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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>The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan</strong> -
<div>
The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.31.506023v1" target="_blank">The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan</a>
</div></li>
<li><strong>Prophylactic Treatment of COVID-19 in Care Homes Trial (PROTECT-CH)</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Coronavirus disease 2019 (COVID-19) is associated with significant mortality and morbidity in care homes. Novel or repurposed antiviral drugs may reduce infection and disease severity through reducing viral replication and inflammation. Objective: To compare the safety and efficacy of antiviral agents (ciclesonide, niclosamide) for preventing SARS-CoV-2 infection and COVID-19 severity in care home residents. Design: Cluster-randomised open-label blinded endpoint platform clinical trial testing antiviral agents in a post-exposure prophylaxis paradigm. Setting: Care homes across all four United Kingdom member countries. Participants: Care home residents 65 years of age or older. Interventions: Care homes were to be allocated at random by computer to 42 days of antiviral agent plus standard care versus standard of care and followed for 60 days after randomisation. Main outcome measures: The primary four-level ordered categorical outcome with participants classified according to the most serious of all-cause mortality, all-cause hospitalisation, SARS-CoV-2 infection and no infection. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included the components of the primary outcome and transmission. Results: Delays in contracting between NIHR and the manufacturers of potential antiviral agents significantly delayed any potential start date. Having set up the trial (protocol, approvals, insurance, website, database, routine data algorithms, training materials), the trial was stopped in September 2021 prior to contracting of care homes and general practitioners in view of the success of vaccination in care homes with significantly reduced infections, hospitalisations and deaths. As a result, the sample size target (based on COVID-19 rates and deaths occurring in February-June 2020) became unfeasible. Limitations: Care home residents were not approached about the trial and so were not consented and did not receive treatment. Hence, the feasibility of screening, consent, treatment and data acquisition, and potential benefit of post exposure prophylaxis were never tested. Further, contracting between the University of Nottingham and the PIs, GPs and care homes was not completed, so the feasibility of contracting with all the different groups at the scale needed was not tested. Conclusions: The role of post exposure prophylaxis of COVID-19 in care home residents was not tested because of changes in COVID-19 incidence, prevalence and virulence as a consequence of the vaccination programme that rendered the study unfeasible. Significant progress was made in describing and developing the infrastructure necessary for a large scale Clinical Trial of Investigational Medicinal Products in care homes in all four UK nations. Future work: The role of post-exposure prophylaxis of COVID-19 in care home residents remains to be defined. Significant logistical barriers to conducting research in care homes during a pandemic need to be removed before such studies are possible in the required short timescale.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.29.22279359v1" target="_blank">Prophylactic Treatment of COVID-19 in Care Homes Trial (PROTECT-CH)</a>
</div></li>
<li><strong>Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants</strong> -
<div>
Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2 infection has changed, with anosmia being less frequent. Several studies have focused on the neuropathogenesis of the original SARS-CoV-2, but little is known about the neuropathological potential of the variants. Here, we assessed the clinical, olfactory and inflammatory conditions of golden hamsters infected with the original SARS-CoV-2, its ORF7-deleted mutant, and three variants: Gamma, Delta and Omicron/BA.1. We show that infected animals developed a variant-dependent clinical disease, and that the ORF7 of SARS-CoV-2 contribute to causing olfactory disturbances. Conversely, all SARS-CoV-2 variants were found to be neuroinvasive, regardless of the clinical presentation they induce. With newly-generated nanoluciferase-expressing SARS-CoV-2, we validated the olfactory pathway as a main entry point towards the brain, confirming that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.31.505985v1" target="_blank">Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants</a>
</div></li>
<li><strong>Impact of reinfection with SARS-CoV-2 Omicron variants in previously infected hamsters</strong> -
<div>
The diversity of SARS-CoV-2 mutations raises the possibility of reinfection of individuals previously infected with earlier variants, and this risk is further increased by the emergence of the B.1.1.529 Omicron variant. In this study, we used an in vivo, hamster infection model to assess the potential for individuals previously infected with SARS-CoV-2 to be reinfected with Omicron variant and we also investigated the pathology associated with such infections. Initially, Syrian hamsters were inoculated with a lineage A, B.1.1.7, B.1.351, B.1.617.2 or a subvariant of Omicron, BA.1 strain and then reinfected with the BA.1 strain 5 weeks later. Subsequently, the impact of reinfection with Omicron subvariants (BA.1 and BA.2) in individuals previously infected with the BA.1 strain was examined. Although viral infection and replication were suppressed in both the upper and lower airways, following reinfection, virus-associated RNA was detected in the airways of most hamsters. Viral replication was more strongly suppressed in the lower respiratory tract than in the upper respiratory tract. Consistent amino acid substitutions were observed in the upper respiratory tract of infected hamsters after primary infection with variant BA.1, whereas diverse mutations appeared in hamsters reinfected with the same variant. Histopathology showed no acute pneumonia or disease enhancement in any of the reinfection groups and, in addition, the expression of inflammatory cytokines and chemokines in the airways of reinfected animals was only mildly elevated. These findings are important for understanding the risk of reinfection with new variants of SARS-CoV-2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.30.505966v1" target="_blank">Impact of reinfection with SARS-CoV-2 Omicron variants in previously infected hamsters</a>
</div></li>
<li><strong>The impact of COVID-19 on prescribing of pancreatic enzyme replacement therapy for people with unresectable pancreatic cancer in England. A cohort study using OpenSafely-TPP</strong> -
<div>
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Background: Cancer treatments were variably disrupted during the COVID-19 pandemic. Despite UK national guidelines recommending pancreatic enzyme replacement therapy to all people with unresectable pancreatic cancer, observational studies demonstrate under-prescribing. Aim: To investigate the impact of the COVID-19 pandemic on the prescribing of pancreatic enzyme replacement to people with unresectable pancreatic cancer. Methods: With the approval of NHS England, we conducted a cohort study using 24 million health records through the OpenSAFELY-TPP research platform. We modelled the effect of COVID-19 with multivariable linear regression. Results: We found no reduction in pancreatic enzyme replacement therapy during the COVID-19 pandemic. Overall, since 2015, the rates of prescribing increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in 2022. There was substantial regional variation. The highest rates of 50% to 60% were in the West Midlands and lowest (20% to 30%) in London. Conclusions: In contrast to many other treatments, prescribing of pancreatic enzyme replacement therapy was not affected during the COVID-19 pandemic. Although overall rates increased over time, substantial under-prescribing existed at the end of this study (March 2022). At just under 50% in 2022, the rates were still below the recommended 100% standard. Prior work evaluating quality of care in this area relied on manual audits which come at increased cost and reduced frequency of updates. With the methodological advantage of OpenSAFELY, we established an automated audit which allows for regular updates.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.08.22277317v3" target="_blank">The impact of COVID-19 on prescribing of pancreatic enzyme replacement therapy for people with unresectable pancreatic cancer in England. A cohort study using OpenSafely-TPP</a>
</div></li>
<li><strong>Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
With more recent SARS-CoV-2 variants, breakthrough infections in vaccinated individuals and reinfections among previously infected individuals are increasingly common, especially during the Omicron wave. Such infections have led to concerns about controlling transmission and underscore a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of persons with SARS-CoV-2 infections, especially in high-risk populations with intense transmission such as prisons. Here, we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing data from system-wide SARS-CoV-2 surveillance across 35 California state prisons, we estimate that Omicron variant infections among unvaccinated cases had a 36% (95% confidence interval (CI): 30-42%) risk of transmitting to close contacts, as compared to 27% (24-30%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone, and both vaccination and prior infection reduced an index case9s risk of transmitting to close contacts by 24% (9-37%), 21% (4-36%) and 41% (23-54%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.08.22278547v2" target="_blank">Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave</a>
</div></li>
