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<title>13 October, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Discovering hub genes involved in the pathophysiological impact of COVID-19 on diabetes kidney disease by differential gene expression and interactome analysis</strong> -
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Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage, and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 DEGs shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes STAT1, IRF7, ISG15, MX1, and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.11.511826v1" target="_blank">Discovering hub genes involved in the pathophysiological impact of COVID-19 on diabetes kidney disease by differential gene expression and interactome analysis</a>
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</div></li>
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<li><strong>Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19</strong> -
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Background Patients with coronavirus disease-19 (COVID-19) are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality. Objectives We aimed to characterise the mechanism of altered platelet function in COVID-19 patients. Methods The platelet proteome, platelet functional responses and platelet-neutrophil aggregates were compared between patients hospitalised with COVID-19 and healthy control subjects using Tandem Mass Tag (TMT) proteomic analysis, Western blotting and flow cytometry. Results COVID-19 patients showed a different profile of platelet protein expression (858 altered out of 5773 quantified). Levels of COVID-19 plasma markers were enhanced in COVID-19 platelets. Gene ontology (GO) pathway analysis demonstrated that levels of granule secretory proteins were raised, whereas some platelet activation proteins, such as the thrombopoietin receptor and PKCalpha, were lowered. Basally, COVID-19 platelets showed enhanced phosphatidylserine (PS) exposure, with unaltered integrin alphaIIbBeta3 activation and P-selectin expression. Agonist-stimulated integrin alphaIIbBeta3 activation and PS exposure, but not P-selectin expression, were significantly decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This interaction was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction. Conclusions Overall, our data suggests the presence of two platelet populations in patients with COVID-19: one with circulating platelets with an altered proteome and reduced functional responses and another with P-selectin expressing neutrophil-associated platelets. Platelet driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.12.511145v1" target="_blank">Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19</a>
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</div></li>
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<li><strong>Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study</strong> -
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Abstract Objectives To evaluate the effects of the Omicron variant on the post-acute symptoms, four months after infection with SARS-CoV-2. Design A nationwide questionnaire study. Setting Denmark. Participants 44,004 individuals aged 15 years or older with either a SARS-CoV-2 RT-PCR positive test result from the period of Delta dominance (July to November 2021), or a positive or negative RT-PCR test result from the period of Omicron dominance (December 2021 to January 2022). Methods A questionnaire based cohort study with outcomes on post-acute physical, fatigue, cognitive, mental health symptoms, and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing cases and controls during the Omicron period, cases during the Delta and Omicron periods, and vaccinated cases with two and three doses during the Omicron period, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation and vaccination status. Results Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced higher risk of 18 out of 26 post-acute symptoms and five out of five new-onset general health problems, compared to controls. Cases during the Omicron period experienced lower risks of 8 of the 18 symptoms and of all five new-onset general health problems, compared to Delta cases. The most prominent RDs estimated when comparing Omicron cases to controls were: memory issues (RD=5.4%, 95% CI 4.8 to 6.1), post-exertional malaise (RD=5.3%, 95% CI 3.1 to 7.7), fatigue/exhaustion (RD=5.2%, 95% CI 3.7 to 6.9), substantial fatigue (RD=5.0%, 95% CI 2.7 to 7.5), and dyspnea (RD=4.8%, 95% CI 3.8 to 5.9). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute altered/reduced sense of smell (dysosmia) (RD=-15.1%, 95% CI -17.0 to -12.9) and -taste (dysgeusia) (RD=-11.6%, 95% CI -13.6 to -9.7). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13 of the 26 post-acute symptoms and of three of the five new-onset general health problems, compared to those vaccinated with two doses. Conclusions A considerable amount of cases infected during the Omicron period experienced post-acute symptoms and new-onset health problems, four months after testing, although milder compared to Delta cases. During the Omicron period, a booster vaccination dose was associated with fewer post-acute symptoms and new-onset health problems, four months after infection, compared to two doses of COVID-19 vaccine.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.12.22280990v1" target="_blank">Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study</a>
