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<title>21 October, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>FAKHRAVAC and BBIBP-CorV vaccine seeds’ binding to angiotensin-converting enzyme 2: A comparative molecular dynamics study</strong> -
<div>
Background: Safety and efficacy of the SARS-CoV-2 inactivated vaccines have been question since the emergence of SARS-CoV-2 variants of concern (VOCs). Using residue fluctuations and statistically comparing RMSF values, have escalated the understanding of the binding dynamics of the viral proteins to their receptors and here in this study, we compared the interaction between inactivated spike proteins (representing FAKHRAVAC and BBIBP-CorV vaccines seed) and the human Angiotensin-Converting Enzyme 2 (hACE2) receptor. Methodology: Through 100 set of accelerated 1 ns comparative molecular dynamics simulations, we analyze the binding dynamics and energy components of these interactions and compared residue backbone fluctuations using entropy and statistics including KL-Divergence and KS-test. Principal Findings: Our results reveal that FAKHRAVAC and Sinopharm exhibit similar binding dynamics and affinity to hACE2. Further examination of residue-wise fluctuations highlights the common behavior of binding key residues and mutation sites between the two vaccines. However, subtle differences in residue fluctuations, especially at critical sites like Q24, Y435, L455, S477, Y505, and F486, raise the possibility of distinct efficacy profiles. Conclusion: These variations may influence vaccine immunogenicity and safety in response to evolving SARS-CoV-2 variants. The study underscores the importance of considering residue-wise fluctuations for understanding vaccine-pathogen interactions and their implications for vaccine design.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.19.563051v1" target="_blank">FAKHRAVAC and BBIBP-CorV vaccine seeds’ binding to angiotensin-converting enzyme 2: A comparative molecular dynamics study</a>
</div></li>
<li><strong>Divergent spike mutations impact the activation of the fusion core in Delta and Omicronvariants of SARS-CoV-2</strong> -
<div>
SARS-CoV-2 infects host cells by binding the receptor-binding domain (RBD) of its spike protein to the receptor, ACE2. A subset of highly effective spike mutations plays critical roles in altering the conformational dynamics of spike protein. Here, we use molecular dynamics simulations to investigate how spike mutations affect the conformational dynamics of spike/ACE2 complex in the D614G, Delta (B.1.617.2) and Omicron (B.1.1.529) SARS-CoV-2 variants. We observe that the increased positive-charged mutations in the Omicron spike amplify its structural rigidity and reduce its structural flexibility. The mutations (P681R in Delta and P681H in Omicron) at the S1/S2 junction facilitate S1/S2 cleavage and aid the activation of the fusion core. We report that high structural flexibility in Delta lowers the barrier for the activation of the S2 core; however, high structural rigidity in Omicron enhances the barrier for the same. Our results also explain why Omicron requires the presence of a higher number of ACE2 to activate its fusion core than Delta.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.19.563184v1" target="_blank">Divergent spike mutations impact the activation of the fusion core in Delta and Omicronvariants of SARS-CoV-2</a>
</div></li>
<li><strong>Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by PBR28 PET correlates with vascular disease measures</strong> -
<div>
The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.19.563117v1" target="_blank">Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by PBR28 PET correlates with vascular disease measures</a>
</div></li>
<li><strong>Analysis of uptake, effectiveness and safety of COVID-19 vaccinations in pregnancy using the QResearch database: research protocol and statistical analysis plan</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background The COVID-19 pandemic has affected millions of people globally with major health, social and economic consequences, prompting development of vaccines for use in the general population. However, vaccination uptake is lower in some groups, including in pregnant women, because of concerns regarding vaccine safety. There is evidence of increased risk of adverse pregnancy and neonatal outcomes associated with SARS-CoV-2 infection, but fear of vaccine-associated adverse events on the baby both in short and longer term is one of the main drivers of low uptake for this group. Other vaccines commonly used in pregnancy include influenza and pertussis. These both have reportedly higher uptake compared with COVID-19 vaccination, which may be because they are perceived to be safer. In this study, we will undertake an independent evaluation of the uptake, effectiveness and safety of COVID-19 vaccinations in pregnant women using the QResearch primary care database in England. Objectives A. To determine COVID-19 vaccine uptake in pregnant women compared to uptake of influenza and pertussis vaccinations. B. To estimate COVID-19 vaccine effectiveness in pregnant women by evaluating the risk of severe COVID-19 outcomes following vaccination. C. To assess the safety of COVID-19 vaccination in pregnancy by evaluating the risks of adverse pregnancy and perinatal outcomes and adverse events of special interest for vaccine safety after COVID-19 vaccination compared with influenza and pertussis vaccinations. Methods This population-based study uses the QResearch database of primary health care records, linked to individual-level data on hospital admissions, mortality, COVID-19 vaccination, SARS-CoV-2 testing data and congenital anomalies. We will include women aged 16 to 49 years with at least one pregnancy during the study period of 30th December 2020 to the latest date available. Babies born during the study period will be identified and linked to the mothers record, where possible. We will describe vaccine uptake in pregnant women by trimester and population subgroups defined by demographics and other characteristics. Cox proportional hazards multivariable regression will be used to identify factors associated with vaccine uptake. The effectiveness of COVID-19 vaccines in pregnant women will be assessed using time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of severe COVID-19 outcomes after each vaccine dose compared with unvaccinated individuals. For the safety analysis, we will we use logistic regression analyses to determine unadjusted and adjusted odds ratios for the occurrence of maternal (e.g. miscarriage, ectopic pregnancy and gestational diabetes) and perinatal outcomes (e.g. stillbirth, small for gestational age and congenital anomalies) by vaccination status compared to unvaccinated individuals. For the adverse events of special interest for vaccine safety (e.g. venous thromboembolism, myocarditis and Guillain Barre syndrome), we will use time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of each outcome by vaccination status to unvaccinated individuals. Ethics and dissemination QResearch is a Research Ethics Approved Research Database with ongoing approval from the East Midlands Multi-Centre Research Ethics Committee (Ref: 18/EM/0400). This study was approved by the QResearch Scientific Committee on 9th June 2022. This research protocol has been developed with support from a patient and public involvement panel, who will continue to provide input throughout the duration of the study. Research findings will be submitted to pre-print servers such as MedRxIv, academic publication and disseminated more broadly through media releases and community groups and conference presentations.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.19.22283660v2" target="_blank">Analysis of uptake, effectiveness and safety of COVID-19 vaccinations in pregnancy using the QResearch database: research protocol and statistical analysis plan</a>
</div></li>
<li><strong>Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+ T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+ CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI associate with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.29.23296222v2" target="_blank">Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination</a>
</div></li>
<li><strong>The gravity of the status quo: the response of research governance to system-level shocks</strong> -
<div>
Using semi-structured interviews with n=69 global research stakeholders, , this research explores the ways in which stakeholders within system-level research governance organisations conceptualised, responded to, and reasoned the realities of disruption caused by the COVID-19 pandemic, and how they positioned procedural changes to their governance mechanisms. Given that shocks to systems present critical challenges to established practices and embedded institutional norms, we use neo-institutional theory as a heuristic device to examine the relationship between the exogenous shock of COVID-19, trajectories of institutional norms and cultures, and the role institutional stakeholders play in managing responses. Across all the research systems studied (with particular focus on the UK, Australia, Norway, New Zealand, Hong Kong SAR and Italy), participants were concerned about how the shock provided by COVID-19 had both revealed and entrenched deep inequalities (between individuals and between organisations) inherent in their research systems and globally. There were tensions in how participants centralised the concept of the ‘normal’ as part of a process of recovery permeating all system-level responses, often with a sense of nostalgia for past structures (a pre-pandemic ‘golden age’ of research), modes of operation, and embedded norms. Aspirations for short-, medium- and long-term plans for research change echoed a dependency on returning to ‘normal’ and reflected an inevitable pull of the norms of the pre-pandemic status quo. Despite the desire of individuals involved in research governance to ‘build back better’, the pull of institutional norms and the gravitational force of the status quo appears too strong for meaningful change to happen in recovering research systems.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3wfcb/" target="_blank">The gravity of the status quo: the response of research governance to system-level shocks</a>
</div></li>
<li><strong>Wastewater as a back door to serology?</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease. Systems for wastewater monitoring were put in place throughout the world during the COVID-19 pandemic. These systems use viral RNA copies as the basis of estimates of COVID-19 cases in the sewershed area, thereby providing data critical for public health responses. However, the potential to measure other biomarkers in wastewater during outbreaks has not been fully explored. Here we report a novel approach for detecting specific human antibodies from wastewater. We measured the abundance of anti-SARS-CoV-2 spike IgG and IgA from fresh samples of community wastewater and from archived frozen samples dating from 2020-22. The assay described can be performed with readily available reagents, at a moderate per-sample cost. Our findings demonstrate the feasibility of noninvasive serological surveillance via wastewater, enabling a new approach to immunity-based monitoring of populations.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.11.22282224v2" target="_blank">Wastewater as a back door to serology?</a>
</div></li>
<li><strong>The benefits of voluntary plasma donations: safety, price, and supply resilience</strong> -
<div>
This article summarizes data on blood and blood component VNRD compared to remunerated donations, in the context of safety for patients and donors, price of products, and supply resiliency. This is particularly relevant given the ongoing debate on the proposal for a regulation on substances of human origin (SoHO). Data indicated that when donors are remunerated and therefore donate very frequently, the safety of the patients receiving these donations and the donors themselves is at risk. Moreover, when donations were VNRD compared to remunerated, PDMP prices increased less between 2018 and 2023 and were therefore more cost-effective for patients and healthcare systems. Lastly, the supply of plasma was found to be more resilient during the COVID-19 pandemic when donors were non-remunerated compared to when they were remunerated. In addition, once countries implement remuneration, it cannot be reversed without risking the supply. We strongly urge policy makers to rely on empirical evidence as a basis for decision-making regarding the proposal for a regulation on SoHO.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/fnhjg/" target="_blank">The benefits of voluntary plasma donations: safety, price, and supply resilience</a>
</div></li>
