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<title>15 September, 2023</title>
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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>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Factors associated with teenage pregnancies during the Covid-19 period in Pakwach district, Northern Uganda: a case-control study</strong> -
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Abstract Background: Teenage pregnancy rates have globally decreased over the years, but remain high, especially in low- and middle-income countries (LMICs). Among girls aged 15-19, teenage pregnancy remains the leading cause of death and a significant barrier to education and productivity. Its prevalence underscores concern about the sexual and reproductive health of youth. However, limited data exist regarding factors contributing to its rise during the COVID-19 pandemic in Uganda. This study explores the factors associated with teenage pregnancy in Pakwach district during this period. Methods: We conducted a matched case-control study, enrolling 362 teenage girls aged 10-19 years, divided into two groups: 181 pregnant teenagers and 181 not pregnant teenagers. We collected exposure data from both groups using questionnaires to evaluate factors associated with teenage pregnancy. The study period covered March 2020 to January 2021, coinciding with lockdown measures. Results: During the COVID-19 lockdown, teenage pregnancies were only associated with having exclusively female peers (AOR 3.0, 95% CI: 0.1-104.4). Conversely, having a Radio/TV at home (AOR 0.2, 95% CI: 0.1-0.6), age at first sexual encounter (AOR 0.1, 95% CI: 0.03-0.9), considering teenage pregnancy as sexual abuse (AOR 0.1, 95% CI: 0.02-0.4), feeling comfortable asking questions during consultations (AOR 0.5, 95% CI: 0.2-1.3), and ensuring sufficient privacy during consultations were protective against teenage pregnancy. Conclusion: The factors contributing to increased teenage pregnancies during the COVID-19 pandemic were consistent with long-standing contextual factors associated with teenage pregnancy. The lockdown environment may have slightly exacerbated these factors, but no direct association was observed. Only having female peers was linked to teenage pregnancy during the lockdown. Conversely, having access to a radio/TV at home and other healthcare system-related factors offered protection. Therefore, interventions should prioritize providing comprehensive information on the risks of teenage pregnancy during any lockdown scenario.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.13.23295521v1" target="_blank">Factors associated with teenage pregnancies during the Covid-19 period in Pakwach district, Northern Uganda: a case-control study</a>
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<li><strong>How COVID-19 continues to affect contraception in Scotland: a retrospective analysis of Scottish prescribing data between 2016 and 2023.</strong> -
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Background In Scotland, the effects of the COVID-19 pandemic on women9s access to contraception are unknown. Globally, COVID-19 restrictions have led to a shift to telehealth service delivery alongside a reduction in contraceptive provision. Research into whether the effects of COVID-19 on contraception have abated after restrictions have been lifted is lacking. Methods This is a retrospective longitudinal study of prescribing data from the Scottish Health and Social Care Open Data repository (https://www.opendata.nhs.scot) between January 2016 and January 2023. Contraceptives were extracted and categorised using truncated British National Formulary codes and analysed using R. Contraceptive provision was compared across four periods: pre-COVID-19 (01/01/2016-23/03/2020), lockdown (24/03/2020-9/05/2020 &amp; 05/01/2021-26/04/2021), restrictions (30/05/2020-04/01/2021 &amp; 27/04/2021-30/04/2022), and post-COVID-19 (01/05/2022-01/01/2023). Results During lockdowns, contraceptive prescribing in Scotland decreased by 82.90% of pre-COVID-19 levels. This trend was more severe for long-acting reversible contraception which fell to 11.80% of pre-COVID-19 prescriptions. After COVID-19, the level of contraceptive prescribing has risen to 108.23% of its pre- pandemic level. Large increases in subcutaneous medroxyprogesterone acetate (499.05%), progestogen- only pills (125.07%), the patch (165.09%), levonorgestrel-IUS (112.54%), and ulipristal acetate emergency contraception prescribing (357.97%). Conversely, combined oral contraceptive pills (75.04%), Cu-IUD (83.63%), the implant (81.10%), and levonorgestrel emergency contraception (67.42%) prescribing has decreased. Conclusions COVID-19 vastly decreased contraceptive prescribing during lockdowns in Scotland. Post-COVID-19, changes in contraceptive prescribing within Scottish general practices are reported, with implications for health policy and service delivery planning.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.14.23295542v1" target="_blank">How COVID-19 continues to affect contraception in Scotland: a retrospective analysis of Scottish prescribing data between 2016 and 2023.</a>
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<li><strong>Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19</strong> -
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The long-term health effects of SARS-CoV-2, termed Post-Acute Sequelae of COVID-19 (PASC), are quickly evolving into a major public health concern, but the underlying cellular and molecular etiology remain poorly defined. There is growing evidence that PASC is linked to abnormal immune responses and/or poor organ recovery post-infection. However, the exact processes linking non-resolving inflammation, impaired tissue repair, and PASC are still unclear. In this report, we utilized a cohort of respiratory PASC patients with viral infection-mediated pulmonary fibrosis and a clinically relevant mouse model of post-viral lung sequelae to investigate the pathophysiology of respiratory PASC. Using a combination of imaging and spatial transcriptomics, we identified dysregulated proximal interactions between immune cells and epithelial progenitors unique to respiratory PASC but not acute COVID-19 or idiopathic pulmonary fibrosis (IPF). Specifically, we found a central role for lung-resident CD8+ T cell-macrophage interactions in maintaining Krt8hi transitional and ectopic Krt5+ basal cell progenitors, and the development of fibrotic sequelae after acute viral pneumonia. Mechanistically, CD8+ T cell derived IFN-{gamma} and TNF stimulated lung macrophages to chronically release IL-1{beta}, resulting in the abnormal accumulation of dysplastic epithelial progenitors in fibrotic areas. Notably, therapeutic neutralization of IFN-{gamma} and TNF, or IL-1{beta} after the resolution of acute infection resulted in markedly improved alveolar regeneration and restoration of pulmonary function. Together, our findings implicate a dysregulated immune-epithelial progenitor niche in driving respiratory PASC and identify potential therapeutic targets to dampen chronic pulmonary sequelae post respiratory viral infections including SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.13.557622v1" target="_blank">Proximal immune-epithelial progenitor interactions drive chronic tissue sequelae post COVID-19</a>
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<li><strong>Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism</strong> -
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TMEM106B is an endolysosomal transmembrane protein not only associated with multiple neurological disorders including frontotemporal dementia, Alzheimer’s disease, and hypomyelinating leukodystrophy but also potentially involved in COVID-19. Additionally, recent studies have identified amyloid fibrils of C-terminal TMEM106B in both aged healthy and neurodegenerative brains. However, so far little is known about physiological functions of TMEM106B in the endolysosome and how TMEM106B is involved in a wide range of human conditions at molecular levels. Here, we performed lipidomic analysis of the brain of TMEM106B-deficient mice. We found that TMEM106B deficiency significantly decreases levels of two major classes of myelin lipids, galactosylceramide and its sulfated derivative sulfatide. Subsequent co-immunoprecipitation assay showed that TMEM106B physically interacts with galactosylceramidase. We also found that galactosyceramidase activity was significantly increased in TMEM106B-deficient brains. Thus, our results reveal a novel function of TMEM106B interacting with galactosyceramidase to regulate myelin lipid metabolism and have implications for TMEM106B-associated diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.14.557804v1" target="_blank">Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism</a>
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<li><strong>Towards mitigating health inequity via machine learning: a nationwide cohort study to develop and validate ethnicity-specific models for prediction of cardiovascular disease risk in COVID-19 patients</strong> -
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Background Emerging data-driven technologies in healthcare, such as risk prediction models, hold great promise but also pose challenges regarding potential bias and exacerbation of existing health inequalities, which have been observed across diseases such as cardiovascular disease (CVD) and COVID-19. This study addresses the impact of ethnicity in risk prediction modelling for cardiovascular events following SARS-CoV-2 infection and explores the potential of ethnicity-specific models to mitigate disparities. Methods This retrospective cohort study utilises six linked datasets accessed through National Health Service (NHS) England9s Secure Data Environment (SDE) service for England, via the BHF Data Science Centre9s CVD-COVID-UK/COVID-IMPACT Consortium. Inclusion criteria were established, and demographic information, risk factors, and ethnicity categories were defined. Four feature selection methods (LASSO, Random Forest, XGBoost, QRISK) were employed and ethnicity-specific prediction models were trained and tested using logistic regression. Discrimination (AUROC) and calibration performance were assessed for different populations and ethnicity groups. Findings Several differences were observed in the models trained on the whole study cohort vs ethnicity-specific groups. At the feature selection stage, ethnicity-specific models yielded different selected features. AUROC discrimination measures showed consistent performance across most ethnicity groups, with QRISK-based models performing relatively poorly. Calibration performance exhibited variation across ethnicity groups and age categories. Ethnicity-specific models demonstrated the potential to enhance calibration performance for certain ethnic groups. Interpretation This research highlights the importance of considering ethnicity in risk prediction modelling to ensure equitable healthcare outcomes. Differences in selected features and asymmetric calibration across ethnicities underscore the necessity of tailored approaches. Ethnicity-specific models offer a pathway to addressing disparities and improving model performance. The study emphasises the role of data-driven technologies in either alleviating or exacerbating existing health inequalities. Keywords Prediction, machine learning, electronic health records, bias, ethnicity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.13.23295489v2" target="_blank">Towards mitigating health inequity via machine learning: a nationwide cohort study to develop and validate ethnicity-specific models for prediction of cardiovascular disease risk in COVID-19 patients</a>
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<li><strong>The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons</strong> -
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The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes, which was confirmed in a COVID-19 mouse model. These findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295190v2" target="_blank">The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons</a>
