pandemic was declared (in November 2019, T1) and after a global pandemic was declared (on June 2020, T2). Results: Results suggest that people who were more focused on prevention prior to the onset of the pandemic (at T1) perceived greater risk of contracting COVID-19, were more worried about being infected, and engaged in more preventative behaviors during the pandemic (at T2). Additionally, they also reported less anxiety and felt healthier (at T2). Conclusions: People focused on prevention (i.e., motivated by security) are more aware of health threats and more likely to engage in health-protective behaviors. Acting in accordance to their motives seems to help these people to experience better health and reduces anxiety about health even during a pandemic.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/k7j6h/" target="_blank">Having a Prevention Regulatory Focus Longitudinally Predicts Distress and Health-Protective Behaviors During the COVID-9 Pandemic</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Individual Motives for Security Influence Sexual Activity During the COVID-19 Pandemic</strong> -
|
|||
|
|
<div>
|
|||
|
|
Amidst a global pandemic, people’ survival needs become salient and the ability for people to regulate feeling and actions might be particularly relevant to protecting oneself from harm. Regulatory Focus Theory (Higgins, 1998) proposes that people pursue their goals by having a focus on prevention (i.e., motivated by security) or promotion (i.e., motivated by pleasure). Prior research indicates that people focused on prevention (vs. promotion) are more likely to engage in health-protective behaviors, including sexual health behaviors, because they perceive more threats. Extending this reasoning to the sexual activity of single people during the COVID-19 pandemic, we conducted a pre-registered longitudinal study (N = 174) examining the role of regulatory focus on people’s sexual behaviors. As hypothesized, results showed that single people who reported having a more prevention focus at the onset of the pandemic perceived greater threats caused by the pandemic two weeks later, which, in turn, predicted less frequent sexual activity and engagement in sex with fewer sexual partners the following two weeks. These effects were consistent even when controlling for promotion (i.e., pleasure motivations), personality, gender, and sexual orientation. Findings are discussed considering their implications for the sexual functioning and sexual health of single people.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/eutp2/" target="_blank">Individual Motives for Security Influence Sexual Activity During the COVID-19 Pandemic</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Relationship difficulties and “technoference” during the COVID-19 pandemic</strong> -
|
|||
|
|
<div>
|
|||
|
|
The COVID-19 pandemic has touched many aspects of people’s lives around the world, including their romantic relationships. While media outlets have reported that the pandemic is difficult for couples, empirical evidence is needed to test these claims and understand why this may be. In two highly powered studies (N = 3,271) using repeated measure and longitudinal approaches, we found that people who experienced COVID-19 related challenges (i.e., lockdown, reduced face-to-face interactions, boredom, or worry) also reported greater self and partner phone use (Study 1) and time spent on social media (Study 2), and subsequently experienced more conflict and less satisfaction in their romantic relationship. The findings provide insight into the struggles people faced in their relationships during the pandemic and suggest that the increase in screen time – a rising phenomenon due to the migration of many parts of life online – may be a challenge for couples.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/3cwv7/" target="_blank">Relationship difficulties and “technoference” during the COVID-19 pandemic</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>The humoral and cellular immune response of a third dose adenoviral-based vectored vaccine after a single or 2 shots of inactivated COVID-19 vaccine in healthy adults.</strong> -
|
|||
|
|
<div>
|
|||
|
|
The coronavirus pandemic is a severe infectious respiratory disease which caused massive loss worldwide. Thailand was affected by the wild-type, and the Delta variant started in mid-2021. Due to the shortage of effective vaccines, the ministry of public health of Thailand suggested the heterologous vaccine scheme, which comprises inactivated COVID-19 vaccine (CoronaVac) and an adenoviral-based vectored vaccine (ChAdOx1). However, data on the humoral and cellular immune responses of the single or 2 shots of inactivated vaccine followed by the adenoviral-based vaccine are very limited. In this current study, the sera from participants who received either single or 2 shots of CoronaVac followed by the ChAdOx1 vaccine were evaluated for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG. The cytokine level was also assessed using Luminex immunoassay. The PBMC were