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<li><strong>Analysis of fatality among COVID-19 cases in Mexican pregnant women: a cross-sectional study</strong> -
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This study aims to analyze the fatality of cases confirmed by COVID-19 among pregnant women in Mexico. It is a cross-sectional and analytical study. We used the registries from pregnant women available in the open database of the National Epidemiological Surveillance System from the General Directorate of Epidemiology. We showed descriptive statistics for all the variables. A suspected case of COVID-19 is any person who presented the following signs and symptoms: fever, headache, cough, and others. A confirmed case is any suspected case with a positive RT- PCR test result. We computed OR and 95% confidence intervals to estimate the effect of independent variables on dying from COVID-19. Also, it was calculated the Case Fatality Ratio (CFR) among pregnant women. The alpha value was fixed at 0.05 as a threshold to show statistical significance. The CFR was 1.09%. For confirmed cases, the average age among those who died was higher than among those who did not die (P <0.05). The average time between the onset of symptoms and registration in the system was higher for those who died (P <0.05). Among the deceased, 76.97% had pneumonia. For the 40-49 years age group, the effect on death was statistically significant (OR 4.97, CI95% 1.77 – 17.85). Outpatient care had a protective effect on dying (OR 0.04, CI95% 0.02 – 0.09). Pneumonia was highly associated with death (OR 8.68, CI95% 5.72 – 13.6). Co-morbidities did not affect dying while considering them in a multivariable logistic regression model. Among pregnant women, smoking has little effect on death by COVID-19. The CFR was low compared with the rest of the Mexican population. The co-morbidities had a low prevalence among pregnant women. Since the reproductive age span is young age, pregnant women have two protective factors for COVID-19 detected so far: being young and woman.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.12.22280996v1" target="_blank">Analysis of fatality among COVID-19 cases in Mexican pregnant women: a cross-sectional study</a>
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<li><strong>Development of SARS-CoV-2 replicons for the ancestral virus and variant of concern Delta for antiviral screening.</strong> -
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SARS-CoV-2 is the aetiologic agent of COVID-19 and the associated ongoing pandemic. As the pandemic has progressed, Variants of Concern (VOC) have emerged with lineage defining mutations. Using a SARS-CoV-2 reverse genetic system, based on transformation associated recombination in yeast, a series of replicons were produced for the ancestral Wuhan virus and the SARS-CoV-2 VOC Delta in which different combinations of the Spike, membrane, ORF6 and ORF7a coding sequences were replaced with sequences encoding the selectable marker puromycin N-acetyl transferase and reporter proteins (Renilla luciferase, mNeonGreen and mScarlet). Replicon RNAs were replication competent in African green monkey kidney (Vero E6) derived cells and a range of human cell lines, with a Vero E6 cell line expressing ACE2 and TMPRSS2 showing much higher transfection efficiency and overall levels of Renilla luciferase activity. The replicons could be used for transient gene expression studies, but cell populations that stably maintained the replicons could not be propagated. Replication of the transiently expressed replicon RNA genomes was sensitive to remedesivir, providing a system to dissect the mechanism of action of antiviral compounds.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.11.511804v1" target="_blank">Development of SARS-CoV-2 replicons for the ancestral virus and variant of concern Delta for antiviral screening.</a>
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<li><strong>COVID19 Diagnosis Using Chest X-rays and Transfer Learning</strong> -
