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<title>03 March, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic</strong> -
<div>
Background: Antibodies play a key role in the immune defence against infectious pathogens. Understanding the underlying process of B cell recognition is not only of fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas the nature of conformational B cell epitope recognition is inherently complicated, linear B cell epitopes offer a straightforward approach that potentially can be reduced to one of peptide recognition. Methods: Using an overlapping peptide approach representing the entire proteomes of the seven main coronaviruses known to infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents and eight pre-pandemic controls. Using a high-density peptide microarray platform, 13-mer peptides overlapping by 11 amino acids were in situ synthesised and incubated with the pooled primary serum samples, followed by development with secondary fluorochrome-labelled anti-IgG and -IgA antibodies. Interactions were detected by fluorescence detection. Strong Ig interactions encompassing consecutive peptides were considered to represent "high-fidelity regions" (HFRs). These were mapped to the coronavirus proteomes using a 60% homology threshold for clustering. Results: We identified 333 human coronavirus derived HFRs. Among these, 98 (29%) mapped to SARS-CoV-2, 144 (44%) mapped to one or more of the four circulating common cold coronaviruses (CCC), and 54 (16%) cross-mapped to both SARS-CoV-2 and CCCs. The remaining 37 (11%) mapped to either SARS-CoV or MERS-CoV. Notably, the COVID-19 serum was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas the pre-pandemic was skewed towards recognising CCC-mapped HFRs. In terms of absolute numbers of linear B cell epitopes, the primary targets are the ORF1ab protein (60%), the spike protein (21%), and the nucleoprotein (15%) in that order; however, in terms of epitope density, the order would be reversed. Conclusion: We identified linear B cell epitopes across coronaviruses, highlighting pan-, alpha-, beta-, or SARS-CoV-2-corona-specific B cell recognition patterns. These findings could be pivotal in deciphering past and current exposures to epidemic and endemic coronavirus. Moreover, our results suggest that pre-pandemic anti-CCC antibodies may cross-react against SARS-CoV-2, which could explain the highly variable outcome of COVID-19. Finally, the methodology used here offers a rapid and comprehensive approach to high-resolution linear B-cell epitope mapping, which could be vital for future studies of emerging infectious diseases.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.29.582263v1" target="_blank">Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic</a>
</div></li>
<li><strong>Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques</strong> -
<div>
Antibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fc{gamma}-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.01.582951v1" target="_blank">Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques</a>
</div></li>
<li><strong>The landscape of biomedical research</strong> -
<div>
The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now being published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D map of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We based our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we used the large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We used our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, the distribution of gender imbalance in academic authorship, and the distribution of retracted paper mill articles. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.10.536208v4" target="_blank">The landscape of biomedical research</a>
</div></li>
<li><strong>Sibling Relationships and Parental Interventions to Sibling Bullying During Covid-19: A Qualitative Comparison of British and Turkish Families of Autistic Adolescents</strong> -
<div>
Background and aims: Despite its high potential for affecting sibling relationships, few studies have explored the impact of the Covid-19 pandemic on this important family dynamic. Of these, the reported evidence has been inconsistent across cultures and lacks cross-cultural comparability. For the first time, we investigated cross-cultural variability in the impact of Covid-19, and the restrictions associated with it, on sibling relationships of autistic adolescents from a Western (United Kingdom) and non-Western (Turkey) country. We also explored how British and Turkish parents intervene in negative sibling interactions – i.e., sibling bullying –when witnessed. Methods: Parents of 164 British and 96 Turkish autistic adolescents, aged 9-20 years, were asked how they perceived the effects of Covid-19 on their children’s sibling relationships, and how they were most likely to react to instances of sibling bullying. Free response data from parents