collected to evaluate spike-specific T-cell and B-cell responses. Participants who received 2 shots of CoronaVac followed by ChAdOx1 possessed significantly (P<0.0001) higher levels of spike RBD-specific IgG. They also exhibited a higher level of CD4+T-cell and IFN-gamma than those who received only 1 shot of CoronaVac followed by the ChAdOx1 vaccine. The volunteers who received two shots of CoronaVac followed by ChAdOx1 had a significantly (p<0.01) higher marginal B-cell response against wild-type SARS-CoV-2 S peptides than those who received only one shot of CoronaVac followed by ChAdOx1. Surprisingly, the class switch B-cell response to Delta variant SARS-CoV-2 S peptides of the volunteers who received 1 shot of CoronaVac followed by ChAdOx1 was significantly (p<0.01) higher than those who received 2 shots of CoronaVac. However, participants who received only a single shot of inactivated vaccine followed by an adenoviral-based vectored vaccine possessed a higher level of TNF-alpha and IL-6. This study indicated that boosting the ChAdOx1 as a third dose after completing 2 shots of CoronaVac induced strong humoral and cellular immune responses.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.18.512323v1" target="_blank">The humoral and cellular immune response of a third dose adenoviral-based vectored vaccine after a single or 2 shots of inactivated COVID-19 vaccine in healthy adults.</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.</strong> -
|
|||
|
|
<div>
|
|||
|
|
We and others have previously shown that the SARS-CoV-2 accessory protein ORF6 is a powerful antagonist of the interferon (IFN) signaling pathway by directly interacting with Nup98-Rae1 at the nuclear pore complex (NPC) and disrupting bidirectional nucleo-cytoplasmic trafficking. In this study, we further assessed the role of ORF6 during infection using recombinant SARS-CoV-2 viruses carrying either a deletion or a well characterized M58R loss-of-function mutation in ORF6. We show that ORF6 plays a key role in the antagonism of IFN signaling and in viral pathogenesis by interfering with karyopherin(importin)-mediated nuclear import during SARS-CoV-2 infection both in vitro, and in the Syrian golden hamster model in vivo. In addition, we found that ORF6-Nup98 interaction also contributes to inhibition of cellular mRNA export during SARS-CoV-2 infection. As a result, ORF6 expression significantly remodels the host cell proteome upon infection. Importantly, we also unravel a previously unrecognized function of ORF6 in the modulation of viral protein expression, which is independent of its function at the nuclear pore. Lastly, we characterized the ORF6 D61L mutation that recently emerged in Omicron BA.2 and BA.4 and demonstrated that it is able to disrupt ORF6 protein functions at the NPC and to impair SARS-CoV-2 innate immune evasion strategies. Importantly, the now more abundant Omicron BA.5 lacks this loss-of-function polymorphism in ORF6. Altogether, our findings not only further highlight the key role of ORF6 in the antagonism of the antiviral innate immune response, but also emphasize the importance of studying the role of non-spike mutations to better understand the mechanisms governing differential pathogenicity and immune evasion strategies of SARS-CoV-2 and its evolving variants.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.18.512708v1" target="_blank">Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Regional epidemic dynamics and Delta variant diversity resulted in varying rates of spread of Omicron-BA.1 in Mexico</strong> -
|
|||
|
|
<div>
|
|||
|
|
The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In Mexico, this subvariant began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in the country. Unlike previous SARS-CoV-2 variants, BA.1 did not acquire local substitutions nor exhibited a geographically distinct circulation pattern in Mexico. However, a regional difference in the speed of the replacement of the Delta variant was observed, as some northern states showed persistence of Delta lineages well into February 2022. Mexican states were divided into four regions (North, Central North, Central South, and Southeast) based on the lineage circulation before the dominance of BA.1 to study possible causes for this difference. For each region, the time to fixation of BA.1, the diversity of Delta sublineages in the weeks preceding BA.1 entry, the population density, and the level of virus circulation during the inter-wave interval were determined. An association between a faster Omicron spread and lower Delta diversity, as well as fewer COVID-19 cases during the Delta-BA.1.x inter-wave period, was observed. For example, the North region exhibited the slowest spread but had the highest diversity of Delta sublineages and the greatest number of inter-wave cases relative to the maximum amount of the virus circulating in the region, whereas the Southeast region showed the opposite. Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics. Nonetheless, if there is a significant difference in the fitness of the variants or the time allowed for the competition is sufficient, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.18.512746v1" target="_blank">Regional epidemic dynamics and Delta variant diversity resulted in varying rates of spread of Omicron-BA.1 in Mexico</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>A collaborative approach to improving representation in viral genomic surveillance</strong> -