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A pandemic of respiratory illnesses from a novel coronavirus known as Sars-CoV-2 has swept across the globe since December of 2019. This is calling upon the research community including medical imaging to provide effective tools for use in combating this virus. Research in biomedical imaging of viral patients is already very active with machine learning models being created for diagnosing Sars-CoV-2 infections in patients using CT scans and chest x-rays. We aim to build upon this research. Here we used a transfer-learning approach to develop models capable of diagnosing COVID19 from chest x-ray. For this work we compiled a dataset of 112120 negative images from the Chest X-Ray 14 and 2725 positive images from public repositories. We tested multiple models, including logistic regression and random forest and XGBoost with and without principal components analysis, using five-fold cross-validation to evaluate recall, precision, and f1-score. These models were compared to a pre-trained deep-learning model for evaluating chest x-rays called COVID-Net. Our best model was XGBoost with principal components with a recall, precision, and f1-score of 0.692, 0.960, 0.804 respectively. This model greatly outperformed COVID-Net which scored 0.987, 0.025, 0.048. This model, with its high precision and reasonable sensitivity, would be most useful as rule-in test for COVID19. Though it outperforms some chemical assays in sensitivity, this model should be studied in patients who would not ordinarily receive a chest x-ray before being used for screening.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.09.22280877v2" target="_blank">COVID19 Diagnosis Using Chest X-rays and Transfer Learning</a>
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<li><strong>Using synthetic controls to estimate the population-level effects of Ontario’s recently implemented overdose prevention sites and consumption and treatment services</strong> -
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Background: Between 2017 and 2020, Ontario implemented overdose prevention sites (OPS) and consumption and treatment services (CTS) in nine of its 34 public health units (PHU). We tested for the effect of booth-hours (spaces within OPS/CTSs for supervised consumption) on opioid-related health service use and mortality rates at the provincial- (aggregate) and PHU-level. Methods: We used monthly rates of all opioid-related emergency department (ED) visits, hospitalizations, and deaths between January 2015 and March 2021 as our three outcomes. For each PHU that implemented OPS/CTSs, we created a synthetic control as a weighted combination of unexposed PHUs. Our exposure was the time-varying rate of booth-hours provided. We estimated the population-level effects of the intervention on each outcome per treated/synthetic-control pair using controlled interrupted time series with segmented regression; and tested for the aggregate effect using a multiple baseline approach. We adjusted for time-varying provision of prescription opioids for pain management, opioid agonist treatment (OAT), and naloxone kits; and corrected for seasonality and autocorrelation. All rates were per 100,000 population. For sensitivity analysis, we restricted the post-implementation period to before COVID-19 public health measures were implemented (March 2020). Results: Our aggregate analyses found no effect per booth-hour on ED visit (0.00, 95% CI: -0.01, 0.01; p-value=0.6684), hospitalization (0.00, 95% CI: 0.00, 0.00; p-value=0.9710) or deaths (0.00, 95% CI: 0.00, 0.00; p-value=0.2466). However, OAT reduced ED visits (-0.20, 95% CI: -0.35, -0.05; p-value=0.0103) and deaths (-0.04, 95% CI: -0.05, -0.03; p-value=<0.0001). Conversely, prescription opioids for pain management modestly increased deaths (0.0008, 95% CI: 0.0002, 0.0015; p-value=0.0157) per 100,000 population, respectively. Except for a few treated PHU/synthetic control pairs, disaggregate results were congruent with overall findings. Conclusion: Booth-hours had no population-level effect on opioid-related overdose ED visit, hospitalization, or death rates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.13.21267739v3" target="_blank">Using synthetic controls to estimate the population-level effects of Ontario’s recently implemented overdose prevention sites and consumption and treatment services</a>
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<li><strong>A common allele of HLA mediates asymptomatic SARS-CoV-2 infection</strong> -
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Despite some inconsistent reporting of symptoms, studies have demonstrated that at least 20% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will remain asymptomatic. Although most global efforts have focused on understanding factors underlying severe illness in COVID-19 (coronavirus disease of 2019), the examination of asymptomatic infection provides a unique opportunity to consider early disease and immunologic features promoting rapid viral clearance. Owing to its critical role in the immune response, we postulated that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection. We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution HLA genotyping data were available in the UCSF Citizen Science smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n=1428) was comprised of unvaccinated, self-identified subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with disease course and identified a strong association of HLA-B<em>15:01 with asymptomatic infection, and reproduced this association in two independent cohorts. Suggesting that this genetic association is due to pre-existing T-cell immunity, we show that T cells from pre-pandemic individuals carrying HLA-B</em>15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF, and 100% of the reactive cells displayed memory phenotype. Finally, we characterize the protein structure of HLA-B<em>15:01-peptide complexes, demonstrating that the NQKLIANQF peptide from SARS-CoV-2, and the highly homologous NQKLIANAF from seasonal coronaviruses OC43-CoV and HKU1-CoV, share similar ability to be stabilized and presented by HLA-B</em>15:01, providing the molecular basis for T-cell cross-reactivity and HLA-B*15:01-mediated pre-existing immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.13.21257065v3" target="_blank">A common allele of HLA mediates asymptomatic SARS-CoV-2 infection</a>
