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<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>Exploring the landscape of the genomic wastewater surveillance ecosystem: a roadmap towards standardization</strong> -
<div>
The landscape of genomic wastewater surveillance in the context of infectious disease monitoring is rapidly evolving, and this came into sharp focus during the COVID-19 pandemic. Here we highlight the significance of wastewater surveillance as a passive monitoring system complementary to clinical genomic surveillance activities. Emphasizing the need for coordination, standardization, and the development of a unified catalog of software tools and services, we aim to streamline the implementation of end-to-end genomic wastewater surveillance pipelines. Key considerations such as defining variants, understanding antimicrobial resistance, and assessing viral fitness within the framework of wastewater surveillance are explored, linking to examples of respective tools and existing pipelines. The challenges of wastewater data analysis, the need for specialized tools and bioinformatics workflows, and the significance of integrated pipelines are also discussed in detail. The article presents case studies, including the V-pipe integrated bioinformatics workflow and the integration of tools into the Galaxy platform, underscoring their role in enhancing data analysis efficiency and standardization within the field. Overall, the review highlights the critical importance of continued research efforts to advance understanding and implementation of bioinformatic approaches in wastewater surveillance for the effective monitoring and management of infectious diseases.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/biohackrxiv/rtgk9/" target="_blank">Exploring the landscape of the genomic wastewater surveillance ecosystem: a roadmap towards standardization</a>
</div></li>
<li><strong>Gods Lockdown: the effect of the April 2022 Colorado low blizzard on SARS-Cov-2 transmission in the midwest United States</strong> -
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Background: Lockdowns have been used as a primary non-pharmaceutical intervention to stop transmission of COVID19. There are many issues with interpreting the causal effects of most of these intentional, policy driven interventions. We leverage a natural experiment to avoid many of these issues to better understand the direct effects of lockdown like conditions on COVID19 transmission. Methods: We exploit a blizzard that interrupted activity across several midwestern states in April 2022. This blizzard broke records for snowfall and caused economic disruption. We leverage this to create control and treatment counties that were more or less affected by the snowfall. We demonstrate effects using event studies comparing these treatment and control counties. Results: We find that mobility within treatment counties was severely curtailed as a result of the blizzard relative to control counties. We find cumulative declines in the number of COVID19 cases per country by 400 and cumulative declines in COVID19 deaths by 1 per county over the 30 days after the storm. We find declines in by one per hospitalization due to COVID19. Conclusions: The April 2022 blizzard caused disruption in activity across the midwest United States akin to a lockdown. It reduced the number of COVID19 cases, deaths, and hospitalizations in treatment counties relative to control counties suggesting that similar policies do limit transmissions of SARS-Cov-2.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.01.23297908v1" target="_blank">Gods Lockdown: the effect of the April 2022 Colorado low blizzard on SARS-Cov-2 transmission in the midwest United States</a>
</div></li>
<li><strong>SARS-CoV-2 infection leads to sustained testicular injury and functional impairments in K18 hACE2 mice</strong> -
<div>
Compromised male reproductive health is one of the symptoms of long COVID with a decrease in male fertility markers including testosterone levels and sperm count for months in recovering patients. However, the long-term impact of SARS-CoV-2 infection on testicular injury and underlying mechanisms remains unknown. We previously demonstrated a disrupted tissue architecture with no evidence of virus replication in the testis during the acute stage of the disease in K18-hACE2 mice. Here, we systematically delineate the consequences of SARS-CoV-2 infection on the testis injury and function both during the acute stage of the disease and up to 4 weeks after recovery in survivor K18-hACE2 mice. The gross morphological defects included sloughing of healthy spermatids and spermatocytes into the lumen, lack of lumen, and increase in apoptotic cells that sustained for at least 2 weeks after infection. Testis injury correlated with systemic and testicular inflammation, and infiltration of immune cells in the interstitial space and seminiferous tubules. Transcriptomic analysis identified dysregulation of key pathways associated with testicular immune homeostasis, spermatogenesis, and cell death at the symptomatic stage and immediately after recovery. Further, a significant reduction in testosterone levels was associated with transient reduction in sperm count and mouse fertility. Most of the testicular impairments except testosterone levels were resolved within 4 weeks, which is almost one spermatogenesis cycle in mice. These findings provide much-needed mechanistic insights beyond our current understanding of testicular pathogenesis, suggesting that recovering COVID-19 patients should be closely monitored to rescue the pathophysiological effects on male reproductive health.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.31.565042v1" target="_blank">SARS-CoV-2 infection leads to sustained testicular injury and functional impairments in K18 hACE2 mice</a>