|
|||
|
|
<div>
|
|||
|
|
The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic. Over subsequent months, poor surveillance enabled variants to emerge unnoticed. Against this backdrop, long-standing social and racial inequities have contributed to a greater burden of cases and deaths among minority groups. To begin to address these problems, we developed a new variant surveillance model geared toward building microbial genome sequencing capacity at universities in or near rural areas and engaging the participation of their local communities. The resulting genomic surveillance network has generated more than 1,000 SARS-CoV-2 genomes to date, including the first confirmed case in northeast Louisiana of Omicron, and the first and sixth confirmed cases in Georgia of the emergent BA.2.75 and BQ.1.1 variants, respectively. In agreement with other studies, significantly higher viral gene copy numbers were observed in Delta variant samples compared to those from Omicron BA.1 variant infections, and lower copy numbers were seen in asymptomatic infections relative to symptomatic ones. Collectively, the results and outcomes from our collaborative work demonstrate that establishing genomic surveillance capacity at smaller academic institutions in rural areas and fostering relationships between academic teams and local health clinics represent a robust pathway to improve pandemic readiness.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.19.512816v1" target="_blank">A collaborative approach to improving representation in viral genomic surveillance</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Taxonium, a web-based tool for exploring largephylogenetic trees</strong> -
|
|||
|
|
<div>
|
|||
|
|
The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. These sequences reveal key insights when represented as a phylogenetic tree, which captures the evolutionary history of the virus, and allows the identification of transmission events and the emergence of new variants. However, existing web-based tools for analysing and exploring phylogenies do not scale to the size of datasets now available for SARS-CoV-2. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes in the browser for the first time. Taxonium links each node to associated metadata and supports mutation-annotated trees, which are able to capture all known genetic variation in a dataset. We describe insights that analysing a tree of five million sequences can provide into SARS-CoV-2 evolution, and provide an application at http://cov2tree.org for exploring a public tree of more than five million SARS-CoV-2 sequences. Taxonium can be applied to any tree, and is available at http://taxonium.org, with source code at https://github.com/theosanderson/taxonium.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.03.494608v4" target="_blank">Taxonium, a web-based tool for exploring largephylogenetic trees</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Clinical antiviral efficacy of remdesivir and casirivimab/imdevimab against the SARS-CoV-2 Delta and Omicron variants</strong> -
|
|||
|
|
<div>
|
|||
|
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
|
Background: Uncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines. Early in the pandemic the monoclonal antibody cocktail, casirivimab/imdevimab, proved highly effective in clinical trials but because of weak or absent in vitro activity against the SARS-CoV-2 Omicron BA.1 subvariant, it is no longer recommended. Methods: In a multicenter open label, randomized, controlled adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days), casirivimab/imdevimab (600mg/600mg), and no study drug. The primary outcome was the viral clearance rate in the modified intention-to-treat population derived from daily log10 viral densities (days 0-7) in standardized duplicate oropharyngeal swab eluates. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). Results: Acceleration in mean estimated SARS-CoV-2 viral clearance, compared with the contemporaneous no study drug arm (n=64), was 42% (95%CI 18 to 73%) for remdesivir (n=67). Acceleration with casirivimab/imdevimab was 58% (95%CI: 10 to 120) in Delta (n=13), and 20% (95%CI: 3 to 43) in Omicron variant (n=61) infections compared with contemporaneous no study drug arm (n=84). In a post hoc subgroup analysis viral clearance was accelerated by 8% in BA.1 (95%CI: -21 to 59) and 23% (95%CI: 3 to 49) in BA.2 and BA.5 Omicron subvariants. Conclusions: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Despite substantially reduced in vitro activities, casirivimab/imdevimab retains in vivo antiviral activity against COVID-19 infections caused by currently prevalent Omicron subvariants.