<li><strong>Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background Seasonal influenza places a substantial burden annually on healthcare services. Policies during the COVID-19 pandemic limited the transmission of seasonal influenza, making the timing and magnitude of a potential resurgence difficult to ascertain and important to forecast its impact. Methods We have developed a hierarchical generalised additive model (GAM) for the short-term forecasting of hospital admissions with a positive test for the influenza virus sub-regionally across England. The model incorporates a multi-level structure of spatio-temporal splines, weekly cycles in admissions, and spatial correlation. Using multiple performance metrics including interval score, coverage, bias, and median absolute error, the predictive performance is evaluated for the 2022/2023 seasonal wave. Performance is measured against autoregressive integrated moving average (ARIMA) and Prophet time series models. Results Across the epidemic phases the hierarchical GAM shows improved performance, at all geographic scales relative to the ARIMA and Prophet models. Temporally, the hierarchical GAM has overall an improved performance at 7 and 14 day time horizons. The performance of the GAM is most sensitive to the flexibility of the smoothing function that measures the national epidemic trend. Conclusions This study introduces an approach to short-term forecasting of hospital admissions for the influenza virus using hierarchical, spatial, and temporal components. The methodology was designed for the real time forecasting of epidemics. This modelling framework was used across the 2022/2023 winter for healthcare operational planning by the UK Health Security Agency and the National Health Service in England.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.19.23297248v1" target="_blank">Influenza Hospitalisations in England during the 2022/23 Season: do different data sources drive divergence in modelled waves? A comparison of surveillance and administrative data.</a>
</div></li>
<li><strong>Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high-HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence/lockdown and a severe lake flooding event, both of which occurred in 2020. Methods: We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda, collected prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence/lockdown and a severe flooding event, to evaluate the impact of natural disasters on the key population-level HIV outcomes listed above. Households impacted by flooding were identified using drone data and through consultation with village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-difference statistical modeling approach. Findings: 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding and 513 (41%) were female. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. Following the COVID-19 pandemic/lockdown, we observed a decline in HIV-associated risk behaviors. Transactional sex declined from 29.4% to 24.8% (p=0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p=0.021) in the pre- and post-COVID periods. ART coverage increased from 91.6% to 97.2% (p&lt;0.001). There was 17% decline in transactional sex (aPR=0.83, 95% CI: 0.75-0.92) and 28% decline in the overall HIV risk score (aPR=0.83, 95% CI: 0.75-0.92) among HIV-seronegatives and 5% increase in ART coverage between the pre- and post-COVID periods. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes comparing those affected by floods to those not affected by floods in the periods before and after COVID in difference-in-difference analyses. Interpretation: Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and or population resilience. Understanding exactly what HIV programs and personal/community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.19.23297262v1" target="_blank">Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda</a>
</div></li>
<li><strong>SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The city of Sao Caetano do Sul, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic. Methods: We selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimating using a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform. Results: Most infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%) and B1.1.33 (9.0%). Gamma and Zeta were associated with larger prevalence of dyspnoea (respectively 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared to B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3% and 17.8% less commonly caused by Gamma, while altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts. Discussion: Our study demonstrates that Gamma was associated with more severe disease, emphasising the role of its increased disease severity in the heightened mortality levels in Brazil.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.19.23297252v1" target="_blank">SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil</a>
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<li><strong>Commentary on the Strategic Interventions for Agriculture, Climate Change, and Food Security Proposed by the National Science and Technology Commission at the 9th Biennial Conference on Science and Technology</strong> -
<div>
Agriculture in Sri Lanka occupies 45.46% of the land and consumes over 80% of the country’s freshwater resources. Rice farming is the most prominent agricultural practice, with 1.8 million families engaged in it. The tea plantation sector produces tea annually, contributing to 285,877 metric tons of export volume. Tea exports contribute nearly 38% of the total agricultural products, with a target of $2,044 million in income by 2025. Climate change and natural resources significantly impact agriculture, with irregular rainfall patterns, temperature variation, and drought causing significant challenges. The proposed interventions under the food crops, plantation, and export crops sectors include enhancing certified seed production, promoting value-added products, and developing training and awareness programs for low-carbon lifestyles. Food security is another area where climate change impacts the agricultural sector, with nearly 26% of the population affected by food security by 2050 due to the COVID-19 pandemic and the conflict between Russia and Ukraine. To address this issue, the proposed strategic interventions aim to achieve SDG 1, SDG 2, and SDG 13, the recommendations of the Paris Agreement on Climate Change, and the actions of the Milan Urban Food Policy Fund. However, more concerns can be put forward to minimize or eliminate diseases in agricultural sectors due to climate change and minimize food waste or loss.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/64grs/" target="_blank">Commentary on the Strategic Interventions for Agriculture, Climate Change, and Food Security Proposed by the National Science and Technology Commission at the 9th Biennial Conference on Science and Technology</a>
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<li><strong>Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection</strong> -
<div>
Leukocyte infiltration of the CNS can contribute to neuroinflammation and cognitive impairment. Brain endothelial cells regulate adhesion, activation, and diapedesis of T cells across the blood-brain barrier (BBB) in inflammatory diseases. The integral membrane protein Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on T cell CNS infiltration in respiratory viral infections is unknown. In this study, we sought to determine the role of Cav-1 at the BBB in neuroinflammation in a COVID-19 mouse model. We used mice genetically deficient in Cav-1 to test the role of this protein in T cell infiltration and cognitive impairment. We found that SARS-CoV-2 infection upregulated brain endothelial Cav-1. Moreover, SARS-CoV-2 infection increased brain endothelial cell vascular cell adhesion molecule-1 (VCAM-1) and CD3+ T cell infiltration of the hippocampus, a region important for short term learning and memory. Concordantly, we observed learning and memory deficits. Importantly, genetic deficiency in Cav-1 attenuated brain endothelial VCAM-1 expression and T cell infiltration in the hippocampus of mice with SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results indicate the importance of BBB permeability in COVID-19 neuroinflammation and suggest potential therapeutic value of targeting Cav-1 to improve disease outcomes.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.18.563024v1" target="_blank">Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection</a>
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<li><strong>Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-vaccinated ACE2-humanized Mice</strong> -
<div>
Vaccines have demonstrated remarkable effectiveness in protecting against COVID-19; however, concerns regarding vaccine-associated enhanced respiratory diseases (VAERD) following breakthrough infections have emerged. Spike protein subunit vaccines for SARS-CoV-2 induce VAERD in hamsters, where aluminum adjuvants promote a Th2-biased immune response, leading to increased type 2 pulmonary inflammation in animals with breakthrough infections. To gain a deeper understanding of the potential risks and the underlying mechanisms of VAERD, we immunized ACE2-humanized mice with SARS-CoV-2 Spike protein adjuvanted with aluminum and CpG-ODN. Subsequently, we exposed them to increasing doses of SARS-CoV-2 to establish a breakthrough infection. The vaccine elicited robust neutralizing antibody responses, reduced viral titers, and enhanced host survival. However, following a breakthrough infection, vaccinated animals exhibited severe pulmonary immunopathology, characterized by a significant perivascular infiltration of eosinophils and CD4+ T cells, along with increased expression of Th2/Th17 cytokines. Intracellular flow cytometric analysis revealed a systemic Th17 inflammatory response, particularly pronounced in the lungs. Our data demonstrate that aluminum/CpG adjuvants induce strong antibody and Th1-associated immunity against COVID-19 but also prime a robust Th2/Th17 inflammatory response, which may contribute to the rapid onset of T cell-mediated pulmonary immunopathology following a breakthrough infection. These findings underscore the necessity for further research to unravel the complexities of VAERD in COVID-19 and to enhance vaccine formulations for broad protection and maximum safety.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.18.563016v1" target="_blank">Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-vaccinated ACE2-humanized Mice</a>
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<li><strong>The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study</strong> -
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The 2022 mpox outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM), while China only has limited recorded importation and no local outbreak. We constructed probabilistic models to simulate the risk of mpox importation in mainland China, with the help of reported monkeypox cases during this multi-country outbreak and the international air-travel data. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Once a mpox case is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to &gt;95% with over six cases. Our study demonstrates the key role of the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic on reducing mpox importations, and the subsequent risk of triggering local outbreaks among MSM.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.24.23294530v2" target="_blank">The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines</strong> - <b>Conditions</b>: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected <br/><b>Interventions</b>: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine <br/><b>Sponsors</b>: Catholic Kwandong University; Korea University Guro Hospital <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Narrative Intervention for Long COVID-19 (NICO)</strong> - <b>Conditions</b>: Long COVID; Long Covid19 <br/><b>Interventions</b>: Behavioral: Narrative Intervention for Long COVID-19 (NICO) <br/><b>Sponsors</b>: University of Colorado, Denver <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>Inspiratory Muscle Training in People With Long COVID- A Pilot Investigation.