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<li><strong>Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey</strong> -
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Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over two years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. Methods: We used data from the Real-Time Insights of COVID-19 in India (RTI COVID-India) cohort study (N=3,662). We used covariate-adjusted linear regression models with generalized estimating equations to assess associations between mental health (PHQ-4 score) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender, and rural/urban residence. Results: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p&lt;0.001). PHQ-4 scores were significantly and independently associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.041 SD units; 95% Confidence Interval 0.030 - 0.053), government stringency index (0.060 SD units; 0.048 - 0.072), self-reported major financial impacts (0.45 SD units; 0.41-0.49), and COVID-19 infection in the household (0.11 SD units; 0.07-0.16). Conclusion: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-age and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.13.23295513v1" target="_blank">Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey</a>
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<li><strong>Neonatal outcomes after proteomic biomarker-guided intervention: the AVERT PRETERM TRIAL</strong> -
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Background Vaginal progesterone, low dose aspirin and care management (comprising increased outreach and education) has been shown to reduce the rate of prematurity in select populations, but identifying at-risk pregnancies has been problematic. 2. Objective(s) Test the hypothesis that screening singleton, non-anomalous pregnancies lacking traditional clinical risk factors with a validated blood test for preterm birth risk prediction, then targeting those with elevated risk for preventive treatment, would improve neonatal outcomes as compared to a large historical population. 3. Study Design The study took place from June 2018-September 2020 at ChristianaCare Hospital (Newark, DE). Singleton non-anomalous pregnancies with no history of preterm birth were enrolled in a prospective study arm and followed through neonatal hospital discharge. Participants were screened using a serum proteomic test for spontaneous preterm birth risk during a gestational age window spanning 19 1/7-20 6/7 weeks. Pregnancies identified by the test to be at elevated risk for preterm birth (≥16.0%, approximately twice the U.S. population risk) were offered aspirin 81 mg daily, open-label vaginal progesterone 200 mg daily and care management. We compared outcomes for women who screened either low-risk or higher-risk accepting treatment with those in a historical study arm of 10,000 pregnancies. Our co-primary outcomes were neonatal hospital length of stay and an ordinal neonatal morbidity index score based on the occurrence of grade III/IV interventricular hemorrhage, necrotizing enterocolitis (Bell stage II/III), respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity (stage III), sepsis, and neonatal death or neonatal intensive care unit length of stay. Cox proportional hazards survival analysis and ordinal logistic regression were utilized to evaluate outcomes and control for population differences. 4. Results A total of 1463 women were screened and tested before research operations were ceased due to the advent of the COVID-19 pandemic, and three women were subsequently deemed ineligible after screening. Of these, 34.72% (507/1460) were deemed high-risk, with 56.41% (286/507) accepting intervention and 43.59% (221/507) forgoing intervention. The remaining 65.3% (953/1460) were designated as low-risk. Women in the prospective arm were older, more obese, more likely to have hypertension and smoke, and less likely to use opioids compared to women in the historical arm. The primary analyses found that neonates in the prospective arm were discharged from the hospital earlier (P=0.01; hazard ratio, 1.35; 95% confidence interval, 1.08-1.70) and had lower neonatal morbidity index scores (P=0.031; odds ratio, 0.81; 95% confidence interval, 0.67-0.98). Average neonatal hospital length of stay decreased by 21%, and severe neonatal morbidity (neonatal morbidity index ≥3) was reduced on average by 18%. 5. Conclusions Identifying singleton, non-anomalous pregnancies lacking traditional risk factors with a validated proteomic blood test for preterm birth risk and providing treatment to those at risk resulted in improved neonatal outcomes compared to controls in a racially diverse cohort. This test-and-treatment strategy shows promise for ameliorating the impacts of premature birth among individuals in this previously unidentified patient population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.13.23295503v1" target="_blank">Neonatal outcomes after proteomic biomarker-guided intervention: the AVERT PRETERM TRIAL</a>
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<li><strong>Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</strong> -
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Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers of de novo responses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on these de novo responses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naive B cells. We conclude that dampened de novo B cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.12.23295384v2" target="_blank">Determinants of de novo B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</a>
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<li><strong>Risk of Coronavirus Disease 2019 (COVID-19) among Those Up-to-Date and Not Up-to-Date on COVID-19 Vaccination by US CDC Criteria</strong> -
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Background. The CDC recently defined being 9up-to-date9 on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those 9up-to-date9 and 9not up-to-date9. Methods. Employees of Cleveland Clinic in Ohio, USA, in employment when the COVID-19 bivalent vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the 9up-to-date9 and 9not up-to-date9 states, by treating COVID-19 bivalent vaccination as a time-dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also evaluated using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, most recent prior SARS-CoV-2 infection, and number of prior vaccine doses. Results. COVID-19 occurred in 1475 (3%) of 48 344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the 9not up-to-date9 than the 9up-to-date9 state. On multivariable analysis, being 9up-to-date9 was not associated with lower risk of COVID-19 (HR, 1.05; 95% C.I., 0.88-1.25; P-value, 0.58). Results were very similar when those 65 years and older were only considered 9up-to-date9 after 2 doses of the bivalent vaccine. Conclusions. Since the XBB lineages became dominant, adults 9up-to-date9 on COVID-19 vaccination by the CDC definition do not have a lower risk of COVID-19 than those 9not up-to-date9, bringing into question the value of this risk classification definition.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23290893v2" target="_blank">Risk of Coronavirus Disease 2019 (COVID-19) among Those Up-to-Date and Not Up-to-Date on COVID-19 Vaccination by US CDC Criteria</a>
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<li><strong>Effectiveness of Canadian travel restrictions in reducing burden of SARS-CoV-2 variants of concern</strong> -
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Evaluating travel restriction effectiveness in mitigating infectious disease burden is critical for informing public health policy. Here, we quantify where and when variants of SARS-CoV-2 were introduced into Canada to evaluate the extent to which travel restrictions averted viral introductions and COVID-19 case burden. Our results suggest that, across SARS-CoV-2 variants of concern subject to travel restrictions, at least 281 introductions were prevented, accounting for an averted burden of approximately 44,064 cases. This corresponds to approximately 441 averted hospitalizations, 24 averted deaths, and cost savings to Canadian health care systems of approximately $11.2 million Canadian dollars. Travel restrictions were found to be most effective when implemented rapidly during exponential case growth in the focal source and when global circulation was limited. Our analyses reveal that COVID-19 travel restrictions mitigated case burdens and highlight their value in future pandemic response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.12.23294140v1" target="_blank">Effectiveness of Canadian travel restrictions in reducing burden of SARS-CoV-2 variants of concern</a>
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<li><strong>Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer</strong> -
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Observational studies are being used more and more in psychology and medicine since they provide a wealth of data for real-world issues. Their biggest drawback is the lack of falsification due to the control mechanisms of control conditions being unavailable. However, the Covid-19 pandemic and the isolation policies related to it have provided an environment in which researchers can use natural experimental design to establish causal pathways in phenomena. Here we demonstrate how Covid-19-related changes can be used to investigate causal effects behind Home Advantage (HA), a robust phenomenon in which sport teams are more successful when they play in front of their fans. HA theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. Covid-19 has provided the perfect control condition for disentangling the causal links of the HA as sport teams have played at home but without the presence of fans. Using our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously instead of in isolation as was previously the case, we demonstrate how Covid-19 enables us to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, our paper also provides information about the practical implementation of mediation and moderated mediation mixed-effects models in the Bayesian framework. Similar implementations can be adapted in other medical and social science fields.
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🖺 Full Text HTML: <a href="https://osf.io/vz7de/" target="_blank">Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer</a>
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<li><strong>Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model</strong> -
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Home Advantage (HA) is a robust phenomenon in which sport teams or individuals are more successful when they play in front of their fans. There are a number of causes of HA, but most theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. The interest in HA has grown during the Covid-19 pandemic as most competitions were taking place behind closed doors, a perfect control condition for disentangling the causal effects behind HA. Despite the presence of useful conceptual frameworks, most previous research has focused on investigating isolated individual factors. Here we review our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously. HAM assumes that the crowd effects are mediated through other relevant factors, such as referee bias and team performance. Most importantly, HAM can be formally expressed as a mediation model, a technique widely employed in social sciences for investigating causal pathways. We demonstrate how researchers can use HAM to model the HA in European football and how moderating variables, such as Covid-19 and absence of fans, can be incorporated in the model to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, we also provide information about practical implementation of mediation and moderated mediation models in the Bayesian framework. Similar implementations can be adapted for use in other sport science domains.