</div></li>
<li><strong>Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds</strong> -
<div>
Protein homeostasis is tightly regulated, with damaged or misfolded proteins quickly eliminated by the proteasome and autophagosome pathways. By co-opting these processes, targeted protein degradation technologies enable pharmacological manipulation of protein abundance. Recently, cysteine-reactive molecules have been added to the degrader toolbox, which offer the benefit of unlocking the therapeutic potential of undruggable protein targets. The proteome-wide impact of these molecules remains to be fully understood and given the general reactivity of many classes of cysteine-reactive electrophiles, on- and off-target effects are likely. Using chemical proteomics, we identified a cysteine-reactive small molecule degrader of the SARS-CoV-2 non-structural protein 14 (nsp14), which effects degradation through direct modification of cysteines in both nsp14 and in host chaperones together with activation of global cell stress response pathways. We find that cysteine-reactive electrophiles increase global protein ubiquitylation, trigger proteasome activation, and result in widespread aggregation and depletion of host proteins, including components of the nuclear pore complex. Formation of stress granules was also found to be a remarkably ubiquitous cellular response to nearly all cysteine-reactive compounds and degraders. Collectively, our study sheds light on complexities of covalent target protein degradation and highlights untapped opportunities in manipulating and characterizing proteostasis processes via deciphering the cysteine-centric regulation of stress response pathways.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.30.564067v1" target="_blank">Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds</a>
</div></li>
<li><strong>Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents</strong> -
<div>
Background and Objectives. Methylation profile scores (MPSs) index biological aging and aging-related disease in adults and are cross-sectionally associated with social determinants of health in childhood. MPSs thus provide an opportunity to trace how aging-related biology responds to environmental changes in early life. Information regarding the stability of MPSs in early life is currently lacking. Method. We use longitudinal data from children and adolescents ages 8-18 (N = 428, M age = 12.15 years) from the Texas Twin Project. Participants contributed two waves of salivary DNA-methylation data (mean lag = 3.94 years), which were used to construct four MPSs reflecting multi-system physiological decline and mortality risk (PhenoAgeAccel and GrimAgeAccel), pace of biological aging (DunedinPACE), and cognitive function (Epigenetic-g). Furthermore, we exploit variation among participants in whether they were exposed to the COVID-19 pandemic during the course of study participation, in order to test how a historical period characterized by environmental disruption might affect children's aging-related MPSs. Results. All MPSs showed moderate longitudinal stability (test-retest rs = 0.42, 0.44, 0.46, 0.51 for PhenoAgeAccel, GrimAgeAccel, and Epigenetic-g, and DunedinPACE, respectively). No differences in the stability of MPSs were apparent between those whose second assessment took place after the onset of the COVID-19 pandemic vs. those for whom both assessments took place prior to the pandemic. Conclusions. Aging-related DNA-methylation patterns are less stable in childhood than has been previously observed in adulthood. Further developmental research on the methylome is necessary to understand which environmental perturbations in childhood impact trajectories of biological aging and when children are most sensitive to those impacts.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.30.564766v1" target="_blank">Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents</a>
</div></li>
<li><strong>Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine</strong> -
<div>
In order to improve vaccine effectiveness and safety profile of existing synthetic RNA-based vaccines, we have developed a self-amplifying RNA (saRNA)-based vaccine expressing membrane-anchored receptor binding domain (RBD) of SARS-CoV-2 S protein (S-RBD) and have demonstrated that a minimal dose of this saRNA vaccine elicits robust immune responses. Results from a recent clinical trial with 5-methylcytidine (5mC) incorporating saRNA vaccine demonstrated reduced vaccine-induced adverse effects while maintaining robust humoral responses. In this study, we investigate the mechanisms accounting for induction of efficient innate and adaptive immune responses and attenuated adverse effects induced by the 5mC-incorporated saRNA. We show that the 5mC-incorporating saRNA platform leads to prolonged and robust expression of antigen, while induction of type-I interferon (IFN-I), a key driver of reactogenicity, is attenuated in peripheral blood mononuclear cells (PBMCs), but not in macrophages and dendritic cells. Interestingly, we find that the major cellular source of IFN-I production in PBMCs is plasmacytoid dendritic cells (pDCs), which is attenuated upon 5mC incorporation in saRNA. In addition, we demonstrate that monocytes also play an important role in amplifying proinflammatory responses. Furthermore, we show that the detection of saRNA is mediated by a host cytosolic RNA sensor, RIG-I. Importantly, 5mC-incorporating saRNA vaccine candidate produced robust IgG responses against S-RBD upon injection in mice, thus providing strong support for the potential clinical use of 5mC-incorporating saRNA vaccines.