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<title>08 April, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>A rapid, low cost, and highly sensitive SARS-CoV-2 diagnostic based on whole genome sequencing</strong> -
<div>
Early detection of infection with SARS-CoV-2 is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosis of SARS-CoV-2 infection, dubbed Pathogen-Oriented Low-Cost Assembly &amp; Re-Sequencing (POLAR), that enhances sensitivity by aiming to amplify the entire SARS-CoV-2 genome rather than targeting particular viral loci, as in typical RT-PCR assays. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. We are able to reliably (&gt;95% accuracy) detect SARS-CoV-2 at concentrations of 84 genome equivalents per milliliter, better than the reported limits of detection of almost all diagnostic methods currently approved by the US Food and Drug Administration. At higher concentrations, we are able to reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy. Such genome assemblies enable the spread of the disease to be analyzed much more effectively than would be possible with an ordinary yes/no diagnostic, and can help identify vaccine and drug targets. Finally, we show that POLAR diagnoses on 10 of 10 clinical nasopharyngeal swab samples (half positive, half negative) match those obtained in a CLIA-certified lab using the Center for Disease Control’s 2019-Novel Coronavirus test. Using POLAR, a single person can process 192 samples over the course of an 8-hour experiment, at a cost of ~$30/patient, enabling a 24-hour turnaround with sequencing and data analysis time included. Further testing and refinement will likely enable greater enhancements in the sensitivity of the above approach.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.04.25.061499v4" target="_blank">A rapid, low cost, and highly sensitive SARS-CoV-2 diagnostic based on whole genome sequencing</a>
</div></li>
<li><strong>The effect of perceived morbidity and mortality risk on risk-taking and patience</strong> -
<div>
Beyond immediate health consequences, the COVID-19 pandemic has profoundly affected people’s environment. People had to adapt to new circumstances and take into account the risks related to COVID-19 in their everyday decisions. Given the unprecedented circumstances associated with the first wave of the COVID-19 pandemic, we might ask how people adapt to their new environment. In particular, we ask how people form their morbidity and mortality risk perception associated with the virus and whether increased perceived risk affects psychological traits, such as risk-taking and patience. To address these questions, we analyzed data from a large survey conducted during the first wave in France on 5,000 nationally-representative people. We find that people use the public information on COVID-19 deaths in the area where they live to form their perceived morbidity and mortality risk. Using a structural model approach to lift endogeneity concerns, we found that higher perceived morbidity and mortality risk increases risk aversion. We also found that higher perceived morbidity and mortality risk leads to less patience, although this was only observed for high levels of perceived risk.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/u768y/" target="_blank">The effect of perceived morbidity and mortality risk on risk-taking and patience</a>
</div></li>
<li><strong>Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background:The coronavirus disease (COVID-19) pandemic has led to an unprecedented public health crisis. Insufficient testing continues to limit the effectiveness of the global response to the COVID-19 pandemic. Molecular testing methods such as reverse transcriptase polymerase chain reaction (RT-PCR) continue to be highly centralized and are a sub-optimal option for population surveillance. Rapid antigen tests (Ag-RDTs) offer multiple benefits including low costs, high flexibility to conduct tests in a wide variety of settings, and faster return of results. Recently, self-test Ag-RDTs (STs) have gained approval in several markets and offer the possibility to expand testing, reaching at-risk populations. While STs have the potential to assist the COVID-19 response, test result integrity, reporting, and appropriate linkage to care continue to hinder the widespread implementation of self-testing programs. Methods:This protocol presents a mixed-methods pragmatic trial (ISRCTN91602092) to better understand the feasibility of self-testing as part of a contact tracing strategy within the Brazilian public health system. Approximately 604 close contacts of 150 index cases testing positive for COVID-19 will be enrolled. Close contacts will be randomized to either serial (daily) self-testing over a 10-day follow-up period or a more traditional approach to contact tracing with a professional Ag-RDT at one time point post-exposure. Usability workshops and focus group discussions will also be conducted. Discussion:This study protocol presents a comprehensive plan to assess the effectiveness, operational feasibility, and stakeholder preferences of a serial self-testing strategy for contact tracing within the Brazilian public health system. Our results will contribute to better understanding of the feasibility of a self-testing strategy within the public sector. Potential risks and limitations are discussed. Our findings will have important implications as governments continue working to mitigate the impact of COVID-19, particularly in the context of where to direct limited resources for testing and healthcare infrastructure.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288207v1" target="_blank">Integration of serial self-testing for COVID-19 as part of contact tracing in the Brazilian public health system: A pragmatic trial protocol</a>
</div></li>
<li><strong>The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein</strong> -
<div>
Coronaviridae is recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15-30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections, as well as enteric and neurological diseases. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50 ranging between 0.05 and 0.15 g/ml and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.13.499346v2" target="_blank">The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein</a>
</div></li>
<li><strong>The role of N-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant</strong> -
<div>
The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impact N-glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additional N-glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody binding. Glycan site-occupancy analyses revealed that the mutation resulted in N-glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535004v1" target="_blank">The role of N-glycosylation in spike antigenicity for the SARS-CoV-2 Gamma variant</a>
</div></li>
<li><strong>Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics</strong> -
<div>
The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5{+/-}72.3, p&lt;0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 units. Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535504v1" target="_blank">Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics</a>
</div></li>
<li><strong>Pre-infection neutralizing antibodies, Omicron BA.5 breakthrough infection, and long COVID: a propensity score-matched analysis</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Importance Investigating the role of pre–infection humoral immunity against Omicron BA.5 infection risk and long COVID development is critical to inform public health guidance. Objective To investigate the association between pre–infection immunogenicity after the third vaccine dose and the risks of Omicron BA.5 infection and long coronavirus disease. Design, Setting, and Participants This nested case–control analysis was conducted among tertiary hospital staff in Tokyo, Japan who donated blood samples in June 2022 (1 month before Omicron BA.5 dominant wave onset [July–September 2022]) approximately 6 months after receiving the third dose of the historical monovalent coronavirus disease 2019 mRNA vaccine. Exposures Live virus–neutralizing antibody titers against Wuhan and Omicron BA.5 (NT50) and anti–SARS–CoV–2 spike protein antibody titers with Abbott (AU/mL) and Roche (U/mL) assays at pre–infection. Main Outcomes and Measures Symptomatic SARS–CoV–2 breakthrough infections during the Omicron BA.5 dominant wave vs. undiagnosed controls matched using a propensity score. Incidence of long COVID (persistent symptoms ≥4 weeks after infection) among breakthrough infection cases. Results Anti–spike antibody titers were compared between 243 breakthrough infection cases and their matched controls among the 2360 staff members who met the criteria. Neutralizing antibodies in 50 randomly selected matched pairs were measured and compared. Pre–infection anti-spike and neutralizing antibody titers were lower in breakthrough cases than in undiagnosed controls. Neutralizing antibody titers against Wuhan and Omicron BA.5 were 64% (95% CI: 42–77) and 72% (95% CI: 53–83) lower, respectively, in breakthrough cases than in undiagnosed controls. Individuals with previous SARS-CoV-2 infections were more frequent among undiagnosed controls than breakthrough cases (19.3% vs. 4.1%), and their neutralizing antibody titers were higher than those of infection–naive individuals. Among the breakthrough cases, pre–infection antibody titers were not associated with the incidence of long COVID. Conclusions and Relevance Pre–infection immunogenicity against SARS–CoV–2 may play a role in protecting against the Omicron BA.5 infection, but not in preventing long COVID.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288162v1" target="_blank">Pre-infection neutralizing antibodies, Omicron BA.5 breakthrough infection, and long COVID: a propensity score-matched analysis</a>
</div></li>
<li><strong>Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction: Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response following vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) versus BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. Methods: The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed for randomized and observational studies using the Risk of Bias 2 tool and the Newcastle-Ottawa Scale, respectively. Evidence was evaluated using the GRADE framework. Results: Overall, 22 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR 0.87, 95% CI 0.79-0.96; P=0.0054; I2=61.9%), COVID-19-associated hospitalization (RR 0.83, 95% CI 0.76-0.90; P&lt;0.0001; I2=0%), and COVID-19-associated mortality (RR 0.62, 95% CI 0.43-0.89; P=0.011; I2=0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials and evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. Conclusion: This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288195v1" target="_blank">Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines in Immunocompromised Individuals: A Systematic Review and Meta-Analysis Using the GRADE Framework</a>
</div></li>
<li><strong>Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The role of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC) is unknown. The objective of this study is to assess the effect of NMV-r in non-hospitalized, vaccinated patients on the occurrence of PASC. Methods: We performed a comparative retrospective cohort study utilizing data from the TriNetX research network, including vaccinated patients ≥18 years old who subsequently developed Covid-19 between December 2021-April 2022. Cohorts were based on NMV-r administration within five days of diagnosis. Based on previously validated broad and narrow definitions, the main outcome was the presence of symptoms associated with PASC. Outcomes were assessed between 30-180 days and 90-180 days after the index Covid-19 infection. Results 1,004 patients remained in each cohort after propensity-score matching. PASC (broad definition) occurred in 425 patients (42%) in the NMV-r cohort, vs. 480 patients (48%) in the control cohort (OR 0.8 CI 0.67-0.96; p=0.01) from 30-180 days and in 273 patients (27%) in the NMV-r cohort, as compared to 347 patients (35%) in the control cohort (OR 0.707, CI 0.59-0.86; p&lt;0.001) from 90-180 days. Narrowly defined PASC was reported in 337 (34%) patients in the NMV-r and 404 (40%) in the control cohort between 30-180 days (OR=0.75, CI 0.62-0.9, p=0.002) and in 221 (22%) in the NMV-r cohort as compared to in 278 (28%) patients in the control cohort (OR=0.7, CI 0.63-0.9, p=0.003) between 90 -180 days. Conclusions NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288196v1" target="_blank">Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir </a>