</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: PrO2 <br/><b>Sponsors</b>: University of Bath; Swansea University <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>Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Dyspnea <br/><b>Interventions</b>: Device: Respiratory Muscle Strength Trainers <br/><b>Sponsors</b>: University of South Florida <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>Inspiratory Muscle Strength Training in Post-Covid Syndrome</strong> - <b>Conditions</b>: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise <br/><b>Interventions</b>: Other: Inspiratory muscle strength training <br/><b>Sponsors</b>: D’Or Institute for Research and Education <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>Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva</strong> - <b>Conditions</b>: SARS-CoV2 Infection <br/><b>Interventions</b>: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication <br/><b>Sponsors</b>: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation Therapy for COVID-19</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education <br/><b>Sponsors</b>: VA Office of Research and Development <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>COVID Rehabilitation</strong> - <b>Conditions</b>: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders <br/><b>Interventions</b>: Behavioral: One day course; Behavioral: Individual follow-ups <br/><b>Sponsors</b>: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology <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 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection</strong> - <b>Conditions</b>: Covid19 <br/><b>Interventions</b>: Drug: Convalescent Plasma; Other: Standard of Care <br/><b>Sponsors</b>: Larkin Community Hospital <br/><b>Withdrawn</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>Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection <br/><b>Interventions</b>: Drug: GST-HG171/ritonavir; Drug: ritonavir <br/><b>Sponsors</b>: Fujian Akeylink Biotechnology Co., Ltd. <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>Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic <br/><b>Interventions</b>: Device: Monoplace Hyperbaric Chamber (Class III medical device). <br/><b>Sponsors</b>: Sunnybrook Health Sciences Centre <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>Education of Medical Staff to Post Acute Covid susTained sYmptoms</strong> - <b>Conditions</b>: Post-acute COVID-19 Syndrome <br/><b>Interventions</b>: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations <br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases <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>Pharmacist Management of Paxlovid eVisits</strong> - <b>Conditions</b>: COVID-19; Quality of Care <br/><b>Interventions</b>: Other: Pharmacist Care; Other: AFM Pool Care <br/><b>Sponsors</b>: Kaiser Permanente <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>tDCS in the Management of Post-COVID Disorders</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training <br/><b>Sponsors</b>: Universidade Federal de Pernambuco; São Paulo State University <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Other: Fact box <br/><b>Sponsors</b>: Harding Center for Risk Literacy <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>Humoral immune response to SARS-CoV-2 and endemic coronaviruses in urban and indigenous children in Colombia</strong> - CONCLUSIONS: Overall, antibody titers, but in particular ACE2 binding inhibition are low within Colombian samples, requiring further investigation to determine any potential clinical significance.</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>ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2</strong> - Apoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus…</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>Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract</strong> - CONCLUSIONS: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production, and administration of interferon alpha-14 may be attractive transmission-blocking interventions.</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>Assembly of SARS-CoV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein</strong> - The Nucleocapsid (N) protein of SARS-CoV-2 compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein SR region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N* or Δ(1-209), that mediates genome packaging despite lacking 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>Update on fungal lipid biosynthesis inhibitors as antifungal agents</strong> - Fungal diseases today represent a world-wide problem. Poor hygiene and decreased immunity are the main reasons behind the manifestation of this disease. After COVID-19, an increase in the rate of fungal infection has been observed in different countries. Different classes of antifungal agents, such as polyenes, azoles, echinocandins, and anti-metabolites, as well as their combinations, are currently employed to treat fungal diseases; these drugs are effective but can cause some side effects 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>Assessment of virus and Leptospira carriage in bats in France</strong> - With over 1,400 species worldwide, bats represent the second largest order of mammals after rodents, and are known to host major zoonotic pathogens. Here, we estimate the presence of pathogens in autochthonous bat populations. First, we set out to check our samples for PCR amplification efficiency by assessing the occurrence of inhibited PCR reactions from different types of bat samples with amplifying the housekeeping gene β-actin. Second, we investigated the presence of five targeted pathogens…</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>Blocking of doublecortin-like kinase 1-regulated SARS-CoV-2 replication cycle restores cell signaling network</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to fatal outcomes for subgroups of patients with pre-existing co-morbidities. We previously reported a significant association between high expression levels of a cancer stem cell protein, doublecortin-like kinase 1 (DCLK1), in the lungs and macrophages of SARS-CoV-2-infected patients and the severity of coronavirus disease 2019 (COVID-19). Herein, we demonstrate a pivotal role of DCLK1 in the viral replication cycle…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Silico Screening of Some Active Phytochemicals to Identify Promising Inhibitors Against SARS-CoV-2 Targets</strong> - CONCLUSION: The present in silico screening study suggested that active phytomolecules from medicinal plants could inhibit SARS-CoV-2 targets. The elite docked compounds with drug-like properties have a harmless ADMET profile, which may help to develop promising COVID-19 inhibitors.</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 SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity</strong> - The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localizes to mitochondria, where it inhibits innate immunity by restricting IFN-β…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors</strong> - A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC(50) range of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral Effects of Micafungin against Pteropine Orthoreovirus, an Emerging Zoonotic Virus Carried by Bats</strong> - Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic…</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>Cellular assays for dynamic quantification of deubiquitinase activity and inhibition</strong> - Deubiquitinases (DUBs) are proteolytic enzymes that catalyze the removal of ubiquitin from protein substrates. The critical role of DUBs in regulating protein ubiquitination makes them attractive drug targets in oncology, neurodegenerative disease, and antiviral development. Biochemical assays for quantifying DUB activity have enabled characterization of substrate preferences and discovery of small molecule inhibitors. However, assessing the efficacy of these inhibitors in cellular contexts to…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transporter modulation of molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-brain barrier in a rat</strong> - CONCLUSIONS: In summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive…</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 and Mechanistic Investigation of Human Milk Oligosaccharide against SARS-CoV-2</strong> - Four human milk oligosaccharides (HMOs), 3’-sialyllactose (3’-SL), 6’-sialyllactose (6’-SL), 2’-fucosyllactose (2’-FL), and 3-fucosyllactose (3-FL), were assessed for their possible antiviral activity against the SARS-CoV-2 spike receptor binding domain (RBD) in vitro. Among them, only 2’-FL/3-FL exhibited obvious antibinding activity against direct binding and trans-binding in competitive immunocytochemistry and enzyme-linked immunosorbent assays. The antiviral effects of 2’-FL/3-FL were…</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>Explore intersection genes of oxymatrine and COVID-19 with lung cancer as potential therapeutic targets based on network pharmacology</strong> - Introduction. Oxymatrine is a natural quinazine alkaloid extracted from Sophora flavescens and has many medicinal values. Oxymatrine showed protective effects, viral inhibition and effects against lung cancer.Hypothesis/Gap Statement. Individuals with lung cancer exhibit heightened vulnerability to COVID-19 infection due to compromised immune function. In conjunction with COVID-19, it is hypothesized that oxymatrine may exert potent pharmacological effects on lung cancer patients.Aim. The…</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 View from My Window in Gaza</strong> - Two days before Israel escalated attacks in the Gaza Strip, my family bought some bread. After we evacuated, I biked home to get it. - <a href="https://www.newyorker.com/news/the-weekend-essay/the-view-from-my-window-in-gaza">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Week When Biden Hugged Bibi</strong> - The President, fresh off a grim trip to the Middle East, makes the case for funding Israel’s war—and Ukraine’s, too. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/the-week-when-biden-hugged-bibi">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Anguished Fallout from a Pro-Palestinian Letter at Harvard</strong> - Students issued a statement blaming Israel for the Hamas attacks. Then a doxing campaign tested the courage of their conviction. - <a href="https://www.newyorker.com/news/dispatch/the-anguished-fallout-from-a-pro-palestinian-letter-at-harvard">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ibram X. Kendi’s Anti-Racism</strong> - The historian espoused grand ambitions to dismantle American racism, but the crisis at his research center suggests that he always had a more limited view of change. - <a href="https://www.newyorker.com/news/our-columnists/ibram-x-kendis-anti-racism">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Another Hospital in Gaza Is Bleeding</strong> - Doctors in southern Gaza are overwhelmed by the dead and the wounded—and by displaced Palestinians sleeping on the floor. - <a href="https://www.newyorker.com/news/news-desk/another-hospital-in-gaza-is-bleeding">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>How young Argentines might put a far-right libertarian into power</strong> -
<figure>
<img alt="Javier Milei, wearing a black leather jacket over a dress shirt and tie, raises his hands aloft and opens his mouth mid-song at his closing rally in Buenos Aires, Argentina, on October 18, 2023." src="https://cdn.vox-cdn.com/thumbor/m40d7TsKOajThRPlGlu4n6XO6UQ=/186x0:5050x3648/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72778941/1743705276.0.jpg"/>
<figcaption>
Argentine presidential candidate Javier Milei, seen here singing at his closing rally on October 18, is known for wielding a chainsaw at his events, symbolizing his plan to slash public spending and unravel Argentina’s generous safety nets.  | Tomas Cuesta/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Javier Milei emerged from the fringe and is leading the polls ahead of Sunday’s election.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VRbhlK">
Hernán Stuchi, a 29-year-old food delivery driver in greater Buenos Aires, grew up as a left-wing activist. During this weekend’s presidential election in Argentina, he will make a starkly different choice, and back Javier Milei, a far-right libertarian trumpeting socially conservative culture war issues and explosive proposals to reshape Argentine society.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eS27tG">
“It was a kind of innocence,” he said of his previous support for left-wing leaders. “It’s not like us poor people ever stopped being poor.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N0v3ZD">
At the polls on Sunday, Stuchi will be far from alone.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ph3km5">
Milei <a href="https://www.lanacion.com.ar/politica/javier-milei-gano-las-paso-y-provoco-un-terremoto-en-la-politica-argentina-nid14082023/#:~:text=Nadie%20lo%20vio%20venir">shocked the country</a> when he <a href="https://www.reuters.com/world/americas/argentina-set-primary-vote-with-ruling-peronists-fighting-survival-2023-08-13/">defeated Argentina’s two main political forces in primary elections in August</a>. Now, he looks poised to <a href="https://www.axios.com/2023/10/19/javier-milei-argentina-presidential-elections">win the most votes </a>over the weekend (though he may be forced into a runoff). A main fount of that support is, surprisingly, young people — and young men in particular.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fBdspL">