were analysed using qualitative content analysis. Results: Our findings indicated more cross-cultural similarities than differences between British and Turkish families. The majority of both British and Turkish parents indicated that Covid-19 worsened sibling relationships between their autistic and non-autistic children. An overwhelming majority of British and Turkish parents also said that they would step in directly when witnessing sibling bullying. Despite the high volume of cross-cultural similarities generally, we also found some cross-cultural differences, for instance in relation to the most common negative impact of Covid-19 on sibling relationships and the most preferred parental responses to sibling bullying. Conclusions and implication: Implications and suggestions are discussed in more detail, drawing on the Etic approach to cross-cultural psychology.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/nqez3/" target="_blank">Sibling Relationships and Parental Interventions to Sibling Bullying During Covid-19: A Qualitative Comparison of British and Turkish Families of Autistic Adolescents</a>
</div></li>
<li><strong>Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis</strong> -
<div>
Objective: SARS-CoV-2 is a severe respiratory disease that primarily targets the lungs and was the leading cause of death worldwide during the pandemic. Investigating the intricate interplay between the oral microbiome and inflammatory cytokines during the acute phase of infection is crucial for understanding host immune responses. This study aimed to explore the relationship between the oral microbiome and cytokines in COVID-19 patients, specifically examining those with and without sputum production. Methods: Saliva and blood samples from 50 COVID-19 patients were subjected to 16S ribosomal RNA gene sequencing to analyze the oral microbiome. Additionally, 65 saliva and serum cytokines were assessed using Luminex multiplex analysis. The Mann-Whitney test compared cytokine levels between individuals with and without sputum production. Results: Our study revealed significant differences in the membership (Jaccard dissimilarity: p=0.016) and abundance (PhILR dissimilarity: p=0.048; metagenomeSeq) of salivary microbial communities between COVID-19 patients with and without sputum production. Seven bacterial genera, including Prevotella, Streptococcus, Actinomyces, Atopobium, Filifactor, Leptotrichia, and Selenomonas, were present in statistically higher proportions of patients with sputum production (p&lt;0.05, Fisher's exact test). Eight bacterial genera, including Prevotella, Megasphaera, Stomatobaculum, Leptotrichia, Veillonella, Actinomyces, Atopobium, and Corynebacteria were significantly more abundant in the sputum-producing group, while Lachnoacaerobaculum was notably more prevalent in the non-sputum-producing group (p&lt;0.05, ANCOM-BC).We observed a significant positive correlation between salivary IFN-gamma (Interferon-gamma) and Eotaxin2/CCL24 (chemokine ligand 24) with sputum production. Conversely, negative correlations were noted in serum MCP3/CCL7 (monocyte-chemotactic protein 3/Chemokine ligand 7), MIG/CXCL9 (Monokine induced by gamma/Chemokine ligand 9), IL1 beta (interleukin 1 beta), and SCF (stem cell factor) with sputum production (p&lt;0.05, Mann-Whitney test). Conclusion: Substantial distinctions in salivary microbial communities were evident between COVID-19 patients with and without sputum production, emphasizing the notable impact of sputum production on the oral microbiome and cytokine levels during the acute phase of infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.29.582705v1" target="_blank">Sputum production and salivary microbiome in COVID-19 patients reveals oral-lung axis</a>
</div></li>
<li><strong>Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo</strong> -
<div>
SARS-CoV-2 pandemic alerts us that spillovers of various animal coronaviruses to human in the future may bring us enormous damages. Thus, there is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses. CV804 against the S2 domain of the spike protein, which is less prone to mutations. CV804 shows not only broad cross-reactivities with representative 20 animal-origin coronaviruses but also with diseases-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and mutant strains of SARS-CoV-2. Other than that, the main characteristics of CV804 are that it has strong antibody-dependent cellular cytotoxicity (ADCC) activity to SARS-CoV2 spike protein-expressed cells in vitro and completely lacks virus-neutralization activity. Comprehensively in animal models, CV804 suppressed disease progression by SARS-CoV-2 infection. Structural studies using HDX-MS and point mutations of recombinant spike proteins revealed that CV804 binds to a unique epitope within the highly conserved S2 domain of the spike proteins of various coronaviruses. Based on the overall data, we suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein expressed on the surface of the infected cells and weakens the viral virulence by supporting host immune cells attack through ADCC activity in vivo. CV804 epitope identified in this study is not only useful for the design of pan-corona antibody therapeutics but also to design next-generation coronavirus vaccines and antiviral drugs.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582480v1" target="_blank">Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo</a>