</div></li>
<li><strong>Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background During the pandemic period, healthcare systems were substantially reorganized for managing COVID-19 cases. The corresponding changes on the standard care of persons with chronic diseases and the potential consequences on their outcomes remain insufficiently documented. This observational study investigates the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR), in particular in those not hospitalized for COVID-19. Methods We conducted a cohort study using the French national health data system which contains all healthcare consumptions in France. Incident persons with end stage kidney disease between January 1, 2015 and December 31, 2020 who received a kidney transplant were included and followed-up from their transplantation date to December 31, 2021. The survival of KTR during the pre-pandemic and pandemic periods was investigated using Cox models with time-dependent covariates, including vaccination and hospitalization events. Findings There were 10,637 KTR included in the study, with 324 and 430 deaths observed during the pre-pandemic (15,115 person-years of follow-up) and pandemic periods (14,657 person-years of follow-up), including 127 deaths observed among the 659 persons with a COVID-19-related hospitalization. In multivariable analyses, the risk of death during the pandemic period was similar to that observed during the pre-pandemic period (hazard ratio (HR) [95% confidence interval]: 0.92 [0.77-1.11]), while COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]). In addition, pre-emptive kidney transplantation was associated with a lower risk of death (HR: 0.71 [0.56-0.89]), as well as a third vaccine dose (HR: 0.42 [0.30-0.57]), while age, diabetes and cardiovascular diseases were associated with higher risks of death. Interpretation Considering persons living with a kidney transplant with no severe COVID-19-related hospitalization, the pandemic period was not associated with a higher risk of death.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.05.23288113v1" target="_blank">Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: a national observational study in France.</a>
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<li><strong>Second-order Citations in Altmetrics: A Case Study Analyzing the Audiences of COVID-19 Research in the News and on Social Media</strong> -
<div>
The potential to capture the societal impact of research has been a driving motivation for the use and development of altmetrics. Yet, to date, altmetrics have largely failed to deliver on this potential because the primary audience who cites research on social media has been shown to be academics themselves. In response, our study investigates an extension of traditional altmetric approaches that goes beyond capturing direct mentions of research on social media. Using research articles from the first months of the COVID-19 pandemic as a case study, we demonstrate the value of measuring ‘second-order citations,’ or social media mentions of news coverage of research. We find that a sample of these citations, published by just five media outlets, were shared and engaged with on social media twice as much as the research articles themselves. Moreover, first-order and second-order citations circulated among Twitter accounts and Facebook accounts that were largely distinct from each other. The differences in audiences and engagement patterns found in this case study highlight the importance of news coverage as a public source of science information and provide strong evidence that investigating these second-order citations can be an effective way of observing non-academic audiences that engage with research content.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.05.535734v1" target="_blank">Second-order Citations in Altmetrics: A Case Study Analyzing the Audiences of COVID-19 Research in the News and on Social Media</a>
</div></li>
<li><strong>Virological characteristics of the SARS-CoV-2 Omicron XBB.1.16 variant</strong> -
<div>
At the end of March 2023, XBB.1.16, a SARS-CoV-2 omicron XBB subvariant, emerged and was detected in various countries. Compared to XBB.1.5, XBB.1.16 has two substitutions in the S protein: E180V is in the N-terminal domain, and T478K in the receptor-binding domain (RBD). We first show that XBB.1.16 had an effective reproductive number (Re) that was 1.27- and 1.17-fold higher than the parental XBB.1 and XBB.1.5, respectively, suggesting that XBB.1.16 will spread worldwide in the near future. In fact, the WHO classified XBB.1.16 as a variant under monitoring on March 30, 2023. Neutralization assays demonstrated the robust resistance of XBB.1.16 to breakthrough infection sera of BA.2 (18-fold versus B.1.1) and BA.5 (37-fold versus B.1.1). We then used six clinically-available monoclonal antibodies and showed that only sotrovimab exhibits antiviral activity against XBB subvariants, including XBB.1.16. Our results suggest that, similar to XBB.1 and XBB.1.5, XBB.1.16 is robustly resistant to a variety of anti-SARS-CoV-2 antibodies. Our multiscale investigations suggest that XBB.1.16 that XBB.1.16 has a greater growth advantage in the human population compared to XBB.1 and XBB.1.5, while the ability of XBB.1.16 to exhibit profound immune evasion is comparable to XBB.1 and XBB.1.5. The increased fitness of XBB.1.16 may be due to (1) different antigenicity than XBB.1.5; and/or (2) the mutations in the non-S viral protein(s) that may contribute to increased viral growth efficiency.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.06.535883v1" target="_blank">Virological characteristics of the SARS-CoV-2 Omicron XBB.1.16 variant</a>
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<li><strong>SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in mice</strong> -
<div>
Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in this set of proteins is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence. However, as a potential drug target, it is imperative to understand how a complete Mac1 deletion impacts the replication and pathogenesis of different CoVs. To this end, we created recombinant bacterial artificial chromosomes (BACs) containing complete Mac1 deletions ({Delta}Mac1) in MHV, MERS-CoV, and SARS-CoV-2. While we were unable to recover infectious virus from MHV or MERS-CoV {Delta}Mac1 BACs, SARS-CoV-2 {Delta}Mac1 was readily recovered from BAC transfection, indicating a stark difference in the requirement for Mac1 between different CoVs. Furthermore, SARS-CoV-2 {Delta}Mac1 replicated at or near wild-type levels in multiple cell lines susceptible to infection. However, in a mouse model of severe infection, {Delta}Mac1 was quickly cleared causing minimal pathology without any morbidity. {Delta}Mac1 SARS-CoV-2 induced increased levels of interferon (IFN) and interferon-stimulated gene (ISG) expression in cell culture and mice, indicating that Mac1 blocks IFN responses which may contribute to its attenuation. {Delta}Mac1 infection also led to a stark reduction in inflammatory monocytes and neutrophils. These results demonstrate that Mac1 only minimally impacts SARS-CoV-2 replication, unlike MHV and MERS-CoV, but is required for SARS-CoV-2 pathogenesis and is a unique antiviral drug target.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.06.535927v1" target="_blank">SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in mice</a>
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<li><strong>Expression of DNA repair genes is modulated during differentiation of olfactory sensory neurons</strong> -
<div>
Olfactory dysfunction is considered a biomarker of several pathological conditions, including age-associated neurodegenerations, glioblastoma and COVID-19. Olfactory sensory neurons (OSNs) are specialized neurons that detect odorants and send olfactory information to the brain through the olfactory bulb. To perform their function, they are in direct contact with the environment, where they are exposed to several environmental toxins such as atmospheric levels of O2 and volatile molecules. Nonetheless, very little is known about DNA damage levels and expression of DNA repair pathways in these cells. Here we measured nuclear and mitochondrial DNA damage in olfactory epithelium (OE) and compared with levels detected in olfactory bulb (OB) and temporal cortex (TC), as a non-olfactory related central nervous system region. Surprisingly, DNA damage was lower in OE and OB when compared with TC, both for nuclear and mitochondrial genomes. Accordingly, expression of representative genes for all excision repair pathways was detected in OSNs. Moreover, expression of most evaluated DNA repair genes was lower in mature versus OSN progenitors, suggesting that DNA repair is downregulated during differentiation. Analysis of single cell expression data confirmed that expression of the most differentially expressed DNA repair genes decreased from progenitor to mature OSNs. Finally, in situ hybridization data showed that APE1 mRNA levels are lower in the mature OSNs layer of the olfactory epithelium, closest to the nasal cavity lumen. Altogether, we show here that DNA repair pathways are relevant in protecting OSNs against DNA damage accumulation and that differentiation through the OE is accompanied by changes in the expression levels of DNA repair genes.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.06.535865v1" target="_blank">Expression of DNA repair genes is modulated during differentiation of olfactory sensory neurons</a>
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<li><strong>Insights into the ISG15 transfer cascade by the UBE1L activating enzyme</strong> -
<div>