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.01.565056v1" target="_blank">Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine</a>
</div></li>
<li><strong>SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2</strong> -
<div>
Cytokine release syndrome (CRS) is one of the leading causes of mortality in COVID-19 patients caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague. This study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more IL-2, which subsequently cooperates with spike protein to facilitate peripheral blood mononuclear cells to release IL-1{beta}, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release TNF- and IFN-{gamma}, as well as T cells to release IFN-{gamma}. Mechanistically, IFN-{gamma} and TNF- enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of TLR4 which serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of NF-{kappa}B. Furthermore, TNF- also activates NF-{kappa}B signaling in monocytes, which further cooperates with IFN-{gamma} and spike protein to modulate NF-{kappa}B-dependent transcription of CRS-related inflammatory cytokines. Targeting TNF-/IFN-{gamma} in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.01.565098v1" target="_blank">SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2</a>
</div></li>
<li><strong>Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models.</strong> -
<div>
Halofuginone hydrobromide has shown potent antiviral efficacy against some viruses such as SARS-CoV-2, Dengue virus or Chikungunya, and has therefore been hypothesized to have antiviral activity against other viruses. In this paper, we aimed to test the broad-spectrum antiviral activity of Halofuginone hydrobomide against relevant viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end we used relevant human models of the airway and intestinal epithelium and regionalised neural organoids. The drug only showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.01.565121v1" target="_blank">Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models.</a>
</div></li>
<li><strong>Performance of A Point-of-care Fluorescence Immunoassay Test to measure anti Severe Acute Respiratory Syndrome Corona Virus 2 Spike, Receptor Binding Domain Antibody Level</strong> -
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Quantitative determination of anti SARSCoV2 S RBD is necessary for the evaluation of vaccination effectiveness. Surrogate viral neutralization test (SVNT) is approved for measuring anti SARSCoV2 S RBD, but a point of care platform is needed to simplify anti SARS CoV 2 S RBD measurement. We aimed to evaluate the performance of a rapid fluorescent immunoassay-based kit, FastBio RBDtm, compared to SVNT. During April to September 2021, we enrolled two groups of subjects; convalescent subject and subject without COVID 19 history. Subjects were tested for anti SARS CoV2 S RBD antibody using FastBio RBDtm and GenScript cPASStm SVNT. We measured the correlation coefficient and conducted ROC analysis to determine the best cut-off value of anti SARS CoV 2 S RBD against SVNT percent inhibition levels of 30% and 60%. We included 109 subjects. Anti-SARS CoV 2 S RBD strongly correlated to SVNT % inhibition with R value = 0,866 (p &lt; 0,0001). ROC analysis showed that anti SARS CoV 2 S RBD of 6,71 AU/mL had 95,7% sensitivity and 87,5% specificity to detect percentage inhibition of 30%. Anti SARS CoV 2 S RBD of 59,76 AU/mL had a sensitivity of 88,1% and specificity of 97,0% to detect percentage inhibition of 60%. FastBio RBDtm can determine the presence and level of anti SARS CoV 2 S RBD with good sensitivity and specificity. It has the potential to be deployed in health facilities with limited resources.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.01.23297911v1" target="_blank">Performance of A Point-of-care Fluorescence Immunoassay Test to measure anti Severe Acute Respiratory Syndrome Corona Virus 2 Spike, Receptor Binding Domain Antibody Level</a>
</div></li>
<li><strong>Equity and efficiency in global respiratory virus genomic surveillance</strong> -