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<li><strong>When thinking you are better leads to feeling worse: Self-other asymmetries in prosocial behavior and increased anxiety during the Covid-19 pandemic</strong> -
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Thinking one is better than peers is generally associated with positive psychological outcomes like increased self-esteem and resilience. However, this tendency may be problematic in the context of collective action problems, wherein individuals are reliant on others9 prosocial behaviors to achieve larger goals. We examined this question in the context of the Covid-19 pandemic, and recruited participants (n = 1022) from a university community in Spring 2020. We found evidence for a self-peer asymmetry, such that participants reported that they were doing more to stop the spread of the disease and were more prosocially motivated than peers. Actual peer reports indicated that these were overestimations. This self-enhancement tendency comes with a cost: the perceived self-peer asymmetry mediated the relationship between Covid-specific worry and general anxiety during the early lockdown period. This indicates that while believing one is doing more than others may be maladaptive in collective action problems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.26.21252547v2" target="_blank">When thinking you are better leads to feeling worse: Self-other asymmetries in prosocial behavior and increased anxiety during the Covid-19 pandemic</a>
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<li><strong>Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention</strong> -
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Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after four weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted (n=20,23,29,37,41,45) to inform early stopping of the trial prior to the planned maximum recruitment (n=150). Final analysis (n=75) showed strong evidence for a positive treatment effect (Bayes factor, BF=1.25 × 10<sup>6</sup>): the immediate arm reported fewer IMs (median=1, IQR=0-3) than the delayed arm (median=10, IQR=6-16.5). With further digital enhancements, the intervention (n=28) also showed a positive treatment effect (BF=7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT04992390 (www.clinicaltrials.gov).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.06.22280777v2" target="_blank">Treating intrusive memories after trauma in healthcare workers: a Bayesian adaptive randomised trial developing an imagery-competing task intervention</a>
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<li><strong>The health impact of long COVID during the 2021-2022 Omicron wave in Australia: a quantitative burden of disease study</strong> -
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Background Long COVID symptoms occur for a proportion of acute COVID-19 survivors, with reduced risk among the vaccinated, and for Omicron compared to Delta variant infections. The health loss attributed to pre-Omicron long COVID has previously been estimated using only a few major symptoms. Methods The years lived with disability (YLDs) due to long COVID in Australia during the 2021-2022 Omicron BA.1/BA.2 wave were calculated using inputs from previously published case-control, cross-sectional, or cohort studies examining the prevalence and duration of individual long COVID symptoms. This estimated health loss was compared with acute SARS-CoV-2 infection YLDs and years of life lost (YLLs) from SARS-CoV-2. The sum of these three components equalled COVID-19 disability-adjusted life years (DALYs), which was compared to DALYs from other diseases. Results 5200 (95% uncertainty interval [UI] 2100-8300) YLDs were attributable to long COVID and 1800 (95% UI 1100-2600) to acute-SARS-CoV-2 infection, suggesting long COVID caused 74% of the overall YLDs from SARS-CoV-2 infections in the BA.1/BA.2 wave. Total DALYs attributable to SARS-CoV-2 were 50 900 (95% UI 21 000-80 800), 2.4% of expected DALYs for all diseases in the same period. Conclusion This study provides a comprehensive approach to estimating the morbidity due to long COVID. Improved data on long COVID symptoms will improve the accuracy of these estimates. As data accumulates on SARS-CoV-2 infection sequalae (e.g., increased cardiovascular disease rates), total health loss is likely to be higher than estimated in this study. Nevertheless, this study demonstrates that long COVID requires consideration in pandemic policy planning given it is responsible for the majority of direct SARS-CoV-2 morbidity, including during an Omicron wave in a highly vaccinated population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.01.22278219v3" target="_blank">The health impact of long COVID during the 2021-2022 Omicron wave in Australia: a quantitative burden of disease study</a>