The attachment of the ubiquitin-like protein ISG15 to substrates is a well-established antiviral signalling mechanism of the innate immune response. However, despite the identification of thousands of substrates and clear roles in antiviral immunity, a molecular understanding of ISG15 selection and transfer through its cognate E1-E2-E3 enzyme cascade is largely unknown. Here, we present a 3.45 angstrom cryo-EM structure of a chemically trapped UBE1L-UBE2L6 complex bound to activated ISG15. This structure reveals the details of the first steps of ISG15 recognition and UBE2L6 recruitment by UBE1L. Taking advantage of viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) and influenza B virus (IBV), we validated the structure and confirmed the importance of the ISG15 C-terminal ubiquitin-like domain in the adenylation reaction. Moreover, biochemical characterization of the UBE1L-ISG15 and UBE1L-UBE2L6 interactions enabled the design of ISG15 and UBE2L6 mutants with altered selectively for the ISG15 and ubiquitin conjugation pathways. Together, our study provides much needed insight into the specificity determinants that ensure the fidelity of ISG15 signalling during the antiviral response.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.06.535837v1" target="_blank">Insights into the ISG15 transfer cascade by the UBE1L activating enzyme</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Nasal Treatment for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Optate;   Drug: Placebo<br/><b>Sponsor</b>:   Indiana 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>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: usual care and follow-up by a nurse;   Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>:   Centre Hospitalier Universitaire de Saint Etienne<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Chinese Herb;   Diagnostic Test: Placebo<br/><b>Sponsor</b>:   Chinese University of Hong Kong<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>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>:   COVID19 Testing<br/><b>Interventions</b>:   Behavioral: FABI tailored COVID-19 testing pamphlet;   Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>:   Texas Woman’s University;   National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Drug: PF-07817883;   Drug: Placebo<br/><b>Sponsor</b>:   Pfizer<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>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Other: conventional western medicine treatment;   Drug: Dexamethasone oral tablet;   Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>:   China-Japan Friendship 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>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsors</b>:   First Affiliated Hospital of Wenzhou Medical University;   REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>:   COVID-19;   Diagnostic Test<br/><b>Intervention</b>:   Device: Lollipop<br/><b>Sponsor</b>:   University of Wisconsin, Madison<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: NP-101;   Other: Placebo<br/><b>Sponsor</b>:   Novatek Pharmaceuticals<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms</strong> - <b>Condition</b>:   Long Covid19<br/><b>Interventions</b>:   Drug: Testofen;   Drug: Microcrystalline cellulose<br/><b>Sponsor</b>:   RDC Clinical Pty Ltd<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial</strong> - <b>Conditions</b>:   Healthy;   COVID-19;   Distress, Emotional<br/><b>Interventions</b>:   Behavioral: RASMUS Resilience Training;   Behavioral: Progressive Muscle Relaxation<br/><b>Sponsor</b>:   Medical University Innsbruck<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>Care for Veterans Post-COVID</strong> - <b>Condition</b>:   Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>:   Behavioral: Concordant Care Training;   Behavioral: Education Packet Training<br/><b>Sponsor</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>Complementary Self-help Strategies for Patients With Post-COVID Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Behavioral: Complementary self-help strategies in addition to treatment as usual;   Other: Treatment as usual<br/><b>Sponsor</b>:   Universität Duisburg-Essen<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety &amp; Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals</strong> - <b>Conditions</b>:   Infectious Disease;   COVID-19<br/><b>Interventions</b>:   Biological: RVM-V001 30 µg;   Biological: RVM-V002 30 µg;   Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration<br/><b>Sponsor</b>:   RVAC Medicines (US), Inc.<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>HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: HH-120 Nasal Spray;   Drug: Placebo<br/><b>Sponsor</b>:   Huahui Health<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>Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection</strong> - Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards…</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>Development of a Peptide Sensor Derived from Human ACE2 for Fluorescence Polarization Assays of the SARS-CoV-2 Receptor Binding Domain</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuing emergence of infectious variants have caused a serious pandemic and a global economic slump since 2019. To overcome the situation and prepare for future pandemic-prone diseases, there is a need to establish a convenient diagnostic test that is quickly adaptable to unexpected emergence of virus variants. Here we report a fluorescent peptide sensor 26-Dan and its application to the fluorescence polarization (FP) assay…</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>Comparison of a rapid fluorescence immunochromatographic test with an enzyme-linked immunosorbent assay for measurement of SARS-CoV-2 spike protein antibody neutralizing activity</strong> - CONCLUSION: FIC had good qualitative agreement with ELISA in the detection of positive NAbs-RBD(%) and could be an alternative for rapid NAbs-RBD(%) testing.</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>Comparison of antibody response to coronavirus disease 2019 vaccination between patients with solid or hematologic cancer patients undergoing chemotherapy</strong> - CONCLUSION: Hematologic cancer patients receiving chemotherapy tended to respond poorly to both COVID-19 mRNA and vector vaccines and had a significantly lower antibody titer compared to those with solid cancers.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication</strong> - Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro,…</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>Factor Xa cleaves SARS-CoV-2 spike protein to block viral entry and infection</strong> - Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation…</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>TRPC6 inhibitor (BI 764198) to reduce risk and severity of ARDS due to COVID-19: a phase II randomised controlled trial</strong> - CONCLUSIONS: TRPC6 inhibition was not effective in reducing the risk and/or severity of ARDS in patients with COVID-19 requiring non-invasive, supplemental oxygen support.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection</strong> - Several viruses have been shown to modulate the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of redox homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, also seems to disrupt the balance between oxidants and antioxidants, which likely contributes to lung damage. Using in vitro and in vivo models of infection, we investigated how SARS-CoV-2 modulates the transcription factor NRF2…</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>Chemical Composition of Honeysuckle (<em>Lonicerae japonicae</em>) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals</strong> - Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. Both…</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>Surfactin-like lipopeptides from <em>Bacillus clausii</em> efficiently bind to spike glycoprotein of SARS-CoV-2</strong> - The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probiotic…</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>Repurposing immune boosting and anti-viral efficacy of <em>Parkia</em> bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods</strong> - The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2,…</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>Attitudes and concerns regarding booster dose of COVID-19 vaccine among Egyptian patients with autoimmune and rheumatic diseases: a cross-sectional survey study</strong> - CONCLUSIONS: There is a low acceptability rate of booster dose of COVID-19 vaccine among Egyptian patients with ARD diseases. Public health workers and policymakers need to make sure that all ARD patients get clear messages about accepting the COVID-19 booster dose.</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>Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?</strong> - Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19</strong> - CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.</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>Propolis effects in periodontal disease seem to affect coronavirus disease: a meta-analysis</strong> - This meta-analysis aimed to investigate the effects of propolis on the severity of coronavirus disease symptoms by reducing periodontal disease. PubMed, EMBASE, SciELO, Web of Science, and SCOPUS databases were systematically searched. Studies have been conducted analyzing propolis’s effects on COVID-19 and periodontitis. The study was conducted according to the PRISMA statement and registered in PROSPERO. Risk of Bias (RoB) assessment and meta-analysis of clinical studies were performed (Review…</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>Inside the Hush-Money Payments That May Decide Trump’s Legal Fate</strong> - Years of interviews with potential witnesses provide insights into the Manhattan D.A.’s case. - <a href="https://www.newyorker.com/news/news-desk/inside-the-hush-money-payments-that-may-decide-trumps-legal-fate">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Putin Criminalized Journalism in Russia</strong> - The case of Evan Gershkovich, a Wall Street Journal reporter being held in Moscow on espionage charges, is only the most recent example of the Kremlin’s crackdown on reporters. - <a href="https://www.newyorker.com/news/our-columnists/how-putin-criminalized-journalism-in-russia">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Same Ole Line Dudes Are Waiting for You</strong> - Donald Trump’s arraignment was a circus for the media, but it was just another day at the office for New York’s professional line sitters. - <a href="https://www.newyorker.com/news/our-local-correspondents/the-same-ole-line-dudes-are-waiting-for-you">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fighting for the Right to Come and Go</strong> - In Mexico, return-migrant activists are asserting their “pocha” heritage and working to end legal and cultural exclusion. - <a href="https://www.newyorker.com/news/annals-of-immigration/fighting-for-the-right-to-come-and-go">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Israel on the Brink: Understanding the Judicial Overhaul, and the Protests Against It</strong> - Two writers, Ruth and Avishai Margalit, talk with David Remnick about the extensive protests against anti-democratic maneuvering by the government. Plus, the country star Margo Price. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/israel-on-the-brink-understanding-the-judicial-overhaul-and-the-protests-against-it">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Meet the MAGA movement’s new favorite autocrat</strong> -
<figure>
<img alt="President Nayib Bukele File Pictures" src="https://cdn.vox-cdn.com/thumbor/upqGchELZ3kaHnYzLaSaSZWl9Ng=/161x0:2737x1932/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72160592/1316520967.0.jpg"/>
<figcaption>
Salvadoran President Nayib Bukele speaks during a military ceremony in 2020. | Aphotografia/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The American right is falling in love with El Salvador’s president, Nayib Bukele, over his crime crackdown. But he’s also tearing down Salvadoran democracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dP4UjY">
When Donald Trump was arrested this week, <a href="https://www.foxnews.com/world/world-media-reacts-trump-indictment-leaders-remain-mostly-silent">most world leaders stayed silent</a>. But Nayib Bukele, the president of El Salvador, tweeted about it immediately.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EVAKEE">
“[J]ust imagine if this happened in any other country, where a government arrested the main opposition candidate,” <a href="https://twitter.com/nayibbukele/status/1643334584082345986?s=46">Bukele wrote</a>. “The United States ability to use ‘democracy’ as foreign policy is gone.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xsPJo0">
Such a development would be convenient for Bukele, who has emerged as one of the most prominent — and flamboyant — elected autocrats on the global stage. In the span of roughly a year, the 41-year-old leader has declared a state of emergency, suspended civil rights protections, detained tens of thousands of citizens indefinitely without charge, built a new <a href="https://www.vox.com/world-politics/2023/3/5/23621004/el-salvador-prison-bukele-ms13-barrio-18">mega-prison</a> made up of cells that cram 100 people in each, and packed the country’s highest court with his picks — who then promptly changed electoral rules to allow him to run again in 2024.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l9kr4m">