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Public health interventions for respiratory virus outbreaks increasingly rely on genomic sequencing for the rapid identification of new (variant) viruses. However, global sequencing efforts are unevenly distributed, with some high-income countries sequencing at &gt;100,000 times the rate of many low-income countries. Given the importance of virus genomic sequencing and substantial global disparities in sequencing capacities, there is a need for meaningful minimum sequencing targets and functional upper bounds that maximise resource efficiency. Here, using mathematical models and analyses of data on global SARS-CoV-2 sequencing output in 2022, we show that increases in sequencing rates typical of low-income countries are &gt;100-fold more effective at reducing time to detection of new variants than increases from rates typical of high-income countries. We find that relative to 2022 sequencing rates, establishing a minimum respiratory virus sequencing capacity of two sequences per million people per week (S/M/wk) with a two-week time from sample collection to sequence deposition in all countries, while simultaneously capping sequencing rates at 30 S/M/wk in all countries, could reduce mean time to first variant detection globally by weeks-to-months while also reducing global sequencing output by &gt;60%. Our results show that investing in a minimum global respiratory virus sequencing capacity is far more effective at improving variant surveillance than expanding local sequencing efforts in countries with existing high-intensity respiratory virus surveillance programs and can guide rightsizing of global respiratory virus genomic surveillance infrastructure.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.01.23297901v1" target="_blank">Equity and efficiency in global respiratory virus genomic surveillance</a>
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<li><strong>Insights From a Generation: A Qualitative Study of the Impact of the COVID-19 Pandemic on Young Adults Mental Health and Beyond</strong> -
<div>
Purpose: Initial discussions about the COVID-19 pandemic often overlooked its impact on young adults. Our research aimed to explore how this group experienced the pandemic, and specifically how it affected their mental health, relationships, and careers. Methods: Data collection involved the use of in-depth semi-structured interviews. Using a pre-determined sampling frame, we purposively recruited 30 participants based on age, gender, ethnicity, and deprivation from the Neuroscience in Psychiatry Network (NSPN). The NSPN cohort, established in 2012, consists of 2403 young people aged 14 to 24 at baseline, recruited from Greater London and Cambridgeshire. Interviews were conducted in Autumn 2022; data were analysed using the framework method. Results: Participants were on average 28 years old (SD = 3 years, range 24-34 years; 53.3% female). The sample comprised individuals from diverse ethnic backgrounds, with 40% from non-White ethnic groups. Participants perceptions regarding their mental health during the pandemic were organised across five domains including general impact, impact on social networks and dynamics, coping strategies, adaptation and personal growth, and work and education. Conclusion: Young adults reported experiencing profound personal growth during the COVID-19 pandemic, re-evaluating their mental health and career priorities. However, the pandemic also caused substantial disruptions, with many returning to their parents homes, facing career challenges, and lacking mental health support. Policy changes are needed to address these issues in the post-pandemic landscape.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/84yv7/" target="_blank">Insights From a Generation: A Qualitative Study of the Impact of the COVID-19 Pandemic on Young Adults Mental Health and Beyond</a>
</div></li>
<li><strong>The correlation between conspiracy mentality and vaccine intentions is moderated by social events: Evidence from longitudinal data during COVID-19 pandemic in the UK</strong> -
<div>
Social events may provide important cues that influence the sense of reality, including the perception that conspiracy theories are plausible. Using longitudinal panel data collected in the UK from March 2020 to December 2021, this study aims to identify whether social events influenced the strength of the association between conspiracy mentality and vaccine intentions during the COVID-19 pandemic. Consistent with previous research, the conspiracy mentality was a significant predictor of vaccine intentions across three-time points, but also that conspiracy mentality at previous points predicted that participants were more hesitant to the vaccines in the following time points. The primary finding was that different social events moderated the strength of the correlation between conspiracy mentality and vaccine intentions within similar participants. Conspiracy mentality became more vital to evaluate COVID-19 vaccines in December 2020, when the vaccination program was about to commence.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/5wcnz/" target="_blank">The correlation between conspiracy mentality and vaccine intentions is moderated by social events: Evidence from longitudinal data during COVID-19 pandemic in the UK</a>
</div></li>
<li><strong>Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings.</strong> -
