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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>What Happened to MSMEs During the Pandemic?</strong> -
<div>
The Covid-19 pandemic causes a huge impact to global economy including peoples income and purchasing power. This has brought deflation which triggered by falling prices in several sectors. Some of the biggest affected sectors are food, beverages and also transportation. With this pandemic that affects in both microeconomics and macroeconomics, government should take control so that Covid-19 cases can be minimalized and gain public trust for economic recovery.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/ygda8/" target="_blank">What Happened to MSMEs During the Pandemic?</a>
</div></li>
<li><strong>Pathogenic neutrophilia drives acute respiratory distress syndrome in severe COVID-19 patients</strong> -
<div>
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing COVID-19 pandemic have caused ~33 million cases and over 585,000 deaths in the United States alone. Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths being Black/African-American (AA) patients in some areas, yet targeted studies to delineate features of disease severity within this demographic are scant. Our multi-omics single-cell analyses of immune profiles from airways and matching blood samples of Black/AA patients revealed pronounced pulmonary neutrophilia and low viral burden as a hallmark of severe disease, where neutrophil phenotypes display advanced features of cytokine release syndrome and acute respiratory distress syndrome (ARDS). Cell-cell communication and trajectory analysis reveal a subset of circulating S100A12+/CXCR4+ mature neutrophils that infiltrate the lung via the IL-8/CXCR2 axis. Recruited neutrophils progress toward a transcriptionally active and pathogenic state characterized by exacerbated production of IL-8, IL-1{beta}, IL-6, and CCL3/4 along with elevated levels of neutrophil elastase and myeloperoxidase. Inflammatory monocytes recruited via neutrophil-derived CCL3/4 also produce elevated neutrophil chemotactic factor IL-8, potentiating the sustained neutrophilia in the airways. The IL-8/CXCR2 axis emerges as a potential therapeutic target to reduce pathogenic neutrophilia and constrain ARDS in severe COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.02.446468v1" target="_blank">Pathogenic neutrophilia drives acute respiratory distress syndrome in severe COVID-19 patients</a>
</div></li>
<li><strong>CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease is autocrine TNF-α/TNFRI-dependent</strong> -
<div>
Lymphopenia is common in severe COVID-19 disease, yet the mechanisms are poorly understood. In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared to recovered, mild disease (p&lt;0.0001). In severe disease, immunodominant CD4+ T cell responses to Spike-1(S1) produced increased in vitro TNF-, but impaired proliferation and increased susceptibility to activation-induced cell death (AICD). CD4+TNF-+ T cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.744, P&lt;0.0001). TNF- blockade including infliximab or anti-TNFRI antibodies strikingly rescued S1-specific CD4+ proliferation and abrogated S1-AICD in severe COVID-19 patients (P&lt;0.001). Single-cell RNAseq demonstrated downregulation of Type-1 cytokines and NF{kappa}B signaling in S1-stimulated CD4+ cells with infliximab treatment. Lung CD4+ T cells in severe COVID-19 were reduced and produced higher TNF- versus PBMC. Together, our findings show COVID-19-associated CD4+ lymphopenia and dysfunction is autocrine TNF-/TNFRI-dependent and therapies targeting TNF- may be beneficial in severe COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.02.446831v1" target="_blank">CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease is autocrine TNF-α/TNFRI-dependent</a>
</div></li>
<li><strong>The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner</strong> -
<div>
The rapid, global dispersion of SARS-CoV-2 since its initial identification in December 2019 has led to the emergence of a diverse range of variants. The initial concerns regarding the virus were quickly compounded with concerns relating to the impact of its mutated forms on viral infectivity, pathogenicity and immunogenicity. To address the latter, we seek to understand how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic, before mass vaccination. We analyzed a total of 330,246 high quality SARS-CoV-2 genome assemblies sampled across 143 countries and all major continents. Strikingly, we found that specific mutational patterns in SARS-CoV-2 diversify T cell epitopes in an HLA supertype-dependent manner. In fact, we observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family. In addition, we show that this predicted global loss of epitopes is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7 supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic. Together, our study lays the foundation to help understand how SARS-CoV-2 mutants shape the repertoire of T cell targets and T cell immunity across human populations. The proposed theoretical framework has implications in viral evolution, disease severity, vaccine resistance and herd immunity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.03.446959v1" target="_blank">The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner</a>
</div></li>
<li><strong>Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip</strong> -
<div>
Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PMBCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.06.03.446968v1" target="_blank">Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip</a>
</div></li>
<li><strong>Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. No drug for prevention or treatment in earlier stages of COVID-19 are yet found; although several new candidates including ivermectin, dutasteride, baricitinib, budesonide and colchicine are being studied with some early promising results. Safe and effective treatments will need to be both affordable and widely available globally. Objectives This analysis will estimate and compare potential generic production costs of a selection of COVID-19 drug candidates with international list prices. Methods Costs of production for new and potential COVID-19 drugs (dexamethasone, ivermectin, dutasteride, budesonide, baricitinib, tocilizumab, sarilumab and colchicine) were estimated using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured at very low per-course costs: ranging from $2.58 for IV dexamethasone (or $0.19 orally) to $0.12 for ivermectin. No export price data was available for baricitinib, tocilizumab or sarilumab. When compared against international list prices, we found wide variations between countries. Drug API availability was generally good, with colchicine being the most available with sufficient annual API exported for 59.8 million treatment courses. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Analysed drugs are widely available and affordable, whilst IV treatment courses are more expensive.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.01.21258147v1" target="_blank">Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19.</a>
</div></li>
<li><strong>Virologic features of SARS-CoV-2 infection in children</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Data on viral factors causing pediatric disease and guidance for pediatric-specific considerations have lagged behind adults throughout the COVID-19 pandemic. As COVID-19 infections and deaths increase in the pediatric population, characterization of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. Methods: Nasal swabs collected from children with COVID-19 were analyzed. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age or symptom duration were analyzed. SARS-CoV-2 whole genome amplification was compared with contemporaneous Massachusetts sequences to assess for clustering patterns. Results: Ninety-seven children with COVID-19 (median age 10 years, range 2 weeks-22 years) were included in this study. Age did not impact SARS-CoV-2 viral load in nasal secretions: children of all ages were equally likely to carry live, replicating virus. Children within the first five days of illness had higher viral loads and rates of culture positivity, and viral load in hospitalized children (n=30) did not differ from hospitalized adults (n=21) with similar duration of symptoms. While pediatric SARS-CoV-2 sequences were representative of those in the community, novel variants were identified. Conclusions: Children can carry high quantities of live, replicating virus, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.30.21258086v1" target="_blank">Virologic features of SARS-CoV-2 infection in children</a>
</div></li>
<li><strong>Why is non-suicidal self-injury more prevalent among women? Mediation and moderation analyses of psychological distress, emotion dysregulation, and impulsivity</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
OBJECTIVE Non-suicidal self-injury (NSSI) appears to be more common among women than men, though the underlying reasons for this remain unclear. In a community sample of young adults (n=996, aged 18-30) assessed during the COVID-19 pandemic, we investigated gendered patterns in NSSI etiology. METHODS Mediation and moderation analyses considered associations between past-year NSSI prevalence, gender, and putative mechanistic variables: self-reported psychological distress (K10), emotion dysregulation (DERS), and impulsivity (UPPS-P). RESULTS Nearly twice as many women as men reported past-year NSSI (14.47% versus 7.78%). Women reported significantly higher psychological distress and significantly lower sensation seeking and positive urgency than men. Psychological distress partially statistically mediated the relationship between gender and past-year NSSI. Gender did not significantly moderate associations between self-reported distress, emotion dysregulation, or impulsivity and past-year NSSI. Past-year NSSI prevalence did not significantly decrease with age and we found no significant age by gender interaction. CONCLUSIONS Greater levels of NSSI in young women are explained by their greater levels of emotional distress. Women do not appear to be more likely than men to report NSSI due to differences in how they manage emotional distress: gender did not moderate the association between psychological distress and past-year NSSI, and there were no gender differences in emotion dysregulation or negative urgency. Furthermore, we show that NSSI remains prevalent beyond adolescence. Early interventions which reduce distress or improve distress tolerance, strengthen emotion regulation skills, and provide alternative coping strategies merit investigation for NSSI.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.01.21258154v1" target="_blank">Why is non-suicidal self-injury more prevalent among women? Mediation and moderation analyses of psychological distress, emotion dysregulation, and impulsivity</a>