Polls indicate <a href="https://www.pagina12.com.ar/593470-sergio-massa-se-acerca-a-javier-milei-patricia-bullrich-los-">almost 50 percent </a>of voters 29 and younger back Milei, the wild-haired outsider and self-described “anarcho-capitalist” who inveighs against traditional politicians, branding them as members of a “caste” that must be done away with. (His campaign slogan, “que se vayan todos,” or “get rid of them all,” carries echoes of the <a href="https://www.vox.com/donald-trump">Trumpian</a> “drain the swamp.”) A win by Milei’s ascendant campaign in Argentina would serve as yet another indicator of the far right’s <a href="https://elpais.com/internacional/2023-05-14/auge-de-la-extrema-derecha-y-declive-de-la-derecha-tradicional-chile-y-el-efecto-contagio-en-latinoamerica.html">rise across the Americas</a> and <a href="https://www.vox.com/world/2022/9/24/23366464/italy-elections-meloni-sweden-europe-far-right">around the world</a>. But young voters’ support sets Milei apart from the far-right stars he is often compared with, including Trump and Brazil’s Jair Bolsonaro, <a href="https://www.cnnbrasil.com.br/politica/lula-venceu-as-eleicoes-em-8-das-10-cidades-mais-jovens-do-brasil/">both of whom</a> were <a href="https://edition.cnn.com/election/2020/exit-polls/president/national-results">shut out by young voters</a> in their recent reelection bids.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EkIohg">
With over 100 percent inflation crushing Argentine pocketbooks, Milei’s proposed solution is a radical plan to abolish the central bank and dollarize the <a href="https://www.vox.com/economy">economy</a> by replacing the Argentine peso with the US dollar — a move untested by countries of Argentina’s scale. He has voiced support for other extreme positions, including liberalizing gun ownership and individuals’ freedom to sell their organs. He denies human-caused <a href="https://www.vox.com/climate">climate change</a> and opposes <a href="https://www.vox.com/abortion">abortion</a>. At rallies, he can often be seen <a href="https://www.lacapitalmdp.com/con-motosierra-en-mano-milei-paseo-su-caravana-por-la-calle-guemes/">wielding</a> a <a href="https://apnews.com/article/milei-argentina-chainsaw-fed35a37c6137b951e4adada3d866436">chainsaw</a>, symbolizing his plan to slash public spending and unravel Argentina’s generous safety nets. In Milei’s view, the state should largely limit itself to homeland security: To that end, he <a href="https://cnnespanol.cnn.com/2023/08/30/milei-ministerios-eliminar-por-que-de-que-se-encargan-orix-arg/">has pledged to axe</a> the ministries of education; environment; and women, gender, and diversity, among others.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZtV4Z0">
That Milei’s platform has seduced the likes of former <a href="https://www.vox.com/media">Fox News</a> firebrand <a href="https://twitter.com/TuckerCarlson/status/1700251942424109552">Tucker Carlson</a> isn’t surprising. But Argentina’s youth, in contrast, have traditionally not been associated with right-wing forces. For much of this century, the bulk of their support has gone to the left-wing Peronist coalition, a dominant electoral force in Argentina. As recently as 2019, when the last presidential election took place, young voters were seen as an <a href="https://elpais.com/elpais/2019/08/19/album/1566208029_440799.html">important group</a> in <a href="https://www.americasquarterly.org/article/the-gen-z-voices-shaping-argentinas-election/">favor of the left-wing candidate and eventual winner</a>. In the 1970s and ’80s, students and young people played a storied role in the <a href="https://www.educ.ar/recursos/157813/el-movimiento-estudiantil-en-los-anos-setenta-militancia-rep">opposition to the ruling military junta</a>. (Both <a href="https://www.perfil.com/noticias/politica/en-tucuman-javier-milei-polemizo-con-el-numero-de-los-desaparecidos-una-vision-tuerta-de-la-historia.phtml">Milei</a> and <a href="https://english.elpais.com/international/2023-09-25/victoria-villarruel-javier-mileis-running-mate-who-vindicates-the-dictatorship-and-opposes-abortion-and-gay-marriage.html">his controversial pick for vice president</a>, who has family ties to the military, have downplayed the dictatorship’s track record of human rights abuses.) In that historical context, young voters’ current pull toward Milei represents something of a paradigm shift.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RHcMbd">
Experts say there are many reasons for that shift, but chief among them is the pain of a prolonged and <a href="https://www.washingtonpost.com/business/2023/04/06/why-70-inflation-is-just-one-of-argentina-s-problems-quicktake/0d56242a-d499-11ed-ac8b-cd7da05168e9_story.html">worsening economic crisis</a>, which has put many in the mood for a sharp turn away from politics-as-usual. It’s also a reactionary impulse: There is a strong backlash against pandemic-era restrictions, which helped popularize Milei’s anti-establishment rhetoric, and a spate of recent progressive wins in Argentina, including a <a href="https://www.theguardian.com/world/2020/dec/30/argentina-legalises-abortion-in-landmark-moment-for-womens-rights">momentous bill that legalized abortion in 2020</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mGQZLG">
What started out as a youth movement powering <a href="https://www.latimes.com/world-nation/story/2023-10-19/desperate-and-disaffected-argentines-to-vote-whether-upstart-milei-leads-them-into-the-unknown">Milei’s campaign has now widened</a> to <a href="https://www.latimes.com/espanol/internacional/articulo/2023-08-25/radiografia-del-voto-a-milei-ricos-y-pobres-jovenes-y-ancianos-hartos-de-la-politica">include groups of all ages,</a> all across the country — Stuchi called it a process of “intergenerational contagion” with people like him working to sway over older relatives. That expanding appeal has put Milei on the precipice of power.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EwFMMA">
In pursuit of that power, he has been accused of fomenting violence and <a href="https://www.nytimes.com/2023/10/10/world/americas/argentina-peso-javier-mile.html#:~:text=His%20ascent%20has%20dominated%20the,the%20peso%20by%2020%20percent.">deepening the socioeconomic crisis he says he wants to solve</a>. His rhetoric, according to <a href="https://www.infobae.com/politica/2023/08/23/axel-kicillof-se-reune-con-sergio-berni-en-puente-12-para-monitorear-la-seguridad-en-el-conurbano/?utm_source=substack&amp;utm_medium=email">Argentine officials from the current ruling party</a>, encouraged looting across the south of the country in August.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GOakmE">
A win for Milei would plunge Argentina into uncertainty at best, sheer dysfunction at worst.
</p>
<h3 id="Qhx3wD">
The politics of 100 percent inflation, explained
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KWwPBK">
No matter the economic indicator you consult, the takeaway is one and the same: Things in Argentina are dire. Annual inflation <a href="https://batimes.com.ar/news/economy/consumer-prices-up-100-since-turn-of-the-year-reveals-indec.phtml">hit 138 percent in September</a>, one of the world’s highest rates. Just <a href="https://www.indec.gob.ar/indec/web/Nivel3-Tema-4-46#:~:text=INDEC%3A%20Instituto%20Nacional%20de%20Estad%C3%ADstica%20y%20Censos%20de%20la%20Rep%C3%BAblica%20Argentina&amp;text=Los%20resultados%20del%20primer%20semestre,%2C1%25%20de%20las%20personas.">over 40 percent of Argentines</a> currently live <a href="https://www.vox.com/poverty">in poverty</a>, up<a href="https://chequeado.com/el-explicador/como-evoluciono-la-pobreza-con-cada-presidente/"> from 25 percent in 2017</a>. The central bank <a href="https://www.ft.com/content/e907fec7-ee9f-4d63-8b12-1340c4a3798d">is almost out of reserves</a>, raising the risk of a potential currency devaluation and <a href="https://www.aljazeera.com/economy/2020/5/22/argentina-defaults-again-as-debt-talks-progress">yet another default</a>. No one is unscathed by the economic malaise, but young people face <a href="https://www.infobae.com/economia/2023/06/24/el-desempleo-entre-los-jovenes-duplica-la-tasa-promedio-a-nivel-nacional/">higher unemployment</a>.
</p>
<figure class="e-image">
<img alt="People stand in line on wet pavement in front of a large blue and yellow billboard listing different cuts of meat alongside their varying prices." src="https://cdn.vox-cdn.com/thumbor/JwklOu3ohpL-Z9ivALHTSBlljfg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25018933/1663299522.jpg"/> <cite>Luis Robayo/AFP via Getty Images</cite>
<figcaption>
People line up in front of a butcher shop next to signs with meat prices in Buenos Aires on September 11, 2023, a month after Argentina recorded its highest inflation rate in over two decades.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LiFfaZ">
“You go [buy something] and you find a price. You go back a couple of days later and it’s changed to something else … It’s like, every day, things get more difficult,” said Carolina Ramos, 19, a college student in the heartland city of Córdoba who will vote for Milei. “Inflation is so out of control that you lose the notion of how much things actually cost.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BFas47">
For many in Ramos’s generation, the only Argentina they’ve known is one in a state of crisis. Since 2012, the Argentine economy has been in recession <a href="https://data.worldbank.org/indicator/NY.GDP.MKTP.KD.ZG?locations=AR">more often than not</a>, and the International Monetary Fund has forecasted <a href="https://batimes.com.ar/news/economy/argentinas-economy-to-contract-25-this-year-says-imf.phtml">yet another economic contraction for 2023</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nvktfa">
“I only have memories of Argentina in decay,” said Adriel Segura, a 19-year-old based in Buenos Aires. “So, you look around and you associate all the political parties and all the movements that were in power during that time … to a decaying country. And you desperately search for other options.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K7lsuD">
Valeria Brusco is a member of the Red de Politólogas, a group of women political scientists. She says the traditional center-left and center-right candidates in this election are so inexorably linked to the economic mismanagement at the origin of the ongoing crisis that it’s as though they were “invisible” to many young voters, leaving only Milei as a viable option.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tiaRtk">
“The more anger and rage a voter has, the more probable it is that they’ll vote for Milei,” said Pablo Vommaro, a University of Buenos Aires sociologist.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nI1pbl">
Milei’s signature proposal to curb inflation — dollarization — is viewed by <a href="https://www.americasquarterly.org/article/mileis-path-to-dollarization-riddled-with-doubts/">experts as likely unworkable</a>, in part because of how few greenbacks are left in the central bank’s coffers. Critics say it could wind up depreciating the peso even further and inducing more pain. In the 1990s, a dollar-peso peg proved <a href="https://www.france24.com/en/americas/20231002-why-hard-right-libertarian-javier-milei-wants-to-dollarise-argentina-s-economy">popular in the short term</a>, but it led to a crushing devaluation, skyrocketing poverty, and bloody riots. According to Vommaro, young Milei voters are nevertheless willing to “press the red button and let everything blow up.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ygY1pW">
“Their thinking is that it’s better for everything to explode than to keep living through this agony with the same leaders as always.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JYSQmC">
Some analysts say young voters are under the naïve impression Milei will be able to seamlessly turn around Argentina’s troubles. But the young people I spoke with have an almost nihilistic understanding that betting on the libertarian could end badly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CXezJr">
“I know that those who are in power now and who were in power before will screw me over, that they’ll continue to steal,” said 24-year-old Buenos Aires resident Alan Monte Bello, referencing <a href="https://www.npr.org/2022/12/06/1141134320/argentina-cristina-fernandez-de-kirchner-corruption-guilty">high-profile corruption cases</a>. “They won’t do a good job. With Javier, I at least have the possibility that he won’t be like that. And maybe it will end up being a failure and things will be worse than now. But at least the benefit of the doubt is there.”