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Innovative methods for evaluating virus risk and spread, independent of test-seeking behavior, are needed to improve routine public health surveillance, outbreak response, and pandemic preparedness. Throughout the COVID-19 pandemic, environmental surveillance strategies, including wastewater and air sampling, have been used alongside widespread individual-based SARS-CoV-2 testing programs to provide population-level data. These environmental surveillance strategies have predominantly relied on pathogen-specific detection methods to monitor viruses through space and time. However, this provides a limited picture of the virome present in an environmental sample, leaving us blind to most circulating viruses. In this study, we explore whether pathogen-agnostic deep sequencing can expand the utility of air sampling to detect many human viruses. We show that sequence-independent single-primer amplification sequencing of nucleic acids from air samples can detect common and unexpected human respiratory and enteric viruses, including influenza virus type A and C, respiratory syncytial virus, human coronaviruses, rhinovirus, SARS-CoV-2, rotavirus, mamastrovirus, and astrovirus.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.28.23290648v2" target="_blank">Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings.</a>
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<li><strong>Motivational and behavioral mechanisms underlying generalized health risking behaviors during the COVID-19 pandemic in smokers</strong> -
<div>
Under the threat of public health challenges such as the recent COVID-19 pandemic, individual citizens active and cooperative participation in precautionary measures is crucial. Although non-compliance is recognized as a recurring problem, it remains unknown why some individuals tend to comply less than others and whether violations of preventive behaviors are observed consistently across different public health issues. To test our hypothesis that individuals would show consistent public health behavior transcending domains, we collected self-reports from two independent samples of participants (total N =2,983) on health risk beliefs and behavioral choices. Participants responses were collected in regard to two separate yet closely related public health issues: smoking and the COVID-19 pandemic. Our data reveal that on average, individuals beliefs and behaviors are consistent across different public health domains. In particular, smokers showed diminished compliance behaviors during the pandemic, which was mediated by their lower motives to protect public health. These results provide a psychological mechanism of how individuals health risk behaviors are generalized across different public health domains that may explain why some individuals (here, current-smokers) are more prone to violate public health behaviors.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/tkfzx/" target="_blank">Motivational and behavioral mechanisms underlying generalized health risking behaviors during the COVID-19 pandemic in smokers</a>
</div></li>
<li><strong>Unequal but Balanced: Highly educated mothers perceptions of work-life balance during the COVID-19 lockdown in Finland and the Netherlands</strong> -
<div>
One year after passage of the European work-life balance directive, and thus recognition of the need for policy support, measures to slow the spread of the COVID-19 pandemic are shaping parents work-life balance in significant ways. Academically, we are challenged to explore whether existing theoretical frameworks hold in this new environment with combined old and new policy frameworks. We are also challenged to understand the nuanced ways in which the first lockdown affects the combination of paid work and care. We address both of these issues, providing a cross-sectional comparative analysis of highly educated mothers perceptions of work-life balance during the COVID-19 pandemic in Finland and the Netherlands. Our findings show that highly educated Finnish mothers have more difficulty combining work and care during the first lockdown than Dutch mothers. The absence of state-provided care during the lockdown creates greater difficulty for full-time working Finnish mothers in a dual-earner/state-carer system than an absence of such care in the Dutch one-and-a-half earner system, where most mothers work part-time. Further analyses suggest variation in part-time and (nearly) full-time hours mitigates the work-life balance experiences of highly educated Dutch mothers. We discuss these findings in light of current theoretical frameworks and highlight avenues for future research.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/652mh/" target="_blank">Unequal but Balanced: Highly educated mothers perceptions of work-life balance during the COVID-19 lockdown in Finland and the Netherlands</a>
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<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>Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting</strong> - <b>Conditions</b>: Post COVID-19 Condition (PCC) <br/><b>Interventions</b>: Device: RDX-19 <br/><b>Sponsors</b>: KNOWBio Inc.; NAMSA <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>CPAP Therapy Through a Helmet or an Oronasal Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study</strong> - <b>Conditions</b>: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia <br/><b>Interventions</b>: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate <br/><b>Sponsors</b>: I.M. Sechenov First Moscow State Medical University <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>A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O)</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) 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>Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Virus Diseases; COVID-19 <br/><b>Interventions</b>: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment <br/><b>Sponsors</b>: AVB Biotechnology <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>A Phase Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O)</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital <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>SAFE Workplace Intervention for People With IDD</strong> - <b>Conditions</b>: Developement of Infectious Airborne Disease Prevention Workplace Curriclulm <br/><b>Interventions</b>: Behavioral: SAFE Employment Training <br/><b>Sponsors</b>: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research <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>Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms</strong> - <b>Conditions</b>: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame <br/><b>Interventions</b>: Behavioral: EMDR <br/><b>Sponsors</b>: University of Pisa <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>Lithium Long COVID Dose-finding Study</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Dietary Supplement: Lithium <br/><b>Sponsors</b>: State University of New York at Buffalo <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>Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Drug: GST-HG171 Tablets <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology 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>Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic</strong> - <b>Conditions</b>: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children <br/><b>Interventions</b>: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education <br/><b>Sponsors</b>: Chung Shan Medical 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>Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Liver Function</strong> - <b>Conditions</b>: COVID-19 Pneumonia <br/><b>Interventions</b>: Drug: GST-HG171 Tablets <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <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>Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19; Coronavirus <br/><b>Interventions</b>: Device: eBAM Cov Testing <br/><b>Sponsors</b>: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains laboratory sas, FRANCE <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>Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: EG-COVII <br/><b>Sponsors</b>: EyeGene Inc. <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>Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers</strong> - <b>Conditions</b>: Viral Infection COVID-19 <br/><b>Interventions</b>: Drug: Aterixen <br/><b>Sponsors</b>: Valenta Pharm JSC <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>A Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment <br/><b>Sponsors</b>: Chinese University of Hong Kong <br/><b>Not yet 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>Surface enhanced Raman scattering investigation of tecovirimat on silver, gold and platinum loaded silica nanocomposites: Theoretical analysis (DFT) and molecular modeling</strong> - As of today, there have been 612 million confirmed cases of coronavirus disease (COVID-19) around the world, with over 6 million fatalities. Tecovirimat (TPOXX) is an anti-viral drug, and it was the first drug approved for the treatment of anti-pox virus in the US. However, the effectiveness of this drug against COVID-19 has not yet been explored. Since TPOXX is an anti-viral drug, an attempt has been made to determine its ability to act as a COVID inhibitor. Recent medical advances have…</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>Plasma cell leukemia in a 34-year-old male: rare scenario case report</strong> - CONCLUSION: This report showcases a rare age presentation with unique manifestations of secondary plasma cell leukaemia. Multiple myeloma should be a differential diagnosis for cases with unexplained back pain despite an unclassical age.</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>Exploring Pharmacy Student Experiences with Student Debt and Perspectives on Future Burnout and Loan Relief</strong> - CONCLUSION: Pharmacy students burdened with debt described a variety of different experiences and attitudes toward that debt and provided their perspectives on how student debt influences short-term education and career decisions. While students accept the trade-off of debt for their education as an inevitable burden, reported coping mechanisms and strategies shared suggest some solutions may be available to ameliorate this burden.</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>Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection</strong> - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung…</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>Proteomic analyses of smear-positive/negative tuberculosis patients uncover differential antigen-presenting cell activation and lipid metabolism</strong> - CONCLUSION: Our study provides valuable insights into the differential molecular mechanisms underlying SNPT and SPPT, reveals the critical role of antigen-presenting cell activation in SNPT for effectively clearing the majority of Mtb in bodies, and shows the possibility of APC activation as a novel TB treatment strategy.</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><em>Antrodia cinnamomea</em> May Interfere with the Interaction Between ACE2 and SARS-CoV-2 Spike Protein in vitro and Reduces Lung Inflammation in a Hamster Model of COVID-19</strong> - CONCLUSION: AC shows potential as a nutraceutical for reducing the risk of SARS-CoV-2 infection by disrupting the interaction between ACE2 and the SARS-CoV-2 spike protein, and for preventing COVID-19-associated lung inflammation.