</div></li>
<li><strong>Implementing Mandatory Testing and a Public Health Commitment to Control COVID-19 on a College Campus</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic has greatly impacted US colleges and universities. As The George Washington University (GWU), a large urban university, prepared to reopen for the Fall 2020 semester, GWU established protocols to protect the health and wellness of all members of campus community. Reopening efforts included a cadre of COVID-19 surveillance systems including development of a public health COVID-19 laboratory, weekly and symptomatic SARS-CoV-2 testing and daily risk screening and symptom monitoring. Other activities included completion of a mandatory COVID-19 training and influenza vaccination for the on-campus population, quarantining of students returning to campus, campus-focused case investigations and quarantining of suspected close contacts, clinical follow-up of infected persons, and regular communication and monitoring. A smaller on-campus population of 4,435 students, faculty and staff returned to campus with later expansion of testing to accommodate GWU students living in the surrounding area. Between August 17 and December 4, 2020, 38,288 tests were performed; 220 were positive. The surveillance program demonstrated a relatively low positivity rate, with temporal clustering of infected persons mirroring community spread, and little evidence for transmission among the GWU on-campus population. These efforts demonstrate the feasibility of safely partially reopening a large urban college campus by applying core principles of public health surveillance, infectious disease epidemiology, behavioral measures, and increased testing capacity, while continuing to promote educational and research opportunities. GWU will continue to monitor the program as the pandemic evolves and periodically reassess to determine if these strategies will be successful upon a full return to in-person learning.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.30.21258071v1" target="_blank">Implementing Mandatory Testing and a Public Health Commitment to Control COVID-19 on a College Campus</a>
</div></li>
<li><strong>Physical integrity of medical exam gloves with repeated applications of disinfecting agents: evidence for extended use</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The COVID-19 pandemic has created global shortages of personal protective equipment (PPE) such as medical exam gloves, forcing healthcare workers to either forgo or reuse PPE to keep themselves and patients safe from infection. In severely resource-constrained situations, limited cycles of disinfection and extended use of gloves is recommended by the U.S. Centers for Disease Control and Prevention (CDC) to conserve supplies. However, these guidelines are based on limited evidence. Methods: Serial cycles of hand hygiene were performed on gloved hands using alcohol-based hand rub (ABHR) (six and ten cycles), 0.1% sodium hypochlorite (bleach) solution (ten cycles), or soap and water (ten cycles) on three types of latex and three types of nitrile medical exam gloves, purchased in the United States and India. A modified FDA-approved water-leak test was performed to evaluate glove integrity after repeated applications of these disinfecting agents. 80 gloves per disinfectant-glove type combination were tested. Within each glove type the proportion of gloves that failed the water-leak test for each disinfectant was compared to that of the control using a non-inferiority design with a non-inferiority margin of five percentage points. Results were also aggregated by glove material, and combined for overall results. Findings: When aggregated by glove material, the dilute bleach exposure demonstrated the lowest difference in proportion failed between treatment and control arms: -2.5 percentage points (95% CI: -5.3 to 0.3) for nitrile, 0.6 percentage points (95% CI: -2.6 to 3.8) for non-powdered latex. For US-purchased gloves tested with six and ten applications of ABHR, the mean difference in failure risk between treatment and control gloves was within the prespecified non-inferiority margin of five percentage points or less, though some findings were inconclusive because confidence intervals extended beyond the non-inferiority margin. The aggregated difference in failure risk between treatment and control gloves was 3.5 percentage points (0.6 to 6.4) for soap and water, and 2.3 percentage points (-0.5 to 5.0) and 5.0 percentage points (1.8 to 8.2) for 10 and 6 applications of ABHR, respectively. The majority of leaks occurred in the interdigital webs (35%) and on the fingers (34%). Conclusion: Current guidelines do not recommend extended use of a single-use PPE under normal supply conditions. However, our findings indicate that some combinations of glove types and disinfection methods may allow for extended use under crisis conditions. We found that ten applications of dilute bleach solution have the least impact on glove integrity, compared to repeated applications of ABHR and soap and water. However, the majority of glove and exposure combinations were inconclusive with respect to non-inferiority with a 5 percentage point non-inferiority margin. Testing specific glove and disinfectant combinations may be worthwhile for settings facing glove shortages during which extended use is necessary. The modified water-leak testing method used here is a low-resource method that could easily be reproduced in different contexts.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.31.21258129v1" target="_blank">Physical integrity of medical exam gloves with repeated applications of disinfecting agents: evidence for extended use</a>
</div></li>
<li><strong>Development of a rapid SARS-CoV-2 neutralisation test by detecting antibodies that block interaction of spike protein receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2)</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The urgent need for a rapid and reliable Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising antibody detection test compatible with routine clinical laboratory testing currently exists. This is necessary to provide accurate estimates of immunity and to monitor vaccine effectiveness. Utilising Biochip Array Technology (BAT), the Randox SARS-CoV-2 Biochip proxy virus neutralisation test (pVNT) has been developed. Immobilising SARS-CoV-2 Spike RBD on the Biochip surface, innovative assay design enables direct sample addition to the Biochip well without the need for off-board sample pre-incubation step. Results are reported within 1.5 hours and testing is carried out without the prerequisite of live virus or biosafety level 3 (BSL3) laboratory facilities. In this study, assay validation is performed using recombinant antibodies and clinical samples and an excellent correlation against conventional virus neutralisation methods is established (100% clinical specificity and 98% clinical sensitivity). Serial dilution of samples with high neutralising antibody levels demonstrate end-point sample dilutions comparable with those obtained using the SARS-CoV-2 microneutralisation test. Species independent neutralising antibody detection capacity of the SARS-CoV-2 Biochip pVNT is also demonstrated. The findings of this study exemplifying the utility of the SARS-CoV-2 Biochip pVNT as a robust and reliable method for the accurate measurement of neutralising antibodies against SARS-CoV-2 and the availability of this test can now positively impact current testing deficiencies in this area.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.03.21255116v1" target="_blank">Development of a rapid SARS-CoV-2 neutralisation test by detecting antibodies that block interaction of spike protein receptor-binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2)</a>
</div></li>
<li><strong>SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In this investigation we examined the magnitude, breadth, and durability of SARS-CoV-2 specific antibodies in two distinct B-cell compartments: long-lived plasma cell-derived antibodies in the plasma, and peripheral memory B-cells along with their associated antibody profiles elicited after in vitro stimulation. We found that magnitude varied amongst individuals, but was the highest in hospitalized subjects. Variants of concern (VoC) -RBD-reactive antibodies were found in the plasma of 72% of samples in this investigation, and VoC-RBD-reactive memory B-cells were found in all but 1 subject at a single time-point. This finding, that VoC-RBD-reactive MBCs are present in the peripheral blood of all subjects including those that experienced asymptomatic or mild disease, provides a reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to limit disease severity and transmission of variants of concern as they continue to arise and circulate.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.05.28.21258025v1" target="_blank">SARS-CoV-2 specific memory B-cells from individuals with diverse disease severities recognize SARS-CoV-2 variants of concern.</a>
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<li><strong>The COVID-19 pandemic storm in India subsides, but the calm is still far away</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In May 2021, the number of new COVID-19 patients in India began to decline, as predicted by the generalized SIR-model (susceptible-infected-removed). The calculations of the final size of this pandemic wave and its duration probably were too pessimistic. New SIR simulations with the use of fresher datasets are necessary in order to update the predictions and to calculate the difference between the registered (laboratory-confirmed) and real number of cases.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.06.01.21258143v1" target="_blank">The COVID-19 pandemic storm in India subsides, but the calm is still far away</a>