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<li><strong>There are Higher Levels of Conspiracy Beliefs in More Corrupt Countries</strong> -
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In four studies, I found evidence that people living in countries with higher levels of corruption have a greater tendency for conspiracy ideation. In Study 1 (21 countries, N = 20,207), participants living in more corrupt countries reported having higher COVID-19 and generic conspiracy beliefs. Study 2 (25 countries, N = 4,935), Study 3 (25 countries, N = 24,424), and Study 4 (24 countries, N = 5,973) replicated the same finding. Internal meta-analysis suggested that this association remained significant after adjusting for other relevant cross-country differences. Studies 1 and 2, but not 3 and 4, also showed that corruption moderated the association between individuals’ gullibility (i.e., lack of education) and their conspiracy beliefs, and this association was significant only in low corruption countries. The findings suggest that country-level corruption breeds conspiracy beliefs and moderates the effect of individuals’ gullibility to conspiracy theories.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2umfe/" target="_blank">There are Higher Levels of Conspiracy Beliefs in More Corrupt Countries</a>
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<li><strong>The SARS-CoV-2 envelope (E) protein forms a calcium- and voltage-activated calcium channel</strong> -
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The function of ion channels is essential in the infectious cycle of many viruses. To facilitate viral uptake, maturation and export, viruses must modify the ionic balance of their host cells, in particular of calcium ions (Ca2+). Viroporins encoded in the viral genome play a key part in altering the cell’s ionic homeostasis. In SARS-Coronavirus-2 (SARS-CoV-2) - the causative agent of Covid-19 - the envelope (E) protein is considered to form ion channels in ERGIC organellar membranes, whose function is closely linked to disease progression and lethality. Deletion, blockade, or loss-of-function mutation of coronaviral E proteins results in propagation-deficient or attenuated virus variants. The exact physiological function of the E protein, however, is not sufficiently understood. Since one of the key features of the ER is its function as a Ca2+ storage compartment, we investigated the activity of E in the context of this cation. Molecular dynamics simulations and voltage-clamp electrophysiological measurements show that E exhibits ion channel activity that is regulated by increased luminal Ca2+ concentration, membrane voltage, post-translational protein modification, and negatively charged ERGIC lipids. Particularly, calcium ions bind to a distinct region at the ER-luminal channel entrance, where they activate the channel and maintain the pore in an open state. Also, alongside monovalent ions, the E protein is highly permeable to Ca2+. Our results suggest that the physiological role of the E protein is the release of Ca2+ from the ER, and that the distinct Ca2+ activation site may serve as a promising target for channel blockers, potentially inhibiting the infectious cycle of coronaviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.11.511775v1" target="_blank">The SARS-CoV-2 envelope (E) protein forms a calcium- and voltage-activated calcium channel</a>
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<li><strong>Perceptions and predictors of COVID-19 vaccine hesitancy among health care providers across five countries in sub-Saharan Africa</strong> -
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The African continent has some of the world’s lowest COVID-19 vaccination rates. While the limited availability of vaccines is a contributing factor, COVID-19 vaccine hesitancy among health care providers (HCP) is another factor that could adversely affect efforts to control infections on the continent. We sought to understand the extent of COVID-19 vaccine hesitancy among HCP, and its contributing factors in Africa. We evaluated COVID-19 vaccine hesitancy among 1,499 HCP enrolled in a repeated cross-sectional telephone survey in Burkina Faso, Ethiopia, Nigeria, Tanzania and Ghana. We defined COVID-19 vaccine hesitancy among HCP as self-reported responses of definitely not, maybe, unsure, or undecided on whether to get the COVID-19 vaccine, compared to definitely getting the vaccine. We used Poisson regression models to evaluate factors influencing vaccine hesitancy among HCP. Approximately 65.6% were nurses and the mean age (±SD) of participants was 35.8 (±9.7) years. At least 67% of the HCP reported being vaccinated. Reasons for low COVID-19 vaccine uptake