</div></li>
<li><strong>Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination</strong> -
<div>
Neutralizing antibodies correlate with protection against SARS-CoV-2. Recent studies, however, show that binding antibody titers, in the absence of robust neutralizing activity, also correlate with protection from disease progression. Non-neutralizing antibodies cannot directly protect from infection but may recruit effector cells thus contribute to the clearance of infected cells. Also, they often bind conserved epitopes across multiple variants. We characterized 42 human mAbs from COVID-19 vaccinated individuals. Most of these antibodies exhibited no neutralizing activity in vitro but several non-neutralizing antibodies protected against lethal challenge with SARS-CoV-2 in different animal models. A subset of those mAbs showed a clear dependence on Fc-mediated effector functions. We determined the structures of three non-neutralizing antibodies with two targeting the RBD, and one that targeting the SD1 region. Our data confirms the real-world observation in humans that non-neutralizing antibodies to SARS-CoV-2 can be protective.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582613v1" target="_blank">Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination</a>
</div></li>
<li><strong>Peptide Mold: A Novel Strategy for Mapping Potential Binding Sites in Protein Targets</strong> -
<div>
A novel concept titled Peptide Mold for mapping potential binding sites in protein targets is presented. A large multiconformer tetrapeptide library comprising of 32 million conformations of all possible combinations of naturally-occurring amino acids was constructed and used for molecular docking analysis in the substrate-binding site of SARS-CoV-2 PLpro enzyme. The top-ranking, structurally-diverse tetrapeptide docked conformations (symbolizing peptide mold, analogous to a clay mold) were used then for elucidating a five-point pharmacophore. Ligand-based virtual screening of a large, multiconformer library of phytoconstituents using the derived five-point pharmacophore led to identification of potential binders for SARS-CoV-2 PLpro at its substrate-binding site. The approach is based on generating the imprint of a macromolecular binding site (cavity) using tetrapeptides (clay), thereby generating a reverse mold (with definitive shape and size), which can further be used for identifying small-molecule ligands matching the captured features of the target binding site. The approach is based on the fact that the individual amino acids in the tetrapeptide represent all possible drug-receptor interaction features (electrostatic, H-bonding, van der Waals, dispersion and hydrophobic among others). The peptide mold approach can be extended to any protein target for mapping the binding site(s), and further use of the generated pharmacophore model for virtual screening of potential binders. The peptide mold approach is a robust, hybrid computational screening strategy, overcoming the present limitations of structure-based methods, e.g., molecular docking and the ligand-based methods such as pharmacophore search. Exploration of the peptide mold strategy is expected to yield high-quality, reliable and interesting virtual hits in the computational screening campaigns during the hit and lead identification stages.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582665v1" target="_blank">Peptide Mold: A Novel Strategy for Mapping Potential Binding Sites in Protein Targets</a>
</div></li>
<li><strong>Influencers in Tourism Digital Marketing: A Comprehensive Literature Review</strong> -
<div>
Almost all business sectors in various developed and developing countries have realized the importance of transforming conventional marketing to digital marketing, the goal is to increase sales. Many marketing strategies can be applied to increase sales, including utilizing influencers in digital marketing. This study aims to identify digital marketing strategies that have been widely used by researchers in various countries and look for new models or new strategies that are relevant to be applied in developing countries after COVID-19 through a systematic literature review. The author searched for scientific articles on the Scopus database that were in English and fully accessible. This research reviewed 19 articles using a systematic literature review. The results showed that the majority of related research was published in 2018-2022, ten related articles were published in 2022 with three articles published in Spain. All authors proposed various variables, but generally conventional in digital marketing, while not many authors concentrated on the utilization of influencers in carrying out digital marketing. Therefore, this research offers a digital marketing strategy combined with the role of influencers in tourist destinations that have a competitive advantage.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/m97kd/" target="_blank">Influencers in Tourism Digital Marketing: A Comprehensive Literature Review</a>