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🖺 Full Text HTML: <a href="https://osf.io/c8tu3/" target="_blank">Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model</a>
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<li><strong>The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</strong> -
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The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
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🖺 Full Text HTML: <a href="https://osf.io/d3xat/" target="_blank">The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions</a>
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<li><strong>Home Advantage during the COVID-19 Pandemic in European football</strong> -
<div>
The home advantage (HA) is a robust phenomenon in soccer whereby the home team wins more games and scores more goals than the away team. One explanation is that the home crowd spurs on home team performance and causes the referee to unconsciously favour the home team. The Covid-19 pandemic provided a unique opportunity to assess this explanation for HA, as European soccer leagues played part of the 2019/2020 season with crowds present and concluded with crowds absent. Using multi-level modelling we compared team performance and referee decisions pre-Covid (crowd present) and post-Covid (crowd absent) across 9,528 games from 15 leagues in 11 countries. HA (goals scored and points gained) was significantly reduced post pandemic, which reflected the inferior performance of the home team. In addition, referees awarded significantly fewer sanctions against the away teams, and home teams created significantly fewer attacking opportunities when they played without fans.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/2gkht/" target="_blank">Home Advantage during the COVID-19 Pandemic in European football</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 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: hAd5-S-Fusion+N-ETSD;   Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>:   ImmunityBio, Inc.<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>:   Immunosuppression;   COVID-19<br/><b>Intervention</b>:   Biological: NVX-CoV2372<br/><b>Sponsors</b>:   University of Wisconsin, Madison;   Novavax<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>Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration<br/><b>Interventions</b>:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention<br/><b>Sponsors</b>:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>:   Bronchoalveolar Lavage<br/><b>Intervention</b>:   Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>:   Mohamed Abd Elmoniem Mohamed;   Marwa Salah Abdelrazek Ghanem;   Mohammad Khairy El-Badrawy;   Tamer Ali Elhadidy;   Dalia Abdellateif Abdelghany<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203)</strong> - <b>Conditions</b>:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>:   Biological: LEM-mR203;   Biological: Placebo<br/><b>Sponsor</b>:   Lemonex<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 I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Intervention</b>:   Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)<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 Determine the Tolerability of Intranasal LMN-301</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: LMN-301<br/><b>Sponsor</b>:   Lumen Bioscience, Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Cognitive Behavioral Therapy on Post-Traumatic Stress Symptoms in Nursing Students</strong> - <b>Condition</b>:   Trauma and Stressor Related Disorders<br/><b>Intervention</b>:   Other: Cognitive Behavioral Therapy Group<br/><b>Sponsor</b>:   Necmettin Erbakan University<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID Immune Profiling</strong> - <b>Conditions</b>:   Long COVID;   POTS - Postural Orthostatic Tachycardia Syndrome;   Autonomic Dysfunction<br/><b>Interventions</b>:   Diagnostic Test: IL-6;   Diagnostic Test: cytokines (IL-17, and IFN-ɣ);   Behavioral: Compass 31<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   American Heart Association<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>:   Critical Illness;   COVID-19;   PICS;   Cognitive Impairment;   Mental Health Impairment;   Weakness, Muscle;   Dysbiosis<br/><b>Intervention</b>:   Behavioral: Fermented Food Diet<br/><b>Sponsor</b>:   Mayo Clinic<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>Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase</strong> - Since the outbreak of the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) has become a main target for antiviral therapeutics due to its essential role in viral replication and transcription. Thus, nucleoside analogs structurally resemble the natural RdRp substrate and hold great potential as inhibitors. Until now, extensive experimental investigations have been performed to explore nucleoside analogs to inhibit the RdRp, and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ebselen: A Review on its Synthesis, Derivatives, Anticancer Efficacy and Utility in Combating SARS-COV-2</strong> - Ebselen is a selenoorganic chiral compound with antioxidant properties comparable to glutathione peroxidase. It is also known as 2-phenyl-1,2-benzisoselenazol-3(2H)-one. In studies examining its numerous pharmacological activities, including antioxidant, anticancer, antiviral, and anti-Alzheimer’s, ebselen has demonstrated promising results. This review’s primary objective was to emphasize the numerous synthesis pathways of ebselen and their efficacy in fighting cancer. The data were collected…</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>Molnupiravir: an antiviral drug against COVID-19</strong> - SARS-CoV-2, the virus responsible for COVID-19, has caused numerous deaths worldwide and poses significant challenges. Researchers have recently studied a new antiviral drug called molnupiravir for treating COVID-19. This review examines the causes and immunopathogenesis of COVID-19, as well as the role of molnupiravir in its treatment. Molnupiravir is a prodrug of β-D-N4-hydroxyctytidine (NHC) and has demonstrated activity against various viruses, including MERS-CoV, SARS-CoV, SARS-CoV-2, and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Overreactive macrophages in SARS-CoV-2 infection: The effects of ACEI</strong> - Among various factors influencing the course of SARS-CoV-2 infection in humans, macrophage overactivation is considered the main cause of the cytokine storm that leads to severe complications of COVID-19. Moreover, the increased expression of angiotensin converting enzyme 2 (ACE2), an obligatory entry receptor of the coronavirus, caused by treatment with ACE inhibitors (ACEI) lowered overall confidence in the safety of these drugs. However, analysis of the course of coronavirus infection in…</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>Omics data analysis reveals common molecular basis of small cell lung cancer and COVID-19</strong> - The impact of COVID-19 infection on individuals with small cell lung cancer (SCLC) poses a serious threat. Unfortunately, the molecular basis of this severe comorbidity has yet to be elucidated. The present study addresses this gap utilizing publicly available omics data of COVID-19 and SCLC to explore the key molecules and associated pathways involved in the convergence of these diseases. Findings revealed 402 genes, that exhibited differential expression patterns in SCLC patients and also play…</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>Whole genome CRISPR screening strategy to identify genes contributing to SARS-CoV-2 spike and VSV-G mediated entry</strong> - Understanding the cellular host factors that promote and inhibit viral entry is important for identifying viral countermeasures. CRISPR whole-genome screens can be used to rapidly discover host factors that contribute to or impair viral entry. However, when using live viruses and cellular lethality for selection, these screens can identify an overwhelming number of genes without specificity for the stage of the viral infection cycle. New screening methods are needed to identify host machinery…</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>On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine</strong> - RNA processing plays a key role in gene expression, allowing for increased protein diversity and functional complexity. Consequently, modulating RNA processing can impact gene function. Given HIV-1’s reliance on host RNA processing machinery for viral protein production/replication, modulators of this process could serve as novel anti-virals to complement and/or enhance existing therapies. In this study, screening of several serine-arginine-rich (SR) kinase inhibitors for their impact on HIV-1…</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>Association between levels of IgG antibodies from vaccines and Omicron symptomatic infection among children and adolescents in China</strong> - CONCLUSION: The risk of developing a symptomatic infection can be predicted independently by tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens. High IgG levels can inhibit viral replication, vastly reduce the risk of symptomatic infections and promote a virus-negative conversion, especially when IgG quantitative detection was ≥3.44 S/CO, a potential threshold for protection and booster strategy in the future. More data and research are needed in the future to validate the predictive…</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>Identification of essential genes associated with SARS-CoV-2 infection as potential drug target candidates with machine learning algorithms</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide concern. Several genes associated with the SARS-CoV-2, which are essential for its functionality, pathogenesis, and survival, have been identified. These genes, which play crucial roles in SARS-CoV-2 infection, are considered potential therapeutic targets. Developing drugs against these essential genes to inhibit their regular functions could be a good approach…</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>Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets</strong> - The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions…</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>Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge</strong> - Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including…</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>Suramin inhibits SARS-CoV-2 nucleocapsid phosphoprotein genome packaging function</strong> - The coronavirus disease 2019 (COVID-19) pandemic is fading, however its etiologic agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues posing - despite the availability of licensed vaccines - a global health threat, due to the potential emergence of vaccine-resistant SARS-CoV-2 variants. This makes the development of new drugs against COVID-19 a persistent urgency and sets as research priority the validation of novel therapeutic targets within the SARS-CoV-2 proteome….</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>Inhalable dry powder containing remdesivir and disulfiram: Preparation and in vitro characterization</strong> - The respiratory tract, as the first and most afflicted target of many viruses such as SARS-CoV-2, seems to be the logical choice for delivering antiviral agents against this and other respiratory viruses. A combination of remdesivir and disulfiram, targeting two different steps in the viral replication cycle, has showed synergistic activity against SARS-CoV-2 in-vitro. In this study, we have developed an inhalable dry powder containing a combination of remdesivir and disulfiram utilizing 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>MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS</strong> - Microvascular endothelial activation/dysfunction has emerged as an important mechanistic pathophysiological process in the development of morbidity and mortality in life-threatening infections. The angiopoietin-Tie2 system plays an integral role in the regulation of microvascular endothelial integrity. Angiopoietin-1 (Ang-1), produced by platelets and pericytes, is the cognate agonistic ligand for Tie2, promoting endothelial quiescence and inhibiting microvascular leak. Angiopoietin-2 (Ang-2),…</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>Prime editor-mediated functional reshaping of <em>ACE2</em> prevents the entry of multiple human coronaviruses, including SARS-CoV-2 variants</strong> - The spike protein of SARS-CoV-2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS-CoV-2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike-focused vaccines and therapeutics. Compared with the fast-evolving spike protein, targeting host ACE2…</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>The Secret Life and Anonymous Death of the Most Prolific War-Crimes Investigator in History</strong> - When Mustafa died, in the earthquakes in Turkey, his work in Syria had assisted in the prosecutions of numerous figures in Bashar al-Assad’s regime. - <a href="https://www.newyorker.com/news/a-reporter-at-large/the-secret-life-and-anonymous-death-of-the-most-prolific-war-crimes-investigator-in-history">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“They Didn’t Know That We Were Here”: New York’s African Asylum Seekers</strong> - A Harlem nonprofit works on behalf of hundreds of African migrants who are languishing in shelters, struggling with language barriers, and trying to make it in New York City. - <a href="https://www.newyorker.com/news/our-local-correspondents/they-didnt-know-that-we-were-here-new-yorks-african-asylum-seekers">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why Gen X Dads Can Appreciate Olivia Rodrigo</strong> - Rodrigo’s music suggests that an artist does not have to live through an era to evoke it. - <a href="https://www.newyorker.com/news/our-columnists/why-gen-x-dads-can-appreciate-olivia-rodrigo">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hasan Minhaj’s “Emotional Truths”</strong> - In his standup specials, the former “Patriot Act” host often recounts harrowing experiences he’s faced as an Asian American and Muslim American. Does it matter that much of it never happened to him? - <a href="https://www.newyorker.com/news/annals-of-communications/hasan-minhajs-emotional-truths">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Rage of the Toddler Caucus on Capitol Hill</strong> - Not even a Biden impeachment can soothe them out of a government shutdown. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/the-rage-of-the-toddler-caucus-on-capitol-hill">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Inside the very strange, very expensive race to “de-age”</strong> -