Salvadoran human rights advocates are <a href="https://www.americasquarterly.org/article/countering-el-salvadors-democratic-backsliding/">sounding the alarm about democracy’s death</a>, and the Biden administration has <a href="https://www.americasquarterly.org/article/from-bad-to-worse-nayib-bukeles-split-with-washington/">sanctioned key members of his government</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RNyIMu">
The response on the American right has been strikingly different. The authoritarian rhetoric, brash right-wing policies, and loud social media presence have captured the imagination of a small but influential group of American conservatives. In the past year, leading figures in MAGA world — including <a href="https://twitter.com/nayibbukele/status/1587972883506151424?lang=en">Tucker Carlson</a>, <a href="https://twitter.com/GenFlynn/status/1630186656232816642?lang=en">Michael Flynn</a>, and <a href="https://twitter.com/RogerJStoneJr/status/1630061937617780736">Roger Stone</a> — have praised Bukele, and even instructed Americans to learn from his example.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uUayyr">
Among the things Bukele’s new right-wing fans like most about him are his harsh criminal justice policies. The Salvadoran murder rate, once one of the highest in the world, has plummeted during Bukele’s time in power (though it should be noted it was <a href="https://dataunodc.un.org/content/country-list">already falling before he came into office</a>). The gangs that have long brutalized El Salvador’s civilians, most notably MS-13 and Barrio 18, seem weaker. Polls show that Bukele is stratospherically popular, with independent surveys showing <a href="https://en.wikipedia.org/wiki/Opinion_polling_on_the_Nayib_Bukele_presidency">favorability ratings in the 80s and even 90s</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mZjslk">
For this, some on the American right — like Sen. Marco Rubio (R-FL) — have cheered him on, largely ignoring his attack on the country’s democracy:
</p>
<div id="i2Pvu4">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
I just returned from <a href="https://twitter.com/hashtag/ElSalvador?src=hash&amp;ref_src=twsrc%5Etfw">#ElSalvador</a> where government officials are been sanctioned by the Biden Administration for rounding up gangs that have extorted,mutilated and murdered people for decades <a href="https://t.co/Cp8uanXlBO">pic.twitter.com/Cp8uanXlBO</a>
</p>
— Marco Rubio (<span class="citation" data-cites="marcorubio">@marcorubio</span>) <a href="https://twitter.com/marcorubio/status/1642939065438806017?ref_src=twsrc%5Etfw">April 3, 2023</a>
</blockquote></div></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6Rw5B1">
Conservative commentators’ praise for Bukele has been even more effusive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gGGPCx">
“‘He’s ‘authoritarian’? He’s wielding authority to do good, to get the bad guys and help the good guys. We should be doing that too,” the Daily Wire’s Michael Knowles said in <a href="https://www.youtube.com/watch?v=DpLciEz5HTU&amp;t=1s">a late February monologue</a>. “‘Authoritarian’ is just a word that liberals use when conservatives wield political power.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ioE4g6">
The conservative attraction to Bukele is primarily concentrated among very online right-wingers like Knowles — not yet approaching <a href="https://www.vox.com/2022/8/5/23292448/orban-cpac-dallas-2022-speech-trump">the widespread Republican admiration for Hungarian autocrat Viktor Orbán</a>. “They’re the useful idiots for Bukele’s worldwide PR campaign,” Daniel DiMartino, a fellow at the center-right Manhattan Institute, says of Bukele’s American fans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="T7pVYI">
But his rising popularity does illustrate the way that the ideas of the post-Trump conservative movement, including its obsession with crime and public disorder, create a very natural on-ramp to outright anti-democratic politics. And it should serve as a warning to liberals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TR0hc4">
El Salvador <a href="https://www.vox.com/2022/5/17/23068682/marcos-duterte-philippine-election-2022-illiberalism">isn’t the only country</a> where an elected authoritarian has become stratospherically popular by launching a crackdown on crime that shreds civil liberties. Attacking liberal rights as a hindrance to enforcing public order is a style of politics that has proven effective around the world, and one that is often bound up with an attack on democracy itself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZghxKY">
Illiberalism has a constituency. Liberals need to take that reality seriously, and not be complacent about liberalism’s popular appeal.
</p>
<h3 id="dD1mls">
The bitcoin dictator
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TDHEZR">
The American right’s love affair with Bukele started with bitcoin.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N7dg7n">
After Bukele won El Salvador’s election in 2019, the first president in 30 years who did not hail <a href="https://www.brookings.edu/blog/order-from-chaos/2019/02/05/the-significance-of-nayib-bukeles-surprising-election-as-president-of-el-salvador/">from either of the country’s two major established parties</a>, he set about turning the country into a haven for cryptocurrency use.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3s0f0j">
In 2021, this culminated in a law that legalized the use of bitcoin as legal tender. He even proposed building something called “<a href="https://www.curbed.com/2022/05/el-salvador-bitcoin-city-crypto-crash.html">Bitcoin City</a>,” an entire new town shaped like a coin built at the base of a volcano, in order to power bitcoin mining with geothermal energy. He has continued to push crypto even after the crash in November 2022, which did <a href="https://english.elpais.com/international/2022-11-14/bitcoins-decline-in-value-is-deadly-blow-for-el-salvador.html">real damage to the Salvadoran government’s balance sheet</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5VN9Od">
The bitcoin obsession demonstrated that he was extremely, extremely online. His active Twitter account used an image of him with <a href="https://www.thedailybeast.com/el-salvador-president-dons-laser-eyes-after-making-bitcoin-legal-tender">laser beams coming out of his eyes as his profile picture</a> — a common meme, <a href="https://www.wealthsimple.com/en-ca/magazine/laser-eyes-crypto">especially in crypto circles</a>, but one that probably would seem odd to his constituents who weren’t scrolling through Twitter and Reddit all day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rVfnXb">
Daniel Rothschild, the executive director of the libertarian Mercatus Center, <a href="https://www.theunpopulist.net/p/the-american-rights-new-authoritarian">sees this as the origin story</a> of Bukele’s popularity on the American right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YzTSTF">
“If you’re locked into the right Twitter circles, he’s been one of those people who has been a consistent presence for the last four years,” Rothschild tells me.
</p>
<figure class="e-image">
<img alt="EL SALVADOR-ECONOMY-POLITICS-BITCOIN" src="https://cdn.vox-cdn.com/thumbor/SNj9nAr3I07sRxq8FKFw7DwYXDc=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24566081/1236700782.jpg"/> <cite>Marvin Recinos/AFP/Getty Images</cite>
<figcaption>
Bukele speaks at the closing ceremony of the Latin Bitcoin conference in El Salvador on November 20, 2021.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="emImeV">
As Bukele’s crypto fan club was growing, his attacks on democracy were becoming more brazen.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SFFkLV">
In February 2020, Bukele asked the Salvadoran Legislative Assembly — then controlled by opposing parties — to grant him over $100 million to purchase new equipment for the Territorial Control Plan, an anti-gang initiative. When the legislature refused, he <a href="https://www.npr.org/2020/02/10/804407503/troops-occupy-el-salvadors-legislature-to-back-president-s-crime-package">sent in military and police forces to occupy the parliament building</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oOXeU1">
In a speech outside the building, he made the message of the act quite explicit. “If we wanted to press the button [and evict legislators by force], we would press the button,” Bukele told supporters.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3cSNzh">
About a year later, Bukele’s party <a href="https://www.washingtonpost.com/world/the_americas/salvador-bukele-legislative-midterm-election-authoritarian/2021/02/28/5f2ac302-77c9-11eb-8115-9ad5e9c02117_story.html">won the country’s legislative elections</a> and gained a two-thirds majority in its Parliament. He wasted little time in securing power: In May of 2021, his party <a href="https://www.wola.org/2021/05/el-salvador-attorney-general-constitutional-court/">voted to remove</a> the country’s attorney general, who was investigating Bukele’s party for corruption and clandestine negotiations with gangs, and all five judges on the Constitutional Court. All were replaced with Bukele allies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ANMWNc">
An open letter issued at the time from <a href="https://www.conectas.org/en/noticias/el-salvador-legislative-assembly-removes-supreme-court-judges/">100 Latin American civil society organizations</a> warned that “the illegitimate capture of judicial authorities connected to political power and the consequent disappearance of the principle of separation of powers are a dangerous precedent for democracy in the hemisphere.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FY9Ecx">
This warning proved prescient. In September 2021, the pliant Supreme Court <a href="https://www.aljazeera.com/news/2021/9/4/el-salvador-court-says-presidents-can-serve-2-straight-terms">ruled</a> that Bukele could run for reelection despite <a href="https://www.aljazeera.com/news/2022/9/16/el-salvadors-bukele-says-he-will-seek-re-election-despite-ban">an explicit ban on a president serving more than one term</a>. Predictably, Bukele later announced that he would be competing in the 2024 presidential contest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IPOp62">
The abolition of term limits has proven to be <a href="https://www.tandfonline.com/doi/full/10.1080/13510347.2021.1997991">a consistent predictor</a> of when an elected president in a weak democracy is moving to install himself in power for life. <a href="https://www.cnas.org/publications/commentary/in-el-salvador-and-elsewhere-leaders-find-ways-to-break-term-limits">Political scientists</a> Andrea Kendall-Taylor, Erica Frantz, and Joseph Wright warned in a 2022 op-ed that Bukele’s behavior could be a “red flag” for democracy in El Salvador, one that typically suggests “a leader’s intention to stay in office by subverting rules established to curb executive power.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3m4L53">
But if you were to read only Bukele’s supporters in the American crypto world, you would be forgiven for getting a different impression of his government. Balaji Srinivasan, a leading crypto figure and anti-woke commentator with nearly 900,000 Twitter followers, <a href="https://twitter.com/search?lang=en&amp;q=(salvador%2C%20OR%20bukele)%20(from%3Abalajis)&amp;src=typed_query">repeatedly promoted El Salvador</a> throughout 2021 and 2022 — praising the country as a “<a href="https://twitter.com/balajis/status/1502363380799078401">freedom jurisdiction</a>” that was offering <a href="https://twitter.com/balajis/status/1446508237822435329">“strong pushback” against the “wokes</a>,” and crediting Bukele personally for <a href="https://twitter.com/balajis/status/1407856335144714240">working</a> “to add El Salvador to the ranks of ascending world countries.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z68CaG">
And in the last year or so, Bukele’s profile has only grown.