</div></li>
<li><strong>Curcumin and turmeric extract inhibit SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion</strong> -
<div>
Turmeric extract (TE) with curcumin as its main active ingredient has been studied as a potential COVID-19 therapeutic. Curcumin has been studied in silico and in vitro against a naive SARS-CoV-2 virus, yet little is known about TE’s impact on SARS-CoV-2 infection. Moreover, no study reveals the potential of both curcumin and TE on the inhibition of SARS-CoV-2 cell-to-cell transmission. Here, we investigated the effects of both curcumin and TE on inhibiting SARS-CoV-2 entry and cell-to-cell transmission using pseudovirus (PSV) and syncytia models. We performed a PSV entry assay in 293T or 293 cells expressing hACE2. The cells were pretreated with curcumin or TE and then treated with PSV with or without the test samples. Next, we carried out syncytia assay by co-transfecting 293T cells with plasmids encoding spike, hACE2, and TMPRSS2 to be treated with the test samples. The results showed that in PSV entry assay on 293T/hACE/TMPRSS2 cells, both curcumin and TE inhibited PSV entry at concentrations of 1 M and 10 M for curcumin and 1 g/ml and 10 g/ml for TE. Moreover, both curcumin and TE reduced syncytia formation compared to control cells. Our study shows that TE and curcumin are potential inhibitors of SARS-CoV-2 infection at entry points, either by direct or indirect infection models.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.28.560070v2" target="_blank">Curcumin and turmeric extract inhibit SARS-CoV-2 pseudovirus cell entry and Spike mediated cell fusion</a>
</div></li>
<li><strong>The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice</strong> -
<div>
Objectives: Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute to the emergence of variants with altered pathogenicity due to persistent infection. This study investigated the impact of immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice and the effectiveness of antiviral treatments in this context. Methods: Mice were immunosuppressed using cyclophosphamide and infected with a B lineage of SARS-CoV-2. Molnupiravir and nirmatrelvir, alone and in combination, were administered and viral load and viral sequence diversity was assessed. Results: Treatment of infected but immune compromised mice with both compounds either singly or in combination resulted in decreased viral loads and pathological changes compared to untreated animals. Treatment also abrogated infection of neuronal tissue. However, no consistent changes in the viral consensus sequence were observed, except for the emergence of the S:H655Y mutation. Molnupiravir, but not nirmatrelvir or immunosuppression alone, increased the transition/transversion (Ts/Tv) ratio, indicative of A&gt;G and C&gt;U mutations. Notably, immunosuppression itself did not appear to promote the emergence of mutations characteristic of variants of concern (VOCs). Conclusions: Further investigations are warranted to fully understand the role of immunocompromised individuals in VOC development and to inform optimised public health strategies. It is more likely that immunodeficiency promotes viral persistence but does not necessarily lead to substantial consensus-level changes in the absence of antiviral selection pressure. Molnupiravir, compared to nirmatrelvir, shows a stronger mutagenic effect in this model.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.582110v1" target="_blank">The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in infected and immune suppressed mice</a>
</div></li>
<li><strong>Virological traits of the SARS-CoV-2 BA.2.87.1 lineage</strong> -
<div>
The highly mutated SARS-CoV-2 BA.2.87.1 lineage was recently detected in South Africa, but its transmissibility is unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for high transmissibility.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.27.582254v1" target="_blank">Virological traits of the SARS-CoV-2 BA.2.87.1 lineage</a>
</div></li>
<li><strong>Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model</strong> -
<div>
Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function may play a key role in Long COVID. Despite its importance, the impact of SARS-CoV-2 on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells, mucus-secreting HT29 cells and human Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin-1, occludin and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir and the TMPRSS2 inhibitor Camostat prevented SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582510v1" target="_blank">Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model</a>
</div></li>
<li><strong>Designed mosaic nanoparticles enhance cross-reactive immune responses in mice</strong> -
<div>
Using computational methods, we designed 60-mer nanoparticles displaying SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) by (i) creating RBD sequences with 6 mutations in the SARS-COV-2 WA1 RBD that were predicted to retain proper folding and abrogate antibody responses to variable epitopes (mosaic-2COMs; mosaic-5COM), and (ii) selecting 7 natural sarbecovirus RBDs (mosaic-7COM). These antigens were compared with mosaic-8b, which elicits cross-reactive antibodies and protects from sarbecovirus challenges in animals. Immunizations in naive and COVID-19 pre-vaccinated mice revealed that mosaic-7COM elicited higher binding and neutralization titers than mosaic-8b and related antigens. Deep mutational scanning showed that mosaic-7COM targeted conserved RBD epitopes. Mosaic-2COMs and mosaic-5COM elicited higher titers than homotypic SARS-CoV-2 Beta RBD-nanoparticles and increased potencies against some SARS-CoV-2 variants than mosaic-7COM. However, mosaic-7COM elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons. These results support using mosaic-7COM to protect against highly mutated SARS-CoV-2 variants and zoonotic sarbecoviruses with spillover potential.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.28.582544v1" target="_blank">Designed mosaic nanoparticles enhance cross-reactive immune responses in mice</a>
</div></li>
<li><strong>The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2</strong> -
<div>
The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity for viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in the receptor binding domain of the S1 subunit of the spike glycoprotein have led to considerable escape from antibody responses, reducing the efficacy of vaccines and monoclonal antibody (mAb) therapies. Therefore, there is a need to interrogate more constrained regions of Spike, such as the S2 subdomain. Here, we describe a collection of S2 mAbs from two SARS-CoV-2 convalescent individuals that target multiple regions in the S2 subdomain and can be grouped into at least five epitope classes. Most did not neutralize SARS-CoV-2 with the exception of C20.119, which bound to a highly conserved epitope in the fusion peptide and showed broad binding and neutralization activity across SARS-CoV-2, SARS-CoV-1, and closely related zoonotic sarbecoviruses. Several of the S2 mAbs tested mediated antibody-dependent cellular cytotoxicity (ADCC) at levels similar to the S1 mAb S309 that was previously authorized for treatment of SARS-CoV-2 infections. Three of the mAbs with ADCC function also bound to spike trimers from HCoVs, such as MERS-CoV and HCoV-HKU1. Our findings suggest there are diverse epitopes in S2, including functional S2 mAbs with HCoV and sarbecovirus breadth that likely target functionally constrained regions of spike. These mAbs could be developed for potential future pandemics, while also providing insight into ideal epitopes for eliciting a broad HCoV response.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.26.582219v1" target="_blank">The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2</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>Phase II Clinical Study of SHEN211 Tablets in the Treatment of Mild and Moderate Novel Corona Virus Infection (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety &amp; Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <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>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation &amp; Development <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>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mindfulness-based Mobile Applications Program</strong> - <b>Conditions</b>: COVID-19; Cell Phone Use; Nurse; Mental Health <br/><b>Interventions</b>: Device: mindfulness-based mobile applications program <br/><b>Sponsors</b>: Yu-Chien Huang <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt</strong> - <b>Conditions</b>: Mucormycosis; Rhinocerebral (Etiology); COVID-19 <br/><b>Interventions</b>: Procedure: debridment <br/><b>Sponsors</b>: Nasser Institute For Research and Treatment <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 <br/><b>Interventions</b>: Drug: Hyperbaric oxygen <br/><b>Sponsors</b>: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk <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>Attention Training for COVID-19 Related Distress</strong> - <b>Conditions</b>: Anxiety <br/><b>Interventions</b>: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training <br/><b>Sponsors</b>: Palo Alto