</div></li>
<li><strong>Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan</strong> -
<div>
To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.05.437224v2" target="_blank">Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan</a>
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<li><strong>Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir</strong> -
<div>
Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3CL main protease inhibitor in vitro (IC50 value of 29 uM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3CL main protease inhibitor in vitro, but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication, albeit this was specific to Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our work shows that combining computational and cellular screening is a means to identify existing drugs with repurposing potential as antiviral compounds. Future studies could be aimed at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.03.19.435806v4" target="_blank">Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir</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>Study of Intravenous COVI-MSC for Treatment of COVID-19-Induced Acute Respiratory Distress</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: COVI-MSC;   Drug: Placebo<br/><b>Sponsor</b>:   Sorrento Therapeutics, Inc.<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 of Allogeneic Adipose-Derived Mesenchymal Stem Cells for Treatment of COVID-19 Acute Respiratory Distress</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: COVI-MSC;   Drug: Placebo<br/><b>Sponsor</b>:   Sorrento Therapeutics, Inc.<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 Evaluate a Single Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With COVID-19 (US)</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: COVI-DROPS;   Drug: Placebo<br/><b>Sponsor</b>:   Sorrento Therapeutics, Inc.<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 Evaluate a Single Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With COVID-19 (UK)</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: COVI-DROPS;   Drug: Placebo<br/><b>Sponsor</b>:   Sorrento Therapeutics, Inc.<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 of Allogeneic Adipose-Derived Mesenchymal Stem Cells to Treat Post COVID-19 “Long Haul” Pulmonary Compromise</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: COVI-MSC<br/><b>Sponsor</b>:   Sorrento Therapeutics, Inc.<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>Intramuscular VIR-7831 (Sotrovimab) for Mild/Moderate COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: VIR-7831<br/><b>Sponsors</b>:   Vir Biotechnology, Inc.;   GlaxoSmithKline<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>CISCO-21 Prevent and Treat Long COVID-19.</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Other: Resistance Exercise<br/><b>Sponsors</b>:   NHS Greater Glasgow and Clyde;   University of Glasgow;   Chief Scientist Office of the Scottish Government<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>Leronlimab in Moderatelly Ill Patients With COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Drug: Leronlimab;   Drug: Placebo<br/><b>Sponsors</b>:   Hospital Israelita Albert Einstein;   CytoDyn, Inc.<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>Collecting Respiratory Sound Samples From Corona Patients to Extend the Diagnostic Capability of VOQX Electronic Stethoscope to Diagnose COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Diagnostic Test: Electronic stethoscope<br/><b>Sponsor</b>:   Sanolla<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>To Evaluate the Safety and Efficacy of TQ Formula in Covid-19 Participants</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Drug: Black Seed Oil Cap/Tab<br/><b>Sponsor</b>:   Novatek Pharmaceuticals<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>Leronlimab in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Drug: Leronlimab;   Drug: Placebo<br/><b>Sponsors</b>:   Hospital Israelita Albert Einstein;   CytoDyn, Inc.<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>CRP-Apheresis for Attenuation of Pulmonary, MYocardial and/or Kidney Injury in COvid-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Device: CRP-apheresis<br/><b>Sponsor</b>:   University Hospital, Essen<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 Proof of Concept Study for the DNA Repair Driven by the Mesenchymal Stem Cells in Critical COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Biological: Mesenchymal Stem Cells Transplantation<br/><b>Sponsors</b>:   SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi;   Istinye University;   Liv Hospital (Ulus)<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>Antigen Rapid Test Screening to Prevent SARS-CoV-2 Transmission (COVID-19) at Mass Gathering Events.</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Diagnostic Test: SARS-CoV-2 antigen rapid test<br/><b>Sponsors</b>:   Norwegian Institute of Public Health;   University of Oslo<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>Evaluation of the INDICAID™ COVID-19 Rapid Antigen Test</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Device: Rapid antigen testing and offsite PCR testing;   Device: Rapid antigen testing and onsite PCR testing<br/><b>Sponsor</b>:   University of California, Los Angeles<br/><b>Completed</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>Essential sufficiency of zinc, omega-3 polyunsaturated fatty acids, vitamin D and magnesium for prevention and treatment of COVID-19, diabetes, cardiovascular diseases, lung diseases and cancer</strong> - Despite the development of a number of vaccines for COVID-19, there remains a need for prevention and treatment of the virus SARS-CoV-2 and the ensuing disease COVID-19. This report discusses the key elements of SARS-CoV-2 and COVID-19 that can be readily treated: viral entry, the immune system and inflammation, and the cytokine storm. It is shown that the essential nutrients zinc, ω-3 polyunsaturated fatty acids (PUFAs), vitamin D and magnesium provide the ideal combination for prevention 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>SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment</strong> - Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 infection and cancer: Evidence for and against a role of SARS-CoV-2 in cancer onset</strong> - Despite huge efforts towards understanding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis, little is known about the long-term consequences of the disease. Here, we critically review existing literature about oncogenesis as a potential long-term effect of SARS-CoV-2 infection. Like other viral infections, SARS-CoV-2 may promote cancer onset by inhibiting tumor suppressor genes. We conclude that, although unlikely, such hypothesis cannot be excluded a priori and we…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A transferable deep learning approach to fast screen potential antiviral drugs against SARS-CoV-2</strong> - The COVID-19 pandemic calls for rapid development of effective treatments. Although various drug repurpose approaches have been used to screen the FDA-approved drugs and drug candidates in clinical phases against SARS-CoV-2, the coronavirus that causes this disease, no magic bullets have been found until now. In this study, we used directed message passing neural network to first build a broad-spectrum anti-beta-coronavirus compound prediction model, which gave satisfactory predictions on newly…</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>An Integrated Computational and Experimental Approach to Identifying Inhibitors for SARS-CoV-2 3CL Protease</strong> - The newly evolved SARS-CoV-2 has caused the COVID-19 pandemic, and the SARS-CoV-2 main protease 3CLpro is essential for the rapid replication of the virus. Inhibiting this protease may open an alternative avenue toward therapeutic intervention. In this work, a computational docking approach was developed to identify potential small-molecule inhibitors for SARS-CoV-2 3CLpro. Totally 288 potential hits were identified from a half-million bioactive chemicals via a protein-ligand docking protocol….</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>Marine Sponge is a Promising Natural Source of Anti-SARS-CoV-2 Scaffold</strong> - The current pandemic caused by SARS-CoV2 and named COVID-19 urgent the need for novel lead antiviral drugs. Recently, United States Food and Drug Administration (FDA) approved the use of remdesivir as anti-SARS-CoV-2. Remdesivir is a natural product-inspired nucleoside analogue with significant broad-spectrum antiviral activity. Nucleosides analogues from marine sponge including spongouridine and spongothymidine have been used as lead for the evolutionary synthesis of various antiviral 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>Resource-efficient internally controlled in-house real-time PCR detection of SARS-CoV-2</strong> - CONCLUSION: The presented RKI/ZBS1 SARS-CoV-2 protocol represents a cost-effective alternative in times of shortages when commercially available ready-to-use kits may not be available or affordable.</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 Dual Inhibitory Effect of Anagliptin, Ramipril, and Lisinopril on Angiotensin-Converting Enzyme and DPP-4 Activities</strong> - CONCLUSION: It seems that while most ACE inhibitors cannot affect DPP-4 activity, inhibitors of DPP-4 vary in their effect on ACE activity. The selection of DPP-4 inhibitors under different clinical situations should take into account the action of these drugs on ACE.