<figure>
<img alt="A man’s face is on a computer screen. The computer is connected to several obscure pieces of machinery, which lead to a more youthful-looking version of himself on a new screen." src="https://cdn.vox-cdn.com/thumbor/SxQNPwzhwoMLSB_xzAoaRUMmeVU=/480x0:1920x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72520937/Vox_DeAging_MinHeo.0.png"/>
<figcaption>
Min Heo for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Young blood,” starvation, fruit-only diets: How the rich are striving to “age in reverse”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9PSKNn">
Rich tech entrepreneurs are by all accounts a hyper-competitive bunch.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D5O2kT">
Whether it’s taking a <a href="https://www.vox.com/the-goods/22911159/new-space-age-billionaires-culture">shuttle to the edge of space</a>, buying the <a href="https://www.newyorker.com/magazine/2022/07/25/the-haves-and-the-have-yachts">biggest yacht</a>, or challenging one another to <a href="https://www.vox.com/culture/2023/6/23/23771769/musk-zuckerberg-cage-match-fight-ufc-mma">a cage fight</a>, with great wealth and power seems to come a voracious desire to engage in games of one-upmanship.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9LNPrD">
The <a href="https://rejuvenationolympics.com/">Rejuvenation Olympics</a>, an online leaderboard launched by tech millionaire Bryan Johnson earlier this year, takes the rivalry of the rich to the next level. The game? “Reversing” your age.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="go0J4Q">
Participants compete not on physical abilities but on how quickly and by how much they can slow their “biological age.” It’s almost who can be the best Benjamin Button. Competitors do this mostly by adjusting their diets (like which macronutrients and supplements they consume), being physically active, and retesting their “age” regularly. They’re not actually reverting to a more youthful version of themselves — that’s <a href="https://www.popularmechanics.com/science/health/a43510158/humans-can-stop-aging-but-not-reverse-it-study/">not biologically possible</a>. Rather, these competitors are racing to see who can age the slowest; as the Rejuvenation Olympics website quips, “You win by never crossing the finish line.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JmEYd3">
A few players of this peculiar game stand out: Steve Aoki, the DJ and heir to the Benihana restaurant chain, appears toward the bottom of the site’s “absolute” ranking, which reflects the 25 competitors with the lowest rate of aging. The biohacker Ben Greenfield makes the list, too, as does millionaire and longevity science advocate Peter Diamandis. Most of the top 25 names, however, don’t spark immediate recognition, and some are anonymous.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ONqU5c">
Right now, tech millionaire Bryan Johnson, who is 46 years old, is leading. But 46 is just what competitors describe as Johnson’s “chronological age,” which means, simply, the years that have passed since his birth date. According to one <a href="https://www.publichealth.columbia.edu/news/epidemiologists-develop-state-art-tool-measuring-pace-aging">well-known “biological age” test</a>, he’s aging at a rate slower than his chronological age. He has made waves for his outlandish lifestyle that’s oriented entirely toward the goal of not just appearing young, but becoming younger: He has claimed that he eats <a href="https://fortune.com/2023/07/14/bryan-johnson-spending-2-million-young-forever/">70 pounds of vegetables</a> per month, most of it pureed. He receives blood transfusions from his 17-year-old son. He wears a red-light cap that’s supposed to stimulate hair growth. His body fat once fell to a dangerous 3 percent (though it has since bumped up a few percentage points).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XZKaCC">
The Rejuvenation Olympics tend to attract this kind of person: those obsessed with collecting and analyzing their <a href="https://www.vox.com/health">personal health</a> data, with the financial means to experiment with the minutiae of their lifestyles. Yet Johnson and the other Olympics competitors are hardly alone in their expensive attempts to gain maximal health. Such extremes are common among the ultrarich, and particularly the Silicon Valley set, a crowd known for its obsession with making moonshot ideas into reality. <a href="https://www.vox.com/twitter">Twitter</a> founder <a href="https://www.vox.com/jack-dorsey">Jack Dorsey</a> is renowned for his eccentric wellness habits; he <a href="https://www.cnbc.com/2020/01/15/twitter-ceo-jack-dorsey-eats-seven-meals-every-week-only-dinner.html">eats one meal a day</a>, meditates for at least two hours daily, and has a penchant for ice baths. For a while, Steve Jobs was a “fruitarian” — as in, only ate fruit. The wealthy indulge in countless health trends of varying dubiousness, whether it’s getting IV drips to reduce hangovers, hyperbaric oxygen therapy, <a href="https://www.theguardian.com/science/2018/sep/21/extreme-biohacking-tech-guru-who-spent-250000-trying-to-live-for-ever-serge-faguet">implanting devices</a> in the body to monitor health and live longer, even <a href="https://www.vanityfair.com/news/2016/08/peter-thiel-wants-to-inject-himself-with-young-peoples-blood">injecting themselves with young blood</a> (a treatment called <a href="https://www.bloomberg.com/news/articles/2023-05-22/bryan-johnson-s-anti-aging-blood-transfusion-involves-dad-and-son">parabiosis, which Johnson is receiving</a>).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="drGCaD">
The optimized lifestyle, with its constant monitoring and regimentation, costs money. This year alone, Johnson will reportedly spend <a href="https://www.bloomberg.com/news/features/2023-01-25/anti-aging-techniques-taken-to-extreme-by-bryan-johnson">at least $2 million</a> on reducing his biological age.
</p>
<hr class="p-entry-hr" id="A9e0IO"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oX3reg">
There’s a certain hubris to the tech founders who insist they’ve cracked the code to a longer, healthier life. Society treats them as <a href="https://www.vox.com/the-goods/2022/12/20/23509726/billionaire-vibe-shift-elon-sbf-2022">idols, geniuses whose savvy has vaulted them into the 0.0001 percent</a> of the wealthiest people on Earth. It’s a small hop from there to believing they’d also be savvier than the rest of us about turning back the clock.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8o4Dj1">
Among various health and wellness fads, longevity is the pursuit receiving much of the attention — and money — from the ultrarich. Last year, according to <a href="https://longevity.technology/news/global-longevity-investment-hit-5-2-billion-in-2022/">a report</a> from the news and market analysis site <a href="https://longevity.technology/news/global-longevity-investment-hit-5-2-billion-in-2022/">Longevity.Technology</a>, more than $5 billion in investments poured into longevity-related companies worldwide, including from some big-name tech founders and investors. Many of these companies are aiming to prolong life by focusing on organ regeneration and gene editing. The buzzy life extension company Altos Labs, which researches biological reprogramming — a way to reset cells to pliable “<a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/pluripotent-stem-cell">pluripotent stem cells</a>” — launched last year with a whopping <a href="https://www.forbes.com/sites/stanfleming/2022/03/09/alta-labs-mega-startup-wretched-excess-or-the-future-of-biotechor-both/?sh=45a1839875bd">$3 billion investment</a>, and counts internet billionaire Yuri Milner and, reportedly, <a href="https://www.vox.com/amazon">Amazon</a> founder <a href="https://www.vox.com/jeff-bezos">Jeff Bezos</a> among its patrons. Bezos was also an investor in the anti-aging startup Unity Biotechnology.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TyDrMf">
OpenAI founder Sam Altman, meanwhile, recently <a href="https://www.technologyreview.com/2023/03/08/1069523/sam-altman-investment-180-million-retro-biosciences-longevity-death/">invested $180 million</a> in Retro Biosciences, a company vying to add a decade to the human lifespan. Some of the most famous names in the death-defying sector are old: Calico Labs, a longevity-research subsidiary of <a href="https://www.vox.com/alphabet">Alphabet</a>, was launched by<a href="https://www.theverge.com/2013/9/19/4748594/understanding-calico-larry-page-google-ventures-and-the-quest-for"> then-Google CEO Larry Page in 2013</a>. Nor is it just Silicon Valley that’s excited about the prospect of living longer. Tally Health, a new biotech company co-founded by Harvard scientist David Sinclair — who is something of a <a href="https://twitter.com/davidasinclair">celebrity in the longevity community</a> — boasts some <a href="https://www.fastcompany.com/90876849/tally-health-anti-aging-test">Hollywood A-list investors</a>: John Legend, Gwyneth Paltrow, Ashton Kutcher, <a href="https://www.vox.com/culture/23594371/last-of-us-pedro-pascal-daddy">Pedro Pascal</a>, and Zac Efron.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eI47nI">
Basically, if you’re anyone with any kind of serious money, chances are you’ve thrown some of it into the life-extension industry.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F2kPlN">
But all this hype and capital also means there’s a higher chance of being sold bullshit. Just because someone appears to be aging more slowly right now doesn’t mean they’ll live longer, and experts are highly skeptical of the idea of turning back the clock entirely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A0IH5H">
“Somebody’s got to blaze the trail,” but there are also plenty of companies offering snake oil, says Michael Lustgarten, a Rejuvenation Olympics competitor who has a PhD in physiology and is a scientist at Tufts University’s Human Nutrition Research Center on Aging. “The longevity community usually gets excited about snake oil — the latest supplement or the latest mouse study that extends lifespan.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PcKQf9">
“It’s not possible to reverse your age,” Stuart Jay Olshansky, an aging expert and professor of epidemiology and biostatistics at the University of Illinois Chicago, tells Vox. “There’s validity to some of the work that’s going on in epigenetics that may be telling us something about the rate of aging. It’s not yet telling us about longevity.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rkJUac">
Life extension does sound like pseudoscience at first blush, but epigenetics, which is concerned with how our genes are expressed depending on environment and lifestyle, is one field that’s widely considered promising, making immense strides over the past decade in unlocking the secrets of how we age.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="37cO4B">
The first epigenetic “clock” was devised by Steve Horvath in 2013, but personal epigenetic age tests for consumers started getting popular <a href="https://www.wired.com/story/new-tests-use-epigenetics-to-guess-how-fast-youre-aging/">just a few years ago</a>. (Contestants in the Rejuvenation Olympics take these tests to track their progress.) Epigenetic age testing can give us a rough idea of how old someone is chronologically if they don’t know — for example, if someone doesn’t have a birth certificate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NrKcKz">
More recent versions of the tests are offering clues not just to chronological age but to how much aging is happening biologically based on environmental factors and lifestyle habits, which can then potentially be used to predict the likelihood of disease or death. Here’s how it works: No two people age in the <a href="https://www.nm.org/healthbeat/medical-advances/science-and-research/What-is-Your-Actual-Age">exact same way</a>. Discrete from chronological age, “<a href="https://pubmed.ncbi.nlm.nih.gov/12849085/">biological age</a>” is the attempt to capture the often invisible difference through epigenetic gene expression, the state of someone’s organs, their immune system, and more. A 40-year-old with a history of heavy drinking and smoking, for example, may have a higher biological age than someone who never drinks or smokes. (In 2018, a Dutch man even complained that he ought to be able to <a href="https://bioethics.hms.harvard.edu/journal/legal-age-change">change his legal age</a> to match his biological age.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ulguZo">
The testing is nothing like an annual physical; it’s more a burgeoning wellness trend for those who have a few hundred dollars to spend on a home DNA test. The makers of such age tests contend that knowing your “biological age” can be the impetus for making healthy lifestyle changes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9UyWMS">
There is some promising evidence behind attempts to extend the human lifespan. Even “young blood” transfusion, despite seeming too <a href="https://en.wikipedia.org/wiki/Elizabeth_B%C3%A1thory">Elizabeth Báthory</a> to be a real medical procedure, has some legitimate science behind it — <a href="https://med.stanford.edu/news/all-news/2014/05/infusion-of-young-blood-recharges-brains-of-old-mice-study-finds.html">research</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764071/">has shown</a> <a href="https://www.nature.com/articles/s42003-020-0797-4">that parabiosis</a> (the scientific term for blood and plasma transfer) in mice can have regenerative effects on some cells. The trouble is that longevity startups often go too far with claims about what new evidence might mean for the future of human aging.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MytXBM">
“I’ve called the anti-aging industry the second-oldest profession,” says Olshansky. “People made the same claims 2,000 years ago about some magical elixir that’s going to make you live longer and healthier.” The difference is that the fountain of youth is now being “pushed by a lot of people who have a lot of money — to make more money.”