</p>
<h3 id="3Kzgig">
A radicalizing pandemic
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="phyD0g">
Milei drastically raised his public profile during the pandemic, when he <a href="https://www.revistaanfibia.com/javier-milei-el-libertario-peinado-por-el-mercado/">joined anti-confinement protests organized by young people</a> and made frequent TV appearances, arguing that the toll of the government’s containment measures would wind up exceeding the toll of Covid itself. There was a receptive audience for those views, in part because of the lockdowns imposed by Argentina in 2020 that <a href="https://www.washingtonpost.com/world/the_americas/coronavirus-argentina-million-quarantine-lockdown/2020/10/26/65eefde2-149c-11eb-bc10-40b25382f1be_story.html">lasted until November of that year</a>. That’s nowhere near the intensity of <a href="https://www.vox.com/world/2022/12/1/23486439/china-covid-zero-protests">China’s zero-Covid policy</a>, which only opened up restrictions earlier this year. But young people’s livelihoods were disproportionately compromised. In Argentina, <a href="https://www.eldiarioar.com/sociedad/no-derechos-laborales-no-temen-quiten-universo-jovenes-informales-seduce-milei_1_10453368.html">almost 45 percent</a> of all workers in the informal economy are between ages 18 and 29. Working remotely isn’t an option, so staying home means forgoing a paycheck.
</p>
<figure class="e-image">
<img alt="Milei stands in the bed of a truck, waving and smiling at a crowd, many of whom wave small yellow flags and take photos. " src="https://cdn.vox-cdn.com/thumbor/EX73cVMsougo1m96fNO1O-4uubg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25019387/1727875796.jpg"/> <cite>Tomas Cuesta/Getty Images</cite>
<figcaption>
Milei waves to supporters during a rally on October 16, 2023, in Buenos Aires, Argentina.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l52d17">
“The people who wanted to [flout restrictions], they had Milei as their representative,” Brusco said. “He became their hero.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SwvBwQ">
In parallel, a right-wing social media ecosystem was gathering strength, with a cadre of Milei-supporting influencers growing significant audiences on <a href="https://www.vox.com/tiktok">TikTok</a> and <a href="https://www.vox.com/youtube">YouTube</a>. Clips of Milei’s TV appearances found a second life on those platforms, and they helped give the firebrand a social reach unrivaled by his competition in this election. On TikTok, Milei’s official account, <a href="https://www.infobae.com/politica/2023/08/22/los-secretos-del-creador-de-la-cuenta-de-javier-milei-en-tik-tok-llegamos-a-300-millones-de-personas/">helmed by a 22-year-old staffer</a>, has garnered nearly four times as many followers as those of the center-left and center-right candidates combined.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T0tIXl">
“[Milei’s] performance on social media is very strong … I’ve interviewed lots of young people who told me that, during the pandemic, they were at home, they didn’t know what to do, and they just started watching videos of Milei,” said Ezequiel Saferstein, a sociologist and researcher at the Universidad Nacional de San Martín.
</p>
<h3 id="G3eIyu">
Backlash against historic abortion laws and other progressive wins
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Fipar5">
In 2021, a landmark law legalizing abortion went into effect. It capped a series of legislative advances — around issues such as <a href="https://www.vox.com/gender">gender identity</a>, gender equality, sexual education, and gay marriage — that put Argentina on the progressive vanguard of Latin America. Since then, the government has <a href="https://www.bbc.com/news/world-latin-america-65772878">removed barriers to contraception</a> and established a <a href="https://eeeuu.cancilleria.gob.ar/en/equal-opportunities-argentine-government-establishes-trans-labor-quota-national-public-sector">trans labor quota</a> in the public sector. The current president has <a href="https://www.lanacion.com.ar/politica/alberto-fernandez-volvio-a-usar-el-lenguaje-inclusivo-y-agradecio-a-cada-argentine-que-se-censo-nid19052022/">publicly used gender-neutral Spanish</a> — a lightning rod of controversy across the Americas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2NuANE">
Some see Milei’s rise as aided by a backlash against those changes. That may explain the gender imbalance in his youth support, which is a <a href="https://www.mdzol.com/sociedad/2023/8/24/un-estudio-revela-por-que-tantos-jovenes-votaron-javier-milei-363211.html">majority male phenomenon</a>. (“I’m not going to apologize for having a penis,” Milei once said <a href="https://www.cronica.com.ar/politica/Milei-polemico-No-voy-a-pedir-perdon-por-tener-pene-20220515-0013.html">in an interview</a>.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vqRYAi">
In addition to opposing abortion rights, Milei has denied the existence of the gender wage gap and dodged a question on a debate stage about gender violence. Those positions fueled large feminist demonstrations across the country late last month, with participants reporting fear that their <a href="https://english.elpais.com/international/2023-09-29/argentinas-feminist-movement-mobilizes-against-javier-milei.html">rights would be in jeopardy</a> under a Milei presidency.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tpVFMZ">
Saferstein told me that right-wing affiliation has carried a degree of stigma for much of the last 40 years because of the long shadows cast by the military dictatorship. But the institutionalization of progressive <a href="https://www.vox.com/policy">policies</a> has changed the way the right is perceived.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gj6CpD">
“Historically, it’s the left that has been associated with being revolutionary … [but] the left has in a way become the status quo,” he said. “The conservative reaction that we have seen has positioned itself as anti-system … Milei has made a cult out of that anti-system rebelliousness.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lkspeD">
Other young voters are less moved by the culture wars and might even disagree with many of Milei’s controversial beliefs. But amid the severe economic crisis, their top priority is Milei’s proposal to stabilize the country’s economy. Most of the young people I spoke with in Argentina, for instance, say they denounce Milei’s <a href="https://english.elpais.com/international/2023-08-15/whats-going-on-inside-javier-mileis-head.html">assertion</a> that climate change is a <a href="https://www.anred.org/2021/08/09/javier-milei-sobre-el-calentamiento-global-es-otra-de-las-mentiras-del-socialismo/">“socialist lie.”</a> Their votes, however, are not based on that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qbbmE1">
“It’s not that the people who vote for Milei are saying, ‘Screw the climate.’ … It’s just that I need to get some money in my pocket first. Then I can worry about the climate,” Stuchi said. “I think the only people that can care about climate change are people who have full fridges. … And it’s like that with every controversial policy item Milei might have, from the sale of organs to abortion.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9sPEgE">
Still, Brusco says electing a president who represents a brand of “angry masculinity” is a real worry. Milei might find it significantly more difficult once in office to implement his radical economic reforms than, for instance, to undermine the implementation of the abortion law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XNqBWL">
“Honestly, if we weren’t living through it, this [election] would seem like something out of a movie,” Brusco said.
</p>
<h3 id="CqRGjk">
What’s next?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zt1sgr">
Despite its moribund economy, Argentina has enjoyed a relatively stable political system in recent years. A Milei win could change that, with analysts predicting a high risk <a href="https://www.wsj.com/articles/argentine-presidential-primary-voters-propel-far-right-outsider-to-surprise-win-ec24e5b4">of social upheaval</a>. Among his first priorities would be to shrink the footprint of the Argentine state, drastically reining in spending and setting up an austerity regime to try to get the country’s books in order. Such moves would disproportionately affect the working class and be almost guaranteed to mobilize powerful <a href="https://www.vox.com/unions">unions</a> and social movements, paralyzing cities nationwide.