University <br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Legacy of RuPaul’s “Drag Race”</strong> - The drag star brought the form mainstream, and made an empire out of queer expression. Now he fears “the absolute worst.” - <a href="https://www.newyorker.com/magazine/2024/03/11/rupaul-doesnt-see-how-thats-any-of-your-business">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Israeli Settlers Attacking Their Palestinian Neighbors</strong> - With the world’s focus on Gaza, settlers have used wartime chaos as cover for violence and dispossession. - <a href="https://www.newyorker.com/magazine/2024/03/04/israel-west-bank-settlers-attacks-palestinians">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What a Major Solar Storm Could Do to Our Planet</strong> - Disturbances on the sun may have the potential to devastate our power grid and communication systems. When the next big storm arrives, will we be prepared for it? - <a href="https://www.newyorker.com/magazine/2024/03/04/what-a-major-solar-storm-could-do-to-our-planet">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Professor Claimed to Be Native American. Did She Know She Wasn’t?</strong> - Elizabeth Hoover, who has taught at Brown and Berkeley, insists that she made an honest mistake. Her critics say she has been lying for more than a decade. - <a href="https://www.newyorker.com/magazine/2024/03/04/a-professor-claimed-to-be-native-american-did-she-know-she-wasnt">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inside North Korea’s Forced-Labor Program in China</strong> - Workers sent from the country to Chinese factories describe enduring beatings and sexual abuse, having their wages taken by the state, and being told that if they try to escape they will be “killed without a trace.” - <a href="https://www.newyorker.com/magazine/2024/03/04/inside-north-koreas-forced-labor-program-in-china">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Are we in the middle of an extinction panic?</strong> -
<figure>
<img alt="A Canada goose stands on the snow-covered figure of a Tyrannosaurus Rex at Cologne Zoo in Cologne, Germany in January 2024." src="https://cdn.vox-cdn.com/thumbor/QlpLDe2oNg-GUtKqVdiwjvdUojo=/0x0:7339x5504/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73179107/1934263114.0.jpg"/>
<figcaption>
A Canada goose stands on the snow-covered figure of a Tyrannosaurus Rex at Cologne Zoo in Cologne, Germany in January 2024. | Federico Gambarini/Picture Alliance via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Inside the wild world of AI doomsdayers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2O2EXa">
If you’ve followed the news in the last year or two, you’ve no doubt heard a ton about <a href="https://www.vox.com/artificial-intelligence">artificial intelligence</a>. And depending on the source, it usually goes one of two ways: <a href="https://www.vox.com/2023/4/28/23702644/artificial-intelligence-machine-learning-technology">AI</a> is either the beginning of the end of human civilization, or a shortcut to utopia.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="chxeVi">
Who knows which of those two scenarios is nearer the truth, but the polarized nature of the AI discourse is itself interesting. We’re in a period of rapid technological growth and political disruption and there are many reasons to worry about the course we’re on — that’s something almost everyone can agree with.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3aTYSd">
But how much worry is warranted? And at what point should worry deepen into panic?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GXCSjD">
To get some answers, I invited Tyler Austin Harper onto <a href="https://www.vox.com/the-gray-area"><em>The Gray Area</em></a>. Harper is a professor of environmental studies at Bates College and the author of a fascinating recent essay in <a href="https://www.nytimes.com/2024/01/26/opinion/polycrisis-doom-extinction-humanity.html">the New York Times</a>. The piece draws some helpful parallels between the existential anxieties today and some of the anxieties of the past, most notably in the 1920s and ’30s, when people were (rightly) terrified about machine technology and the emergence of research that would eventually lead to nuclear weapons.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jHaTlz">
Below is an excerpt of our conversation, edited for length and clarity. As always, there’s much more in the full podcast, so listen to and follow <a href="https://www.vox.com/the-gray-area"><em>The Gray Area</em></a> on <a href="https://podcasts.apple.com/gb/podcast/the-gray-area-with-sean-illing/id1081584611">Apple Podcasts</a>, <a href="https://podcasts.google.com/search/vox%20conversations">Google Podcasts</a>, <a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP">Spotify</a>, <a href="https://www.stitcher.com/show/vox-conversations">Stitcher</a>, or wherever you find podcasts. New episodes drop every Monday.