</p>
<h3 id="6cufQg">
Tough on crime, tough on freedom
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RGhoGY">
El Salvador has long had one of the world’s highest murder rates. UN data shows that, despite a multi-year decline, the country still had one of the highest global murder rates at <a href="https://dataunodc.un.org/dp-intentional-homicide-victims">the beginning of 2022</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MQlKj9">
March 25 and 26 of that year were unusually violent even by Salvadoran standards: 76 people were killed in that span, roughly as many as were murdered <a href="https://www.pbs.org/newshour/world/el-salvador-declares-state-of-emergency-amid-killings">in the entire month of February 2022</a>. On March 27, Bukele announced a state of emergency (also called a “state of exception”) and a new crackdown on crime. Per the US State Department, the crackdown <a href="https://www.state.gov/reports/2022-country-reports-on-human-rights-practices/el-salvador/#:~:text=In%20addition%2C%20the%20state%20of,and%20to%20freedom%20of%20association.">suspended some of the most basic civil rights</a> in a democratic society.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m42T0G">
“Security forces were empowered to arrest anyone suspected of belonging to a gang or providing support to gangs,” the State Department explained in a 2022 report on Salvadoran human rights. “In addition, the state of exception suspended the rights to be informed immediately of the reason for detention, to legal defense during initial investigations, to privacy in conversations and correspondence, and to freedom of association.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kKlUla">
A year into the crackdown, there’s clear evidence that murder rates have continued to decline. But the extent to which Bukele’s crackdown contributed <a href="https://www.vox.com/world-politics/2023/3/5/23621004/el-salvador-prison-bukele-ms13-barrio-18">is debatable</a>. Previous harsh crackdowns in El Salvador had temporarily led to declines in gang violence, only for it to pick back up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pk92BT">
Yet experts say there are <a href="https://www.lawfareblog.com/bukele-has-defeated-el-salvadors-gangs%E2%80%94-now-how-and-what-does-it-mean-region">some reasons</a> to believe this one might be different: Bukele hit the gangs fast at a time when they weren’t prepared for it, potentially creating a leadership vacuum that might make it hard for the organizations to fully recover. It’ll take time to know just how effective it was.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h5sqdl">
The consequences for human rights, however, have been undeniably dire. Tens of thousands of Salvadoran citizens have been arrested and imprisoned. An <a href="https://icg-prod.s3.amazonaws.com/s3fs-public/2022-10/096-el-salvadors-prison-fever.pdf">October 2022 report from the International Crisis Group</a> found that “El Salvador now has the highest incarceration rate in the world, at around 2 per cent of the adult population.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VHShqy">
And yet the years of gang violence have been so painful, and so sustained, that many Salvadorans have welcomed the crackdown — hence Bukele’s currently high approval ratings.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FNHmWU">
The fact that the people approve of his behavior does not make it less autocratic. Latin American dictators often start out with popular support while consolidating power — see Alberto Fujimori in Peru or Hugo Chávez in Venezuela. Eliminating basic protections, including rights against unlawful arrest and protections for press freedom, are so dangerous to liberal democracy that they should worry any observer regardless of how popular they might be in the moment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FlgLhr">
But his attacks on liberal freedoms are precisely what has earned Bukele a new following on the American right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cLQ4CH">
It certainly helps that, on Twitter and in public appearances, Bukele has proven himself fluent in American right-wing argot. Take his Tucker Carlson interview, which aired in November 2022. In that conversation, Bukele speaks extensively about bitcoin, but transitions seamlessly into a harangue about the alleged malfeasance of the American liberal elite.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aoY8rV">
“I’m from El Salvador, a third-world country in Central America, and I myself see cities here [in the US] and say, ‘I wouldn’t live here,’” Bukele told Carlson. “The demise of the US has to come from within. No external enemy can cause this much damage.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6Esdu6">
The following tweet from Bukele, seemingly an attempt to encourage Americans to emigrate to El Salvador, is another good example. Look at the image’s 1950s trad aesthetic, the way it presents a white family watching an old-timey TV excited about “no fentanyl crisis” and “USD and Bitcoin as legal tenders” in “The New Land of the Free”:
</p>
<div id="FIO6sK">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="zxx">
<a href="https://t.co/CnAsA2kjI9">pic.twitter.com/CnAsA2kjI9</a>
</p>
— Nayib Bukele (<span class="citation" data-cites="nayibbukele">@nayibbukele</span>) <a href="https://twitter.com/nayibbukele/status/1640168857800253441?ref_src=twsrc%5Etfw">March 27, 2023</a>
</blockquote>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xOTfXW">
This PR campaign, which includes striking videos showing Bukele’s new mega-prison and mass arrests, has captured the imagination of many on the <a href="https://twitter.com/josh_hammer/status/1630388722591047680">American New Right and extended MAGA universe</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Tup6o1">
Gavin Wax, the president of the New York Young Republicans Club, <a href="https://americanmind.org/salvo/american-bukele/">writes</a>, “Americans could … look to El Salvador, a small but proud nation, as a blueprint for governance and public safety.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RhRFBv">
Rod Dreher, one of Viktor Orbán’s biggest boosters in the American media, wrote a piece titled “Nayib Bukele: Serious about Saving Civilization,” in which he <a href="https://www.theamericanconservative.com/nayib-bukele-serious-about-saving-civilization/">argued</a>, “[W]e are going to need a politician like that to de-wokify the US Government and, to the extent that it is legally possible, American society.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JLjOBq">
Right-wing Twitter is replete with New Right types praising Bukele’s war on crime. Here’s Jack Posobiec, a conservative influencer with 2 million Twitter followers, calling for Bukele to be named “<a href="https://twitter.com/JackPosobiec/status/1630958207530065927">Man of the Year</a>” and gushing over images of hunched-over and shirtless prisoners:
</p>
<div id="SIppjJ">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
It’s so beautiful <a href="https://t.co/DoblV36suP">https://t.co/DoblV36suP</a>
</p>
— Jack Posobiec (<span class="citation" data-cites="JackPosobiec">@JackPosobiec</span>) <a href="https://twitter.com/JackPosobiec/status/1630394518179659777?ref_src=twsrc%5Etfw">February 28, 2023</a>
</blockquote>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xuqrQh">
Here’s Charlie Kirk, the founder of Turning Point USA, praising a video allegedly depicting prisoners being made to destroy gravestones of gang members:
</p>
<div id="ufl9g5">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
The President of El Salvador, Nayib Bukele, sends out teams of prisoners to destroy any tombstones with gang symbols. <br/><br/>His reforms to end violent crime in his country have been so effective that his approval sits above 80%. <a href="https://t.co/cCyInbaZt3">pic.twitter.com/cCyInbaZt3</a>
</p>
— Charlie Kirk (<span class="citation" data-cites="charliekirk11">@charliekirk11</span>) <a href="https://twitter.com/charliekirk11/status/1631312034590752771?ref_src=twsrc%5Etfw">March 2, 2023</a>
</blockquote>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EGqYt7">
Bukele enthusiastically promotes all of this stuff on his own Twitter feed, either by retweeting it directly or repackaging it into his own propaganda videos. One such video, for example, begins with a series of right-wing American talk show hosts praising Bukele’s crime crackdown in English:
</p>
<div id="G1Vd5p">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="und">
<a href="https://t.co/5Rx7hlSN0Y">pic.twitter.com/5Rx7hlSN0Y</a>
</p>
— Nayib Bukele (<span class="citation" data-cites="nayibbukele">@nayibbukele</span>) <a href="https://twitter.com/nayibbukele/status/1632521369635233792?ref_src=twsrc%5Etfw">March 5, 2023</a>
</blockquote>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UFQQrV">
There is no attempt in these encomia to reckon with his attacks on democracy, like literally sending the armed forces into the National Assembly. If the consequences of the crime crackdowns for civil liberty are mentioned, it’s only to dismiss them as the whining of human rights-obsessed liberals who are unable to take crime seriously. They look at his heavy-handed response and abuse of civil liberties as the basic building blocks of a model to be imported to the US.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nuAtS8">
This “lusting after caudillismo,” as Rothschild put it in <a href="https://www.theunpopulist.net/p/the-american-rights-new-authoritarian">an article in the UnPopulist</a>, is what worries him and people on the right like DiMartino. After the Trump experience, they certainly should be worried.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Bx7Fi">
But conservatives aren’t the only ones who should do some soul-searching.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GI5ED4">
The worry for liberals is that Bukele’s popularity — and the popularity of his brand of illiberalism — is real, as <a href="https://www.voanews.com/a/hostile-attacks-surveillance-a-threat-to-el-salvador-media/6964706.html">confirmed by international surveys</a>. The crime crackdown is the biggest reason why, with somewhere in the neighborhood of <a href="https://uca.edu.sv/iudop/wp-content/uploads/Bol.-Eva-de-anio-2022-Seguridad.pdf">95 percent of Salvadorans</a> crediting his policies with the reduction in violence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CDuWeB">
The Salvadoran strongman is not the only authoritarian-inclined leader in the world to ride illiberal anti-crime politics to popularity. It’s a common pattern in Southeast Asia in particular, a kind of politics that political scientist Tom Pepinsky terms <a href="https://tompepinsky.files.wordpress.com/2016/06/disorder.pdf">“democracy against disorder</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uYfnBu">
This is a mode of politics wherein democratic politicians gain support by promising ultra-harsh, or even illegal, measures against crime and criminality. The key is the elevation of “order above law,” arguing that maintaining social cohesion and safety is a value above the law itself. It’s a political style that has paid dividends for the former leader of the Philippines, Rodrigo Duterte, as well as politicians in <a href="https://www.reuters.com/article/us-thailand-thaksin-probe/thailand-to-probe-thaksins-deadly-anti-drug-war-idUSBKK30039820070802">Thailand</a> and <a href="https://www.csmonitor.com/World/Global-News/2016/0729/What-s-behind-Indonesia-s-executions-of-drug-traffickers">Indonesia</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b0rbqC">
And now it is paying off for Bukele. The American right is watching and taking notes.