<li><strong>Symptoms of depression and anxiety among Vietnamese immigrants in Japan during the COVID-19 pandemic; a cross-sectional web-based study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Mental health among immigrants in Japan may be related to aspects of COVID-19 infection as well as pandemic-related lifestyle changes, investigating mental health status among Vietnamese residents remains an important public health concern. The mental health status of Vietnamese immigrants in Japan during the COVID-19 epidemic remains unclear. We aimed to examine the mental health status and related factors among Vietnamese immigrants in Japan during the coronavirus disease 2019 (COVID-19) pandemic using data from an online cross-sectional survey administered from September 21 to October 21, 2021. Methods: Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scores were considered the main outcome measures. Multivariable logistic regression was used to identify factors related to symptoms of depression and anxiety, and the chosen variables were entered simultaneously in the survey. Results: Among 621 participants (age: 26.0 ± 4.8 years; male: 347 [55.9%]) who completed the questionnaire, 73.7% reported a decrease in income when compared with the period before the COVID-19 pandemic, and 60.4% reported being recently affected by poor socioeconomic status. Moderate to severe symptoms of depression (PHQ-9 score ≥ 10 points) and mild-to-severe symptoms of anxiety (GAD-7 ≥ 5 points) were observed in 203 (32.7%) and 285 (45.9%) individuals, respectively. Factors related to depressive symptoms were age (odds ratio [OR]=0.94, p=0.043), pre-existing health conditions (OR=2.46, p&lt;0.001), and subjective socioeconomic status (OR=2.47, p&lt;0.001). Factors related to anxiety symptoms were being single (OR=1.72, p=0.044), pre-existing health conditions (OR=2.52, p&lt;0.001), subjective socioeconomic status (OR=2.72, p&lt;0.001), and a partner with whom to discuss ones health (OR=1.66, p=0.013). Conclusions: The current findings demonstrate that, when compared with non-Vietnamese Japanese people, people with Vietnamese backgrounds experienced a decrease in income, worsening working conditions, and poor mental health status during the COVID-19 pandemic. These findings highlight the potential contribution of low socioeconomic status and social isolation to poor mental health status.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.09.22271973v3" target="_blank">Symptoms of depression and anxiety among Vietnamese immigrants in Japan during the COVID-19 pandemic; a cross-sectional web-based study</a>
</div></li>
<li><strong>Recent SARS-CoV-2 infection abrogates antibody and B-cell responses to booster vaccination</strong> -
<div>
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SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a two-month period, we evaluated antibody and B-cell responses to a third dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies, and memory B cells. Spike-specific B-cell responses from recent infection were elevated at pre-boost but comparatively less so at 60 days post-boost compared to uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B-cell responses to booster vaccines are impeded by recent infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.30.22279344v1" target="_blank">Recent SARS-CoV-2 infection abrogates antibody and B-cell responses to booster vaccination</a>
</div></li>
<li><strong>Receptor binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2</strong> -
<div>
Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on details of the experimental assay. Here we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. But for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.29.505713v1" target="_blank">Receptor binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2</a>
</div></li>
<li><strong>Entropic overcompensation of the N501Y mutation on SARS-CoV-2 S binding to ACE2</strong> -
<div>
Recent experimental work has shown that the N501Y mutation in the SARS-CoV-2 S glycoprotein’s receptor binding domain (RBD) increases binding affinity to the angiotensin-converting enzyme 2 (ACE2), primarily by overcompensating for a less favorable enthalpy of binding by a greatly reducing the entropic penalty for complex formation, but the basis for this entropic overcompensation is not clear [Pr’evost et al., J. Biol. Chem. (2021) 297;10115]. We use all-atom molecular dynamics simulations and free-energy calculations to qualitatively assess the impact of the N501Y mutation on enthalpy and entropy of binding of RBD to ACE2. Our calculations correctly predict that N501Y causes a less favorable enthalpy of binding to ACE2 relative to the original strain. Further, we show that this is overcompensated for by a more entropically favorable increase in large-scale quaternary flexibility and intra-protein root-mean squared fluctuations of residue positions upon binding in both RBD and ACE2. The enhanced quaternary flexibility stems from N501Y’s ability to remodel the interresidue interactions between the two proteins away from interactions central to the epitope and toward more peripheral interactions. These findings suggest that an important factor in determining protein-protein binding affinity is the degree to which fluctuations are distributed throughout the complex, and that residue mutations that may seem to result in weaker interactions than their wild-type counterparts may yet result increased binding affinity thanks to their ability to suppress unfavorable entropy changes upon binding.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.30.505841v1" target="_blank">Entropic overcompensation of the N501Y mutation on SARS-CoV-2 S binding to ACE2</a>
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<li><strong>Identifying Women with Post-Delivery Posttraumatic Stress Disorder using Natural Language Processing of Personal Childbirth Narratives</strong> -
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Background: Maternal mental disorders are considered a leading complication of childbirth and a common contributor to maternal death. In addition to undermining maternal welfare, untreated postpartum psychopathology can result in child emotional and physical neglect, and associated significant pediatric health costs. Some women may experience a traumatic childbirth and develop posttraumatic stress disorder (PTSD) symptoms following delivery (CB-PTSD). Although women are routinely screened for postpartum depression in the U.S., there is no recommended protocol to inform the identification of women who are likely to experience CB-PTSD. Advancements in computational methods of free text has shown promise in informing diagnosis of psychiatric conditions. Although the language in narratives of stressful events has been associated with post-trauma outcomes, whether the narratives of childbirth processed via machine learning can be useful for CB-PTSD screening is unknown. Objective: This study examined the utility of written narrative accounts of personal childbirth experience for the identification of women with provisional CB-PTSD. To this end, we developed a model based on natural language processing (NLP) and machine learning (ML) algorithms to identify CB-PTSD via classification of birth narratives. Study Design: A total of 1,127 eligible postpartum women who enrolled in a study survey during the COVID-19 era provided short written childbirth narrative accounts in which they were instructed to focus on the most distressing aspects of their childbirth experience. They also completed a PTSD symptom screen to determine provisional CB-PTSD. After exclusion criteria were applied, data from 995 participants was analyzed. An ML-based Sentence-Transformer NLP model was used to represent narratives as vectors that served as inputs for a neural network ML model developed in this study to identify participants with provisional CB-PTSD. Results: The ML model derived from NLP of childbirth narratives achieved good performance: AUC 0.75, F1-score 0.76, sensitivity 0.8, and specificity 0.70. Moreover, women with provisional CB-PTSD generated longer narratives (t-test results: t=2.30, p=0.02) and used more negative emotional expressions (Wilcoxon test: 9sadness9: p=8.90e-04, W=31,017; 9anger9: p=1.32e-02, W=35,005.50) and death-related words (Wilcoxon test: p=3.48e-05, W=34,538) in describing their childbirth experience than those with no CB-PTSD. Conclusions: This study provides proof of concept that personal childbirth narrative accounts generated in the early postpartum period and analyzed via advanced computational methods can detect with relatively high accuracy women who are likely to endorse CB-PTSD and those at low risk. This suggests that birth narratives could be promising for informing low-cost, non-invasive tools for maternal mental health screening, and more research that utilizes ML to predict early signs of maternal psychiatric morbidity is warranted.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.30.22279394v1" target="_blank">Identifying Women with Post-Delivery Posttraumatic Stress Disorder using Natural Language Processing of Personal Childbirth Narratives</a>
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<li><strong>A case-crossover study of the effect of vaccination on SARS-CoV-2 transmission relevant behaviours during a period of national lockdown in England and Wales</strong> -
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Background: Studies of COVID-19 vaccine effectiveness show increases in COVID-19 cases within 14 days of a first dose, potentially reflecting post-vaccination behaviour changes associated with SARS-CoV-2 transmission before vaccine protection. However, direct evidence for a relationship between vaccination and behaviour is lacking. We aimed to examine the association between vaccination status and self-reported non-household contacts and non-essential activities during a national lockdown in England and Wales. Methods: Participants (n=1,154) who had received the first dose of a COVID-19 vaccine reported non-household contacts and non-essential activities from February to March 2021 in monthly surveys during a national lockdown in England and Wales. We used a case-crossover study design and conditional logistic regression to examine the association between vaccination status (pre-vaccination vs. 14 days post-vaccination) and self-reported contacts and activities within individuals. Stratified subgroup analyses examined potential effect heterogeneity by sociodemographic characteristics such as sex, household income or age group. Results: 457/1,154 (39.60%) participants reported non-household contacts post-vaccination compared with 371/1,154 (32.15%) participants pre-vaccination. 100/1,154 (8.67%) participants reported use of non-essential shops or services post-vaccination compared with 74/1,154 (6.41%) participants pre-vaccination. Post-vaccination status was associated with increased odds of reporting non-household contacts (OR 1.65, 95% CI 1.31-2.06, p&lt;0.001) and use of non-essential shops or services (OR 1.50, 95% CI 1.03-2.17, p=0.032). This effect varied between men and women and different age groups. Conclusion: Participants had higher odds of reporting non-household contacts and use of non-essential shops or services within 14 days of their first COVID-19 vaccine compared to pre-vaccination. Public health emphasis on maintaining protective behaviours during this post-vaccination time period when individuals have yet to develop full protection from vaccination could reduce risk of SARS-CoV-2 infection.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.29.22279333v1" target="_blank">A case-crossover study of the effect of vaccination on SARS-CoV-2 transmission relevant behaviours during a period of national lockdown in England and Wales</a>
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<li><strong>Polygenic Risk Scores for Asthma and Allergic Disease Predict COVID-19 Severity in 9/11 Responders</strong> -