included concern about vaccine effectiveness, side effects and fear of receiving unsafe and experimental vaccines. COVID-19 vaccine hesitancy affected 45.7% of the HCP in Burkina Faso, 25.7% in Tanzania, 9.8% in Ethiopia, 9% in Ghana and 8.1% in Nigeria. Respondents reporting that COVID-19 vaccines are very effective (RR:0.21, 95% CI:0.08, 0.55), and older HCP (45 or older vs.20-29 years, RR:0.65, 95% CI: 0.44,0.95) were less likely to be vaccine-hesitant. Nurses were more likely to be vaccine-hesitant (RR 1.38, 95% CI: 1.00,1.89) compared to doctors. We found higher vaccine hesitancy among HCP in Burkina Faso and Tanzania. Information asymmetry among HCP, beliefs about vaccine effectiveness and the endorsement of vaccines by the public health institutions may be important. Efforts to address hesitancy should address information and knowledge gaps among different cadres of HCP and should be coupled with efforts to increase vaccine supply.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.11.22280952v1" target="_blank">Perceptions and predictors of COVID-19 vaccine hesitancy among health care providers across five countries in sub-Saharan Africa</a>
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<li><strong>A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients</strong> -
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We previously reported that a second dose of COVID-19 mRNA vaccine was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. However, some of these patients did not achieve seroconversion. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in Japanese allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of COVID-19 mRNA vaccine. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID19 mRNA vaccine (BNT162b2 [n = 15] and mRNA1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23-71) years. Median time from HSCT to the third vaccination and from the second to the third vaccination was 1842 (range, 378-4279) days and 219 (range, 194-258) days, respectively. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Median optical density of S1 IgG titers before and after the third dose was 0.099 (range, 0.001-0.713) and 1.315 (range, 0.006-1.730), respectively. Among 22 evaluable patients, 21 (95%) seroconverted after the third dose. Four of the five patients treated with steroids or CI seroconverted after the third vaccination. One patient with a serum IgG level of 173 mg/dL who received steroids did not achieve seroconversion. On one-week follow-up, none of our patients had > grade 3 or serious adverse events, new onset graft versus host disease (GVHD), or GVHD exacerbation after vaccination. The most frequent adverse event was mild pain at the injection site. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.08.22280863v1" target="_blank">A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study of 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>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A 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>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: DILTIAZEM TEVA 60 mg or placebo<br/><b>Sponsors</b>: Hospices Civils de Lyon; Signia Therapeutics<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 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>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of COVID-19 Vaccine, AdCLD-CoV19-1 OMI, as a Booster</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Biological: AdCLD-CoV19-1 OMI (Part A); Biological: AdCLD-CoV19-1 OMI (Part B); Other: Placebo (Part B)<br/><b>Sponsor</b>: Cellid Co., Ltd.<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Personalized Computerized Training Program for Cognitive Dysfunction After COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19; Long COVID<br/><b>Intervention</b>: Device: CogniFit’s CCT Post COVID-19<br/><b>Sponsor</b>: Universidad Antonio de Nebrija<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families</strong> - <b>Condition</b>: Psychological Disorder<br/><b>Intervention</b>: Other: Qualitative research interview<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sequential Enhanced Safety Study of a Novel Coronavirus Messenger RNA (mRNA) Vaccine in Adults Aged 18 Years and Older.</strong> - <b>Condition</b>: Corona Virus Disease 2019(COVID-19)<br/><b>Intervention</b>: Biological: 0.3ml of mRNA vaccine<br/><b>Sponsor</b>: Yu Qin<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of Teeth Brushing in Ventilated COVID-19 Patients.