</p>
<ul>
<li><strong>In Showing up, Michelle Williams is an artist desperately trying to get anything done</strong> -
<figure>
<img alt="A woman sculpts a figure in an art studio." src="https://cdn.vox-cdn.com/thumbor/PlaiNWQ8Rd_GveSY48K_gj5_A4w=/751x0:3000x1687/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72160512/showingup1.0.jpg"/>
<figcaption>
Michelle Williams in <em>Showing Up.</em> | A24
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Kelly Reichardt’s latest film turns the frustration of mundane distractions thwarting art into gentle comedy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gL3ySc">
When you’re young, you think doing creative work is all about the lightning strike of inspiration, the muse turning up and giving you some gift. But read interviews with artists, or become one yourself, and you realize that actually making art means a life of simply turning up, most days. Sometimes it’s good. Sometimes it sucks. And when life knocks you off course, you just keep going.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NexfWA">
I think that’s why Kelly Reichardt named her new film <em>Showing Up</em>, and it’s probably why I love it so much. Like all of Reichardt’s films — among them <em>Wendy and Lucy</em>, <em>Meek’s Cutoff</em>, and <a href="https://www.vox.com/culture/2020/3/6/21158250/first-cow-interview-kelly-reichardt"><em>First Cow</em></a> — it is a movie about trudging toward an uncertain destination, at times enjoying and at times enduring your companions, and sometimes sitting down to rest. In this case, that destination is art.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="keVlbb">
It’s Reichardt’s fourth collaboration with Michelle Williams and seventh with co-writer Jon Raymond, significant not just because it’s relatively unusual but because it signals that Reichardt knows a thing or two about working with, and around, other people. Williams plays Lizzy, a stressed-out Portland sculptor with a show coming up and a broken water heater. Her landlord, Jo (Hong Chau, always terrific) is an artist, too, and has <em>two</em> shows coming up, which makes her slowness in fixing the water heater all the more galling to Lizzy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PxbdUG">
<em>Showing Up —</em> an unusually cheerful and funny film for Reichardt — is, in its essence, a chronicle of a Sisyphean quest rendered against the backdrop of laid-back Portland. Lizzy needs to get work done, but the most mundane stuff keeps throwing itself in the way, and she can barely keep the rock from rolling back on her. There’s the matter of the water heater. There’s also the bird her cat injures, which becomes her responsibility. Her parents (Maryann Plunkett and Judd Hirsch), artists themselves, are being annoying; her dad has house guests that Lizzy is pretty sure are taking advantage of him. Her creatively inclined brother (John Magaro) seems to be on a downward spiral, and Lizzy isn’t sure what to do. She is barely keeping her head above water, and meanwhile her creeping fear that nobody will come to her show, will even want to see her work, is lurking in the background.
</p>
<figure class="e-image">
<img alt="Two women stand on a sidewalk, looking up toward the sky." src="https://cdn.vox-cdn.com/thumbor/dYq9RTmoeLIjzDcUA2uNXSBmEhM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24567282/showingup2.jpg"/> <cite>A24</cite>
<figcaption>
Michelle Williams and Hong Chau in <em>Showing Up</em>.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pxlrtV">
Reichardt is a master at weaving a plot that’s so subtle that the inattentive viewer might be tempted to mistake it for merely a premise, a movie where “nothing happens.” That’s in part because what does happen is very everyday stuff, the kinds of things that happen to us all. You’re just trying to get your work done, but the phone keeps ringing, and that package needs mailing, and you don’t know what to have for lunch today, the dog needs walking, and you forgot the plumber had to be let in at noon. Like running on a treadmill, you’re doing a lot and going nowhere.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E83vrH">
But Reichardt’s genius is in turning the frustrations of life — which have, in past films, ranged from a broken-down car to a broken-down covered wagon — into fodder for characters to either grow, or not. Her movies are road movies, even the ones that aren’t on the road, like this one; people are on a journey without a definite destination, with mishaps along the way, and, most often, with companions they find a little less than ideal.
</p>
<div class="c-float-right">
<aside id="LXWjYa">
<q>Reichardt’s movies are road movies, even the ones that aren’t on the road</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UKeUXf">
In <em>Showing Up</em>, then, the task is to get a little further down the road. If you pay attention, you start to realize that this episode in Lizzy’s life is important precisely because it’s the point at which she might be tempted to quit — to give up making art, assume she’ll never be as celebrated as Jo, and take up some other task. The film’s tension comes from that question, though it never telegraphs it loudly: Which path will she choose?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lnr4NG">
It’s a particularly poignant tale coming from Reichardt, whose work is well-regarded by fans and critics. Her films premiere at prestigious festivals, and major actors seek her out. But her filmmaking practice is still deliberately minimalist and understated; she shoots in Portland, on small budgets, and has been a professor at Bard for a long time. Less disciplined and skilled filmmakers have lept from small-budget films to big-budget schlock and watched their work suffer as a result. Reichardt’s acclaim stems in part from her consistency and commitment to artistic freedom.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PYrO8T">
It’s not a freedom available to everyone, nor can everyone be good at their work. But it’s not hard to understand Lizzy as a stand-in for all the artists who find themselves working quietly, worrying that they might never get beyond the point they’re at, worrying that even thinking that way makes them less, somehow, of a real artist.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="haOc2X">
<em>Showing Up </em>is a knowing nod at everyone who finds making creative work a nearly impossible task amid the mundane distractions of ordinary life. So I take it as another road movie, one in which we’re the protagonists alongside Lizzy, and the movie is a companion along the way. For the attentive, those willing to settle into the film’s rhythm, it’s a balm and a wink — a gentle exhortation to keep, well, showing up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4xVRxG">
Showing Up <em>is playing in theaters.</em>
</p></li>
<li><strong>A Texas judge just issued a national ruling against medication abortion. What now?</strong> -
<figure>
<img alt="A photo of a box of mifepristone." src="https://cdn.vox-cdn.com/thumbor/WXGgfqIW_h9ATdG1gk357DCM42E=/222x0:3778x2667/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72159733/1241524355.0.jpg"/>
<figcaption>
Robyn Beck/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The status of mifepristone in America, explained.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FtsGp7">
A <a href="https://www.dropbox.com/s/jnm4r233xat6tv4/ND%20Tex%20FDA%20decision.pdf?dl=0">decision</a> in a highly anticipated federal court case was issued today: A district judge in Texas suspended the federal approval of mifepristone, a US Food and Drug Administration-approved drug used to induce abortions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QfpdGm">
But the decision will not go into effect for seven days to allow the federal government time to appeal the decision or seek emergency relief, meaning that for now, the medication will remain available.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cWF2nB">
Judge Matthew Kacsmaryk of the Northern District of Texas issued a ruling revoking the FDA’s approval of the drug. If the ruling goes into effect after the seven-day window passes, it would mean that US health care providers, which are subject to FDA rules and regulations, could no longer prescribe mifepristone — even in blue states where abortion is not otherwise restricted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XhYKgr">
The case will almost certainly be appealed, and one possibility is that the appellate court or the Supreme Court issues a stay while<strong> </strong>the lawsuit continues, meaning mifepristone could continue to be prescribed in the states <a href="https://www.guttmacher.org/state-policy/explore/medication-abortion">where it is currently legal</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BnuoTt">
A federal judge in Washington State issued a directly contradictory <a href="https://storage.courtlistener.com/recap/gov.uscourts.waed.102225/gov.uscourts.waed.102225.80.0.pdf">ruling</a> on Friday evening, moments after Kacsmaryk’s, prohibiting the FDA from pulling mifepristone from the market.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="clM6fx">
The availability of the drug will ultimately be decided by higher courts. But if mifepristone were to be pulled off the market, the consequences for access to abortion would be severe.<strong> </strong>Medication abortion — referring to the combination of both mifepristone and misoprostol — accounts for <a href="https://www.guttmacher.org/article/2022/02/medication-abortion-now-accounts-more-half-all-us-abortions">more than half</a> of all abortions in the US, and is used typically within the first 10 to 12 weeks of a pregnancy. It’s <a href="https://www.guttmacher.org/article/2022/02/medication-abortion-now-accounts-more-half-all-us-abortions">become the most common method</a> for ending pregnancies in the United States, partly due to its <a href="https://www.guttmacher.org/evidence-you-can-use/medication-abortion">safety record</a>, its <a href="https://www.healthaffairs.org/doi/10.1377/hlthaff.2021.01528">lower cost</a>, diminished access to in-person care, and greater opportunities for privacy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s2y3cY">
The anti-abortion movement has been trying to restrict access to medication abortion since before the overturn of <em>Roe</em>,<strong> </strong>but those tactics were focused primarily on curbing access state by state, not through sweeping national action. The Texas lawsuit represents the increasing aggressiveness of the anti-abortion movement to take aim not only at abortion access in conservative states controlled by Republicans, but also deep blue states run by Democrats.