</p>
<figure class="e-image">
<img alt="National Gendarmerie guards walk past market stalls full of fruits and vegetables, wearing army green uniforms, helmets, and black flak jackets." src="https://cdn.vox-cdn.com/thumbor/EibW2EKBVEQdNIhGqFZBFslhBMU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25018944/1626444447.jpg"/> <cite>Pablo Barrera/Anadolu Agency via Getty Images</cite>
<figcaption>
Argentina deployed members of the National Gendarmerie in August after acts of violence and looting that government officials said Milei’s rhetoric helped incite.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4lCIkF">
But it’s unclear whether Milei would even be able to enact reforms in the first place. Functionally a one-man party, the libertarian would have scant allies in the legislature and none in provincial governorships across the country — an<a href="https://www.ft.com/content/ce3d73e3-60be-467c-9b09-f8f17dfc57dd"> unprecedented lack of support</a> for an Argentine president. Coalition building might prove complicated given the Milei camp’s lack of governing experience. Resorting to decrees and referendums would <a href="https://www.eldiarioar.com/economia/milei-candidato-fanatico-mercado-no-convence-mercado_1_10499753.html">be largely off-limits</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="76Ozaa">
Those governability challenges could make it difficult for Milei to inspire confidence in the investor class — an ironic twist given his market absolutism. After Milei came out on top during preliminary elections in August, the<a href="https://www.wsj.com/articles/argentinas-dollar-bonds-plummet-after-far-right-outsider-wins-primary-vote-b7ab9b72"> country’s financial markets plummeted</a>, accelerating the peso’s decline against the dollar.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="unVcF6">
“His government will face so many obstacles and I’m afraid there will be lootings, I’m afraid there will be revolutionaries in the streets,” said Natalia Fernandez, a lawyer in Córdoba. “That’s what I’m most worried about [if Milei wins]: the potential for unrest.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bGZcme">
If no candidate clears one of two bars Sunday (either receiving more than 45 percent of the vote, or notching 40 percent while also finishing more than 10 points ahead of the closest candidate), the top two contenders will advance to a runoff on November 19.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G74qNY">
“Milei won’t have an easy time governing,” Vommaro said. “All those problems young people have, they will get worse … and that is going to generate more anger, without a doubt.”
</p></li>
<li><strong>What the end of Killers of the Flower Moon means</strong> -
<figure>
<img alt="A man in a cowboy hat looks into the middle distance, and a woman stands with her head on his shoulder." src="https://cdn.vox-cdn.com/thumbor/cTXxksdY3Mp_Nah8g4MKhpeaAZk=/61x0:2170x1582/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72777868/killers.0.jpg"/>
<figcaption>
Leonardo DiCaprio and Lily Gladstone in <em>Killers of the Flower Moon.</em> | Paramount
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The final scenes of Martin Scorsese’s recent films are part of a larger project.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xGJ7Jg">
To paraphrase Soren Kierkegaard: A movie must be watched forward, but the <a href="https://www.vox.com/movies">best movies</a> beg to be understood backward. <a href="https://www.vox.com/culture/23919458/killers-flower-moon-review-martin-scorsese-leonardo-dicaprio-robert-deniro"><em>Killers of the Flower Moon</em></a>, Martin Scorsese’s latest epic, is such a movie. What he’s really doing isn’t evident until the film’s very final moments. The last scenes are a rhetorical gesture calculated to knock us flat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bVSNBN">
This is not unusual for Scorsese throughout his career — people have argued about the ending of <em>Taxi Driver</em> for longer than I’ve been alive — but something’s been going on with him in the last decade or so. The last few shots of movies like <em>Silence</em> and <em>The Irishman</em> are revelatory filters for the hours of drama that have just transpired. Scorsese has arguably been the greatest living American filmmaker for a long time, but his late work is almost painfully reflective, introspective in a way that invites viewers to look inside themselves, if they’re willing.
</p>
<aside id="3vz6H7">
<div>
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</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="edGiiK">
For <em>Killers of the Flower Moon</em>, he once again holds his fire till the very end, though there are hints of what he’s doing — questions about who gets to tell the story of other people’s tragedies and whether they should at all — sprinkled throughout the film. It’s not a twist so much as an unfolding, and a bold move from a man who has spent his life telling stories. It is perhaps his boldest ending yet. Couple it with a few other recent films and a whole project emerges. He is a man approaching the end of his life (he’s turning 81 this November), reevaluating it all.
</p>
<figure class="e-image">
<img alt="Image reads “spoilers below,” with a triangular sign bearing an exclamation point." src="https://cdn.vox-cdn.com/thumbor/uPQF4l3Wvpgo7pB7TTD6_3CasSQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/8565937/spoilers_below.png"/>
<figcaption>
Spoilers for <em>Silence</em>, <em>The Irishman</em>, and <em>Killers of the Flower Moon</em> follow.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fbytiV">
You could reach way back to films like <em>Shutter Island</em> and <em>Wolf of Wall Street</em>, movies about men who have one delusion about themselves and discover, a bit too late, how they really look to the people around them. But this crystallized in <em>Silence</em> (2016), which centers on Father Rodrigues (Andrew Garfield), a 17th-century Portuguese priest who has traveled to Japan with a fellow priest. They aim to convert the Japanese and minister to the Christians who’ve been forced underground by a government hostile to European influence, including their religion.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s3Hk7f">
Scorsese spoke often about the impetus for that film (adapted from a 1966 novel by the Japanese Catholic writer Shūsaku Endō), which he tried to make for 25 years before finally succeeding. He’d first been introduced to Endō’s book after being the target of vitriol for 1988’s <em>The Last Temptation of Christ</em>, which Scorsese considered to be an act of devotion while others, most of whom hadn’t seen the film, disagreed. The book addresses faith, doubt, and what it might mean for God to go silent in the face of extreme pain.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VyTrTw">
There’s a lot to say about <em>Silence</em> (in <a href="https://www.vox.com/culture/2016/12/21/14005760/silence-review-spoilers-martin-scorsese-andrew-garfield-adam-driver">my review</a>, I wrote that it was “the kind of film that cuts at everyone’s self-perceptions, including my own”). Yet the most lingering, complicating image in the film comes right at the end, when we discover that Father Rodrigues, despite having publicly renounced his faith and lived without it for decades, has been cremated with a crucifix. That scene isn’t in the novel; it’s Scorsese’s addition. Suddenly we’re not sure what exactly to believe about Rodrigues or, indeed, about the nature of faith and apostasy itself. Scorsese, a cradle Catholic who once thought of being a priest, has spoken about his return to faith in his later years, and has <a href="https://www.vox.com/culture/2019/11/26/20975991/scorsese-career-god-sacred-profane-irishman-netflix-streets-bull-innocence-last-temptation">always been looking for God in one way or another</a>. It’s a profound question in search of an answer, one he designed because he’s asking the question himself. The availability of divine forgiveness (and retribution) is a recurring theme throughout Scorsese’s movies. Here, though, he is asking the older man’s question: If God is really out there, caring about the actions of humans, then what would God be willing to forgive at the end of a man’s life?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2DbbJS">
That very theme deepens with <em>The Irishman</em>, which starts out, quite purposefully, as a redux of <em>Goodfellas</em>: a story of mobsters, violent men, men with egos to guard and vendettas to serve and a lot of skeletons stashed in the closet. But about an hour from the end, things flip on their head: Suddenly Frank Sheeran (Robert De Niro), a hitman for the mob and the antihero of the story, is made to confront an important truth. All his life, he’s told himself that he did what he did to protect and provide for his family, his daughters, his friends. Now, nearing the end of his life, the truth comes into focus. He hurt his family; he betrayed his friend; his favorite daughter won’t even speak to him. At the end of his life, he is alone, wholly alone. The weight of his sins is too much to bear. He can live only through self-delusion.
</p>
<figure class="e-image">
<img alt="An old man is seen through a half-open door." src="https://cdn.vox-cdn.com/thumbor/3VMW_jd8KQHqm6Me73S_KsGc1Ak=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25015939/irishman.jpg"/> <cite>Netflix</cite>
<figcaption>
Robert De Niro in the final shot of <em>The Irishman.</em>
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ATP1NJ">
The final shot of <em>The Irishman</em> is immensely painful; it might be the saddest ending I’ve ever seen. Having just been informed by a visiting priest at his nursing home that it’s just about Christmas, he asks the priest to leave the door open. Through the half-ajar opening, we see the big man, once celebrated by hundreds, now utterly alone with himself. It’s a stunning moment of self-implication for Scorsese, who in <a href="https://www.gq.com/story/martin-scorsese-profile">a recent <em>GQ </em>profile</a> spoke at length about mortality, guilt, forgiveness, and the feeling of your friends and family slipping away. “I just wanna be as honest with myself as possible,” Scorsese says. “And if I’m honest in the work, maybe I could be honest as a person. <em>Maybe</em>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SdAQYy">
This context is good to keep in mind while watching <em>Killers of the Flower Moon</em>. The film, which <a href="https://www.vox.com/culture/23919458/killers-flower-moon-review-martin-scorsese-leonardo-dicaprio-robert-deniro">reshuffles the elements</a> of David Grann’s nonfiction book of the same title, centers on two characters: Mollie Kyle (Lily Gladstone), an Osage woman who marries Ernest Burkhart (Leonardo DiCaprio), a dissipated veteran under the sway of his uncle William Hale (Robert De Niro) and his plot to steal the Osage people’s wealth.
</p>
<aside id="GmyzgJ">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wWConu">
As Grann notes in his book, <a href="https://www.vox.com/culture/23920002/killers-flower-moon-true-story-osage-murders-reign-of-terror-mollie-burkhart-what-happened">the Osage murders</a> — which involved dozens, maybe hundreds of people — were a media sensation after they were investigated 100 years ago, but were largely forgotten far too rapidly. Dead Osage people simply weren’t a story to America the way dead white people would have been. In 1932, the still-nascent FBI, which had investigated the case, started <a href="https://archives.fbi.gov/archives/news/stories/2005/october/jfrench_radio102405">working with a radio program</a> called <em>The Lucky Strike Hour</em> to dramatize cases the bureau had worked on, with the full cooperation of J. Edgar Hoover. Among its first episodes was the Osage murders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BG6qDe">
In the hands of a 1930s radio show — an early <a href="https://www.vox.com/true-crime">true crime</a> show, really — the story became, in essence, entertainment. Grann explains that fictional scenes were written by one of the FBI agents and shared with the producers of the program. “In one of those scenes, Ramsey shows Ernest Burkhart the gun he plans to use to kill Roan, saying, ‘Look at her, ain’t she a dandy?’” Grann recounts. The goal of the broadcast was, in essence, to convince the American public that the FBI was a great force for good: “The broadcasted radio program concluded, ‘So another story ends and the moral is identical with that set forth in all the others of this series … [The criminal] was no match for the Federal Agent of Washington in a battle of wits.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6ytwwj">
None of this was particularly unusual in the 1930s, when the exploits of high-profile bank robbers and fugitives like Bonnie Parker and Clyde Barrow, or John Dillinger, were followed breathlessly across America. Still, there’s an obvious queasiness in turning other people’s incredible tragedy — the exploitation and even murder of your family by men who considered themselves more worthy of their wealth simply because they were white — into entertainment. It’s a difficult ethical wicket, and especially thorny in the case of Scorsese, whose movies have often (though not always) focused on bad men doing bad things, but less often on the people who are collateral damage.