|
|||
|
|
</p>
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.17.22281161v1" target="_blank">Clinical antiviral efficacy of remdesivir and casirivimab/imdevimab against the SARS-CoV-2 Delta and Omicron variants</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers</strong> -
|
|||
|
|
<div>
|
|||
|
|
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
|
|||
|
|
Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against COVID-19. However, the induction of multiple layers of immunity following SARS-CoV-2 exposure has complicated the establishment of nAbs as a mechanistic correlate of protection (CoP) and hindered the definition of a protective nAb threshold. Here, we show that a half-life extended monoclonal antibody (adintrevimab) provides approximately 50% protection against symptomatic COVID-19 in SARS-CoV-2-naive adults at low serum nAb titers on the order of 1:30. Vaccine modeling supports a similar 50% protective nAb threshold, suggesting low levels of serum nAb can protect in both monoclonal and polyclonal settings. Extrapolation of adintrevimab pharmacokinetic data suggests that protection against susceptible variants could be maintained for approximately 3 years. The results provide a benchmark for the selection of next-generation vaccine candidates and support the use of broad, long-acting monoclonal antibodies as an alternative or supplement to vaccination in high-risk populations.
|
|||
|
|
</p>
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.18.22281172v1" target="_blank">Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Daily Dynamics of Parental Mental Health: Investigating Depressive Symptoms and Negative Parental Experiences</strong> -
|
|||
|
|
<div>
|
|||
|
|
Background: Investigating psychopathological processes and how these are connected to psychiatric symptoms is important to understand how disorder states emerge and are maintained over time. Focusing on within-person relationships between variables further allows investigation of how these relations on average unfold within individuals. Methods: This preregistered intensive longitudinal study investigates connections between depressive symptoms, psychopathological processes, and negative parental experiences. Daily observations from 1036 parents were retrieved from two 40-day periods during the COVID-19 pandemic. The data was modelled using multilevel dynamic network analysis, unveiling across-day associations and contemporaneous interactions within the same time window. Results: On an across-day basis, helplessness was strongly interwoven with and predictive of the cognitive-affective features of depression and the other psychopathological processes. Being overwhelmed by the parental role (parenting stress) and emotionally drained as a parent (parental burnout) reciprocally reinforced each other from one day to the next, indicating how these components can manifest as a vicious loop over time. Finally, depressive symptomatology and negative parental experiences displayed within-day connections, with emotion regulation difficulties being connected to all parental components. Conclusions: The findings suggest that vicious cycles between helplessness and worthlessness predict the prolonged experience of depressed states in parents and that elevations in parenting stress and parental burnout reinforce each other over time.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/rvawg/" target="_blank">Daily Dynamics of Parental Mental Health: Investigating Depressive Symptoms and Negative Parental Experiences</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Generalized trust rather than perception of relational mobility correlates with nominating close friends in a social network</strong> -
|
|||
|
|
<div>
|
|||
|
|
A social environment, such as relational mobility, which represents the availability of opportunities to develop new relationships in society, cultivates an individual’s psychology and social network. Generalized trust, which represents trust among people in general, is a tendency to expand individuals’ social ties in a fluid society. Using the data of 170 students, we analyzed whether an individual’s belief of generalized trust and perception of relational mobility are related to the social network. We conducted a survey to assess psychological measures and social networks under the COVID-19 pandemic for first-year university students. The analyses revealed that generalized trust was significantly associated with the presence of outdegrees (i.e., the nomination of close friends) and the absence of indegrees (i.e., being nominated by others). In contrast, perception of relational mobility was not significantly associated with generalized trust and any social network measures. Behavioral trust, measured using a Trust Game approximately six months later, was not significantly associated with network characteristics. The results support the argument that the belief of generalized trust functions as a psychological mechanism to expand individuals’ relationships in their social networks.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://psyarxiv.com/xu8k3/" target="_blank">Generalized trust rather than perception of relational mobility correlates with nominating close friends in a social network</a>
|
|||
|
|