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Background. Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals. Methods. Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection=56.06, standard deviation [SD]=7.37, 918 (93.4%) male, 813 (82.7%) European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category, that included hospitalization and other adverse outcomes; 306 (31.1%) reported at least one post-acute COVID-19 symptom at the 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates. Findings. In responders with European ancestry, the asthma PRS was associated with severe COVID-19 category (odds ratio [OR]=1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β=.09, p=.01), independently of respiratory disease diagnosis. The allergic disease PRS similarly associated with severe COVID-19 category (OR=1.97, [1.26-3.07]). The PRS for COVID-19 hospitalization was associated with the risk of severe COVID-19 category (OR=1.35, [1.01-1.82]), but this association was smaller than for the asthma PRS. PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity. Interpretation. Taken together, the results indicate that recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population. Funding. National Institute for Occupational Safety and Health, CDC.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.30.22279383v1" target="_blank">Polygenic Risk Scores for Asthma and Allergic Disease Predict COVID-19 Severity in 9/11 Responders</a>
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<li><strong>Can SARS-CoV-2 transmit from a dead body?</strong> -
<div>
Although it has been 2.5 years since the COVID-19 pandemic began, the transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a dead infected body remains unclear, and often, in Japan bereaved family members are not allowed to view in-person a loved one who has died from COVID-19. In this study, we analyzed the possibility of SARS-CoV-2 transmission from a dead body by using the hamster model. We also analyzed the effect of Angel-care–in which the pharynx, nostril, and rectum are plugged–and embalming on reducing transmissibility from dead bodies. We found that SARS-CoV-2 could be transmitted from the body of animals that died within a few days of infection; however, Angel-care and embalming were effective in preventing transmission from the dead body. These results suggest that protection from infection is essential when in contact with a SARS-CoV-2-infected dead body, and that sealing the cavities of a dead body is an important infection control step if embalming is not done.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.29.505777v1" target="_blank">Can SARS-CoV-2 transmit from a dead body?</a>
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<li><strong>Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization</strong> -
<div>
The ability of serum antibody to protect against pathogens arises from the interplay of antigen-specific B cell clones of different affinities and fine specificities. These cellular dynamics are ultimately responsible for serum-level phenomena such as antibody imprinting or “Original Antigenic Sin” (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells that responded to a stimulus upon exposure to related antigens. Imprinting/OAS is thought to pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-2. Precise measurement of the extent to which imprinting/OAS inhibits the recruitment of new B cell clones by boosting is challenging because cellular and temporal origins cannot readily be assigned to antibodies in circulation. Thus, the extent to which imprinting/OAS impacts the induction of new responses in various settings remains unclear. To address this, we developed a “molecular fate-mapping” approach in which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that, upon sequential homologous boosting, the serum antibody response strongly favors reuse of the first cohort of B cell clones over the recruitment of new, naive-derived B cells. This “primary addiction” decreases as a function of antigenic distance, allowing secondary immunization with divergent influenza virus or SARS-CoV-2 glycoproteins to overcome imprinting/OAS by targeting novel epitopes absent from the priming variant. Our findings have implications for the understanding of imprinting/OAS, and for the design and testing of vaccines aimed at eliciting antibodies to evolving antigens.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.29.505743v1" target="_blank">Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SIM0417;   Drug: Placebo<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<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>Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: Self-management of post COVID-19 respiratory outcomes<br/><b>Sponsor</b>:   University of Manitoba<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>Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: SARS-CoV-2 subunit protein recombinant vaccine;   Biological: Active Comparator<br/><b>Sponsors</b>:   PT Bio Farma;   Faculty of Medicine Universitas Padjadjaran;   Faculty of Medicine Universitas Udayana<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 Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: SCTV01E-1 on D0;   Biological: SCTV01E-1 on D28;   Biological: SCTV01E-1 on D150;   Biological: SCTV01E on D0;   Biological: SCTV01E on D28;   Biological: SCTV01E on D150;   Biological: SCTV01E-1 on D120;   Biological: SCTV01E on D120<br/><b>Sponsor</b>:   Sinocelltech Ltd.<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>The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BCG (Bacillus Calmette-Guérin) vaccine;   Other: Placebo<br/><b>Sponsors</b>:   Oswaldo Cruz Foundation;   University of Sao Paulo;   Federal University of Juiz de Fora<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>Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Diagnostic Test: Nasal Swab;   Diagnostic Test: Nasopharyngeal swab<br/><b>Sponsor</b>:   LumiraDx UK Limited<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 Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Diagnostic Test: the LIT test<br/><b>Sponsors</b>:   Gazi University;   Oxford MediStress<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>Efficacy and Safety of ES16001 in Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: ES16001 40 mg;   Drug: ES16001 80 mg;   Drug: ES16001 160 mg;   Drug: Placebo<br/><b>Sponsor</b>:   Genencell Co. Ltd.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)<br/><b>Sponsors</b>:   The Aurum Institute NPC;   Coalition for Epidemic Preparedness Innovations<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>UNAIR Inactivated COVID-19 Vaccine Phase III (Immunobridging Study)</strong> - <b>Conditions</b>:   COVID-19 Pandemic;   COVID-19 Vaccines<br/><b>Interventions</b>:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-19 Vaccine<br/><b>Sponsors</b>:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study</strong> - <b>Conditions</b>:   COVID-19;   Kidney Transplant<br/><b>Intervention</b>:   Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   PPD;   Johns Hopkins University;   Sanofi Pasteur, a Sanofi Company<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>Safety and Immunogenicity of COVID-19 Vaccine, AdCLD-CoV19-1</strong> - <b>Conditions</b>:   COVID-19;   Vaccines<br/><b>Intervention</b>:   Biological: AdCLD-CoV19-1<br/><b>Sponsors</b>:   International Vaccine Institute;   Cellid Co., Ltd.<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>Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection</strong> - <b>Conditions</b>:   COVID-19;   Child, Only<br/><b>Intervention</b>:   Drug: Jinzhen oral liquid or Jinhuaqinggan granules<br/><b>Sponsor</b>:   The Affiliated Hospital of Qingdao University<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Smartphone Intervention for Overdose and COVID-19</strong> - <b>Conditions</b>:   Substance Use Disorders;   Overdose;   COVID-19<br/><b>Intervention</b>:   Device: iThrive WI Intervention<br/><b>Sponsors</b>:   University of Wisconsin, Madison;   National Institute on Drug Abuse (NIDA)<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>Phase 2 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>:   COVID-19;   Influenza<br/><b>Interventions</b>:   Drug: CIC Vaccine;   Drug: qNIV Vaccine;   Drug: SARS-CoV-2 rS Vaccine;   Drug: Influenza Vaccine<br/><b>Sponsor</b>:   Novavax<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural Insights into Binding of Remdesivir Triphosphate within the Replication-Transcription Complex of SARS-CoV-2</strong> - Remdesivir is an adenosine analogue that has a cyano substitution in the C1’ position of the ribosyl moiety and a modified base structure to stabilize the linkage of the base to the C1’ atom with its strong electron-withdrawing cyano group. Within the replication-transcription complex (RTC) of SARS-CoV-2, the RNA-dependent RNA polymerase nsp12 selects remdesivir monophosphate (RMP) over adenosine monophosphate (AMP) for nucleotide incorporation but noticeably slows primer extension after 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>The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial</strong> - CONCLUSIONS: The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo. However, Aviptadil improves the likelihood of survival from respiratory failure at day 60 in critical COVID-19 across all sites of care. Given the absence of drug-related serious adverse events and acceptable safety profile, we believe the benefit versus risk for the use of Aviptadil is favorable for patient treatment.</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>Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals</strong> - Pirfenidone (PFN) is an anti-fibrotic drug with significant anti-inflammatory property used for treatment of fibrotic conditions such as idiopathic pulmonary fibrosis (IPF). In the coronavirus disease 2019 (Covid-19) era, severe acute respiratory syndrome 2 (SARS-CoV-2) could initially lead to acute lung injury (ALI) and in severe cases may cause acute respiratory distress syndrome (ARDS) which is usually resolved with normal lung function. However, some cases of ALI and ARDS are progressed to…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers</strong> - Pulmonary surfactant has been attempted as a supportive therapy to treat COVID-19. Although it is mechanistically accepted that the fusion peptide in the S2 subunit of the S protein plays a predominant role in mediating viral fusion with the host cell membrane, it is still unknown how the S2 subunit interacts with the natural surfactant film. Using combined bio-physicochemical assays and atomic force microscopy imaging, it was found that the S2 subunit inhibited the biophysical properties of 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>Synthesis, Molecular Docking, c-Met inhibitions of 2,2,2-Trichloro-ethylidene-cyclohexane-1,3-dione Derivatives Together With Their Application as Target SARS-CoV-2 main Protease (Mpro) And as Potential Anti-Covid-19</strong> - CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas, compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h…</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>Cannabinoids receptors in Covid-19: Perpetrators and victims</strong> - COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral…</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>Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study</strong> - CONCLUSIONS: Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, with the highest responses being with the 30-μg SCB-2019 + CpG + aluminium hydroxide formulation.