</p>
<h3 id="PW2iha">
What is mifepristone?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gIKglI">
Mifepristone is a prescription drug that works by blocking the hormone progesterone, which maintains the interior of the uterus. If progesterone is blocked, the uterus can’t support a pregnancy and the embryo is detached.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hij7LE">
For medication abortions, a second drug — misoprostol — is then used. Misoprostol has been around since the 1970s, and was first developed to treat stomach ulcers. An individual seeking to end a pregnancy would take misoprostol 24 to 48 hours after mifepristone, causing their cervix to soften, and their uterus to contract and expel the embryo.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RGp1bb">
Mifepristone is also used for other situations like miscarriage management, and <a href="https://www.mayoclinic.org/drugs-supplements/mifepristone-oral-route/side-effects/drg-20067123?p=1">helping patients</a> with Cushing’s syndrome who also have Type 2 diabetes. Lawyers for the plaintiffs insist restricting mifepristone for abortion won’t impact patients who use the drug for other reasons, but already some pharmacists and doctors have <a href="https://slate.com/news-and-politics/2022/05/abortion-texas-pharmacies-refusing-prescriptions-misoprostol-methotrexate.html">resisted prescribing misoprostol to patients</a>, wary of breaking new laws or suspicious patients will use the drugs covertly for an abortion. Walgreens <a href="https://www.politico.com/news/2023/03/02/walgreens-abortion-pills-00085325">recently confirmed</a> it would not dispense mifepristone even in states where the drug remains legal, following threats from anti-abortion groups and Republican attorneys general.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xYPylP">
The drug was authorized by the FDA in 2000 and is approved for ending a pregnancy in the US up to 10 weeks’ gestation, though the World Health Organization recommends mifepristone up to 12 weeks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uSkCID">
Between 2000 and 2018, more than 3.7 million women in the United States used the medication — sold under the brand Mifeprex — to end an early pregnancy. In 2016 the FDA <a href="https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/020687Orig1s020MedR.pdf">reported</a> mifepristone’s “efficacy and safety have become well-established by both research and experience, and serious complications have proven to be extremely rare.” Three years later the agency approved a generic version, <a href="https://www.vox.com/identities/2019/8/20/20750226/abortion-pill-mifepristone-pregnancy-genbiopro-mifeprex-generic">GenBioPro</a>.
</p>
<h3 id="JAY5G2">
Why is there a lawsuit attacking mifepristone?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JYndly">
Back in November, a <a href="https://adfmedialegalfiles.blob.core.windows.net/files/AllianceForHippocraticMedicineComplaint.pdf">lawsuit</a> challenging the legality of mifepristone was filed on behalf of a coalition of anti-abortion groups and doctors known as the Alliance for Hippocratic Medicine. Led by the conservative legal advocacy group Alliance Defending Freedom, the lawsuit claims the FDA caved to political pressure under Bill Clinton when it approved mifepristone more than 22 years ago, and it should thus be pulled from the market.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XuTwGm">
The lawsuit claims the FDA didn’t properly assess mifepristone’s safety, and that the federal government has put people at risk more recently by making the medication easier to obtain. Examples it cites include the FDA extending in 2016 the recommended window of time to take mifepristone from seven weeks of a pregnancy up to 10, and removing a requirement in 2021 that women must pick up mifepristone in-person, thereby making telehealth and mail-orders more accessible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rzE18y">
The National Academies of Sciences, Engineering, and Medicine <a href="https://nap.nationalacademies.org/catalog/24950/the-safety-and-quality-of-abortion-care-in-the-united-states">has affirmed</a> medication abortion as a safe method to terminate pregnancy, and concluded that there is no medical need for the drugs to be administered in the physical presence of a health care provider. The FDA has also <a href="https://www.regulations.gov/document/FDA-2019-P-1534-0016">repeatedly rejected</a> the evidence the plaintiffs claim shows medication abortion is unsafe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vTjOW0">
The case has virtually no scientific merit, and challenging the use of a drug that has been studied and safely used for over two decades is highly unusual. Most Americans also believe medication abortion should be accessible. A poll <a href="https://t.co/LhufDvcQLF">released in early March</a> found majorities of Americans — including majorities of Democrats and independents — support keeping medication abortion legal and allowing women to use it at home to end an early-stage pregnancy. Another <a href="https://www.dataforprogress.org/blog/2023/2/28/an-overwhelming-majority-of-voters-support-protecting-access-to-abortion">recent survey</a> found 59 percent of voters disapprove of overturning the FDA’s approval of abortion medication, including 72 percent of Democrats, 65 percent of Independents, and 40 percent of Republicans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lpPOCA">
But legal experts concede these are legally unpredictable times given the politicization of the courts. The federal lawsuit was intentionally filed in Amarillo, Texas, so that Kacsmaryk, a conservative judge, would hear the case. Kacsmaryk was appointed by Donald Trump and is a former Christian activist who has <a href="https://www.thepublicdiscourse.com/2015/09/15612/">denounced the sexual revolution</a> of the 1960s and ’70s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="htFy3Z">
Last year, he <a href="https://www.vox.com/policy-and-politics/2022/12/17/23512766/supreme-court-matthew-kacsmaryk-judge-trump-abortion-immigration-birth-control">ruled</a> that federal law prohibiting certain forms of discrimination by health providers does not protect against anti-LGBTQ discrimination, and in a separate case, he concluded <a href="https://storage.courtlistener.com/recap/gov.uscourts.txnd.330752/gov.uscourts.txnd.330752.63.0_2.pdf">that teenagers can’t access birth control</a> without their parents’ permission under Title X, a federal program that provides family planning and preventative health services. Kacsmaryk claimed allowing teenagers to decide for themselves about birth control would “violat[e] the constitutional right of parents to direct the upbringing of their children.”
</p>
<h3 id="ku5ZMI">
What are the implications of the decision?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GTGPxz">
This was a lower-court decision, so this legal battle is not over —<strong> </strong>and the judge’s decision gives the federal government seven days to seek emergency relief. The federal government will either appeal to the United States Court of Appeals for the Fifth Circuit, or directly to the US Supreme Court.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iVsbYN">
One possibility is that the appellate court or the Supreme Court issues a “stay” as the case continues to be litigated, meaning mifepristone could continue to be prescribed, even once the seven-day window has passed, while the lawsuit goes on. When <em>Roe </em>was on the books, there were lots of court-ordered abortion bans upheld in district courts like Kacsmaryk’s, but then never enforced because pro-abortion rights attorneys would successfully win “stays” as they proceeded to appeal the bans in higher-level courts. Whether an appellate court in a post-<em>Roe </em>environment would be as willing to block a lower judge’s order while the case continues is an open question.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8OMI0d">
David Cohen, a law professor at Drexel University who specializes in reproductive rights law, said before Kacsmaryk issued his order that typically an appellate court would consider whether a lower court order would be so disruptive to the status quo that it needs to be put on hold while they consider the case. In normal times, abruptly taking off the market an FDA-approved drug that has been safely used by millions of women for over 20 years would certainly meet the threshold of “very disruptive” to the status quo.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HhSfGZ">
“But I think we are in a world where the conservative Fifth Circuit feels very emboldened, so we can’t count on [a stay],” Cohen told Vox. Another option is the FDA appeals directly to the Supreme Court, skipping the Fifth Circuit. “We’ve seen more litigants doing that in recent years, though usually it’s been conservative litigants,” Cohen explained. “I don’t know if the FDA would want to do that, but it’s possible they think they’d get a fairer shake at the Supreme Court.”