</p>
<div id="eeJhgc">
</div>
<hr class="p-entry-hr" id="6BN4Us"/>
<h4 id="OflXU1">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iDeosD">
When you track the current discourse around AI and existential risk, what jumps out to you?
</p>
<h4 id="muVh3Z">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lTXNTb">
Silicon Valley’s really in the grip of kind of a science fiction ideology, which is not to say that I don’t think there are real risks from AI, but it is to say that a lot of the ways that Silicon Valley tends to think about those risks come through science fiction, through stuff like <em>The Matrix</em> and the concern about the rise of a totalitarian AI system, or even that we’re potentially already <a href="https://www.vox.com/future-perfect/2019/4/10/18275618/simulation-hypothesis-matrix-rizwan-virk">living in a simulation</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eayx2u">
I think something else that’s really important to understand is what an existential risk actually means according to scholars and experts. An existential risk doesn’t only mean something that could cause human extinction. They define existential risk as something that could cause human extinction or that could prevent our species from achieving its fullest potential.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ce0gQI">
So something, for example, that would prevent us from colonizing <a href="https://www.vox.com/space">outer space</a> or creating digital minds, or expanding to a cosmic civilization — that’s an existential risk from the point of view of people who study this and also from the point of view of a lot of people in Silicon Valley.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pajXWK">
So it’s important to be careful that when you hear people in Silicon Valley say AI is an existential risk, that doesn’t necessarily mean that they think it could cause human extinction. Sometimes it does, but it could also mean that they worry about our human potential being curtailed in some way, and that gets in wacky territory really quickly.
</p>
<h4 id="C5JDpq">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1EElam">
One of the interesting things about the AI discourse is its all-or-nothing quality. AI will either destroy humanity or spawn utopia. There doesn’t seem to be much space for anything in between. Does that kind of polarization surprise you at all, or is that sort of par for the course with these kinds of things?
</p>
<h4 id="e7UZ0a">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2qLhUb">
I think it’s par for the course. There are people in Silicon Valley who don’t have 401(k)s because they believe that either we’re going to have a digital paradise, a universal basic income in which capitalism will dissolve into some kind of luxury communism, or we’ll all be dead in four years, so why save for the future?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1M1i9U">
I mean, you see this in the climate discourse, too, where it’s either total <a href="https://www.vox.com/climate/23885799/climate-change-denial-fossil-fuel-companies-exxon-mobil">denialism</a> and everything is going to be fine, or they imagine that we’re going to be living in a future hellscape of <a href="https://www.vox.com/the-weeds/2024/1/24/24048407/hannah-ritchie-climate-change-optimism-book-action-interview">an uninhabitable earth</a>. And neither of those extremes are necessarily the most likely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jm7sNA">
What’s the most likely is some kind of middle ground where we have life like we have it now except worse in every way, but something short of full-scale apocalypse. And I think the AI discourse is similar, where it’s a sort of zero-sum game: we’ll have a paradise of techno-utopia and digital hedonism, or we will live as slaves under our <a href="https://www.vox.com/robots">robot</a> overlords.
</p>
<h4 id="3gE5dH">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bZWZZj">
What makes an extinction panic a panic?