</div></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell); Biological: Inactivated COVID-19 vaccine (Vero Cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; First Affiliated Hospital Bengbu Medical College<br/><b>Active, not recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase III Study to Evaluate Immunogenicity and Safety of COVID-19 Vaccine EuCorVac-19 in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics Co.,Ltd<br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Tri-City COVID Attitudes Study<br/><b>Sponsor</b>: University of Kansas Medical Center<br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>JT001 (VV116) for the Treatment of COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Vinnerna Biosciences Co., Ltd.; Sponsor GmbH<br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Boost Intentions and Facilitate Action to Promote Covid-19 Booster Take-up</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Eligibility reminder; Behavioral: Link to a narrow set of vaccine venues; Behavioral: Link to a broad set of vaccine venues; Behavioral: Doctors’ recommendation and value of vaccine<br/><b>Sponsor</b>: University of California, Los Angeles<br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Prompt to Bundle Covid-19 Booster and Flu Shot</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder to boost protection against COVID-19; Behavioral: Flu Tag Along; Behavioral: COVID-19 Booster & Flu Bundle<br/><b>Sponsor</b>: University of California, Los Angeles<br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder that facilitates action; Behavioral: Consistency framing; Behavioral: Information provision about the uniqueness of the bivalent booster; Behavioral: Information provision about bivalent booster eligibility; Behavioral: Information provision about the severity of COVID-19 symptoms<br/><b>Sponsor</b>: University of California, Los Angeles<br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination</strong> - <b>Conditions</b>: Immunization; Infection; Pregnancy Related; COVID-19<br/><b>Interventions</b>: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care<br/><b>Sponsors</b>: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles<br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Respiratory Muscles After Inspiratory Muscle Training After COVID-19</strong> - <b>Conditions</b>: COVID-19; Diaphragm Injury<br/><b>Intervention</b>: Device: Inspiratory Muscle Training (IMT)<br/><b>Sponsors</b>: RWTH Aachen University; Philipps University Marburg Medical Center<br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Simulation Education on Nursing Students</strong> - <b>Conditions</b>: COVID-19 Pandemic; Simulation of Physical Illness<br/><b>Interventions</b>: Behavioral: Simulation training; Other: Control Group<br/><b>Sponsor</b>: Mehmet Akif Ersoy University<br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial</strong> - <b>Conditions</b>: COVID-19; Immunodeficiency<br/><b>Interventions</b>: Drug: Paxlovid 5 days; Drug: Paxlovid 10 days; Drug: Tixagevimab and Cilgavimab<br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; University Hospital, Geneva<br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Booster Dose Reminder/Recall for Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccines<br/><b>Intervention</b>: Behavioral: Reminder/Recall Sent Via Preferred Method of Communication<br/><b>Sponsor</b>: Marshfield Clinic Research Foundation<br/><b>Active, not recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation</strong> - <b>Conditions</b>: SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability</strong> - <b>Conditions</b>: Sars-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Device: Rapid SARS-CoV-2 Antigen Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: V-01/V-01-B5; Biological: V-01-351/V-01-B5; Biological: V-01<br/><b>Sponsor</b>: Livzon Pharmaceutical Group Inc.<br/><b>Active, not recruiting</b></p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combined Molnupiravir and Nirmatrelvir Treatment Improves the Inhibitory Effect on SARS-CoV-2 in Rhesus Macaques</strong> - The periodic emergence of SARS-CoV-2 variants of concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, and nirmatrelvir (PF-07321332), a 3C-like protease inhibitor, have each recently been approved as monotherapy for use in high risk COVID-19 patients. As preclinical data are only available for rodent and ferret models, we…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection</strong> - Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and tissue injury and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases</strong> - CONCLUSION: IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19</strong> - The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. To…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Vaccination in Kidney Transplant Recipients-Stratified Analysis of the Humoral Immune Response</strong> - CONCLUSIONS: Apart from immunosuppressive therapy, the humoral vaccination response is largely affected by nonmodifiable factors in kidney transplant recipients. With the currently leading and clinically easier Omicron variant, this puts into perspective the strategy to significantly enhance the protective efficacy of the available vaccines by reducing or temporarily stopping proliferation inhibitors, not least considering the inherent rejection risk with a possible deterioration of graft…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients co-morbidly affected by type 2 diabetes</strong> - CONCLUSIONS: The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those co-morbid patients. This article is protected by…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DNA damage contributes to age-associated differences in SARS-CoV-2 infection</strong> - Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to disproportionately affect older individuals. How aging processes affect SARS-CoV-2 infection and disease progression remains largely unknown. Here, we found that DNA damage, one of the hallmarks of aging, promoted SARS-CoV-2 infection in vitro and in vivo. SARS-CoV-2 entry was facilitated by DNA damage caused by extrinsic genotoxic stress or telomere dysfunction and…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of natural polymorphisms in SARS-CoV-2 RNA-dependent RNA polymerase on its activity and sensitivity to inhibitors in vitro</strong> - SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is the key enzyme required for viral replication and mRNA synthesis. RdRp is one of the most conserved viral proteins and a promising target for antiviral drugs and inhibitors. At the same time, analysis of public databases reveals multiple variants of SARS-CoV-2 genomes with substitutions in the catalytic RdRp subunit nsp12. Structural mapping of these mutations suggests that some of them may affect the interactions of nsp12 with its cofactors…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Xuanfei Baidu Formula attenuates LPS-induced acute lung injury by inhibiting the NF-κB signaling pathway</strong> - CONCLUSION: This study identified the potential practical components of XFBD, combined with network pharmacology and experimental validation to demonstrate that XFBD can alleviate lung injury caused by ALI by inhibiting the NF-κB signaling pathway.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Does income inequality reshape the environmental Kuznets curve (EKC) hypothesis? A nonlinear panel data analysis</strong> - The COVID-19 pandemic has further increased income inequality. This work is aimed to explore the impact of income inequality on the environmental Kuznets curve (EKC) hypothesis. To this end, income inequality is set as the threshold variable, economic growth is set as the explanatory variable, while carbon emission is set as the explained variable, and the threshold panel model is developed using the data of 56 countries. The empirical results show that income inequality has changed the…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Astersaponin I from Aster koraiensis is a natural viral fusion blocker that inhibit the infection of SARS-CoV-2 variants and syncytium formation</strong> - The continuous emergence of SARS-CoV-2 variants prolongs COVID-19 pandemic. Although SARS-CoV-2 vaccines and therapeutics are currently available, there is still a need for development of safe and effective drugs against SARS-CoV-2 and also for preparedness for the next pandemic. Here, we discover that astersaponin I (AI), a triterpenoid saponin in Aster koraiensis inhibits SARS-CoV-2 entry pathways at the plasma membrane and within the endosomal compartments mainly by increasing cholesterol…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and possible Treatments: All options on the Table</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is cause of the novel coronavirus disease (COVID-19). In the last two years, SARS-CoV-2 has infected millions of people worldwide with different waves, resulting in the death of many individuals. The evidence disclosed that the host immune responses to SARS-CoV-2 play a pivotal role in COVID-19 pathogenesis and clinical manifestations. In addition to inducing antiviral immune responses, SARS-CoV-2 can also cause dysregulated…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trim69 is a microtubule regulator that acts as a pantropic viral inhibitor</strong> - Through a screen that combines functional and evolutionary analyses, we identified tripartite motif protein (Trim69), a poorly studied member of the Trim family, as a negative regulator of HIV-1 infection in interferon (IFN)-stimulated myeloid cells. Trim69 inhibits the early phases of infection of HIV-1, but also of HIV-2 and SIV(MAC) in addition to the negative and positive-strand RNA viruses vesicular stomatitis virus and severe acute respiratory syndrome coronavirus 2, with magnitudes that…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Glycyrrhizin through liquorice intake modulates ACE2 and HMGB1 levels-A pilot study in healthy individuals with implications for COVID-19 and ARDS</strong> - CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In-silico structural inhibition of ACE-2 binding site of SARS-CoV-2 and SARS-CoV-2 Omicron spike protein by lectin antiviral dyad system to treat COVID-19</strong> - Spike glycoprotein of SARS-CoV-2 binds ACE-2 receptors via its receptor-binding-domain (RBD) and mediates virus-to-host cell fusion. Recently emerged omicron variant of SARS-CoV-2 possess around 30 mutations in spike protein where N501Y tremendously increases viral infectivity and transmission. Lectins interact with glycoproteins and mediate innate immunity displaying antiviral, antibacterial and anticarcinogenic properties. In this study, we analysed the potential of lectin, and lectin-antibody…</p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
|||
|
|
|
|||
|
|
|
|||
|
|
<script>AOS.init();</script></body></html>
|