</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 molecular targets and mechanisms of xuebijing injection for the treatment of COVID-19 via network parmacology and molecular docking</strong> - Xuebijing Injection have been found to improve the clinical symptoms of COVID-19 and alleviate disease severity, but the mechanisms are currently unclear. This study aimed to investigate the potential molecular targets and mechanisms of the Xuebijing injection in treating COVID-19 via network pharmacology and molecular docking analysis. The main active ingredients and therapeutic targets of the Xuebijing injection, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 infection induces the activation of tissue factor-mediated coagulation by activation of acid sphingomyelinase</strong> - SARS-CoV-2 infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. Sphingomyelin (SM) is responsible for maintaining TF in the encrypted state, and hydrolysis of SM by acid sphingomyelinase (ASMase) increases TF activity. ASMase was shown to play a role in virus infection biology. In the present study, we investigated the role of ASMase in SARS-CoV-2 infection-induced…</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>Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization</strong> - Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3…</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>Combination of a Sindbis-SARS-CoV-2 spike vaccine and alphaOX40 antibody elicits protective immunity against SARS-CoV-2 induced disease and potentiates long-term SARS-CoV-2-specific humoral and T-cell immunity</strong> - The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 is a major global public threat. Currently, a worldwide effort has been mounted to generate billions of effective SARS-CoV-2 vaccine doses to immunize the worlds population at record speeds. However, there is still demand for alternative effective vaccines that rapidly confer long-term protection and rely upon cost-effective, easily scaled-up manufacturing. Here, we present a Sindbis alphavirus vector (SV), transiently expressing the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evidence of neutralizing antibodies against SARS-CoV-2 in domestic cats living with owners with a history of COVID-19 in Lima - Peru</strong> - SARS-CoV-2 can infect a variety of wild and domestic animals worldwide. Of these, domestic cats are highly susceptible species and potential viral reservoirs. As such, it is important to investigate disease exposure in areas with active community transmission and high disease prevalence. In this report we demonstrate the presence of serum neutralizing antibodies against the receptor binding-domain (RBD) of the SARS-CoV-2 in cats whose owners had been infected with SARS-CoV-2 in Lima, Peru, using…</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>Single-Molecule Dynamics of SARS-CoV-2 5 Cap Recognition by Human eIF4F</strong> - Coronaviruses initiate translation through recognition of the viral RNA 5 m ⁷ GpppA (m) cap by translation factor eIF4F. eIF4F is a heterotrimeric protein complex with cap-binding, RNA-binding, and RNA helicase activities. Modulating eIF4F function through cellular regulation or small-molecule inhibition impacts coronavirus replication, including for SARS-CoV-2. Translation initiation involves highly coordinated dynamics of translation factors with messenger or viral RNA. However, how the eIF4F…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Nsp14 activates NF-kappaB signaling and induces IL-8 upregulation</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU324964715">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA)</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU323956811">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU323295937">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DEEP LEARNING BASED SYSTEM FOR DETECTION OF COVID-19 DISEASE OF PATIENT AT INFECTION RISK</strong> - The present invention relates to Deep learning based system for detection of covid-19 disease of patient at infection risk. The objective of the present invention is to solve the problems in the prior art related to technologies of detection of covid-19 disease using CT scan image processing. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN324122821">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE</strong> - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN322882412">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU323295498">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种预判重症新冠肺炎COVID-19的标志物及其产品和用途</strong> - 本发明提供了一种预判重症疾病的标志物所述的预判重症疾病的标志物为S100A12序列为SEQ ID NO.1所述的重症疾病为重症新冠肺炎、重症感染中的一种。S100A12基因作为标志物在预判重症疾病时对全血中的S100A12基因的表达水平进行检测即可无需对白细胞进行分离简化检测流程。S100A12的表达水平可以指导感染类疾病包括新冠肺炎重症的预判从而及早施治降低病死率具有很好的临床应用前景。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN325296031">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INDICATING SYSTEM</strong> - A visual indicating system for use with a hospital bed, the hospital bed comprising a bed frame extending between a head end and a foot end of the bed frame, the visual indicating system comprising: an indicating member adapted to be coupled with the bed frame wherein the indicating member comprises an indicia for indicating one of a plurality of pre-determined health conditions.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">FIGURE 1 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU322897510">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU322897928">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种高灵敏SARS-CoV-2中和抗体的检测方法、检测试剂盒</strong> - 本发明公开了一种高灵敏SARSCoV2中和抗体的检测方法、检测试剂盒属于生物医学检测技术领域本发明试剂盒包括层析试纸、卡壳和样本稀释液所述层析试纸包括底板、样品垫、结合垫、NC膜和吸水垫所述NC膜上依次设置有捕获线、检测线和质控线所述捕获线包被有ACE2蛋白所述检测线包被有RBD蛋白所述结合垫设置有RBD蛋白标记物本发明采用阻断法加夹心法原理提高检测中和抗体的灵敏度通过添加捕获线的方式将靶向RBD的非中和抗体提前捕获保证后续通过夹心法检测中和抗体的特异性。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN323798634">link</a></p></li>
</ul>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Peril of Not Vaccinating the World</strong> - Absent a concerted global commitment to vaccine equity, the virus will continue to evolve, and humanity may be consigned to a never-ending pandemic. - <a href="https://www.newyorker.com/tech/annals-of-technology/the-peril-of-not-vaccinating-the-world">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Unique Dangers of the Supreme Courts Decision to Hear a Mississippi Abortion Case</strong> - The most pressing question now may be not whether Roe and Casey can survive but how reproductive rights can be sustained without them. - <a href="https://www.newyorker.com/magazine/2021/06/07/the-unique-dangers-of-the-supreme-courts-decision-to-hear-a-mississippi-abortion-case">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Purpose of Political Correctness</strong> - A conversation with the columnist Nesrine Malik about who makes the changing rules of public speech. - <a href="https://www.newyorker.com/news/q-and-a/the-purpose-of-political-correctness">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protests in Colombia, Elections in Peru, and Other Chaos in the Andes</strong> - Hopes for a sustained democratic rebirth in the seven Andean nations have waned, again. - <a href="https://www.newyorker.com/news/daily-comment/protests-in-colombia-elections-in-peru-and-other-chaos-in-the-andes">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Age of Reopening Anxiety</strong> - What if were scared to go back to normal life? - <a href="https://www.newyorker.com/culture/dept-of-returns/the-age-of-reopening-anxiety">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Mays solidly meh jobs report</strong> -
<figure>
<img alt="A now hiring sign outside of a store." src="https://cdn.vox-cdn.com/thumbor/bFm7FkYU2n3CqKlOuEjAWZ94p4s=/0x0:4539x3404/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/69405651/1321572864.0.jpg"/>
<figcaption>
A pedestrian walks by a “Now Hiring” sign outside of a store in San Francisco on June 3. | Photo by Justin Sullivan/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Love it or hate it, the newest jobs report means were going to have to wait to understand whats happening with work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oHrXXE">
The US economy added 559,000<strong> </strong>jobs in May, according to the <a href="https://www.bls.gov/news.release/pdf/empsit.pdf">monthly report</a> released by the Bureau of Labor Statistics on Friday. Its a bit short of the <a href="https://www.wsj.com/articles/may-jobs-report-unemployment-rate-2021-11622764467">671,000</a><strong> </strong>jobs economists expected. The unemployment rate dropped to 5.8<strong> </strong>percent from 6.1 percent last month. Black unemployment fell to 9.1 percent while white unemployment dipped to 5.1 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yCOvlm">
The numbers this report contains both do and dont matter. It matters in that its a snapshot of what is going on in the labor market during an unprecedented and uncertain economic moment that should <a href="https://www.cnbc.com/2021/06/03/may-jobs-expected-to-be-strong-could-add-to-fed-debate-on-tapering.html">inform policy decisions</a> going forward. It doesnt matter that some of the discourse around workers and the economy has become quite disconnected from any interest in whats actually going on. Whatever the data shows, plenty of people have their talking points set anyway — <a href="https://www.vox.com/policy-and-politics/2021/6/3/22465160/states-ending-unemployment-labor-shortage-texas">and many Republican-led states are acting on them</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O1uiIl">
As highly anticipated as any jobs report can be at the start of the summer, this was a big one, in large part because of the prior report. <a href="https://www.vox.com/policy-and-politics/2021/5/7/22424859/april-jobs-report-economy">The April jobs report</a> released at the end of last month fell well below economists expectations, showing just 266,000 jobs added instead of the expected 1 million. The latest report increased Aprils numbers slightly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ISbiYA">
Mays report was neither stellar nor disastrous. “This numbers OK. We wanted it to be higher,” said Austan Goolsbee, former chair of the Council of Economic Advisers under President Obama, in an appearance on CNBC Friday. He added that its “weird” to view adding over a half-million jobs in a single month as only modestly better, given that in normal times, such a figure would be terrific. But these arent normal times: The US is still digging itself out of a pandemic-size hole and is still 7 million jobs short of where it was when the virus hit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PHbIrq">
Jobs picked up particularly in leisure and hospitality, education, and health care. Construction shed jobs for the second consecutive month. The number of people who have been out of work for over half a year <a href="https://twitter.com/bcheungz/status/1400795281751412738">fell significantly</a>, though its unclear if that means those people went back to work or stopped looking for jobs. The labor force participation rate has been in about the same range since June 2020.