</p>
<h3 id="56UD4B">
What options for abortion are still available right now?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WVAdMg">
For the next seven days, nothing will change, according to Kacsmaryk’s order.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Lh3YZf">
Even if the drug is ultimately pulled from the market, people seeking abortions could still access care at in-person clinics for the surgical abortion procedure. But those abortions typically <a href="https://www.healthaffairs.org/doi/10.1377/hlthaff.2021.01528">cost more money</a>, and require more time and resources from the already-strapped clinics. In its legal filing opposing the lawsuit, the US Justice Department warned that taking mifepristone off the market would lead to delays and overcrowding at these in-person clinics, which were already managing an influx of out-of-state patients since <em>Roe </em>was overturned.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RpyoJ9">
Another option that would remain even if the order takes effect is ordering pills from the European-based nonprofit <a href="https://www.vox.com/23056530/aid-access-abortion-roe-wade-pills-mifepristone">Aid Access</a>, which bypasses US restrictions by prescribing the drugs to patients from overseas. This European organization services people in all 50 states, but because the medication ships internationally, it can often take two to three weeks for pills to arrive.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wb4IVv">
A third option would be pursuing medication abortion using only misoprostol. This method is not FDA-approved, but it is backed by the World Health Organization, and a common way of ending pregnancies <a href="https://www.theatlantic.com/health/archive/2022/09/abortion-pill-misoprostol-effectiveness/671465/">around the world</a>. Last month, the <a href="https://onlinelibrary.wiley.com/doi/10.1363/psrh.12219">first study to examine misoprostol-only abortions in the US</a> was published and researchers found the drug to be 88 percent effective, with few incidents of serious adverse events or signs of a potential abortion complication. In comparison, research in the US on using mifepristone and misoprostol together have shown success rates of <a href="https://www.guttmacher.org/evidence-you-can-use/medication-abortion">95 percent</a>. But research on misoprostol-only abortions in other countries have also shown similar efficacious results, ranging between <a href="https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0001139">95</a> and <a href="https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0001139">99 percent</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jvvxrc">
Abortion providers, though they express adamant opposition to the Texas lawsuit, have also been preparing to offer misoprostol-only abortions if mifepristone is taken off market. The National Abortion Federation, <a href="https://prochoice.org/wp-content/uploads/2022-CPGs.pdf">in its clinical guidelines</a>, says that “where mifepristone is either not legally available or inaccessible, misoprostol-alone regimens may be offered.” Because misoprostol has been FDA approved to treat stomach ulcers and can be prescribed off-label for solo use, there is less concern that access to that drug will disappear.
</p>
<h3 id="7slosp">
There are also pending federal lawsuits to expand access to medication abortion
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E5Ve9n">
In addition to battling this lawsuit from anti-abortion groups, reproductive health organizations have been planning their own legal strategies to expand access to abortion pills. In January, two such lawsuits were filed, claiming two states’ restrictions on mifepristone illegally preempt the FDA.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f3DZ8m">
Through the passage of the Federal Food, Drug, and Cosmetic Act<strong> </strong>in 1938, Congress empowered the FDA as the sole agency to approve drugs in the US. It’s responsible for reviewing a drug’s safety, weighing its risks and benefits, and regulating appropriate conditions for safe and effective use.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SDqdkD">
With this in mind, GenBioPro, the generic manufacturer of mifepristone, <a href="https://democracyforward.org/wp-content/uploads/2023/01/33-0-Complaint.pdf">argued in a new lawsuit</a> that West Virginia’s state abortion ban is unconstitutional because it violates the supremacy and commerce clauses of the US Constitution, which empowers the FDA as the sole regulator of drugs across the country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DXOpIH">
A similar case, filed in January by an OB-GYN in North Carolina, <a href="https://www.dropbox.com/s/u9n7lfezh3ywmvu/2023-01-25%20%5B01%5D%20Complaint.pdf?dl=0">challenged state officials</a> for imposing restrictions on mifepristone that go beyond what the FDA requires. North Carolina requires doctors to provide mifepristone in-person at a particular type of facility after a 72-hour waiting period and, in some cases, an ultrasound.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ckFLes">
Experts say there is a <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4032931">“strong, though legally uncertain”</a> argument that the Supremacy Clause of the Constitution gives the federal government authority over these conflicting state rules. This idea — that federal regulation of drugs would take precedence, and a state cannot ban a drug that has been given federal approval — is known as the preemption argument.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MVCd5e">
For now, legal scholars say it’s unclear how preemption arguments will play out in court. Courts often grant deference to the FDA, though there are relatively few examples involving drugs. The main precedent is a 2014 case where a federal judge <a href="https://www.bostonglobe.com/metro/2014/04/15/federal-judge-says-patrick-administration-cannot-block-sale-painkiller-zohydro-massachusetts/DlLIz9qETePxqC29Ob27CN/story.html#:~:text=A%20federal%20judge%20struck%20down,District%20Court%20Judge%20Rya%20W.">struck down a Massachusetts effort</a> to restrict the opioid Zohydro, since the FDA had approved the painkiller. If the plaintiffs win their case, millions more people could have easier access to mifepristone.
</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>Indian boxing squad for World Championships</strong> - Shiva Thapa, Mohammad Hussamuddin and Deepak Bhoria headline Indian challenge</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>Expert view: Viswanathan Anand runs an eye over Nepomniachtchi vs. Ding</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Morning Digest | House panel apprised of collusive threat from China and Pakistan; T.N. sanctions graft case probe against EPS, and more</strong> - Here’s a select list of stories to read before you start your 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>Super Giants spinners leave Sunrisers in a tangle, make it a walk in the park</strong> - Krunal scalps three, including Markram for a golden duck; Mishra, Bishnoi prove ideal foil; Lucknow chases down the target with four overs to spare</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>Romualdo, who has been well tuned, may score in the first division of the Nilgiris Police Trophy</strong> -</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>PM Modi flags off Chennai-Coimbatore Vande Bharat Express in Tamil Nadu</strong> - Railway Minister Ashwini Vaishnaw, TN Governor R.N. Ravi, Chief Minister M.K. Stalin and Union Minister of State L. Murugan were present.</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>Challenging Samastha, CIC goes ahead with augmented syllabus</strong> - CIC to introduce new academic streams in Wafi and Wafiya system, including science programmes. Coaching for NEET, JEE and Civil Services exam too is being planned</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>Silverware seized from car of Boney Kapoor’s company in Davangere</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>CJ bench sets aside single-judge order in Musaddilal ED seizure case</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>BJP plans to air 100th Mann Ki Baat in U.P. madrassas and dargahs</strong> - An Urdu translation of the Prime Minister Narendra Modi’s 12 Mann Ki Baat speeches made in 2022 will also be made distributed to maulanas and Muslim religious scholars on April 30</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine to export electricity again after months of Russian attacks</strong> - Russia’s assault on Ukraine’s energy infrastructure led to blackouts throughout winter.</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>One Romanian family’s fatal attempt to reach the US</strong> - What drove the Iordache family to make a desperate bid to reach the US from Canada?</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>Evan Gershkovich: Russia charges US journalist with spying - reports</strong> - Evan Gershkovich, who was arrested last week, categorically rejects the accusations, reports say.</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>Becker says time in prison was ‘brutal’</strong> - Former Wimbledon champion Boris Becker says he is building his “third chapter” after eight months in prison.</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>People were taking drugs in Spain 3,000 years ago, study finds</strong> - A new study finds people in Menorca got high on hallucinogenic drugs during the Bronze Age.</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>Klaus Teuber made Catan, and it changed the world’s expectations for board games</strong> - One man’s quest to re-create ancient exploration opened up new tabletop worlds. - <a href="https://arstechnica.com/?p=1929865">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>We’re one step closer to reading an octopus’s mind</strong> - A recording device and electrodes were implanted in the very flexible cephalopods. - <a href="https://arstechnica.com/?p=1930115">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New photo reveals extent of Centaur V anomaly explosion [Updated]</strong> - “A column of burning, clear hydrogen shot up into a mushroom cloud.” - <a href="https://arstechnica.com/?p=1929875">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Artists astound with AI-generated film stills from a parallel universe</strong> - A Q&amp;A with “synthographer” Julie Wieland on the #aicinema movement. - <a href="https://arstechnica.com/?p=1904461">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RIP to Dropcams, Nest Secure: Google is shutting down servers next year</strong> - Sales ended years ago, but they’ll turn into bricks when the servers shut down. - <a href="https://arstechnica.com/?p=1930106">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>3 drunk guys entered a taxi</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The taxi driver knew that they were drunk so he started the engine &amp; turned it off again. Then said, “We have reached your destination”. The 1st guy gave him money &amp; the 2nd guy said “Thank you”. The 3rd guy slapped the driver. The driver was shocked thinking the 3rd drunk knew what he did. But then he asked “What was that for?”. The 3rd guy replied, “Control your speed next time, you nearly killed us!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/creydth"> /u/creydth </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12fghsj/3_drunk_guys_entered_a_taxi/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12fghsj/3_drunk_guys_entered_a_taxi/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s the difference between a poorly dressed man on a tricycle and a well-dressed man on a bicycle?</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Attire
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Inevitable-Cellist23"> /u/Inevitable-Cellist23 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12ezrl4/whats_the_difference_between_a_poorly_dressed_man/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12ezrl4/whats_the_difference_between_a_poorly_dressed_man/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I was stranded on an island with nothing but dark red grass, dark red sand, dark red trees everything was darkred.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“AHHH!” i yelled “I’ve been marooned!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/BluLeaf1"> /u/BluLeaf1 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12fa1jo/i_was_stranded_on_an_island_with_nothing_but_dark/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12fa1jo/i_was_stranded_on_an_island_with_nothing_but_dark/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One Easter Sunday, a man goes to church and returns home with two black eyes.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His wife inquires as to how he got the black eyes.
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The man goes on to say, “a lady stood up in front of me during mass, I saw her dress was stuck in the butt crack, so I reached out and tugged it out. She whirled around, became furious, and punched me in the eye.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“That explains one black eye,” the wife says, “but what about the other?” The man explains, “I figured she must have liked her dress stuck up in her butt crack, so when she turned around I stuffed it back up there”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/SmackEh"> /u/SmackEh </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12ewx96/one_easter_sunday_a_man_goes_to_church_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12ewx96/one_easter_sunday_a_man_goes_to_church_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What is the most dangerous type of canoes?</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Volcanoes
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/marcEmarc1966"> /u/marcEmarc1966 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12fhqvz/what_is_the_most_dangerous_type_of_canoes/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12fhqvz/what_is_the_most_dangerous_type_of_canoes/">[comments]</a></span></p></li>
</ul>
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