</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>5-HT/CGRP pathway and Sumatriptan role in Covid-19</strong> - Coronavirus disease 2019 (Covid-19) is a pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In Covid-19, there is uncontrolled activation of immune cells with a massive release of pro-inflammatory cytokines and the development of cytokine storm. These inflammatory changes induce impairment of different organ functions, including the central nervous system (CNS), leading to acute brain injury and substantial changes in the neurotransmitters, including serotonin…</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 potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rapidly spreading worldwide. Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections. However, the emergence of SARS-CoV-2 variants of concern (VOCs), such as Delta (B.1.617.2) and the recently emerged Omicron (B.1.1.529), has seriously challenged the application of current therapeutics. Therefore, there is still a pressing need for identification of…</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>Brequinar and dipyridamole in combination exhibits synergistic antiviral activity against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in &gt;400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet…</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>Nafamostat Mesylate for Treatment of COVID-19 in Hospitalised Patients: A Structured, Narrative Review</strong> - The search for clinically effective antivirals against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is ongoing. Repurposing of drugs licensed for non-coronavirus disease 2019 (COVID-19) indications has been extensively investigated in laboratory models and in clinical studies with mixed results. Nafamostat mesylate (nafamostat) is a drug licensed in Japan and Korea for indications including acute pancreatitis and disseminated intravascular coagulation. It is available only…</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>Crystal structure of SARS-CoV-2 nsp10-nsp16 in complex with small molecule inhibitors, SS148 and WZ16</strong> - SARS-CoV-2 nsp10-nsp16 complex is a 2’-O-methyltransferase (MTase) involved in viral RNA capping, enabling the virus to evade the immune system in humans. It has been considered a valuable target in the discovery of antiviral therapeutics, as the RNA cap formation is crucial for viral propagation. Through cross-screening of the inhibitors that we previously reported for SARS-CoV-2 nsp14 MTase activity against nsp10-nsp16 complex, we identified two compounds (SS148 and WZ16) that also inhibited…</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>Human Claudin-Derived Peptides Block the Membrane Fusion Process of Zika Virus and Are Broad Flavivirus Inhibitors</strong> - Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged in the Pacific islands in 2007 and spread to the Americas in 2015. The infection remains asymptomatic in most cases but can be associated with severe neurological disorders. Despite massive efforts, no specific drug or vaccine against ZIKV infection is available to date. Claudins are tight-junction proteins that favor the entry of several flaviviruses, including ZIKV. In this study, we identified two peptides derived from 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>Peptidomimetic Small-Molecule Inhibitors of 3CLPro Activity and Spike-ACE2 Interaction: Toward Dual-Action Molecules against Coronavirus Infections</strong> - The development of molecules able to target protein-protein interactions (PPIs) is of interest for the development of novel therapeutic agents. Since a high percentage of PPIs are mediated by α-helical structure at the interacting surface, peptidomimetics that reproduce the essential conformational components of helices are useful templates for the development of PPIs inhibitors. In this work, the synthesis of a constrained dipeptide isostere and insertion in the short peptide epitope EDLFYQ of…</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>Nonstructural Protein 1 of Variant PEDV Plays a Key Role in Escaping Replication Restriction by Complement C3</strong> - Zoonotic coronaviruses represent an ongoing threat to public health. The classical porcine epidemic diarrhea virus (PEDV) first appeared in the early 1970s. Since 2010, outbreaks of highly virulent PEDV variants have caused great economic losses to the swine industry worldwide. However, the strategies by which PEDV variants escape host immune responses are not fully understood. Complement component 3 (C3) is considered a central component of the three complement activation pathways and plays a…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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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>Mikhail Gorbachev, the Fundamentally Soviet Man</strong> - The last leader of the U.S.S.R. attempted to modernize and reform his country, even as he failed to imagine it as anything but an empire. - <a href="https://www.newyorker.com/news/postscript/mikhail-gorbachev-the-fundamentally-soviet-man">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Joe Biden’s Big Month</strong> - The President is getting things done and reaffirming that his historic role is to defeat Trump and Trumpism. - <a href="https://www.newyorker.com/news/our-columnists/joe-bidens-big-month">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Biden’s Student-Debt Plan Could Chip Away at the Racial Wealth Gap</strong> - Loan forgiveness and other measures don’t solve the problem of rising tuition costs, but they could help some Black families start to catch up. - <a href="https://www.newyorker.com/news/daily-comment/bidens-student-debt-plan-could-chip-away-at-the-racial-wealth-gap">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Elif Batuman Reads Sylvia Townsend Warner</strong> - The author joins Deborah Treisman to read and discuss the story “Truth and Fiction,” which was published in a 1961 issue of the magazine. - <a href="https://www.newyorker.com/podcast/fiction/elif-batuman-reads-sylvia-townsend-warner">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Rise and Fall of Vibes-Based Literacy</strong> - Is a controversial curriculum, entrenched in New York City’s public schools for two decades, finally coming undone? - <a href="https://www.newyorker.com/news/annals-of-education/the-rise-and-fall-of-vibes-based-literacy">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The long road ahead for American-made electric vehicles</strong> -
<figure>
<img alt="Joe Biden sitting in the driver’s seat of an electric Jeep." src="https://cdn.vox-cdn.com/thumbor/omu_5FwaMh3RhTAGRJj2C3e7HKA=/393x0:3540x2360/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71311447/GettyImages_1234490225.0.jpg"/>
<figcaption>
President Joe Biden wants half of the new cars sold in the US to be electric by 2030. | Al Drago/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Inflation Reduction Act lays the groundwork for an EV supply that starts in the United States.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MjRIjI">
Much hay has been made about how the Inflation Reduction Act represents America’s <a href="https://www.vox.com/policy-and-politics/2022/7/28/23282217/climate-bill-health-care-drugs-inflation-reduction-act">biggest climate investment ever</a>. But reading between the lines of the legislation, which tackles everything from taxes to health care, shows that the nearly $740 billion law has some caveats, including new provisions to a more than decade-old EV tax credit.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dFyFb8">
For years, prospective electric vehicle buyers could count on a federal vehicle tax credit, which amounts to a $7,500 discount on a wide range of EV models. The incentive was originally <a href="https://slate.com/technology/2022/08/ev-tax-credit-cars-tesla-gm-inflation-reduction-act.html">authorized in 2008</a> and played a critical part in promoting early EV startups and encouraging price-conscious consumers to take the plunge and go electric. The IRA extends the tax credit until <a href="https://www.jdsupra.com/legalnews/the-ira-s-electric-vehicle-and-battery-3876820/">2032</a> and establishes an additional $4,000 credit for <a href="https://www.marketwatch.com/story/mulling-an-ev-a-first-ever-4-000-tax-incentive-for-used-electric-vehicles-is-part-of-manchins-compromise-11659019423">used EVs</a>.
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But there are new rules, too, for a vehicle to qualify for that credit. The <a href="https://www.electrificationcoalition.org/wp-content/uploads/2022/08/SAFE_1-sheet_Webinar.pdf">final assembly</a> of any qualified vehicles must also take place in North America, and the credit will also <a href="https://www.pbs.org/newshour/nation/everything-you-need-to-know-about-the-new-electric-vehicle-tax-credit">hinge</a> on the vehicle’s size, its total cost, and potential buyers’ income. Starting in 2024, at least 40 percent of the critical minerals and at least half of the battery components used to build new eligible EVs will need to come from the US or one of its free trade <a href="https://www.reuters.com/business/autos-transportation/skorea-raise-concerns-about-ev-credits-battery-sourcing-us-visit-2022-08-29/">partners to </a><a href="https://www.eenews.net/articles/climate-bill-would-create-roadblock-for-full-ev-tax-credit/">access the full credit</a><a href="https://www.reuters.com/business/autos-transportation/skorea-raise-concerns-about-ev-credits-battery-sourcing-us-visit-2022-08-29/">. </a>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hbHbmi">
But for most consumers, the new tax credit could prove elusive. Around <a href="https://www.autosinnovate.org/posts/blog/what-if-no-evs-qualify-for-the-ev-tax-credit">70 percent</a> of the electric, hydrogen, and hybrid cars currently sold in the US won’t be eligible for the credit, according to the Alliance of Automotive Innovation, a trade group that represents the car industry. An August analysis of the IRA proposal from the Congressional Budget Office estimates that only about <a href="https://www.reuters.com/business/autos-transportation/us-congress-office-sees-few-tax-breaks-evs-under-democratic-plan-2022-08-03/">11,000</a> vehicles could receive the credit in 2023, and around <a href="https://www.consumerreports.org/cars/hybrids-evs/electric-vehicles-that-qualify-for-new-ev-tax-credit-a9310530660/">60,000 vehicles</a> in 2024, according to an August analysis of the IRA proposal. While the Internal Revenue Service is charged with determining which vehicles are <a href="https://home.treasury.gov/news/press-releases/jy0923">eligible</a>, experts told Recode that they expect very few cars to receive the credit over the next several years, especially since the law’s sourcing requirements are designed to become more stringent.