</p>
<hr class="p-entry-hr" id="KAnBYj"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kdx3f7">
Johnson, who made his hundreds of millions after selling a payments platform he developed to eBay in 2013, has become renowned not for what he’s invented, sold, or designed, as is the case for many other Silicon Valley entrepreneurs, but for the unimaginably strict lifestyle he leads. According to <a href="https://blueprint.bryanjohnson.co/">his website</a> and the <a href="https://www.vice.com/en/article/z34ay8/bryan-johnson-blueprint-aging-biotech">many interviews</a> he has given, he exerts constant vigilance over the 78 organs of the human body, consistently tracking everything from BMI to brain white matter. Johnson is often described as the “most measured man in human history.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WiLK8e">
The point isn’t merely being healthy. It’s laser-precision optimization of his health.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J76jOO">
Johnson, for example, never eats pizza or drinks alcohol. It’s simply not a part of his algorithm. “I was just a slave to myself and my passions and my emotions and my next desire,” he said in an <a href="https://www.vice.com/en/article/z34ay8/bryan-johnson-blueprint-aging-biotech">interview with Vice Motherboard</a>. That doesn’t mean he never stumbles, but when he does, he calls it an “infraction,” as though he has committed a minor crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Riuua">
Johnson tops the Rejuvenation Olympics leaderboard; he created the game along with Oliver Zolman — who leads Johnson’s team of 30-plus doctors and other health experts — and TruDiagnostic, an epigenetics lab based in Kentucky that provides the biological age test kits that participants in the Olympics must submit. The cheaper version costs $229. The more expensive one, at $499, provides <a href="https://trudiagnostic.com/products/biological-age-overall-immune-system-ages">more data</a> on your results, including how habits like smoking or drinking alcohol have impacted a person’s aging speed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ukFge3">
Hannah Went, director of operations at TruDiagnostic, tells Vox the company is hopeful that, eventually, a wider swath of consumers will join in on epigenetic testing. But right now, their clients tend to be wealthy — the kind of people who can dedicate money and time to de-aging. To date, almost 30,000 people have measured their biological age with Went’s lab, and a little more than 1,700 of them have consented to submit their results to the Rejuvenation Olympics. Only the top 25 are posted on the homepage rankings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dMNJrh">
Lustgarten, the Olympics competitor, believes he’ll move into the top 10 the next time the leaderboard is updated. Like other longevity chasers, he constantly monitors his biomarkers and makes tweaks to his diet or exercise regimen as needed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lgGa5C">
It’s a contest that participants hope never ends — the most ultra of ultramarathons. The most dedicated members in the longevity community are, in essence, spending their lives obsessing over living. Says Lustgarten: “I plan on doing this for at least the next 70-plus years.”
</p></li>
<li><strong>Why are so many useless cold medicines littering pharmacy shelves?</strong> -
<figure>
<img alt="Red and white boxes of Sudafed PE on a store shelf." src="https://cdn.vox-cdn.com/thumbor/ja2zo08MjG4CMHtmKLcJ2FCmRAg=/253x0:2748x1871/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72650183/71300080.0.jpg"/>
<figcaption>
Pfizer’s Sudafed PE nasal decongestant is displayed on a shelf at a Walgreens store in 2006 in Chicago, Illinois. | Tim Boyle/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Phenylephrine and other medications that contain it, like Sudafed PE, don’t work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4vjy4o">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bCIIVX">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wo8z1H">
</p>
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</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vU0OZA">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kcWoV8">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="u9sRpw">
On September 12, a Food and Drug Administration (FDA) advisory panel <a href="https://www.usatoday.com/story/news/health/2023/09/12/fda-panel-declares-decongestant-phenylephrine-ineffective/70835249007/#:~:text=The%20group%20of%20experts%20gathered,materials%20shared%20by%20the%20agency.">agreed unanimously</a> that phenylephrine, a common decongestant that’s part of many over-the-counter cough and cold medications, is ineffective as an oral medication.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VhUQxl">
That means name-brand medicines like Sudafed PE and Dayquil, which contain the drug, aren’t working as advertised. If you have a runny nose, these medications likely aren’t doing anything to clear it up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ezkvit">
(The FDA’s opinion did not include phenylephrine preparations administered through the nose, like drops and sprays. These are more likely to actually reduce congestion because they’re not metabolized by the body before getting to their point of action.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ozVLnx">
It’s not yet clear exactly what this will mean for pharmacy shelves — but it’s highly likely that in the near future, the FDA will decide to ban the ingredient from over-the-counter sales. That would mean a big change in the range of medications available to consumers: The other commercially available (and more effective) decongestant, pseudoephedrine, is more complicated to obtain. Because of its illicit use in producing methamphetamine, that medication is held behind counters and sold in only limited quantities to consumers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eDf4Fo">
The latest on phenylephrine makes for confusing news with a long backstory. Scientists have been publishing studies suggesting the drug is ineffective since the <a href="https://www.jacionline.org/article/S0091-6749(06)00633-6/fulltext">early 1970s</a>. In 2007, after researchers from the University of Florida brought questions about the drug’s utility to the FDA, the agency convened a <a href="https://www.fda.gov/media/171915/download">panel to address phenylephrine’s effectiveness</a>. Among many of the researchers’ concerns was the fact that the relatively ancient studies of the drug had used a problematic and outdated measure as a primary indicator that it worked. Still, the FDA urged more research, and the drug has remained on shelves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RbFbEJ">
Since then, researchers have<strong> </strong>conducted three large clinical trials with stronger measures, which apparently were enough for the latest FDA panel to accept that this drug clearly doesn’t work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vTyXdu">
Phenylephrine isn’t alone: Due to some quirks in the agency’s history and policy, the FDA is engaged<strong> </strong>in an ongoing process of reviewing drugs that came on the market before its current efficacy standards went into effect. That means a variety of <strong> </strong>older drugs can be sold without proof that they work.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ODRC9W">
How is this possible?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4ppAaf">
I recently spoke to <a href="https://doctors.umiamihealth.org/provider/Mikkael+A.+Sekeres/1692745">Mikkael Sekeres</a>, chief of hematology at the University of Miami’s Sylvester Comprehensive Cancer Center and author of the book <em>Drugs and the FDA</em>, to find out. The FDA has been reviewing the efficacy of older drugs for years, he says, and they’re really far behind, largely because of the agency’s limited resources. And while removing drugs that are familiar to the public might be confusing, he thinks it’s the right thing to do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C2km6P">
<em>This conversation has been edited for length and clarity. </em>
</p>
<h4 id="KJq23G">
Keren Landman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DHkOsK">
Why do we have drugs on store shelves that are FDA approved without being effective?
</p>
<h4 id="EFHNfp">
Mikkael Sekeres
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YRyzA1">
It’s interesting to think about this in terms of a historical perspective. Before the 1930s, the FDA didn’t require safety in any drugs — it just required that the label accurately describe what’s on the bottle. It was the <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/elixir-sulfanilamide">sulfanilamide tragedy</a> [a spate of more than 100 deaths due to a drug formulation that included diethylene glycol, a toxic compound] that eventually led to the passage of the Food and Drug Act [an updated version of the original 1906 law] in 1938. And that’s the first time that drugs were required to be safe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DoZkpt">
Efficacy wasn’t required until the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101807/">Kefauver-Harris Amendments </a>in the 1960s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yddeNI">
So up until the 1960s, drugs could be on the market, and they had to be safe, but they didn’t have to work — which is really convenient for your marketing folks at pharmaceutical companies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="96qt6M">
There needed to be some cleanup of drugs that had already been on the market and were safe but hadn’t been proven to be effective. That started in the 1970s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RWJX8K">
<a href="https://journals.lww.com/anesthesia-analgesia/fulltext/2018/12000/clarifying_misconceptions_about_us_food_and_drug.7.aspx"></a>
</p>
<h4 id="wPQb3a">
Keren Landman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0HD6lv">
What’s wrong with the science on phenylephrine?