</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>Computational Screening Using a Combination of Ligand-Based Machine Learning and Molecular Docking Methods for the Repurposing of Antivirals Targeting the SARS-CoV-2 Main Protease</strong> - CONCLUSION: Results demonstrated the efficiency of LBVS combined with MD. This combined strategy provided positive evidence showing that the top screened drugs, including CCX-140, which had the lowest MD score, can be reasonably advanced to the in vitro phase. This combined method may accelerate the discovery of therapies for novel or orphan diseases from existing drugs.</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>Impact of influenza immunity on the mortality among older adults hospitalized with COVID-19: a retrospective cohort study</strong> - It has been suggested that the outcomes of coronavirus disease 2019 (COVID-19) are better in individuals having recently received an influenza vaccine than in non-vaccinated individuals. We hypothesized that this association depends on the humoral responses against influenza viruses. We aim to assess the relationship between the humoral immunity against influenza and the 3-month all-cause mortality among hospitalized older patients with COVID-19. We performed an exploratory retrospective study…</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>Superior anti-pulmonary viral potential of Natrialba sp. M6-producing surfactin and C50 carotenoid pigment with unveiling its action modes</strong> - CONCLUSION: This study declared the promising efficacy of Sur as an efficient pharmacological treatment option for these pulmonary viruses and considered as guide for further in vivo research.</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>Identifying the Potential of miRNAs in <em>Houttuynia cordata</em>-Derived Exosome-Like Nanoparticles Against Respiratory RNA Viruses</strong> - INTRODUCTION: Pathogenic respiratory RNA viruses, including influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2, are major causes of causes of acute respiratory infection globally. Plant-derived exosome-like nanoparticles containing miRNAs have shown substantial cross-kingdom regulatory effects on both viral and human transcripts. Houttuynia cordata (H. cordata), a traditional Chinese medicine frequently used to treat respiratory diseases. However, the role of H….</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>Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol</strong> - Patients with chronic lung disease, obesity, and other co-morbid conditions are at increased risk of severe illness and death when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hypercapnia, the elevation of CO(2) in blood and tissue, commonly occurs in patients with severe acute and chronic lung disease, including those with pulmonary infections, and is also associated with high mortality risk. We previously reported that hypercapnia increases viral replication 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>Clinical and Immunological Impacts of Latent Toxoplasmosis on COVID-19 Patients</strong> - Background Parasites are well-known immune-modulators. They inhibit some aspects of the immune system to ensure persistence inside the host for a long time; meanwhile, they stimulate other immune aspects to assure the survival of the host. Wide variations in the severity of coronavirus disease 2019 (COVID-19) among developed and developing countries were reported during the COVID-19 pandemic. Parasitic infections, including Toxoplasma gondii (T. gondii), were claimed to contribute to such…</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>IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination</strong> - CONCLUSIONS: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.</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>Neurotoxic effects of chloroquine and its main transformation product formed after chlorination</strong> - Pharmaceutical transformation products (TPs) generated during wastewater treatment have become an environmental concern. However, there is limited understanding regarding the TPs produced from pharmaceuticals during wastewater treatment. In this study, chloroquine (CQ), which was extensively used for treating coronavirus disease-19 (COVID-19) infections during the pandemic, was selected for research. We identified and fractionated the main TP produced from CQ during chlorine disinfection 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>Development of Pan-Anti-SARS-CoV-2 Agents through Allosteric Inhibition of nsp14/nsp10 Complex</strong> - SARS-CoV-2 nsp14 functions both as an exoribonuclease (ExoN) together with its critical cofactor nsp10 and as an S-adenosyl methionine-dependent (guanine-N7) methyltransferase (MTase), which makes it an attractive target for the development of pan-anti-SARS-CoV-2 drugs. Herein, we screened a panel of compounds (and drugs) and found that certain compounds, especially Bi(III)-based compounds, could allosterically inhibit both MTase and ExoN activities of nsp14 potently. We further demonstrated…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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