</p>
<figure class="e-image">
<img alt="Four women in Osage garb sit on the ground, holding fans." src="https://cdn.vox-cdn.com/thumbor/k3BzmlWSihdURiOcdMPfTA0nkZg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25015946/killers5.jpg"/> <cite>Paramount</cite>
<figcaption>
<em>Killers of the Flower Moon</em> feels like Scorsese’s attempt to grapple with responsibility, and complicity, in storytelling.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R1MoKB">
Had the movie ended with its nearly final scene — Mollie confronting Ernest about poisoning her insulin, him unable to confess, and her walking out — it would have been a stunner. But Scorsese tags on what feels, at first, like a hilarious but incongruous epilogue on the set of the radio show. We watch a narrator, vocal performers, and a foley artist re-create the rest of the story in a hokey old-timey way. It’s funny. You have to laugh.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BCRm83">
Then Scorsese himself — a man <a href="https://www.theringer.com/movies/2023/10/18/23921581/martin-scorsese-movies-cameo-appearances-taxi-driver-robert-de-niro">who has done many cameos</a>, in his own films and others’ — steps onto the radio stage. I was at the premiere screening at Cannes, and a hush instantly fell over the room. His lines are simple: He explains that Mollie’s obituary didn’t mention the murders. Then we cut to people of the Osage Nation, in what appears to be a contemporary ceremony, dancing in a circle, shot from overhead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Bo8kSK">
There’s more than one legitimate way to interpret this choice by Scorsese, which amounts, I think, to essentially breaking the fourth wall. What’s clear is that it’s a choice designed to make you think about everything that’s come before. As one of the film’s Osage language consultants, Christopher Cote, pointed out at a premiere while voicing his conflicted feelings, <a href="https://www.hollywoodreporter.com/movies/movie-news/killers-of-the-flower-moon-osage-consultant-mixed-feelings-1235620231/?fbclid=IwAR0gTf0sbesKkZ70AielY0FWhrOtugdiVXYL1RYLb9fzbZmQCIXrMrNxYXA">this is not a film for the Osage</a> (though members of the Osage nation have praised the film and participated in its making and promotion). Furthermore, having DiCaprio, one of the world’s biggest stars, in one of the lead roles means that the center of gravity is continually getting pulled toward him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pZysas">
Scorsese is no idiot; he knows this. He also knows the fact about Hollywood, which is that he and DiCaprio (and De Niro) are the reason this movie is getting made and heavily promoted. The complexity of making a movie, a work of entertainment, about a tragedy that’s still very much living in the memories of the Burkhart family and the Osage more broadly is complex. Having to balance the Osage perspective with the white characters — even if Gladstone’s performance is clearly the heart and soul of the film — is further messy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t4RZCV">
Scorsese’s appearance at the end of <em>Killers of the Flower Moon</em> represents another anchor in his recent self-reflection, prompted by a lifetime of telling stories. He’s <a href="https://www.gq.com/story/martin-scorsese-profile">upfront in the GQ<em> </em>profile</a> about what matters to him now, in his sixth decade of filmmaking: God, family and friends, and movies. Few filmmakers have done more to promote the work of directors from underrepresented communities than Scorsese, whose <a href="https://www.criterion.com/boxsets/1021-martin-scorseses-world-cinema-project-no-1">World Cinema Project</a> and extensive work as <a href="https://mubi.com/en/cast/martin-scorsese/films/executive_producer">an executive producer</a> is stunning. He cares about the art form and about who gets to tell stories — the major reason for his <a href="https://www.vox.com/2019/11/8/20950451/martin-scorsese-marvel-movies-cinema-feige">much-maligned comments</a> about the artistry of the most successful movies in the world.
</p>
<div class="c-float-right">
<aside id="6EbmUk">
<q>Scorsese’s appearance at the end of <em>Killers of the Flower Moon</em> represents another anchor in his recent self-reflection, prompted by a lifetime of telling stories</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yaLPHE">
Showing up at the end of <em>Killers of the Flower Moon</em> to specifically note how the story of the murders and of Mollie’s family was largely ignored is a tacit acknowledgment that he knows this isn’t a perfectly constructed story, either. Here he is, a man whose success comes at least in small part from proximity to the kind of men who murdered, asking for forbearance. For forgiveness, in a sense. An admission that these real events are not really fodder for an award-winning movie with a red-carpet Cannes premiere. None of it ever really has been.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GpEaRG">
<em>Killers of the Flower Moon</em>, he’s said <a href="https://scroll.in/reel/1057688/a-story-of-complicity-sin-by-omission-martin-scorsese-on-killers-of-the-flower-moon">in interviews</a>, is “a story of complicity, silent complicity in certain cases, sin by omission.” Read that backward over his late career and you start to see what he’s getting at: Where have I been complicit, even silently? Where have I sinned by omission? And in an imperfect world, where is there forgiveness to be sought? That it’s conveyed in masterpieces of cinema, made by a genius, makes it easy to forget the point: These are questions for us to ask, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="amhdMb">
Killers of the Flower Moon <em>is playing in theaters.</em>
</p></li>
<li><strong>The GOP speaker contest has entered its “who?” era</strong> -
<figure>
<img alt="Patrick McHenry stands with a gavel in front of the red and white stripes of a large US flag in the House of Representatives." src="https://cdn.vox-cdn.com/thumbor/8jVasfuIfSi30Y_ntKGdfv_3Y4M=/137x0:4970x3625/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72777449/GettyImages_1746740057.0.jpg"/>
<figcaption>
Speaker Pro Tempore Rep. Patrick McHenry (R-NC) presides over the House of Representatives at the US Capitol on October 20, 2023, in Washington, DC. | Drew Angerer/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Jim Jordan lost. Now the party is searching for new speaker candidates.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HcCeB8">
Republicans’ search for a new speaker of the House has gone back to square one.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sVeVE8">
After Rep. Jim Jordan (R-OH) fell short of the votes he needed on the House floor a third time, House Republicans voted to ditch Jordan as their party’s speaker nominee. Jordan lost the closed-door secret ballot vote 112 to 86, <a href="https://twitter.com/AnnieGrayerCNN/status/1715429122636132602">per CNN</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mtDgA7">
The House GOP will open the contest up to new candidates and meet again on Monday.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vYOZ5q">
Jordan’s defeat means that three of the most prominent figures in the House GOP — former speaker Kevin McCarthy, Majority Leader Steve Scalise, and Jordan — have now failed to unite the fractious conference.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4W4oFJ">
Right-wing holdouts deposed McCarthy and doomed Scalise’s speakership bid by insisting on a hardliner as speaker. But those holdouts have now been counterbalanced by a newly emerged bloc of mainstream members who took down Jordan and are insisting the speaker <em>not</em> be a hardliner.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m0adk5">
The tremendously difficult challenge is that just one GOP candidate somehow needs to unite nearly all members of both camps, even though they have seemingly irreconcilable demands.
</p>
<h3 id="Llia1a">
The “some rando” option
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y3wUFl">
With such long-established, high-profile Republicans falling flat, several much less well-known members of Congress will now try their luck. Reps. <a href="https://twitter.com/bresreports/status/1715430724310872424">Kevin Hern</a> (R-OK), <a href="https://twitter.com/MicaSoellnerDC/status/1715429956484812940">Jack Bergman</a> (R-MI), <a href="https://twitter.com/elwasson/status/1715431203275186282">Austin Scott</a> (R-GA), <a href="https://twitter.com/MZanona/status/1715443301120196912">Byron Donalds</a> (R-FL), and <a href="https://twitter.com/MZanona/status/1715443848275534182">Mike Johnson</a> (R-LA) declared their candidacies Friday afternoon after the GOP voted to drop Jordan. So did <a href="https://twitter.com/JakeSherman/status/1715441677576376633">Tom Emmer</a> (R-MN), who’s currently the House Majority Whip — No. 3 in GOP leadership. More may follow.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rcygl6">
But here’s the math problem that has bedeviled every speaker contender so far this year:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L7PCcF">
A GOP speaker candidate needs the votes of 217 out of 221 Republicans on the House floor (if no Democrats offer their backing).
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4uDbbA">
Roughly 180 Republicans appear to be team players who will happily back any nominee preferred by most of the conference.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xR8FYu">
But there are about 20 holdouts on the right who have embraced hardball tactics to try and force a more right-wing speaker to be elected.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pElplR">
And now there’s a newly emerged roughly 20-person anti-hardliner bloc composed of mostly mainstream or swing-district members.