</p>
<h4 id="J335Cn">
Mikkael Sekeres
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F4HKxj">
Phenylephrine has been over-the-counter in pill form <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Phenylephrine">since the 1930s</a> — this is an old drug, and the studies that were done, a lot of them were before the 1990s. And the endpoints for those trials weren’t necessarily the most rigorous and may not have been consistent from one study to the next. For example, [in some studies] you’re looking at <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112320/">nasal air resistance</a>, or [in others] you’re looking at self-reporting from patients that they feel better.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2E1VCG">
A better endpoint would be something standardized. If you wanted a patient-reported outcome, you could develop a validated and reliable instrument that accurately reflects when patients have a stuffy nose and when they don’t.
</p>
<h4 id="237DCX">
Keren Landman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="caGzQK">
A group of researchers from the University of Florida first brought <a href="https://pubmed.ncbi.nlm.nih.gov/17264159/">concerns about phenylephrine’s ineffectiveness</a> to the FDA back in 2007. Why did it take so long for the FDA to seriously consider taking this drug off the over-the-counter market? And why is this happening now?
</p>
<h4 id="3Hn0Xj">
Mikkael Sekeres
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AhPpQ4">
If I had to speculate, I would say go back to the FDA history.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a9Pueq">
The FDA is primarily going to be concerned about the safety of drugs. So they’re going to be focused on removing drugs that are <em>unsafe</em> from the market.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZfxoDk">
A classic example of that, as I wrote about in my book, is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744967/#:~:text=On%20November%2018%2C%202011%2C%20US,the%20treatment%20of%20breast%20cancer.">Avastin</a> [generic name, bevacizumab] for breast cancer — a drug that was shown to be ineffective and also toxic. They took that drug off the market.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yLIdkJ">
You can imagine the conversations they had. Are they going to focus on, “Oh my god, we’ve got to get this cancer drug off the market that isn’t helping people and people are dying,” or, “We really need to deal with this placebo”?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oqfRHy">
The FDA has limited resources and is also under a lot of pressure to bring new drugs to the market for patients who have serious diagnoses. And I just think that’s going to be their focus.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pJzbCb">
So I don’t think there’s anything magical about 2023 to explain why this is happening now. I just think it took 16 years for the FDA to gather the resources and to deal with other drugs that had more serious safety signals before they could now address this drug — which even they’ve said is relatively safe, it just doesn’t work.
</p>
<h4 id="JUIfKi">
Keren Landman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4BDjiL">
Does the FDA still sometimes approve drugs when they are unsure how well they work?
</p>
<h4 id="VqhquL">
Mikkael Sekeres
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LUrpQR">
When <a href="https://www.fda.gov/about-fda/fda-leadership-1907-today/scott-gottlieb">Scott Gottlieb</a> headed the FDA [between 2017 and 2019], he said quite clearly that he was in favor of having free market forces influence the prescription of drugs. He wanted to get more drugs out there and let the doctors and patients decide which ones were going to be used.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hy28Bv">
What we saw as a result was a tsunami of drug approvals, and a lot of those under the <a href="https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program#:~:text=The%20FDA%20instituted%20its%20Accelerated,based%20on%20a%20surrogate%20endpoint.">accelerated approval</a> mechanism. That mechanism was created by an act of <a href="https://www.vox.com/congress">Congress</a> in 1992. It was born out of the need for HIV medicines — it was meant to address <a href="https://www.vox.com/health-care">health care</a> needs in people who are desperate for treatments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="woDwqo">
For a drug to qualify for accelerated approval, it needs to meet a need that isn’t already being met — something that HIV drugs definitely did. But the big asterisk with that is that these drugs are approved based on preliminary data showing a clinically meaningful benefit: A follow up trial has to at least confirm that initial benefit, if not extended to something that is clinically meaningful, like an improvement in overall survival.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xITKZy">
Now, we’re starting to see the comeuppance of the wave of drugs approved under accelerated approval during Gottlieb’s leadership, as the so-called confirmatory trials aren’t confirming those initial signs of efficacy and safety. And we’re seeing more cancer drugs in particular being removed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ufVvkB">
[A <a href="https://oig.hhs.gov/oei/reports/OEI-01-21-00401.asp">2022 report from the Office of the Inspector General</a> found that 104 of 278 drugs approved under the accelerated approval mechanism haven’t yet had their effectiveness confirmed by a trial.]
</p>
<h4 id="19c19r">
Keren Landman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="taShYy">
In a New York Times <a href="https://www.nytimes.com/2023/09/12/health/cold-medicine-decongestant-fda.html?smid=nytcore-ios-share&amp;referringSource=articleShare">article</a> about the latest phenylephrine news, an industry representative said that if this drug is removed from store shelves, “the burdens created from decreased choice and availability of these products would be placed directly onto consumers.” How do you respond to that?
</p>
<h4 id="4DhprQ">
Mikkael Sekeres
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gQjpcR">
It’s ludicrous. To say that consumers would be strained because we’re taking a placebo away from them is silly. I won’t say anything stronger than that because you’re quoting me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zuAnbm">
I wouldn’t say it’s a strain on consumers. We’re empowering consumers to take the right drug.
</p>
<h4 id="yOVr0F">
Keren Landman
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ElIV7R">
But if these medications don’t have side effects, what’s the harm of keeping them as ingredients in medicines?
</p>
<h4 id="ti60GY">
Mikkael Sekeres
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iSPPlO">
By keeping these ingredients in drugs and telling patients that they’re going to help them, we’re lying to people.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="40RLvW">
It used to be acceptable for hospital formularies to carry the drug “obecalp.” If you type it on your computer and read it backward, you’ll see what it is: placebo.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ll0T0G">
That’s not ethical! It’s not ethical to lie to patients. And it’s not ethical to lie to patients by giving them obecalp in a hospital, just like it’s not ethical to lie to patients and say that phenylephrine is going to help them with a cold.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wmyX4C">
For consumers, it’s a hard sell when the FDA allows a drug to be on the market and then takes it away from us. We feel as if we’re missing something. But it’s actually a demonstration of how the FDA works: When the FDA removes a drug from the market, they’re protecting the health of the public — and they’re protecting truth in medicine.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HvdBcj">
</p></li>
<li><strong>Three reasons Biden is struggling with Black and Latino voters</strong> -
<figure>
<img alt="President Biden speaks before a crowd at the White House’s Hispanic Heritage Month reception." src="https://cdn.vox-cdn.com/thumbor/4lzcX-1KqUxfJSh_vRdqBRk4yRM=/0x0:4691x3518/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72650121/1429135955.0.jpg"/>
<figcaption>
President Joe Biden and first lady Jill Biden host a reception to celebrate Hispanic Heritage Month in the East Room of the White House. | Chip Somodevilla/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A recent spate of polling paints a bad picture of declining support for the president from voters of color. But just how worrisome is it?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uIk7MH">
Though we’re still more than a year out from the <a href="https://www.vox.com/2024-elections">2024 presidential election</a>, the season for <a href="https://www.politico.com/newsletters/playbook/2023/09/06/an-obama-vets-message-on-biden-bedwetting-00114179">Democratic “bedwetting”</a> has come early this cycle. Leading the <a href="https://www.wsj.com/articles/democrats-start-to-panic-about-biden-president-voters-polls-election-2024-politics-donald-trump-34706a96?mod=hp_opin_pos_1">apparent panic</a> this month are a <a href="https://www.vox.com/politics/2023/9/8/23861488/polls-trump-biden-2024">series of polls and accompanying analysis</a> showing something that’s been pretty obvious for some time: <a href="https://www.vox.com/joe-biden">Joe Biden</a> is a really unpopular president — and that dissatisfaction will make a 2024 showdown with a Republican opponent pretty competitive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AwV2WJ">
Those recent surveys, from <a href="https://www.documentcloud.org/documents/23940784-cnn-poll">CNN</a> and the <a href="https://s.wsj.net/public/resources/documents/WSJ_GOP_Primary_Poll_Aug_2023.pdf">Wall Street Journal</a>, have shown Biden and his likely Republican opponent, former president <a href="https://www.vox.com/donald-trump">Donald Trump</a>, essentially tied or with a narrow Trump lead. <a href="https://www.realclearpolitics.com/epolls/2024/president/us/general-election-trump-vs-biden-7383.html">Polling averages</a> reflect the same dynamic. None of it should be surprising — though Democrats have openly or anonymously been torn about just how much to be worried by these polls. Some longtime Democratic operatives have dismissed the fears from insiders and donors: Former Obama campaign manager Jim Messina, for example, has been <a href="https://www.politico.com/newsletters/playbook/2023/09/06/an-obama-vets-message-on-biden-bedwetting-00114179">quick to tell</a> fellow Democrats to relax and “just take a step back,” while others have argued that it’s too early, or attacked the polls <a href="https://www.hindustantimes.com/world-news/x-users-call-out-cnn-for-oversampling-republican-voters-in-poll-to-set-anti-biden-narrative-101694156169568.html">themselves</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QWRKoG">
But <a href="https://www.vox.com/politics/2023/9/8/23861488/polls-trump-biden-2024">there <em>is</em> value in looking at the polls</a> because they reveal something else: At this point in the campaign, it’s unarguable that Democrats, especially Biden, are facing a problem with voters of color. And that weaker standing with Black and <a href="https://www.vox.com/politics/2023/5/4/23708278/joe-biden-kamala-harris-2024-election-latino-voters-julie-chavez-rodriguez">Latino voters</a> specifically seems to be fueling those tight national polling numbers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YwSICv">
That lower level of support for Biden is distinct from previous election cycles. The New York Times’ Nate Cohn, who has been tracking this for <a href="https://www.nytimes.com/2023/09/05/upshot/biden-trump-black-hispanic-voters.html">some time</a>, analyzed last year and this year’s New York Times/Siena polls of over 1,500 nonwhite respondents. He reports that Biden leads Trump 53 percent to 28 percent among registered nonwhite voters — a sharp drop off from the 70 percent support Biden garnered from voters of color in the <a href="https://www.vox.com/2020-presidential-election">2020 election</a>. Those numbers aren’t exclusive to the Times, either, but show up across surveys. That’s a much worse position than a Democratic candidate has been in <a href="https://www.nytimes.com/2023/09/06/upshot/biden-polls-black-voters.html">for the last few election cycles</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6o8HR5">
Whether this is a new problem or not is debatable (as <a href="https://www.vox.com/politics/23770342/latino-voters-democrats-2022-2024-election-new-reality">I’ve written before</a>, some Democratic operatives don’t want to concede they have a real problem with nonwhite voters). The causes for this weaker level of support are also up for debate: Some, <a href="https://www.liberalpatriot.com/p/its-official-the-democrats-have-a?r=8atam&amp;utm_medium=ios&amp;utm_campaign=post">like the liberal researcher and writer Ruy Teixeira</a>, argue that progressive cultural politics are largely to blame, while other Democratic operatives argue this is a problem with messaging). But the trends in polls over the last year are all pointing at something, even if people disagree on the specific numbers at the margins.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5c2xN1">
So, to understand these trends, I’ve assembled a few theories, informed by conversations with pollsters, strategists, and Democratic party operatives, for why this polling gap continues. Though there is some disagreement, some of it is due to Biden specifically, to the state of the <a href="https://www.vox.com/economy">economy</a>, to differences among voters, and perceptions of the Democratic party. Here are three ways to view Biden’s nonwhite voter problem.