</strong> - <b>Conditions</b>: Microbial Colonization; COVID-19 Respiratory Infection; Dysbiosis; VAP - Ventilator Associated Pneumonia; HAI<br/><b>Intervention</b>: Procedure: Oral Procedure<br/><b>Sponsor</b>: University Hospital in Krakow<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity</strong> - <b>Condition</b>: Post-acute Sequelae of SARS-CoV-2 Infection<br/><b>Intervention</b>: Behavioral: Exercise<br/><b>Sponsor</b>: University of Colorado, Denver<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 3 Study to Evaluate Immunogenicity and Safety of BBV154 Booster Dose</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Interventions</b>: Biological: BBV154 Intranasal Vaccine; Biological: Intramuscular vaccine COVAXIN; Biological: Covishield<br/><b>Sponsor</b>: Bharat Biotech International Limited<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Scaling Well-Being for Educators During COVID-19</strong> - <b>Conditions</b>: Anxiety; Depression<br/><b>Intervention</b>: Behavioral: Healthy Minds Program Foundations Training<br/><b>Sponsors</b>: University of Wisconsin, Madison; Chan Zuckerberg Initiative<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“It’s a kind of freedom”: adolescents and parents speak about motivations for active travel and COVID-19</strong> - CONCLUSIONS: The findings point to the influence of positive parent perceptions, active and supportive family and community norms on adolescent AT. Peer norms and social networks as well as features of the built environment also have the potential to influence AT. The COVID-19 pandemic encouraged use of AT and provided a setting for positive AT experiences.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro inhibition of SARS-CoV-2 Infection by dry algae powders</strong> - Chlorella spp., Spirulina spp., and fucoidan dry powders, are commercialized as food supplements and are considered safe for human consumption. Their broad-spectrum antiviral properties have been studied, however, their effect against SARS-CoV-2 remains unknown. We investigated the potential antiviral activity of three algae powders: Chlorella vulgaris, Arthrospira maxima (Spirulina) and fucoidan purified from marine brown algae Sargassum spp. against SARS-CoV-2 infection in vitro. Vero cells…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reactivity and binding mode of disulfiram, its metabolites, and derivatives in SARS-CoV-2 PL<sup>pro</sup>: insights from computational chemistry studies</strong> - The papain-like protease (PL^(pro)) from SARS-CoV-2 is an important target for the development of antivirals against COVID-19. The safe drug disulfiram (DSF) presents antiviral activity inhibiting PL^(pro) in vitro, and it is under clinical trial studies, indicating to be a promising anti-COVID-19 drug. In this work, we aimed to understand the mechanism of PL^(pro) inhibition by DSF and verify if DSF metabolites and derivatives could be potential inhibitors too. Molecular docking, DFT, and ADMET…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico analysis of the antidepressant fluoxetine and related drugs at SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro)</strong> - CONCLUSION: In an in silico perspective, it is likely that the SSRIs and other anti-depressants could interact with Mpro and cause the enzyme to malfunction. Unfortunately, the same drugs did not present similar results on PLpro crystal, therefore no inhibition is expected on an in vitro trial. Anyway, in vitro test are necessary for the better understanding the links between SARS-CoV-2 proteases and anti-depressants.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation of Streptomyces sp. Strain EMB24 Secondary Metabolite Profile Has Unraveled Its Extraordinary Antibacterial Potency Against Drug-Resistant Bacteria</strong> - With the overuse and misuse of antibiotics amid COVID-19 pandemic, the antimicrobial resistance, which is already a global challenge, has accelerated its pace significantly. Finding novel and potential antibiotics seems one of the probable solutions. In this work, a novel Streptomyces sp. strain EMB24 was isolated and found to be an excellent source of antimicrobials as confirmed by agar-plug assay. It showed antibacterial activity against infection-causing bacteria, namely Staphylococcus…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A First in man study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RP7214, a Dihydroorotate Dehydrogenase (DHODH) inhibitor in Healthy Subjects</strong> - Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that is essential for pyrimidine de-novo synthesis. Rapidly growing cancer cells and replicating viruses are dependent on host cell nucleotides, the precursors of which are provided by DHODH. Hence DHODH becomes an ideal target for pharmacological intervention. RP7214 is a potent and selective inhibitor of human DHODH and has shown anti-viral and anti-leukemic activity in preclinical studies. This paper describes the Phase I study…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Face masks inhibit facial cues for approachability and trustworthiness: an eyetracking study</strong> - Wearing face masks during the Covid-19 pandemic has undeniable benefits from our health perspective. However, the interpersonal costs on social interactions may have been underappreciated. Because masks obscure critical facial regions signaling approach/avoidance intent and social trust, this implies that facial inference of approachability and trustworthiness may be severely discounted. Here, in our eyetracking experiment, we show that people judged masked faces as less approachable and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rapid Generation of Circulating and Mucosal Decoy Human ACE2 