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But that may not be the case forever. The tax credit is only one part of the Biden administration’s plan for a new era of American auto manufacturing, which includes everything from a new push to <a href="https://www.whitehouse.gov/briefing-room/statements-releases/2022/05/11/readout-of-the-white-houses-first-stakeholder-convening-on-mining-reform/">rethink mining regulations</a> to the Bipartisan Infrastructure Act’s <a href="https://www.energy.gov/articles/biden-administration-announces-316-billion-bipartisan-infrastructure-law-boost-domestic">$3 billion investment</a> in the domestic battery supply chain. Together, these efforts, and a surge in new EV factories based in the US, could make American-made electric vehicles much more common in the latter part of the decade. At the same time, this credit won’t necessarily disincentivize people from buying EVs that are made abroad, especially as <a href="https://www.consumerreports.org/hybrids-evs/electric-cars-are-becoming-less-expensive-a6548270716/">electric vehicle prices decline</a> and as geopolitics continue to complicate the world’s access to fossil fuels.
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“People will still go ahead and purchase EVs that do not qualify for the tax credit,” explains Jane Nakano, a senior fellow at the Center for Strategic and International Studies’ energy security and climate change program. “EVs do have some real consumer benefits. It’s not just for decarbonization. It’s household economic benefits, and then to some extent, energy security benefits.”
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Right now, China is <a href="https://www.theguardian.com/global-development/2021/nov/25/battery-arms-race-how-china-has-monopolised-the-electric-vehicle-industry">the undisputed world leader</a> in EVs. Though the critical minerals used in electric vehicle batteries are currently sourced from all over the world –– the <a href="https://www.abc.net.au/news/2022-02-24/cobalt-mining-in-the-congo-green-energy/100802588#:~:text=Beneath%20Congo's%20rich%20red%20earth,closest%20competitors%2C%20Australia%20and%20Russia.">lion’s share of cobalt</a> comes from the Democratic Republic of the Congo, while lithium tends to come from <a href="https://www.theguardian.com/news/2020/dec/08/the-curse-of-white-oil-electric-vehicles-dirty-secret-lithium">South America and Australia</a> — much of the <a href="https://www.canarymedia.com/articles/clean-energy/chart-china-dominates-production-of-minerals-needed-for-clean-energy">processing</a> of those <a href="https://www.iea.org/reports/the-role-of-critical-minerals-in-clean-energy-transitions/executive-summary">materials</a> takes place in China. China is also responsible for <a href="https://www.iea.org/reports/electric-vehicles">more than 70 percent</a> of global battery cell production. The country not only makes much of the world’s battery components, like <a href="https://www.reuters.com/markets/commodities/us-hits-ev-accelerator-cut-chinese-metals-ties-2022-08-16/">cathode materials,</a> but is also home to the <a href="https://spectrum.ieee.org/the-top-10-ev-battery-makers">largest battery manufacturer</a>, Contemporary Amperex Technology Co. 
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The overhauled vehicle tax credit aims to catch up and compete by putting increasing pressure on automakers, though they do get one major piece of help. The earlier version of the credit included a provision that after an automaker made 200,000 eligible vehicles, people could no longer <a href="https://www.tesla.com/blog/what-you-need-know-about-federal-ev-tax-credit-phase-out">claim the $7,500 credit</a>. That means companies like Tesla and <a href="https://www.irs.gov/newsroom/plug-in-electric-vehicle-manufacturer-crosses-200000-sold-threshold-tax-credit-for-eligible-consumers-begins-phase-down-on-april-1">GM</a> haven’t been able to offer the credit for some time. The latest version of the law eliminates that limitation, so car models built by larger EV manufacturers could become eligible for the credit <a href="https://www.barrons.com/articles/ev-tesla-tax-credit-inflation-reduction-act-51660555636">once again</a>.
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Car manufacturers will face an uphill battle in meeting those requirements, especially since the percentage of components and materials that must come from the US or its partners is <a href="https://www.electrificationcoalition.org/wp-content/uploads/2022/08/SAFE_1-sheet_Webinar.pdf">designed to increase</a> in the coming years. <a href="https://www.energy.gov/sites/default/files/2021-06/FCAB%20National%20Blueprint%20Lithium%20Batteries%200621_0.pdf">US reserves of minerals like cobalt, lithium, and nickel</a> are just a small fraction of the world’s current supply. Even stricter rules will eventually kick in: By 2024, eligible vehicles <a href="https://www.electrificationcoalition.org/wp-content/uploads/2022/08/SAFE_1-sheet_Webinar.pdf">can’t incorporate</a> any battery components from China or other “foreign entities of concern,” and in 2025, they can’t include any critical minerals from these countries, either.
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“This is the very moment for those automakers to decide the next pathway of their business model and where they’re going to invest and shore up their production,” explains Katherine Stainken, the vice president of policy at the Electrification Coalition, an organization that promotes EV adoption.
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The US was making progress on this front even before Biden signed the IRA earlier this month. Automakers and electronics manufacturers have been slowly adding to the number of battery production facilities in the US over the past several years. Earlier this week, Honda and LG Energy Solution announced that they would build <a href="https://www.cnbc.com/2022/08/29/honda-lg-energy-solution-to-build-4point4-billion-battery-plant-in-us.html">a $4 billion battery plant</a> in the US, with mass production <a href="https://www.reuters.com/business/autos-transportation/honda-motor-lg-energy-build-ev-battery-plant-ohio-nikkei-2022-08-29/">expected in 2025</a>. Panasonic, which said it would open a battery factory in Kansas last month, now says it may build <a href="https://www.reuters.com/business/autos-transportation/panasonic-plans-additional-4-bln-ev-battery-plant-us-wsj-2022-08-26/">a second facility</a> in Oklahoma. The Department of Energy <a href="https://electrek.co/2021/12/27/13-battery-gigafactories-coming-us-2025-ushering-new-era/">estimated</a> at the end of last year that <a href="https://www.energy.gov/eere/vehicles/articles/fotw-1217-december-20-2021-thirteen-new-electric-vehicle-battery-plants-are">at least 13 new gigafactories</a> may be coming to the US, joining the several plants that companies like Tesla and GM have already opened.
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These efforts are buoyed by the Biden administration’s other investments in the tech supply chain. The White House has already appropriated funding from last year’s Bipartisan Infrastructure Act to support new projects focused on lithium production and critical mineral recycling, and the Department of Energy is loaning out billions to support the construction of <a href="https://www.eenews.net/articles/doe-offers-2-5b-loan-to-boost-gms-battery-plans/">new GM and LG Chem battery factories</a>. The White House is also supporting an effort in Congress to overhaul the Mining Law of 1872, which still governs <a href="https://www.washingtonpost.com/politics/2022/05/11/democrats-push-overhaul-mining-law-citing-clean-energy/">much of the mining</a> within the US today. Biden declared the key metals used in EVs critical to national security when he <a href="https://www.eenews.net/articles/bidens-defense-production-act-order-promises-money-to-miners/">invoked</a> the Defense Production Act in April, setting the groundwork for the Department of Defense to boost the domestic mining industry.
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The CHIPS and Science Act could give American-made EVs a lift, too. The <a href="https://www.vox.com/recode/2022/7/27/23277664/chips-act-solve-chip-shortage-biden-manufacturing">$52 billion package subsidy</a>, which Biden formally approved earlier this summer, will subsidize the construction of several new semiconductor factories in the US, including plants focused on making automotive chips. This is especially important for EVs, which can easily require <a href="https://www.eenews.net/articles/commerce-secretary-chip-shortage-threatens-biden-ev-plans/">double the number</a> of computer chips that comparable internal combustion vehicles do.