</p>
<h3 id="G47vJY">
The path back to “normal” is going to be rocky
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V8YBPN">
The word “unprecedented” gets thrown a lot lately but for good reason: We really are in some pretty uncharted territory. The US economy is emerging from a global pandemic that cost millions of jobs and has distorted the economy in all sorts of ways. From computer chips to cars to lumber, <a href="https://www.businessinsider.com/why-supply-shortages-economy-inventory-chips-lumber-cars-toilet-paper-2021-5">it feels like shortages are everywhere</a>. Theres some concern about inflation, but the answers to whether price changes are temporary or permanent, something to worry about or something to consider, are that <a href="https://www.vox.com/policy-and-politics/22435400/economy-unemployment-inflation">nobody really knows</a>. (The Federal Reserve and the White House hold that its temporary.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k6oKPi">
Any single point of data says something, but it doesnt paint a complete picture. As J.W. Mason and Mike Konczal of the progressive think tank the Roosevelt Institute <a href="https://rooseveltinstitute.org/2021/06/03/zoom-out-keeping-the-latest-jobs-numbers-in-perspective/">wrote</a> ahead of the May report, the numbers are “noisy,” and its important not to put too much weight on a single month. Whats important is to look at the trend. And what the trend shows is that in the labor market, jobs are coming back. Maybe not as fast as the most optimistic people thought they would, but theyre coming.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jDMETI">
“The big picture over the past year is a rapid recovery of employment as pandemic-related restrictions have been lifted,” Mason and Konczal wrote. “This is very different from the last several recessions, which were followed by long jobless recoveries, with employment continuing to fall for months or even years after economic growth resumed.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nrIJFI">
To be sure, Fridays numbers are unlikely to change some of the political narratives on the right and on the left around the economy. Especially given that they didnt really signal anything strongly positive or negative. Democrats are going to keep insisting that their economic agenda needs time to work and that the economy is coming back, and theyll continue making the case for <a href="https://www.vox.com/2021/4/2/22364100/biden-human-infrastructure-jobs-plan">infrastructure proposals</a>. Republicans, meanwhile, will make their arguments, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CwxQer">
Many Republicans and business groups insist that generous unemployment insurance is a major hindrance to the recovery, arguing that people are sitting out of the workforce because theyre making more money staying home and collecting the extra $300 a week in pandemic benefits put in place by Congress. Half of states, all Republican-led, <a href="https://www.vox.com/policy-and-politics/2021/6/3/22465160/states-ending-unemployment-labor-shortage-texas">have decided to shut off unemployment benefits early</a> over the coming weeks. They all made that decision <em>before </em>the May jobs report, a move that <a href="https://twitter.com/byHeatherLong/status/1397641138488725504?ref_src=twsrc%5Etfw%7Ctwcamp%5Etweetembed%7Ctwterm%5E1397641138488725504%7Ctwgr%5E%7Ctwcon%5Es1_&amp;ref_url=https%3A%2F%2Fwww.vox.com%2Fpolicy-and-politics%2F2021%2F6%2F3%2F22465160%2Fstates-ending-unemployment-labor-shortage-texas">even JPMorgans economists</a> said was political, not economic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b0DWNH">
The evidence suggests that extra unemployment might deter a small sliver of workers but not the vast majority. A <a href="https://www.frbsf.org/economic-research/files/wp2021-13.pdf">working paper</a> out of the Federal Reserve Bank of San Francisco estimated that if seven of 28 workers receive job offers they would normally accept in the early months of this year, just one would say no in order to hold on to the $300.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iTjTBR">
There are also policy ideas floating around regarding how to get people back to work, <a href="https://www.wsj.com/articles/labor-shortage-draws-attention-of-u-s-lawmakers-11622712602">such as federally funded hiring bonuses and tax credits for employers</a>, to try to speed things up. Its also worth noting that in May leisure and hospitality — one of the hardest-hit sectors of the pandemic — added nearly 300,000 jobs, suggesting the service sector <a href="https://twitter.com/hshierholz/status/1400798711488204803?s=20">isnt in some enormous labor supply crisis</a>.
</p>
<div id="Tx8oS7">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
Hard to argue that restaurants cant hire workers when &gt;50% of added jobs in a single month are in leisure and hospitality. Compared to construction and manufacturing numbers, seems much more like a supply shortage than a worker shortage.
</p>
— Elizabeth Pancotti (<span class="citation" data-cites="ENPancotti">@ENPancotti</span>) <a href="https://twitter.com/ENPancotti/status/1400795717615108096?ref_src=twsrc%5Etfw">June 4, 2021</a>
</blockquote></div></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Vb4vK">
There are plenty of other factors influencing work right now: People are still nervous about the virus, parents lack access to child care, or people are waiting to see if they can get a job at their skill level. A massage therapist who shut down her business at the start of the pandemic<strong> </strong>told me<strong> </strong>she doesnt want to work for minimum wage at McDonalds; she wants to reopen her business.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="u4VK6j">
Some are also trying to find something better. <a href="https://www.washingtonpost.com/business/2021/05/07/jobs-report-labor-shortage-analysis/">Heather Long at the Washington Post</a> recently wrote that we might be in the midst of a “great reassessment of work in America,” a moment where people who worked low-paying, thankless jobs before the pandemic are reconsidering what they might want to do. US businesses have sort of assumed there would always be an <a href="https://twitter.com/thestalwart/status/1391707291863420933?lang=en">endless pool of low-wage labor</a>, and the economy might work differently if thats not the case.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kz8ZTn">
Fridays numbers suggest the economy is improving, and people are headed back to work. But they also exemplify that the puzzle of the US economy is going to be a bit challenging to put back together, and we dont know where all the pieces fit anymore.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NBq4Bj">
</p>
<ul>
<li><strong>A weed dealer in NYC on how legalization could affect his business</strong> -
<figure>
<img alt="Cannabis and a rolled joint lie on a table." src="https://cdn.vox-cdn.com/thumbor/1tsJmqJRiFy2WsU2vaLeC8TpxBc=/682x0:6442x4320/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/69405463/GettyImages_1161409422.0.jpg"/>
<figcaption>
Will corporate cannabis threaten the livelihoods of independent dealers? | Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Weed dealers might have the opportunity to go legit. Should they?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RIyEGg">
Jeff, a weed dealer whos been active in New York for six years, read the news during a morning bathroom trip. Suddenly, it was a brand new world. On April 30, Gov. Andrew Cuomo signed a bill that made the production, possession, and use of recreational cannabis legal in New York City. By 2022, the <a href="https://www.nytimes.com/article/new-york-marijuana-legalization-facts.html">New York Times speculates</a>, dispensaries will begin to propagate throughout the metro area, ushering in the downfall of one of the last major dominoes in prohibition. New York joins 22 other states that have fully authorized marijuana, and currently there are only six states — Idaho, Wyoming, Kansas, Tennessee, Alabama, and South Carolina — that maintain an outright ban on all CBD or THC commodities, medicinal or otherwise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Fh5uUo">
Jeff, who is being referred to by a pseudonym for this story to protect his privacy, knows that his job doesnt carry nearly the same risks as some of his peers in the field. He is white, and tells me that law enforcement is far more likely to be lenient on him and his business than other dealers in more surveilled neighborhoods in the city. <a href="https://www.aclu.org/gallery/marijuana-arrests-numbers">The American Civil Liberties Union reports</a> that Black Americans are nearly four times as likely to be arrested on marijuana charges as white Americans. But the prohibition rollback still has Jeff, and many of his friends, considering all the anxieties and possibilities of the future. Could he go legit? Should he go legit?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UKrOpQ">
Maybe he has a real chance to break ground on his very own cannabis delivery app or a brick-and-mortar emporium, and to reach a much higher economic ceiling in the process. Or maybe instead, a swath of moneyed investors will end up descending on the city to lobby the state assembly, and will dump a bureaus worth of paperwork on top of the independent dealers. If the financialized weed sector slowly squeezes out the, uh, “mom-and-pop shops”? Everything could change.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="emKn4e">
Jeff learned everything about his business from his mother, whos spent her career running a small wine retailer. Shes nurtured great relationships with vineyards and her clientele, while building a true community around her storefront. The same mindset can be easily applied to his work, Jeff tells me. Weed is an industry about people and connections, just as much as its about the product. We talked about how that system is threatened by private equity, the dysfunctionality of the underground trade, and how much longer he sees himself in the cannabis hustle.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OvaXyr">
<strong>So how long have you been selling weed?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WyWoUb">
I got into the game when I was 13 or 14, and I moved to New York in 2013. For the first year or two I wasnt really dealing, but I got back in around 2015 for a number of different cannabis delivery services. But for the past few years, Ive been working independently.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9VsX3x">
<strong>Was it hard breaking into the industry up here in New York?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VnmxmO">
In the city, you can get anything you want. The hardest thing for me up here is filling out your clientele. Anyone with five grand in their pocket can start dealing. Its not hard to do. Its about how you want to cultivate your business. But you cant advertise yourself — not until recently, I guess, on Craigslist. But accessibility has never been an issue.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qNmdVd">
<strong>When the news broke, did you have a clear idea of what exactly was legal in the city? Weed legalization can be pretty confusing sometimes.</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g0tXAZ">
Its changed a lot. Theyll put one thing on the docket, and people will hear all these rumors, and thats not what ultimately passes. I dont think the general public has easy access to that kind of information. I think thats intentional, too. I dont think the police department wants people to know all the rules. They like that gray area. But I encourage people to go on the NYPD website and read what youre legally allowed to carry and where youre allowed to smoke when the new law is passed.