</p>
<h3 id="LhfxYm">
<ol type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">It’s just too early
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GXkWaE">
No one I spoke with denied that there is <em>something</em> going on with Biden and Black and Latino voters — though it’s taken some time to admit it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xwji8g">
“We can’t bury our head in the sand and give excuses about why the polling is wrong,” Chuck Rocha, the Democratic Latino consultant who has frequently been critical of his party’s work with voters of color, told me. “Times have changed and if we continue to rely on these constituencies to vote at such a high number, I’m afraid Democrats will be disappointed unless we put in the work needed to get them there.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n88Ub8">
The go-to explanation among the Democratic establishment, including the Biden campaign and the Democratic National Committee, is that it’s just too early — that most Americans, including voters of color across the country, aren’t tuned into the political process at this point in the year and aren’t yet aware of what the Biden administration has accomplished. They argue that is partially because the reelection campaign, though underway, hasn’t ramped up yet. And they say that they still have a lot of time to ramp up their outreach.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xqtgaq">
There’s a lot of truth to that feeling: Coming off of the summer season, political news does not tend to be the priority for most Americans, and Biden’s<a href="https://www.vox.com/politics/23697855/joe-biden-popularity-legislative-record"> major accomplishments</a> — the <a href="https://www.vox.com/2022/8/8/23296951/inflation-reduction-act-biden-democrats-climate-change">Inflation Reduction Act</a>, the Bipartisan Infrastructure Act, the investments in manufacturing and technology in the CHIPS Act — may not seem to be affecting the lives of the average American.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CDZN0b">
“There hasn’t been the same kind of linkage between the legislation that Biden has helped pass, his overall agenda, and getting credit for it,” Daniel Cox, a pollster and the director of the American Enterprise Institute’s Survey Center on American Life, told me. “[Voters ask], ‘Okay, he did this thing, it passed. Do I see any evidence in my own community or my own neighborhood? Are any of these things having any impact in my life?’ I think for a lot of voters, the answer is no.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lWMruK">
Campaign and party operatives acknowledge this fact — but time and messaging alone don’t explain what the polling is showing.
</p>
<h3 id="qX1Aah">
<ol start="2" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">“Voters of color” aren’t monolithic — and have complicated feelings about the Democrats
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dETNTU">
The term “nonwhite” voter itself hides a lot of complexity — and “Democrat” itself is only partially helpful. Support among <a href="https://www.vox.com/race">Black Americans</a> for Biden, for example, is much higher than among Hispanic or Latino voters. Latino voters tend to be younger than Black voters. Democrats seem to face bigger hurdles to retaining support from Black and Latino men, compared with women, while Biden specifically is underperforming with lower-income voters of color.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rWltCF">
Bad feelings about the economy are still the single largest issue affecting Biden’s standing with all voters, including voters of color. Though the state of the economy is objectively improving (there’s no recession in sight, inflation is improving, and unemployment remains low), those material conditions take longer to improve when you’re on the lower end of the economic spectrum.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M7wv8S">
“This is very similar to 2012 — Barack Obama had the same issues with the economy and dissatisfaction with the economic recovery. But just like then, we have to tell a story, and keep talking about our solutions,” Kristian Ramos, a Democratic Latino consultant, told me. “We have work to do. We have the time to do it. And everything that I’ve seen, when people hear about what we’ve done, they like it. It moves these undecided voters to our side.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zBq4PG">
The youth of the average Black or Latino voter also complicates the picture: younger voters tend to be dissatisfied with Biden, but that does not mean they are switching sides to vote for Republicans en masse. Cox argues that distinguishing between Biden and the Democratic Party is important to understand this dynamic: While younger voters of color might not want to say they’re Biden supporters at this point, they still have an affinity for the Democratic Party and its identity as the more progressive force in <a href="https://www.vox.com/politics">national politics</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="erYqhD">
“If you look at the Democratic Party among young people, it tends to be more positive than views of Biden. So it’s possible that Biden has artificially deflated support just because of who he is: his age, his background, his approach to politics, him being an old-school politician in a party that has increasingly become more progressive and wants more dynamism in their leaders,” Cox said. And that dissatisfaction also shows up in polling about Biden’s accomplishments: <a href="https://www.politico.com/news/2023/04/29/biden-advantage-older-voters-00094515">older voters</a> are <a href="https://www.americansurveycenter.org/research/the-2024-presidential-election-evolving-political-coalitions-and-familiar-partisan-divisions/">more willing</a> to give Biden credit than <a href="https://news.gallup.com/poll/391733/biden-job-approval-down-among-younger-generations.aspx">younger voters</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FyQX3Q">
Some of that gap can be explained by the different ways younger people consume political information, Rocha told me. “There’s lots of reasons. There’s more than three TV channels. There’s social media. Younger Black and Latino folks are acting much differently than their mothers and fathers,” Rocha said. “That just means there’s going to be more work needed —most of these campaigns are running broadcast TV commercials, because that’s where older people that are the regular voters are consuming information and you’re not reaching these younger Black and brown voters because they’re consuming all their information on mobile devices and streaming devices.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dy8hH0">
And there’s a cultural divide: voters of color tend to be a bit more conservative on social issues than the white college-educated voters that have been growing more Democratic in the Trump era, as reflected in the varied opinions by <a href="https://fivethirtyeight.com/features/why-so-many-black-voters-are-democrats-even-when-they-arent-liberal/">Black</a> and <a href="https://www.vox.com/policy-and-politics/23378427/culture-economy-abortion-lgbtq-latino-democrats">Latino</a> voters on <a href="https://www.vox.com/abortion">abortion</a>, immigration, <a href="https://www.vox.com/gender">gender identity</a>, and crime. As Cox’s AEI colleague Texeira <a href="https://www.liberalpatriot.com/p/its-official-the-democrats-have-a?r=8atam&amp;utm_medium=ios&amp;utm_campaign=post">has written before</a>, those more moderate leanings don’t mean nonwhite voters are running to the GOP, but it does suggest that Democrats have more work to do to overcome the feeling among some nonwhite voters that they are not represented in the Democratic Party’s more progressive identity.