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“What the United States is doing right now is securing its own supply over the next 10 years,” explains Nathan Iyer, a senior associate at RMI, “and making sure that what currently is 0.7 percent of the global market goes up to a more reasonable amount, closer to 5, 6, 10, 13 percent of the global market, to really ensure that our own demand is being covered by supply chains.”
</p>
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Biden’s plan does have some real flaws, however. Federal mining applications and approvals <a href="https://www.eenews.net/articles/biden-wants-minerals-but-mine-permitting-lags/">have decreased</a> over the past several years, and environmental regulations may stall the opening of new mining projects Critically, the prospect of building or expanding new mines introduced the risk of pollution, potential damage to agriculture and wildlife, and disproportionate impacts on local communities. In Minnesota, members of tribes who live nearby are already raising concerns about a mine from which Talon Metals, a company that has won a contract with Tesla and praise from the Biden administration, is planning to <a href="https://www.nytimes.com/2022/08/30/business/economy/electric-cars-us-nickel-mine.html">extract nickel for EVs</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kxBsBD">
There are logistical hurdles as well. The IRS needs to figure out how to accurately determine which EV models meet the new credit’s tough sourcing requirements, a task the tax agency is not currently equipped for. Other countries, including the European Union and South Korea, <a href="https://www.reuters.com/business/autos-transportation/eu-says-us-plan-ev-tax-breaks-discriminatory-may-breach-wto-rules-2022-08-11/">have suggested</a> that the clean vehicle tax credit may be unfair to foreign carmakers and could violate international trade rules. It’s also possible that automakers will accept a $7,500 markup to avoid the government’s new requirements entirely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Pyc7Ht">
These efforts are a reminder that even though the US has a long history of building cars, the country is mostly starting from scratch when it comes to electric vehicles. The investments the Biden administration is making in EV manufacturing capabilities largely won’t produce components or vehicles for at least several years, which means consumers may have to wait to reap the full benefits of the extended credit. Only time will tell whether Biden’s dreams for an EV renaissance for the American auto industry ultimately pan out.
</p>
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<em>This story was first published in the Recode newsletter. </em><a href="https://www.vox.com/pages/newsletters"><em>Sign up here</em></a><em> so you don’t miss the next one!</em>
</p></li>
<li><strong>Why movie tickets will be $3 across America this Saturday</strong> -
<figure>
<img alt="Rows of empty red-velour theater seats." src="https://cdn.vox-cdn.com/thumbor/qlrl0j-tOBEKFaYl8xxKhcTl4F8=/147x0:3854x2780/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71311248/GettyImages_1227313654.0.jpg"/>
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For one day only, you can go to the movies for $3. Will you go back? | Valerio Rosati/EyeEm via Getty Images
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See a movie for the price of a coffee on National Cinema Day and contemplate the future of theaters.
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“National Cinema Day” sounds like another made-up holiday designed for meme-posting, like National Twin Day or National Dog Day or <a href="https://nationaltoday.com/national-bubble-wrap-appreciation-day/">National Bubble Wrap Appreciation Day</a>. But this one comes with a bonus: On Saturday, September 3, in 3,000 movie theaters across America, you can get a movie ticket for just $3. And with it comes a window into what’s going on with movie theaters.
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Three dollars is a considerable bargain; <a href="https://www.the-numbers.com/market/">the average movie ticket price in America</a> has been hovering around $9 for about five years, and if you live in a major metropolitan area, you can pay double that. That does mean moviegoing is still just about the cheapest option for a night out, especially if you don’t succumb to the fragrance of slightly burned popcorn. But $3 is better than $9.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lgnDNH">
The discount day was announced by the Cinema Foundation, which is the nonprofit arm of the National Association of Theater Owners, a trade organization for all the major theater chains in America plus hundreds of independent theater owners. More than 3,000 theaters (which means over 30,000 screens) will be participating in the $3 ticket deal, which includes chains like AMC and Regal as well as art house theaters, and the major movie studios have bought in as well.
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The move is kind of a nice one; if nothing else, it’s a good incentive to take a risk on a film you wouldn’t see in a theater otherwise. And it could be a smart move for theaters, too. September 3 is the Saturday before Labor Day, which has long been a dismal weekend for box office revenue. (The beach beckons.) But it’s hot outside, and it’s a holiday, and the cheaper ticket could be a good enticement to build moviegoing into your Saturday plans.
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National Cinema Day — which could become an annual thing akin to Black Friday, if it works out well — feels like a harbinger of … well, of <em>something</em>. I probably don’t need to tell you that the movie business is hurting, and theaters are getting the brunt of it. The reasons are abundant and overlapping: streaming, the pandemic, and the <a href="https://theweek.com/articles/442542/how-fix-american-movie-theater">sometimes-abysmal</a> experience some theaters provide.
</p>
<figure class="e-image">
<img alt="Tom Cruise wearing pilot gear and standing beside a plane in the movie Top Gun Maverick." src="https://cdn.vox-cdn.com/thumbor/jmzTiX_DV6Q5TUw_X-lzbyu9Fpo=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23985135/top_gun_maverick.jpg"/> <cite>Paramount Pictures</cite>
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<em>Top Gun: Maverick</em> is the No. 1 movie of the year so far — and audiences flocked to it in droves this summer.
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Yet Americans are not ready to give up on movie theaters. This summer, in fact, audiences in North America went back in droves, with ticket sales numbers of well over $3 billion. <em>Top Gun: Maverick</em>, <em>Doctor Strange in the Multiverse of Madness</em>, <em>Jurassic World Dominion</em>, <em>Minions: The Rise of Gru</em>, and <em>Thor: Love and Thunder</em> were the summer’s top five earners, and they represent five of the top six movies so far this year. (The sixth, <em>The Batman</em>, sits at No. 4 on the chart, but it was released in early March.)
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Three billion and change in ticket sales is still 20 percent less than summer 2019. But there’s a good reason for it: There were about 30 percent fewer widely released movies to see. Widely released essentially means a blockbuster movie from a major studio, the kind of film that will play in every multiplex in America.
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And you may have felt that lack. <em>Thor: Love and Thunder</em> was the last big franchise film to come out, and it opened on July 8. There have been splashy and popular hits since, like Jordan Peele’s <em>Nope </em>(currently No. 12 for the year), novel adaptation <em>Where The Crawdads Sing</em> (No. 18), and Brad Pitt starrer <em>Bullet Train</em> (No. 20), plus a bevy of smaller specialty movies like <em>Emily the Criminal</em>, <em>Bodies Bodies Bodies</em>, and <em>Resurrection</em>. Earlier summer movies like <em>Elvis</em> (No. 10) and <em>The Black Phone</em> (No. 16) have been hits as well.
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But for those who gravitate toward tentpole movies with existing IP — and that’s a lot of people — this summer movie season felt like it ended right after the Fourth of July weekend.
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<figure class="e-image">
<img alt="In a pink and black tux, Elvis plays a guitar onstage." src="https://cdn.vox-cdn.com/thumbor/gtphL5hB5WmVPcze6X9_KAGeDz4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23647733/elvis.jpg"/> <cite>Warner Bros.</cite>
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Austin Butler in <em>Elvis</em>, which leaves the summer as the No. 10 movie of the year.
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Why? Once again, there’s a confluence of factors at play. During the first two years of the pandemic, movie release dates kept getting pushed into the future, when studios hoped theaters would be open in major markets. They need revenue from ticket sales to earn back the budget on these films. (Straight-to-streaming is just not a sustainable business model for megabudget movies.) But that means other movies got pushed even further into the future, either for story reasons or just to give the film as wide a berth as possible. Similarly, the pandemic made making a movie a lot trickier, and the bigger the movie, the harder (and more expensive) it is to adjust. That just results in fewer movies.
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The next big tentpole IP movie — that is, the ones that are virtually guaranteed to gross a ton of money right out of the gate — is <em>Black Adam</em>, the DC Comics movie starring Dwayne “The Rock” Johnson, due out on October 21. And October 21 is a long way away.
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August is traditionally a slow time for movies, so this is not completely unusual. But last summer, for instance, releases included <em>The Suicide Squad</em> (which went to theaters and HBO Max on the same day), <em>Free Guy</em> (which ended up at No. 10 on the year-end list), and <em>Candyman</em> (which landed at No. 20). 2020 was a wash, but August 2019 saw the release of <em>Fast &amp; Furious Presents: Hobbs &amp; Shaw, </em>plus <em>The Lion King</em> and <em>Spider-Man: Far From Home</em> were only a few weeks into their super-successful releases.