</p>
<div class="c-float-right">
<div id="eRntoM">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uA6Ygx">
<strong>From your conversation with other people in the business, whats the consensus opinion about it?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zJPj0o">
Its definitely long overdue. I have a lot of friends whove had bad encounters with the law. It depends on the cop you get, or the judge, and all sorts of factors. But if youre dealing with strictly cannabis charges, its usually just a slap on the wrist. If youre high enough up, you dont worry about the legal ramifications as much. You have a lawyer or a retainer. A lot of these guys have been in the business for 20 or 30 years. They know what theyre doing. That isnt the worry. Instead, people are talking about the capital. You have customers who are curious. They want to go into dispensaries and see the options. Theres a novelty of going into a brick-and-mortar location and purchasing something thats been so taboo for so long. But I did that in California, and when I got back in the car, I was like, “How the hell did I spend that much money?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iK6kc4">
A lot of my business partners, and the people I work with, weve developed our own customers. Weve developed our own family and relationships with them. Think of restaurants — thats how I like to compare it. In New York, you can have a block with five or six restaurants, and some make it and some dont. How do you make it? Whats your niche, whos your clientele? But the shops that are gonna open might be able to go for five or six years without making a profit because they have the investors that are willing to fund that. Itll be huge for tourism, but I think if you live in New York, youre gonna want deals, youre gonna want to establish relationships, and youre not going to want to go into a Circuit City-type dispensary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fwrgC9">
<strong>Have you thought about ramping up your own advertising efforts? Would you be open to posting on Craigslist?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jnutkZ">
Personally, Im not interested in expanding and taking on new clients. Ive got a close-knit network, and a bit of a waiting list. Its not something that Im worried about. But Ive given it a lot of thought. I know of 15 different delivery services operating in Brooklyn right now, and they all talk to each other because they like to source from the same growers. If someone runs out of a certain strain … again, back to my restaurant metaphor. If the restaurant across the street has their ice machine break, and they run over to you to borrow a couple buckets of ice, youre not going to say no. Its better business for you later on when your ice machine breaks. When I think about those guys trying to expand, all of the money is going to need to go into app design. Youll need a team. And if you dont have some serious investors backing you, youre looking at a lot of money.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="odDhiB">
<strong>Could you see that for yourself? Now that prohibition is over, could you see yourself growing your business into an app-based, or even brick-and-mortar-based, legit business? Or are you happy with how things are now?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tXnOq8">
Ive gotten into the dirty side of the business. It was an illegal infrastructure, so theres no checks and balances. Ive had guys steal $30,000 from me. Ive been in debt. One business was using my credit line and said they werent paying the bill. What do you do? Youre not gonna call the cops. Now that things are becoming legal, there are still just as many ugly demons that will raise their heads.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kMfA53">
In an ideal world, where I could put together my dream team of people, Id give it a shot. But the way Ive seen things go with these Fortune 500 companies, something toxic is going to get involved.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UK4Z67">
My mom runs a wine shop. Shes sold wine for 30 years. I base my entire business model on what she taught me. She worked with wine wholesalers for the first 15 years, and she made a lot of awesome connections with vineyard owners. With her own private enterprise and those connections, she was able to beat Costco or Total Wines or whatever. Thats what Im going to be able to do. Ive got an awesome clientele base, and connections to my growers. Its a mom-and-pop shop. Lets keep America authentic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Gaove">
<strong>Do you expect to be in cannabis long term?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0IBrzv">
The world is all opportunity. I didnt see myself staying in it this long. I use cannabis. I medicate for anxiety. As soon as I had access to cannabis and could smoke independently of the confines of whats taboo, it really helped me a lot. Ive made a lot of friends along the way. A good percentage of my customers are hospital patients or the elderly. It really does help a lot of people, and theres not a lot of access to it — even medicinally. I never intend to stop helping those close to me. Eventually, Id prefer to set up something that can stay in place and run itself. But at the end of the day, its a job. You retire. Everyone has an endgame in sight.
</p></li>
<li><strong>The fastest way to get more people to buy electric vehicles</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/lEnHWRhVTg_glgEB1GMjE-UzqVY=/619x0:5568x3712/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/69405177/1232464562.0.jpg"/>
<figcaption>
A person charges an electric vehicle at an EVgo charging station at Union Station in Washington on April 22, 2021. | Caroline Brehman/CQ-Roll Call, Inc via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Americas EV charging station infrastructure is woefully lacking.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jgTxJU">
Whether the United States can get to net-zero emissions by 2050 hinges hugely on our love of cars: Theyre the dominant mode of transportation in America — ridership on trains, buses, and other public transit pales in comparison.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3QuNAO">
Other transportation options are limited, and cars are ingrained in American culture. This makes switching to electric vehicles an attractive way to decarbonize.<strong> </strong>But in order to encourage more people to buy electric vehicles (EVs), the US needs a better charging station infrastructure.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cHtPIn">
That is a key part of<strong> </strong>President Joe Bidens <a href="https://www.whitehouse.gov/briefing-room/statements-releases/2021/03/31/fact-sheet-the-american-jobs-plan/">American Jobs Plan</a>, which proposes spending $174 billion on EVs, a sum that would boost supply chains for automakers, help subsidize the cost of cars for American drivers, and dramatically scale up the number of public electric vehicle charging stations along the nations roadways.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ToToqR">
There are currently about <a href="https://afdc.energy.gov/fuels/electricity_locations.html#/find/nearest?fuel=ELEC&amp;country=US">42,490 public charging EV stations</a> in the US, counting Level 2 chargers (taking about an hour of charging for 10 to 20 miles of range), and DC Fast chargers (taking about 20 minutes of charging for 60 to 80 miles of range). In comparison, there are about 115,000 gas stations in the US, most of which have multiple pumps.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G7afyf">
Bidens plan would increase the number of charging stations more than tenfold by establishing grant and incentive programs for state and local governments and private companies to build 500,000 charging stations around Americas highways and in hard-to-reach communities by the year 2030. With a number of US carmakers pledging to go totally electric by 2035, that buildout could make EV charging ports as ubiquitous as gas pumps.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BF1bRm">
At the moment, there arent enough reliable charging stations to accommodate a sudden increase in EV usage. About 627,000 plug-in EVs were bought in 2019 and 2020, and demand is expected to increase — especially as carmakers phase out gas-powered cars.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h9xPaH">
“Were so much better off than we were even five years ago … but we still have a huge gap,” a Biden administration official told Vox. “This is an essential piece of the shift to EVs and its not going to happen on its own.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KXy8Gf">
Transitioning American car drivers to electric vehicles is a crucial piece of the Biden administrations overall plan to get the United States on a path to net-zero emissions by 2050, as well as its <a href="https://www.vox.com/22397364/earth-day-us-climate-change-summit-biden-john-kerry-commitment-2030-zero-emissions">more immediate goal</a> of<strong> </strong>limiting catastrophic climate change by<strong> </strong>cutting greenhouse gas emissions by 50 to 52 percent relative to 2005 levels by 2030.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="H3wdYY">
The US is the second-largest greenhouse gas emitter, after China, and cars are a big part of that. Transportation emissions account for <a href="https://www.epa.gov/ghgemissions/sources-greenhouse-gas-emissions">29 percent of total US greenhouse gas emissions</a> (more than the electricity sector and industry), and light-duty vehicles like cars account for the vast majority of transportation emissions — <a href="https://ourworldindata.org/co2-emissions-from-transport#:~:text=Road%20travel%20accounts%20for%20three,comes%20from%20trucks%20carrying%20freight.&amp;text=International%20shipping%20contributes%20a%20similar%20amount%2C%20at%2010.6%25.">close to 60 percent</a>, as of 2018.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gk8bqt">
Getting EV charging stations to be as ubiquitous as gas stations would help change that, but its just one piece of the puzzle. Even more important is increasing the availability and access for home and work charging stations — where experts believe most people will ultimately charge their cars.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hR8i98">
“Home charging is the most important; thats where the highest number of charging [stations] will be needed,” said Scott Hardman, a researcher studying hybrids and EVs at the University of California Davis Institute of Transportation Studies. “Its the cheapest; its the most convenient.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QK1pHl">
In addition to building public charging stations, the Biden administration plans to propose expanding tax credits for private infrastructure for home EV chargers, giving people an incentive to install them. This is key, experts told me; making charging station access equitable — ensuring they are affordable<strong> </strong>and accessible<strong> </strong>— is as important as increasing the total number of charging stations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HomOse">
Both are doable but will take serious government investment. But as with the rest of Bidens agenda, the fate of this proposed network of charging stations could hinge on the fate of bipartisan infrastructure negotiations and whether the president decides to pass his plan with only Democratic votes.