using mRNA Nanotherapeutics for the Potential Treatment of SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause lethal pulmonary damage in humans. It contains spike proteins on its envelope that bind to human angiotensin-converting enzyme 2 (hACE2) expressed on airway cells, enabling entry of the virus, and causing infection. The soluble form of hACE2 binds SARS-CoV-2 spike protein, prevents viral entry into target cells, and ameliorates lung injury; however, its short half-life limits therapeutic utilities. Here, synthetic mRNA is…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Therapeutic potential of kaempferol on Streptococcus pneumoniae infection</strong> - Co-infections with pathogens and secondary bacterial infections play significant roles during the pandemic coronavirus disease 2019 (COVID-19) pathogenetic process, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Notably, co-infections with Streptococcus pneumoniae (S. pneumoniae), as a major Gram-positive pathogen causing pneumonia or meningitis, severely threaten the diagnosis, therapy, and prognosis of COVID-19 worldwide. Accumulating evidences have emerged indicating…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of the COVID-19 pandemic on changes in temperature-sensitive cardiovascular and respiratory disease mortality in Japan</strong> - Some cardiovascular and respiratory diseases are triggered by changes in ambient temperature or extremes of temperature. This study aimed to clarify the changes in mortality associated with temperature-sensitive diseases in Japan during the COVID-19 pandemic. We used data from three major cities (Sapporo City, Tokyo 23 wards, and Osaka City) from 2010 to 2019 to determine disease mortality rates and monthly mean temperatures from April to December. If the pandemic had not occurred in 2020, the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity to SARS-CoV-2 Omicron variant among school-aged children with 2-dose of inactivated SARS-CoV-2 vaccines followed by BNT162b2 booster</strong> - CONCLUSION: A regimen of 2-dose of inactivated vaccine followed by BNT162b2 booster dose elicited high neutralizing antibody against the Omicron variants in healthy school-aged children.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A photoelectrochemical immunosensor based on magnetic all-solid-state Z-scheme heterojunction for SARS-CoV-2 nucleocapsid protein detection</strong> - Rapid, convenient and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed to timely diagnosis of coronavirus pandemic (COVID-19) and control of the epidemic. In this study, a signal-off photoelectrochemical (PEC) immunosensor was constructed for SARS-CoV-2 nucleocapsid (N) protein detection based on a magnetic all-solid-state Z-scheme heterojunction (Fe(3)O(4)<span class="citation" data-cites="SiO">@SiO</span>(2)<span class="citation" data-cites="TiO">@TiO</span>(2)<span class="citation" data-cites="CdS/Au">@CdS/Au</span>, FSTCA). Integrating the advantages of magnetic materials and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemical screen uncovers novel structural classes of inhibitors of the papain-like protease of coronaviruses</strong> - The papain-like protease (PLpro) of coronaviruses is an attractive antiviral target to inhibit both viral replication and interference of the host immune response. We have identified and characterized three novel classes of small molecules, thiophene, cyanofuran, and triazoloquinazoline, as PLpro inhibitors Thiophene inhibited the PLpro of two major coronaviruses, Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) including…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of SARS-CoV-2-specific memory B cells on the immune response after mRNA-based Comirnaty vaccine in seronegative health care workers</strong> - CONCLUSION: IgG<sup>(-)MBC</sup>(-) individuals showed the worst humoral and cellular responses, both in frequency and magnitude, after vaccination. Individuals whose antibodies wane and become undetectable after a given period of time post vaccination and show no specific MBCs are less protected and hence are good candidates for boosting vaccine. On the other hand, seronegative individuals with specific MBC showed faster and higher responses compared to the IgG<sup>(-)MBC</sup>(-) group.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, spectroscopic, topological, hirshfeld surface analysis, and anti-covid-19 molecular docking investigation of isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate</strong> - Isopropyl 1-benzoyl-4-(benzoyloxy)-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate (IDPC) was synthesized and characterized via spectroscopic (FT-IR and NMR) techniques. Hirshfeld surface and topological analyses were conducted to study structural and molecular properties. The energy gap (E(g)), frontier orbital energies (E(HOMO), E(LUMO)) and reactivity parameters (like chemical hardness and global hardness) were calculated using density functional theory with B3LYP/6-311++G (d,p) level…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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