</p>
<h3 id="G4tFKl">
<ol start="3" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Black and Latino voters tend to be neglected
</li></ol></h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2CZ3lS">
Across most of the conversations I had with party insiders one thing was clear: Biden’s campaign and the Democratic apparatus supporting him are off to a good start. They’ve made the right hires of Black and Latino staffers to guide efforts with voters of color, they’ve made <a href="https://www.cnn.com/2023/08/20/politics/joe-biden-2024-republican-primary/index.html">huge early investments in advertising to Black and Latino voters in battleground states</a>, launched outreach efforts <a href="https://themessenger.com/politics/dnc-chair-jaime-harrison-says-latino-and-black-men-wont-be-taken-for-granted-in-2024-exclusive">specifically targeted at Black and Latino men,</a> and hosted engagement events in <a href="https://mississippitoday.org/2023/08/17/democratic-party-gulf-coast-competitive/">Mississippi</a>, Florida, Wisconsin, and Kentucky. The next few months will be crucial in seeing whether this engagement begins to pay off, and whether this softer support for Biden bottoms out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GnQmqO">
“If you’re asking me about Joe Biden, the first thing I’d say is, well, you need a person of color leading the campaign. Check. Did you start really early? Well, they started early, whether it’s the DNC or the campaign or Building Back Together (a Democratic-aligned outside group),” Rocha told me. “We need to admit that there’s an erosion in these constituencies, but that we have plenty of time to get it back to close where it needs to be.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gPA0Yq">
Antjuan Seawright, a Democratic strategist working with the DNC to support Biden and reach Black voters, echoed this explanation, and noted that it’s encouraging to see early investment from the Biden campaign and the DNC in specifically reaching Black and Latino men.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="poW8c2">
“We tend to be called low-propensity voters, but I call them low-priority voters — we’re the number one targets of misinformation and disinformation, intentionally, to suppress our vote or keep us from participating or being motivated to participate,” he said. “We have to work overtime to make certain that we continue to invest in Black voters and invest in Black talent and keep us engaged even in a non-election year.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ESQAwB">
Democrats working to elect Biden are also optimistic that voters will begin to see the contest as less of a referendum on the incumbent president and more of a choice between Biden and Trump once the contours of the <a href="https://www.vox.com/politics/2023/2/23/23611828/2024-republican-presidential-candidates-trump-hurd">GOP primary</a> field become clearer. Ramos told me that once that divide becomes clear, it will become easier to pitch Biden to nonwhite voters — but that pitch requires talking about “<a href="https://www.pnas.org/doi/10.1073/pnas.1718155115">status threats</a>” — that the betterment of one group of voters isn’t coming at the expense of others, and that a rising tide lifts all boats — as a way to offset potential cultural criticisms of Democrats by the GOP.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4HXC5f">
Democratic insiders also point to another fact — while support is lagging for Biden and Democrats, there are no clear signs in polling or in real life of a mass exodus of voters of color to the Republican Party.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4DnGRH">
“We have seen this erosion of support for Democrats, but there hasn’t been a ton of evidence that these folks are flocking to the GOP,” Cox, of AEI, told me. “What we’re talking about is Democrats can no longer rely on these voters to be solid Democrats. That doesn’t mean that they’re not winnable, but that means that both parties seem to be well positioned to capture this increasing bloc of voters.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Meaypz">
Still, these margins matter — though 2024 is not likely to be the year that Republicans win a majority of Black or Latino voters, polling this far out does paint a picture of lower enthusiasm that could turn into lower turnout for Biden and congressional Democrats. As my colleague Andrew Prokop <a href="https://www.vox.com/politics/2023/9/8/23861488/polls-trump-biden-2024">has explained</a>, the polls conducted over the last year have told a consistent story — one of near-even support for Biden and his Republican rivals in battleground states and nationally. The lower numbers among Black and Latino voters are an equally consistent finding. And that makes the mission for the Democrats leading these campaigns even more urgent.
</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>Rohan Bopanna gets ready for Davis Cup farewell, India starts overwhelming favourite against Morocco</strong> - Defeats in winnable matches, has hurt the Indian Davis Cup team badly in the last few years, but relegation to World Group II was a new low the Indian team hit in February.</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>Srikanth eyes elusive Asian Games medal, hopes to be third time lucky</strong> - Srikanth, who has endured a topsy-turvy 2023 to fall to world number 21, finished at the round of 16 and 32 in 2014 and 2018 editions of Asian Games</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>Asia Cup 2023 | India vs Bangladesh: India opts to field, Tilak Varma makes ODI debut against Bangladesh</strong> - India made wholesale changes to their playing XI, resting Virat Kohli, Hardik Pandya, Mohammed Siraj, Jasprit Bumrah and Kuldeep Yadav.</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>Rohan Bopanna – the consummate team man who found the sweet spot</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>Morning Digest | Central team of officials to visit Nipah-hit areas, Joe Biden’s son Hunter indicted on gun charges, and more</strong> - Here is a select list of stories to start the day</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>Wanted Maoist Sanjoy Deepak Rao apprehended by Cyberabad police</strong> - The Telangana state’s Intelligence Bureau has been tracking this high profile target for a long time, said the DGP of the state, Anjani Kumar.</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>Chandrababu Naidu’s arrest exposed YSRCP regime’s ‘vendetta politics’ in AP: Bandi Sanjay</strong> - Arresting the former chief minister without his name figuring in the FIR is indicative of the vengeful attitude of the YSRCP, says BJP national general secretary</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>Edayar industrial unit responsible for discoloration in Periyar River, finds Kerala State Pollution Control Board</strong> - Tests conducted at central lab of the board in Ernakulam found the presence of chromium, which indicated that the discharge was from the industrial unit</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.K. Chaturvedi is Palakkad DRM</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>Nipah outbreak: Animal Husbandry department steps up surveillance, issues guidelines</strong> - A district surveillance team has been tasked with finding out whether pig farms exist within five km of the epicentre of the outbreak and to keep them under surveillance</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>Luis Rubiales tells Spanish court Women’s World Cup kiss was consensual</strong> - Prosecutors ask a court to bar Spain’s ex-football boss from approaching player Jenni Hermoso.</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>Apple to update iPhone 12 in France over radiation</strong> - Apple will update the phone in France but not elsewhere over what it says is “not a safety concern”.</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>UK, France and Germany to keep nuclear sanctions on Iran</strong> - The three nations say Iran is in breach of the 2015 nuclear deal by producing enriched uranium.</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>Kim Jong Un-Putin talks: What do the optics tell us?</strong> - The meeting between North Korean and Russian leaders aimed to send a message to the West.</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>Greta Thunberg charged after blocking Sweden oil port for second time</strong> - The climate activist refused to end the protest, hours after being convicted of a similar offence.</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>Rocket Report: New Shepard may fly soon; ULA changes mind on DoD competition</strong> - “No one wants a monopoly choking out one point of the value chain.” - <a href="https://arstechnica.com/?p=1968050">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Private AI summit with senators, titans of tech garners controversy</strong> - With 14 of 22 attendees being CEOs, some experts say key voices were missing. - <a href="https://arstechnica.com/?p=1968348">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Meet the winners of the 2023 Ig Nobel Prizes</strong> - The award ceremony features miniature operas, scientific demos, and the 24/7 lectures. - <a href="https://arstechnica.com/?p=1965450">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Birds’ problem-solving skills linked to song complexity</strong> - But other measures of intelligence, like learning associations, are unconnected. - <a href="https://arstechnica.com/?p=1968585">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Google extends Chromebook support from 8 years to 10 after heightened backlash</strong> - Automatic Chromebook expiration dates still “fundamentally flawed,” critics say. - <a href="https://arstechnica.com/?p=1968412">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A priest goes in a safari…</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A priest goes in a safari in Africa. He gets separated from the group and has the bad luck of finding himself alone, facing a hungry lion. Priest: “Dear Lord, I haven’t asked for much in life, but if it is of Thy all-knowing will, please concede me the grace that this lion be imbued with Christian moral and values!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A sound of trumpets echoes in the sky and a heavenly beam of light shines upon the lion, who now is able to speak. The lion: “Oh Lord, we give Thee thanks for this meal that we are about to have!”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HugoLDSC"> /u/HugoLDSC </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16iumfa/a_priest_goes_in_a_safari/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16iumfa/a_priest_goes_in_a_safari/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A guy walks into a bar and sits down. He orders a drink. The bartender asks him, “What’d you do this weekend?”</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The guy says, “I picked off a scab.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh, so it wasn’t very eventful?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well, actually, I’m on strike with the sniper’s union.”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/memerminecraft"> /u/memerminecraft </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16j12b2/a_guy_walks_into_a_bar_and_sits_down_he_orders_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16j12b2/a_guy_walks_into_a_bar_and_sits_down_he_orders_a/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three guys go in for a job interview.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The first guy goes in and kicks ass, best job interview he’s ever done in his life. End of the interview comes around, the interviewer says: “By the way, do you notice anything strange about me?” “Yeah,” says the guy… “Your nose is really huge, man!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I’m sorry, says the interviewer, but I’m very sensitive about my nose, I’m afraid you’re not the right person for this job, get the hell out of my office!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The second guy goes in, it’s the same thing, he is doing amazing, best job interview ever. Talks himself into 20K a year more than the advertised salary. End of the interview comes around, the interviewer says: “By the way, do you notice anything strange about me?” “Well I mean yes,” says the guy… “You have an abnormally large nose, but you probably knew that.” “I’m sorry, says the interviewer, but I’m very sensitive about my nose, I’m afraid you’re not the right person for this job, get out of my office!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So the third guy’s about to go in, but the first and second guy stop him and warn him “Hey, I don’t care how good you’re doing, how comfortable you feel, don’t say ANYTHING about his nose, he’ll throw you right out!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So the third guy goes in. Again, same thing, an AMAZING interview. End of the interview comes around, the interviewer says:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“By the way, do you notice anything unusual about me?” Third guy looks real close, squints his eyes a bit and says “Yeah. You wear contact lenses, don’t you?” “WOW!” says the interviewer, “That is REALLY perceptive of you! How did you know?” “Well, you’d play hell trying to find glasses to fit that motherfucking nose!”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HoLiTzhit"> /u/HoLiTzhit </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16iyper/three_guys_go_in_for_a_job_interview/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16iyper/three_guys_go_in_for_a_job_interview/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A city gent was driving through the countryside</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
when he notices, out in a field, an old man fucking a donkey. Somewhat bemused, he continued down the country lane where he soon saw a cottage with a young man standing outside. He decided to stop.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Hey, young man, I don’t know if you’re aware of this, or if you might want to intercede, but in the field just aways back there appears to be an old man having sex with a donkey.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh! That’s my dad, HEE HAWlways does that!”
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/bumpy713"> /u/bumpy713 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16j6unm/a_city_gent_was_driving_through_the_countryside/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16j6unm/a_city_gent_was_driving_through_the_countryside/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I got a girlfriend</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This is the only subreddit I can post this.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/lossmemefound"> /u/lossmemefound </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16j6qka/i_got_a_girlfriend/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16j6qka/i_got_a_girlfriend/">[comments]</a></span></p></li>
</ul>
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