</p>
<h3 id="LesPvw">
A charging station is not the same as a gas station
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9mlcNO">
Because gas stations are the most common method of refueling cars in the United States, powering up electric vehicles might call to mind clusters of charging stations next to convenience stores next to a highway or road.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8xrai3">
But the two modes of powering up are fundamentally different. For one thing, driving into a gas station, filling up, and driving out typically takes just a few minutes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oim3yn">
The fastest EV charging stations — like DC Fast — on the other hand, take up to 20 minutes to charge enough to power the vehicle to a 60- to 80-mile range. Some state and city planners and EV experts are working on putting charging stations outside of restaurants, grocery stores, and shops, so that people can go off and eat a meal or shop while their car is refueling.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kYQB6X">
“Most charging, we would hope and expect, is happening while people are doing something else,” said Eric Wood, a research engineer at the National Renewable Energy Laboratorys Center for Integrated Mobility Sciences. “The idea that charging is happening slowly can be convenient for the driver as well as the grid.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iNeqIG">
More rapid charging technology is being developed, but the vast majority of available public charging stations currently in the US are the more sluggish Level 2 chargers, which require far more time to get to a full charge. There are just <a href="https://afdc.energy.gov/fuels/electricity_locations.html#/find/nearest?fuel=ELEC&amp;country=US&amp;ev_levels=dc_fast">5,141 DC Fast chargers in the US</a>, with big gaps in parts of the Midwest and Mountain West, according to the Energy Departments <a href="https://afdc.energy.gov/fuels/electricity_locations.html#/find/nearest?fuel=ELEC&amp;country=US&amp;ev_levels=dc_fast">map of charging stations</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zv5l0I">
“If your batterys down to 20 percent, youre going to have to stay plugged in for hours and hours,” said Ellen Hughes-Cromwick, the former chief global economist at Ford Motor Company, now a senior resident fellow at Third Way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hu9i5I">
The lack of charging infrastructure can mean headaches for drivers going on road trips, who need to plan their route to hit available charging stations. An <a href="https://go.redirectingat.com?id=66960X1516588&amp;xs=1&amp;url=https%3A%2F%2Ftoday.yougov.com%2Ftopics%2Fconsumer%2Farticles-reports%2F2020%2F10%2F23%2Fwhats-stopping-americans-buying-electric-cars&amp;referrer=vox.com&amp;sref=https%3A%2F%2Fwww.vox.com%2F22463219%2Felectric-vehicles-charging-station-infrastructure" rel="sponsored nofollow noopener" target="_blank">October 2020 poll from YouGov</a> found that charging time, hassle of charging, and cost of charging at home were all top reasons buyers who were looking for a new car werent considering an electric vehicle.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DsrJym">
As climate expert and activist Bill McKibben recently found while on a road trip from Vermont to Boston, if youre in need of some juice and another driver is already using a public charger, you could be in for a nerve-wracking drive home.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aIUhSb">
“The plug was in use once more, so I swallowed hard, did a little math, and drove on, arriving home with red lights flashing on the dashboard and a display indicating that my range was down to two miles,” McKibben <a href="https://www.newyorker.com/news/daily-comment/your-electric-vehicle-cant-get-there-from-here-at-least-not-without-a-charge">recently wrote in the New Yorker</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8WMgpi">
Competition and congestion around EV charging stations has gotten particularly bad in cities like San Francisco, where theres a growing number of electric car drivers. (The places with the <a href="https://afdc.energy.gov/files/u/publication/electric_vehicle_charging_infrastructure_trends_third_quarter_2020.pdf">highest density of charging stations</a> per 100,000 people are Vermont, California, Colorado, Hawaii, and Washington, DC.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uGOSBA">
“In San Francisco, theres a huge congestion problem, and there are simply not enough plugs for EVs in that metro area,” said Hughes-Cromwick. “There is congestion in areas where EV demand has flourished. If we dont get going on this, we will have roadblocks, especially for longer trips.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PUPNEv">
Another complication is that some electric car companies like Tesla — frustrated at the lack of investment in EV charging stations — have built out their own networks of superchargers that are only compatible with their cars. So if a driver of a Chevy Bolt or Nissan Leaf is running low on battery and the only charger around is a Tesla, theyre out of luck.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ESdoV8">
The White House official I spoke to told me that any federal investment in EV charging stations will require universal chargers that can work with the full range of electric vehicles on the market.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XmSpZX">
“Its been incredibly important for Tesla to have done that buildout, but were thinking about this investment as chargers that can support any vehicle,” the official said. “Its very clear it needs to be accessible for any driver of an EV.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="njWGCC">
That accessibility — along with the sheer number the White House hopes will be built — ought to, in theory, eliminate lines and congestion around chargers, while also ensuring charging is affordable. One thing it wont do is solve the problem of charging times, but charging companies are developing faster chargers, and the second part of the White Houses proposal hopes to address that issue as well.