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All of this means people who take advantage of the $3 ticket offer will have a limited set of options. Since they haven’t been crowded out by other tentpoles, the summer’s hits are still lingering in theaters (<em>Top Gun: Maverick</em> is still in nearly 3,000 theaters nationwide). August’s specialty offerings are there, too, and a few new movies will open over the weekend, including <a href="https://www.vox.com/culture/23321982/three-thousand-years-everything-elvis-summer-2022"><em>Three Thousand Years of Longing</em></a> (from <em>Mad Max: Fury Road</em> director George Miller) and <em>Honk for Jesus, Save Your Soul</em>, starring Regina Hall and Sterling K. Brown.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eCxziG">
Overall, though, the discount day feels like part of a broader effort to bring people into theaters and convince them to make moviegoing a part of their lives again, even if their couch beckons. You can see it in various theater chains’ membership programs, like the Regal Unlimited Movie Pass, AMC Stubs, and the Alamo Season Pass. Some independent theaters have created similar programs, <a href="https://www.nbcnewyork.com/entertainment/local-movie-theaters-in-ny-rethink-experience-as-streaming-services-impact-business/3799296/">designed</a> to create loyal customers while also providing a solid revenue stream to backstop individual ticket sales.
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And there’s always MoviePass, that rogueish merry-go-round of a program that <a href="https://www.vox.com/culture/2019/9/23/20874031/moviepass-shut-down-explained">crashed and burned</a> spectacularly in 2019 after almost a year of allowing subscribers to watch a nearly unlimited number of movies in theaters for about $10 a month. (Then it <a href="https://www.vox.com/22526008/moviepass-ftc-complaint-password-block-scam">started scamming people</a>.) <a href="https://www.npr.org/2022/08/27/1119670180/moviepass-cost-start-date-movies-cinema">It’s back,</a> sort of, with a new business model (including “tiers” and “credits”) that might<em> </em>help it survive, after the company’s original co-founder Stacy Spikes regained ownership. But the jury is still out.
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The next few months are crucial for telling what the future of theaters might be, and the $3 ticket experiment feels like a way to remind people that they do, actually, like going to the movies, and that it might be cool to do it again soon. Trailers for movies coming out this fall, traditionally a time for prestige and awards-driven movies, frequently trumpet an “in theaters only” release plan. Even Netflix, which usually only puts its movies in limited theaters for a week or two before releasing to the platform, seems to be testing the longer theatrical release waters with films like Rian Johnson’s <em>Glass Onion: A Knives Out Mystery</em> and Alejandro González Iñárritu’s <em>Bardo</em>. And since it seems like HBO’s grand experiment — releasing blockbusters in theaters and on HBO Max on the same day — <a href="https://www.wired.com/story/hbo-max-discovery-plus-combined/">was a huge flop</a>, smart executives could be rethinking their digital-first plans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UD7tej">
But you know what? I have no idea what’s about to happen. Nobody does, and anyone who says they do is probably trying to get investors on board for some new scheme. Movie theaters have struggled to prove their importance since the birth of TV, and every new technological innovation has presented an additional challenge. There’s a ton of value to seeing a movie in a theater, just like there’s value to going to a concert or a play, not least because it injects elements of <a href="https://www.vox.com/22841390/movie-theaters-cinema-pandemic">community</a> and <a href="https://www.vox.com/22380021/movie-theaters-covid-reopening">attention</a> into the experience that’s hard to match at home. But there are a lot of factors in the mix, and whether theaters survive is largely up to the people in the seats.
</p></li>
<li><strong>Reviving the case for reparations</strong> -
<figure>
<img alt="Photo illustration of Nkechi Taifa and quotation marks." src="https://cdn.vox-cdn.com/thumbor/LjBxsbviOQFTOLWOBcN2CqSyPJY=/225x0:1576x1013/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71311114/40_acres_nkechi_board_2.0.jpg"/>
<figcaption>
Christina Animashaun/Vox; courtesy of Nkechi Taifa
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Lawyer and activist Nkechi Taifa explains why reparations is a policy issue “whose time has come.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J5EPrT">
The conversation about reparations for slavery started not long after slavery ended. More than 150 years later, reparations for slavery, Jim Crow, and ongoing racial discrimination still <a href="https://polsci.umass.edu/toplines-and-crosstabs-april-2021-slavery-reparation-payments-blm-and-dc-puerto-rico-statehood">do not have broad popular support</a> — but activists are keeping the age-old conversation alive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NZd8c0">
The Democratic primaries for the 2020 election briefly seemed like a breakthrough. Candidates for the presidency spoke out about reparations — many<strong> </strong><a href="https://www.vox.com/policy-and-politics/2019/3/11/18246741/reparations-democrats-2020-inequality-warren-harris-castro">expressed approval</a>, while others deflected — and America’s duty to provide redress for centuries of injustice. After the mass racial justice uprisings of that year in response to the police killings of unarmed Black Americans, talk about reparations only grew. When Joe Biden secured the presidency, his administration promised to launch a study of reparations. Yet, almost two years into his presidency, he hasn’t — nor has he even uttered the word about it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QRPrxD">
In May, a coalition of human rights organizations and social justice groups <a href="https://www.vox.com/the-highlight/23133146/reparations-freedom-cash-payment">urged</a> Biden to issue an executive order to create a commission to study reparations, bypassing HR 40, the bill first introduced in 1989 that would create the commission. The Biden administration has not responded.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RMEd4V">
For the next four weeks on <em>Vox Conversations</em>, through a <a href="https://www.vox.com/e/23093413">new series called 40 Acres</a>, I’m having conversations with activists, scholars, and a philanthropist that explore what reparations mean right now and where the fight is going.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1NsI0I">
I reached out to one of the letter’s signatories — Nkechi Taifa, a lawyer, scholar, activist, and longtime reparations advocate — for the latest episode of <em>Vox Conversations</em> and for the first episode of the <a href="https://www.vox.com/e/23093413">series</a>. Taifa has pushed for reparations for 50 years. She helped found N’COBRA — the National Coalition of Blacks for Reparations in America — in the 1980s, the organization that helped the late US Rep. John Conyers write HR 40, and is the founder of the nonprofit organization the Reparation Education Project.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OJuq1Q">
In our conversation, Taifa starts with the 1970s, when she first learned about reparations, and explains how the idea moved from the “radical fringe” to the mainstream.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="udQ159">
“Reparations was radical and fringe, but it was on the platform of just about any and every organization that was dealing with Black folks back then in the ’60s and ’70s,” Taifa told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3XUc14">
At a time when racial justice progress is facing backlash, Taifa makes a renewed case for reparations: “Everything that’s going on today leaves me very, very hopeful that it will in fact happen in my lifetime. I’m confident that there will be a national reckoning on race in America, and that reckoning will not be complete until there is reparatory justice,” Taifa said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z0qcso">
Below is an excerpt of our conversation, edited for length and clarity. There’s much more in the full podcast, so subscribe to <em>Vox Conversations</em> on <a href="https://apps.apple.com/us/app/vox-conversations/id1215557536">Apple Podcasts</a>, <a href="https://podcasts.google.com/search/vox%20conversations">Google Podcasts</a>, <a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP">Spotify</a>, <a href="https://www.stitcher.com/show/vox-conversations">Stitcher</a>, or wherever you listen to podcasts.
</p>
<div id="E0Ij0o">
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="unlgbZ">
</p>
<hr class="p-entry-hr" id="6ABcVN"/>
<h4 id="D1tnkR">
Fabiola Cineas
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Aeur5X">
What are reparations?
</p>
<h4 id="HznnVI">
Nkechi Taifa
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JJVGYu">
Reparations are what is owed for human rights abuses, usually in the aftermath of war or other gross injustices, such as enslavement, but also to the descendants of those who were adversely impacted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hHVjtQ">
In the context of Black people in this country, I always say that reparations are for injustices, not just for the enslavement era but for its living legacies that continue down through to today. It involves the historic acknowledgment of historic wrong and a recognition that the injury continues. It involves a commitment to redress. It also involves all the culpable parties, whether it’s the United States government, state and local governments, academic or religious institutions, corporations, private estates — any entity that was culpable and [that] has accrued unjust enrichment from the era.
</p>
<h4 id="xcvj8n">
Fabiola Cineas
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0W0FPK">
What was it like to advocate for reparations back [when you helped found N’COBRA in the ’80s], when there was so much pushback to like ideas like affirmative action? And we still see pushback to affirmative action today. Can you talk about any kind of pressure you faced to not be talking about reparations?
</p>
<h4 id="MJ8CSH">
Nkechi Taifa
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WzhRHO">
Oh, yeah. I was constantly laughed at and ridiculed. They would say, “There go Nkechi again!” Never did I dream that the seeds that I was planting back in those days where I was ridiculed and ostracized — that I just might be able to stand under the shade of those trees that were planted with those seeds.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7MC6Ix">
So, you know, it’s like, how do you keep your eyes on the prize? Or keep struggling when it seems like all the odds are against you? You do it because there’s just a profound sense within you and within your bones for justice.