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yrRZ7o">
The GOP’s new speaker candidates have little national profile. But perhaps it will take someone who is less firmly associated with either the existing leadership or the hardline-right faction to unite the GOP — someone who can make nice-sounding promises to both sides.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N1KzRK">
At least, it’s worth a shot. I guess. We are clearly at a “throwing things at the wall and seeing if anything sticks” phase of the speaker election morass. So next week, we’ll see if the “some rando” solution manages to fix things.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="puvEII">
That will mainly be a question for the right-wingers. The mainstream and swing district members generally want to get the House back open and elect a speaker — they just had specific grievances against Jordan — but they’d likely support Generic Republican for the job. The hardliners on the right, though, will have to decide whether to keep holding out in hopes of getting the far-right speaker of their dreams, or whether to come to some sort of compromise.
</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>NED vs SL | Engelbrecht, Van Beek’s maiden fifties push Netherlands past 260</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>Ind vs NZ | Boult expecting fireworks as unbeaten Kiwis and hosts clash</strong> - Both teams have won their opening four games with the Black Caps leading the standings from India due to their better net run rate</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>Aus vs Pak | After big ton, Warner credits IPL for success in ODIs</strong> - Warner’s 163 off 124 and his 259-run association with fellow centurion Mitchell Marsh helped Australia score a 62-run win over Pakistan, and the result has lifted them to fourth on the table</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 | Hamas releases two U.S. hostages as Israel readies for ground invasion; ISRO’s Gaganyaan first test flight today, and more</strong> - Here is a select list of stories to start the day</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>Cricket World Cup 2023 ENG vs SA | We’re fully focused on the South Africa game, says Jos Buttler</strong> - In ODIs, the two teams have met 69 times so far, with South Africa winning 33 times</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>Mangrove mom’s forest cries for conservation</strong> - Mangroves form a vast coastal barrier of trunks and roots against soil erosion and provide a breeding ground for fresh water fish stock, says conservationist K. Binu</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>Almost 95% hotels rooms booked in Mysuru as Dasara enters final phase</strong> - A few rooms are being held over for last-minute arrivals, or for regular clients</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 petition challenging Rohingya refugees’ ‘illegal detention’ in India | Explained</strong> - A writ petition in the Supreme Court alleges that India’s arrest and detention of the world’s most persecuted ethnic minority population is illegal and unconstitutional.</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>What does Supreme Court’s abortion verdict mean for reproductive justice in India?</strong> - A reproductive rights academic decodes the Supreme Court’s verdict, the ‘pro-life-pro-choice’ debate in India and the future of reproductive justice discourse in India.</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>ED files charge sheet against man named in Panama Papers for holding undisclosed foreign assets</strong> - The ED said Sanjay Vijay Shinde established an offshore company in tax haven British Virgin Islands in the name of Venus Bay Offshore Ltd</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>Poland election: Women and youth force PiS from power</strong> - A record high turnout in the poll brings momentous change to Poland’s political landscape.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>French arrests after bomb scares trigger evacuations at airports and Versailles</strong> - The Palace of Versailles, the Louvre as well as schools, airports and hospitals have been targeted.</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>Italy PM Giorgia Meloni splits from partner after off-air lewd TV remarks</strong> - Giorgia Meloni says the relationship is over after a TV show airs her partner’s off-air comments.</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>United States Grand Prix: Charles Leclerc takes pole position for Sunday’s race</strong> - Ferrari’s Charles Leclerc takes pole position in a tight qualifying session in the United States Grand Prix, with Max Verstappen down in sixth on the grid.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>French minister Darmanin spars with footballer Karim Benzema in Gaza row</strong> - The former French international threatens to sue Gérald Darmanin for accusing him of Islamist links.</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>Space is starting to look like the better mining operation</strong> - Mining in space might be less environmentally harmful than mining asteroids on Earth. - <a href="https://arstechnica.com/?p=1977659">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Space Wreck is a hardcore, combat-optional, break-the-game RPG that clicks</strong> - It’s a deep simulation, a retro throwback, and a funny few hours at a time. - <a href="https://arstechnica.com/?p=1977497">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Carbon capture pipeline nixed after widespread opposition</strong> - Navigator CO₂ says regulatory hurdles are too much to overcome. - <a href="https://arstechnica.com/?p=1977635">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Feel-good story of the week: 2 ransomware gangs meet their demise</strong> - One is fatally hacked, the other shut down in international police dragnet. - <a href="https://arstechnica.com/?p=1977607">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Okta says hackers breached its support system and viewed customer files</strong> - Hackers obtained valid credentials, but Okta doesn’t say how. - <a href="https://arstechnica.com/?p=1977688">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 man with a penis growing on his forehead visits the doctor, worried.</strong> - <!-- SC_OFF --></p>
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“Doctor, I have a penis growing on my forehead!”
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The doctor examines the situation, sits the man down and asks, “Have you been to South America?”
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“South America? No, not at all!”
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The doctor responds, “You should go, they have stunning beaches and beautiful girls there.” Then asks again, “Or maybe you’ve visited Africa?”
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“No, doctor, not Africa either!”
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The doctor chuckles, “You should consider it, they have incredible wildlife. But have you been to Europe, perhaps?”
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“No, not Europe either! Doctor, why are you asking about my travels? I have a penis on my forehead!”
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The doctor grins and says, “Well, my friend, you better start traveling because once those balls cover your eyes, you won’t see a damn thing!”
</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/blueblueelephant"> /u/blueblueelephant </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17coljb/a_man_with_a_penis_growing_on_his_forehead_visits/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17coljb/a_man_with_a_penis_growing_on_his_forehead_visits/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Canadian man loses his wife.</strong> - <!-- SC_OFF --></p>
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He goes to the stonemason and asks for a tombstone that says “rest in peace.” A couple days before the funeral, he comes to check on the stone and sees that it says “Rest in Piece.”
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“Sorry,” he says to the mason, “but I meant ‘peace’, with an ‘a’.”
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On the eve of the funeral, the mason shows the widower the corrected version of the stone. “I’ve done it with the ‘a’,” he says.
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Upon the stone is inscribed, “Rest in Piece, Eh?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/scalpdragon"> /u/scalpdragon </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17csgwo/a_canadian_man_loses_his_wife/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17csgwo/a_canadian_man_loses_his_wife/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A nail company wants to expand their business…</strong> - <!-- SC_OFF --></p>
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The firm, a long-established family company called Wilson’s Nails, has seen their revenue declining in recent years and decides to try an ad campaign to boost sales. They contact a highly regarded Madison Avenue ad agency to produce an ad for them; After a few weeks, the agency sits the owners and senior managers down to view the initial proof for their TV ad.
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The ad opens on a shot of a lonely, barren desert.
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Slowly it zooms in… they can see that there is a hill in the desert.
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The camera zooms in more… they can see movement, like ants, around the hill.
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It zooms in further… they see that they’re not ants, but people.
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Further yet… they see that there are three crosses sticking out of the top of the hill.
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Then the camera zooms in on the middle cross: A gaunt, bleeding man in a white loincloth is suspended there, wearing a crown of thorns; On a ladder next to him, a Roman centurion is nailing him onto the beams. As the camera comes closer, he turns to it and says: "We always use Wilson’s Nails!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Even before the clip fades out, the room practically explodes - the board and the owners are on their feet, shouting and protesting that this is the worst thing they’ve ever seen - How could the agency <em>possibly</em> think this was a good idea for their brand?!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The agency reps are immediately apologetic -They completely misunderstood the direction, they absolutely messed up, they will do everything in their power to make this right - Eventually they are able to mollify the company and get them to agree to a complete reimagining of the campaign, totally free of charge. While skeptical, the company decides to give them one more chance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A few weeks later, the board and the owners reconvene; The agency reps assure them that they’ve completely incorporated their feedback and they’re <em>positive</em> that they’ll be delighted with this new direction. They sit down and the agency plays the video proof:
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The camera opens on a tranquil and beautiful blue sea.
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It zooms in slightly; They can see that there’s an island in the sea.
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It zooms in further; The island is a paradise - Palm trees, coral and white sand beaches.
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As the camera comes closer, they see that there are three figures strolling along the beach.
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A little closer, and it becomes apparent that the figures are not walking, but running.
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Closer, and they can see that two of the figures are chasing the other one.
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As the camera zooms in, they see a gaunt man in a white loincloth, running for his life across the sand; Suddenly it pans to his pursuers, two Roman Centurions in full armor. As the camera focuses on one of them, he turn to it, sweaty and exhausted, and says: “We should have used Wilson’s Nails!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
​
</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/vonbixler"> /u/vonbixler </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17cwqqg/a_nail_company_wants_to_expand_their_business/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17cwqqg/a_nail_company_wants_to_expand_their_business/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Dean of Women at an exclusive all girls’ school was lecturing her students on sexual morality.</strong> - <!-- SC_OFF --></p>
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“We live today in very difficult times for young people. In moments of temptation,” she said. “Ask yourself just one question: Is an hour of pleasure worth a lifetime of shame?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A young woman rose in the back of the room and said, “Excuse me, but how do you make it last an hour?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/nothinlefttochoose"> /u/nothinlefttochoose </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17cjucf/the_dean_of_women_at_an_exclusive_all_girls/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17cjucf/the_dean_of_women_at_an_exclusive_all_girls/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A 7 year old and a 4 year old are in their bedroom. “You know what, I think it’s time we started swearing” said the 7 year old.</strong> - <!-- SC_OFF --></p>
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“When we go downstairs for breakfast, I’ll swear first, then you.”<br/> “Sure.” replied the 4 year old.<br/> They make their way downstairs and their mum asks the 7 year old what he wants for breakfast.<br/> “I’ll have Frosties, bitch”<br/> WHACK, he flew out the chair crying his eyes out. Mum looks at the 4 year old and says sternly “And what do you want?”<br/> “I don’t know, but it won’t be fucking Frosties”
</p>
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<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Reecethehawk"> /u/Reecethehawk </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/17c9myz/a_7_year_old_and_a_4_year_old_are_in_their/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/17c9myz/a_7_year_old_and_a_4_year_old_are_in_their/">[comments]</a></span></p></li>
</ul>
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