</p>
<h3 id="87ogDF">
Home charging is really important
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9OxVXP">
The most common and easiest way to charge an electric car doesnt necessarily happen alongside a roadway; an at-home charging station “ends up for a lot of Americans being the only place theyd need to charge on a regular basis,” said Wood.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OfUOz0">
Home charging is especially convenient for people who primarily use their electric car for short trips around their town or city; especially if a car has a 200- to 300-mile range, that could get them a couple of days or weeks on a single charge. This is important because Americans do the vast majority of their driving for short trips: Nearly <a href="https://nhts.ornl.gov/vehicle-trips">77 percent of vehicles</a> drove distances of 10 miles or less per trip, according to the 2017 National Household Travel Survey (the most recent available). In other words, its <a href="https://nhts.ornl.gov/vehicle-trips">far more often</a> that were driving home, to work, or to run an errand than going on a long road trip.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zvstY1">
Home charging may be the most convenient, but home charging is also typically relegated to higher-income people who can actually afford to charge from within their home. For lower-income people who dont have a garage or a dedicated parking spot with easy access to a charger, the logistics of charging at home become much more complicated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j2z6I3">
Just as policymakers are figuring out how to make EVs cheaper, experts told me that any expansion of charging stations needs to focus on how to make home charging more equitable and accessible for middle- and lower-income people.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IoGfXi">
One option is getting more charging stations on residential streets, powered by the same electrical lines for street lights. This was <a href="https://www.fleeteurope.com/en/new-energies/europe/analysis/1300-street-lights-converted-ev-chargers-london?a=JMA06&amp;t%5B0%5D=Siemens&amp;t%5B1%5D=Ubitricity&amp;t%5B2%5D=electric%20vehicle&amp;t%5B3%5D=charging%20infrastructure&amp;t%5B4%5D=London&amp;curl=1#:~:text=A%20major%20residential%20road%20in,not%20have%20off%2Dstreet%20parking.">piloted in London</a> in 2020, with a number of street lights converted. But this is a relatively small project, and it hasnt been adopted widely yet in other countries. Another option is increasing the number of charging stations at peoples workplaces, giving them another place to charge while their car is parked for hours.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gHzfcn">
“Everyone parks their car somewhere at night; thats where we need to get the charging to,” said Hardman. “We have to be careful its not just the privileged households that get the lower running costs.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DWMZVw">
The Biden administration official told Vox that the presidents infrastructure plan is proposing an extended or expanded tax credit to expand private infrastructure like charging stations at home.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q1Lt4V">
“Theres an outsize public role for that infrastructure,” the official said. “You have to have a mix of home charging, workplace, and public.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3BAoXD">
Overall, Bidens goal is to make EVs more attractive in large part by making charging more convenient. But it will take significant government investment for Bidens desired 500,000-EV network to become a reality.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x3cPtA">
Getting a bipartisan group of lawmakers — particularly in the Senate, where Democrats need 10 Republican votes to pass legislation under normal rules — to agree to spend nearly $200 billion on EVs wont be easy, as prolonged infrastructure negotiations have shown. But the US will need to make this change in order to meet its climate commitments, and to decrease its contribution to climate change.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rlhle8">
<strong> </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K4KwCj">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uDtZvT">
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</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>Olympic 100m hurdles champ Brianna McNeal banned for doping violation: AIU</strong> - McNeal, 29, can still take part in the US trials for the Tokyo Olympics later this month.</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>Usman Khawaja working with Cricket Australia to ensure more South Asian representation in Australian cricket</strong> - When he made his international debut at the SCG, his home ground, in an Ashes Test in 2011, the top-order batter became the first Muslim and the first player of Pakistani descent to represent Australia</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>Tennis player arrested in Paris on suspicion of match-fixing</strong> - French newspaper Le Parisien reported that the player is Yana Sizikova of Russia.</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>India, NZ pretty even but Black Caps might have edge in WTC final because of conditions, says Lee</strong> - India and New Zealand will fight it out from June 18 in the marquee clash for which the Indians landed in England on Thursday</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>Bindra congratulates Tokyo-bound athletes for “exceptional” feat amid the pandemic</strong> - So far, 100 athletes have qualified for the Tokyo Games, including 56 men and 44 women.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</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>Hydrographic survey ship INS Sandhayak decommissioned</strong> - It was the first of its class indigenously designed and built.</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>Cong. petitions President seeking free vaccination for all</strong> - The Karnataka Pradesh Congress Committee on Friday made a representation to President Ram Nath Kovind through Governor Vajubhai Vala to demand free un</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>Maharashtra caps rates for black fungus treatment</strong> - Different rates set for rural and urban areas to ensure affordable care</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>NIOS cancels Class 12 exams in view of COVID-19</strong> - Students who are not satisfied with the assessment will be given the option to appear in a public examination.</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>B.1.617 variant of SARS-CoV-2 drove surge in the COVID-19 cases in last 2 months</strong> - According to INSACOG, the B.1.1.7 lineage of the virus, which was first identified in the United Kingdom, is declining in proportion across India in the last one and half month</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</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>Roman Protasevich: Belarus journalists confession was forced - family says</strong> - In a tearful interview, Roman Protasevich appeared to admit to organising anti-government protests.</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>Brexit: UK announces trade deal with Norway, Iceland and Liechtenstein</strong> - Liechtenstein - another non-EU country - is also included in the post-Brexit deal.</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>Top German cleric asks to quit over Church sex abuse failures</strong> - Top Catholic cleric Reinhard Marx calls sexual abuse by Church officials “a catastrophe”.</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>French Open: Yana Sizikova arrested amid match-fixing inquiry</strong> - Russias Yana Sizikova is detained as part of an investigation into fixing at the French Open.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Covid-19: Portugal queries amber status as UK tightens rules</strong> - Robert Jenrick says the government is being “cautious” to protect the UKs progress against Covid.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ransomware will now get priority treatment at the Justice Department</strong> - Directive comes as ransomware is exposing the fragility of critical supply chains. - <a href="https://arstechnica.com/?p=1769834">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rocket Report: SpaceX breaks streak of used launches, FAA clears Electron</strong> - “Listen to customers, dont listen to pundits and market analysts.” - <a href="https://arstechnica.com/?p=1769761">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What to expect from WWDC 2021: iOS 15, M2, and more</strong> - Software is usually the focus, but well probably see a new Mac chip. - <a href="https://arstechnica.com/?p=1769720">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Researchers rewire the genetics of E. coli, make it virus-proof</strong> - A revised genetic code is a pathway for bacteria to do things that seem unnatural. - <a href="https://arstechnica.com/?p=1769691">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supreme Court reins in definition of crime under controversial hacking law</strong> - Justices reject US govs broad interpretation of Computer Fraud and Abuse Act. - <a href="https://arstechnica.com/?p=1769621">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>Professor X asks a girl, “what is your mutant power?”</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Girl replies: “I can guess how many pulls to turn a ceiling fan off on the first try!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She points up and says: “3 pulls”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Professor X stands up and pulls 3 times. After the third pull the fan turns off.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Professor X: “Yeah thats cool and all, but not really a super power…”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Girl: “Yeah I was jut kidding, I can heal paraplegics”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Professor X, still standing: “Oh my god”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Blorb-Man"> /u/Blorb-Man </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nrp0xt/professor_x_asks_a_girl_what_is_your_mutant_power/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nrp0xt/professor_x_asks_a_girl_what_is_your_mutant_power/">[comments]</a></span></p></li>
<li><strong>A man loses his hat and decides the easiest way to get another one is to steal it.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He goes to the church cloakroom to get a hat. A sermon about the Ten Commandments was going on. The man pauses to listen and then changes his mind. On nearing the exit, he runs into the pastor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He says, “I came here with sin in my heart. I must say, you saved me from crime.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The pastor replies, “Thats nice to hear. What sin were you about to commit?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man replies, “I came here to steal a hat, but your sermon made me change my mind.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The priest says, “May I know what part of my sermon made you see the error of your ways?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man replies, “When you reached the Thou shalt not commit adultery part, I suddenly remembered where I left my hat.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/SleazySerpent1469"> /u/SleazySerpent1469 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nryulf/a_man_loses_his_hat_and_decides_the_easiest_way/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nryulf/a_man_loses_his_hat_and_decides_the_easiest_way/">[comments]</a></span></p></li>
<li><strong>An elderly man is stopped by the police around 2 a.m. and is asked where he is going at this time of night. The man replies, “I am on my way to a lecture about alcohol abuse and the effects it has on the human body, as well as smoking and staying out late.”</strong> - <!-- SC_OFF -->
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The officer then asks, “Really? Who is giving that lecture at this time of night?” The man replies, “That would be my wife.”
</p>
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<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/since1700"> /u/since1700 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nrc979/an_elderly_man_is_stopped_by_the_police_around_2/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nrc979/an_elderly_man_is_stopped_by_the_police_around_2/">[comments]</a></span></p></li>
<li><strong>3 guys bet on who can make their wife scream more from sex</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They make the bet and decide to all go home and have sex with their wives and compare results the next day.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Next day comes along and they meet to discuss. Guy #1 says “I fucked my wife so hard, she was screaming for like 20 minutes.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Guy #2 says “thats nothing. I fucked my wife with a dildo in her ass at the same time and she was screaming for an hour!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Guy #3 says “amateurs! I fucked my wife for 15 seconds, came on the curtains, and shes still screaming at me!”
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/heavenkiller"> /u/heavenkiller </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nrpaum/3_guys_bet_on_who_can_make_their_wife_scream_more/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nrpaum/3_guys_bet_on_who_can_make_their_wife_scream_more/">[comments]</a></span></p></li>
<li><strong>2 married ladies are having lunch in a coffee shop…</strong> - <!-- SC_OFF -->
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One lady whispers Im getting a boob job
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2nd lady: Thats nothing, Im getting my assh*le bleached
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1st lady says: Really? I cant imagine your husband as a blonde
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Altar-83"> /u/Altar-83 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/nrxw6v/2_married_ladies_are_having_lunch_in_a_coffee_shop/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/nrxw6v/2_married_ladies_are_having_lunch_in_a_coffee_shop/">[comments]</a></span></p></li>
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