</p>
<h4 id="HcQKok">
Fabiola Cineas
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ok6aOE">
You say that reparations is an idea whose time has come. My question is why now? And why do you feel like there’s so much conversation about reparations right now?
</p>
<h4 id="AMVMvZ">
Nkechi Taifa
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uFkuwJ">
I call George Floyd the Emmett Till of the 21st century. Emmett Till served to galvanize not only people in this country, but [also people] across the world, to see the injustices that were happening here.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2KjZLa">
I think the election of Donald Trump had a lot to do with this. The blinders were stripped off of people’s eyes that, well, maybe we’re not quite in this kumbaya moment that we thought we were in. [With] the January 6 insurrection at the Capitol, people saw raw, naked violence by white people who seemed to have a continuous strand of the mentalities from the past. I think masses of Black people are waking up and saying, “Well, reparations needs to be part of this mix as well.” This is now an issue whose time has come.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wyis3K">
<em>The </em>40 Acres Vox Conversations<em> series explores where the reparations debate stands now and where it is headed. This series is made possible by a grant from the Robert Wood Johnson Foundation to Canopy Collective, an independent initiative under fiscal sponsorship of Multiplier. All Vox reporting is editorially independent and produced by our journalists. Views expressed are not necessarily those of Canopy Collective or the Robert Wood Johnson Foundation</em>.
</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>A top-16 finish will be great, feels Sathiyan</strong> - Sharath says the men’s team has the capability and firepower to take on the best in the world</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>Indian women’s national team players Guguloth, Jyoti join Croatia’s Dinamo Zagreb; first ever overseas recruits for the club</strong> -</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>ISL 2022-23 season to begin on October 7 with Kerala Blasters vs East Bengal</strong> - Indian Super League matches for the 2022-23 season are scheduled between Thursday and Sunday, bringing the ISL in line with the top global football leagues</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>AIFF Polls: Kalyan vs. Bhaichung as football body set to get first ‘Player President’</strong> - On the eve of AIFF polls, 45-year-old Bhaichung Bhutia, one of the biggest legends in Indian football, will have a straight fight with former Mohun Bagan and East Bengal goalkeeper Kalyan Chaubey</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>Transfer deadline day 2022: Premier League clubs not finished after $2 billion outlay</strong> - A wild summer transfer window is coming to an end with English Premier League clubs still very active in the market despite already spending more than $2 billion on new players</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>Commercial LPG price reduced</strong> - Hoteliers in Chennai welcome the move and want relief in GST rates</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's electricity grid to be more future ready, insulated from cyber attacks soon: Union Power Minister</strong> - Electricity Amendment Bill, 2022 to make provisions for inspection of the national electricity grid for maintaining cyber hygiene in the network</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>Norwegian fellowship for Cusat students</strong> - Youth to meet eminent professors from NTNU, besides visiting cutting edge research labs</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>Police detain three on rape charge in Kannur</strong> - Gang-rape of a woman who had come to Kannur a week back in search of work</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>Housing satisfaction for CAPF jawans to go up to 74% by 2024: Amit Shah</strong> - Union Home Minister launched the ‘eAwas’ portal saying the government has been able to enhance the housing satisfaction for the troops of the CAPF by 13%</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>Russian oil chief Maganov dies in ‘fall from hospital window’</strong> - Lukoil boss Ravil Maganov is the latest Russian businessman to die in mysterious circumstances.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In the east, Ukraine braces to launch counter-attack</strong> - Quentin Sommerville reports from the Donbas front line as Ukraine tries to seize the initiative from 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>Spain’s Tomatina food fight returns after Covid hiatus</strong> - Thousands of people have gathered in the town of Buñol to splatter each other with tomatoes.</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>EU Russia: Bloc toughens visa regime but no ban</strong> - The bloc remains divided on whether to issue a total ban on entry for Russian travellers.</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>Munich Olympics massacre compensation deal struck</strong> - Nearly 50 years after 11 Israeli athletes were killed, the German government agrees to pay relatives €28m.</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>Hands-on: Lenovo’s second foldable PC addresses the first’s biggest problems</strong> - A bigger screen, better specs, and more fitting OS could finally make foldable PCs a thing. - <a href="https://arstechnica.com/?p=1876903">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Microsoft finds TikTok vulnerability that allowed one-click account compromises</strong> - Flaw resided in the app’s deeplink verification process. - <a href="https://arstechnica.com/?p=1877506">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>19th century art form revived to make tactile science graphics for blind people</strong> - “Everything I can see with my eyes, a person who is blind can feel with their fingers.” - <a href="https://arstechnica.com/?p=1874119">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>FCC has approved $6 billion in broadband grants despite rejecting Starlink</strong> - Fixed wireless and fiber ISPs get money as FCC continues cleanup of Pai program. - <a href="https://arstechnica.com/?p=1877448">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AI wins state fair art contest, annoys humans</strong> - Stealth win for AI-generated art inspires heated ethics debate on social media. - <a href="https://arstechnica.com/?p=1877433">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>A mathematics professor noticed that his kitchen sink at his home leaked</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The plumber came the next day and sealed a few screws, and everything was working as before.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The professor was delighted. However, when the plumber gave him the bill a minute later, he was shocked.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“This is one-third of my monthly salary!” he yelled.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Well, all the same he paid it and then the plumber said to him, “I understand your position as a professor. Why don’t you come to our company and apply for a plumber position? You will earn three times as much as a professor. But remember, when you apply, tell them that you completed only seven elementary classes. They don’t like educated people.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So it happened. The professor got a job as a plumber and his life significantly improved. He just had to seal a screw or two occasionally, and his salary went up significantly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One day, the board of the plumbing company decided that every plumber had to go to evening classes to complete the eighth grade. So, our professor had to go there too. It just happened that the first class was math. The evening teacher, to check students’ knowledge, asked for a formula for the area of a circle. The person asked was the professor. He jumped to the board, and then he realized that he had forgotten the formula. He started to reason it, and he filled the white board with integrals, differentials, and other advanced formulas to conclude the result he forgot. As a result, he got “minus pi times r square.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He didn’t like the minus, so he started all over again. He got the minus again. No matter how many times he tried, he always got a minus. He was frustrated. He gave the class a frightened look and saw all the plumbers whisper: “Switch the limits of the integral!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Esqimoo"> /u/Esqimoo </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/x2uedv/a_mathematics_professor_noticed_that_his_kitchen/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/x2uedv/a_mathematics_professor_noticed_that_his_kitchen/">[comments]</a></span></p></li>
<li><strong>I took my wife to the doctor’s to sort our her Tourette’s.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Turns out she she doesn’t have it after all. I am a cunt and she does want me to fuck off.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/127peter"> /u/127peter </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/x2dct3/i_took_my_wife_to_the_doctors_to_sort_our_her/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/x2dct3/i_took_my_wife_to_the_doctors_to_sort_our_her/">[comments]</a></span></p></li>
<li><strong>My girlfriend said to me “Are you even listening to me?!”</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Strange way to start a conversation.
</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/friendlyfitnessguy"> /u/friendlyfitnessguy </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/x34umb/my_girlfriend_said_to_me_are_you_even_listening/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/x34umb/my_girlfriend_said_to_me_are_you_even_listening/">[comments]</a></span></p></li>
<li><strong>When you think about it, a vagina is a lot like a university.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They’re both a lot easier to get into, if you’re rich or an athlete.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Mattski1984"> /u/Mattski1984 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/x2gn7b/when_you_think_about_it_a_vagina_is_a_lot_like_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/x2gn7b/when_you_think_about_it_a_vagina_is_a_lot_like_a/">[comments]</a></span></p></li>
<li><strong>3 jokes told to me by an older gentleman at the grocery store</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Have you heard the one about the jump rope? That’s OK we’ll skip it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Have you heard the one about the bed? It hasn’t been made up yet.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Do you know why blind people don’t skydive? It scares the hell out of the dog.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Backstory: I have pretty severe PTSD and things like running to the grocery store for food are very hard for me because they get very frustrating. As I was leaving some people were moving rather sluggishly out the door and I was stuck behind them since they were taking up the entire path. I believe that my frustration was visible. An older gentleman behind me who I believe saw this visible frustration then told me these three jokes. Thank you sir for the distraction and laugh.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/golde62"> /u/golde62 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/x2rtrf/3_jokes_told_to_me_by_an_older_gentleman_at_the/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/x2rtrf/3_jokes_told_to_me_by_an_older_gentleman_at_the/">[comments]</a></span></p></li>
</ul>
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