</p>
<h4 id="2IkePq">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DIh6WG">
Extinction panics are usually in response to new scientific developments that seem to come on suddenly, like rapid changes in technology, or geopolitical crises, when it feels like everything is happening too fast all at once. And then you have this collective and cultural sense of vertigo, that we don’t know where things go from here, everything seems in flux and dangerous, and the risks are stacking up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S1SpTg">
I compare extinction panics to moral panics, and one of the defining features of a moral panic for sociologists is that it’s not necessarily based on nothing. It’s not always the case that a moral panic has no basis in reality, but rather it’s blowing up a kernel of reasonableness into a five-alarm fire. And that’s how I view our present moment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Tlc2pp">
I’m very concerned about <a href="https://www.vox.com/climate">climate change</a>. I’m concerned about AI a little differently than the Silicon Valley folks, but I’m concerned about it. But it does seem that we are blowing up super reasonable concerns into a panic that doesn’t really help us solve them, and that doesn’t really give us much purchase on what the future’s going to be like.
</p>
<h4 id="9odFf4">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sboN6C">
For something to qualify as an extinction panic, does it have to be animated by a kind of fatalism?
</p>
<h4 id="Yi8v6O">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IWEdMs">
There’s a kind of tragic fatalism or pessimism that defines an extinction panic where there is a sense that there’s nothing we can do, this is already baked in, it’s already foretold. And you see this a lot in AI discourse, where many people believe that the train is already too far down the tracks, there’s nothing we can do. So yeah, there is a fatalism to it for sure.
</p>
<h4 id="5ev2nN">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0fZqCe">
We had a major extinction panic roughly 100 years ago, and there are a lot of similarities with the present moment, with plenty of new and repurposed fears. Tell me about that.
</p>
<h4 id="5EvSdj">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cXZmF2">
Right after the end of World War I, we entered another period of similar panic. We tend to think of the end of World War II with a dropping of two atomic bombs and the ushering in of the nuclear age. We tend to think of that as the moment when humanity became worried that it could cause its own destruction. Those fears happened much earlier, and they were already percolating in the 1920s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TGtjim">
Winston Churchill wrote a little essay called “<a href="https://winstonchurchill.hillsdale.edu/churchills-scientific-imagination-2/">Shall We All Commit Suicide?</a>” And that predicted bombs the size of an orange that could lay waste to cities. And these weren’t fringe views. The president of Harvard at the time blurbed that essay Churchill wrote and called it something all Americans need to read.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HOygNl">
There was a pervasive sense, particularly among the elites, that the Second World War might be the last war humanity fights. But even concerns about a machine age, the replacement of human beings by machines, the automation of labor, those appear in the ’20s, too.
</p>
<h4 id="9TW7zP">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="85zLf8">
In their defense, the people panicking in the ’20s don’t look that crazy in retrospect, given what happened in the following two decades.
</p>
<h4 id="qtBqNo">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9PYcYC">
Absolutely. I think that’s one of the important pieces of what I’m trying to get at, is that panics are never helpful. It doesn’t mean that the fears aren’t grounded in real risks or real potential developments that could be disastrous.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B4WjIe">
Obviously, a lot of things in the 1920s were right, but a lot was wrong, too. H.G. Wells, the great science fiction novelist, who in his own day was actually more famous as a political writer, famously said, “On my tombstone, you should put, ‘I told you so, you damned fools.’” And he thought as soon as we had nuclear weapons, we’d be extinct within a few years, and yet we’ve survived eight decades with nuclear weapons. We’ve never used them since 1945.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s6abfd">
That’s a remarkable accomplishment, and it’s one of the reasons why I’m really resistant to this notion that we have an accurate sense of what’s coming down the pipeline or that we have an accurate sense of what humanity’s capable of. Because I don’t think many would’ve predicted that we could semi-responsibly have nuclear weapons without another nuclear war.
</p>
<h4 id="VTO3lM">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="s7btre">
You wrote that something we’re seeing now, which is something we’ve seen before, is this belief that the real threat posed by human extinction is nihilism. The idea that to go extinct is to have meant nothing cosmically. What does that mean, exactly?
</p>
<h4 id="veY4dQ">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HGmt6N">
That’s at the core of <a href="https://www.vox.com/future-perfect/23298870/effective-altruism-longtermism-will-macaskill-future">longtermism</a>, right? This sense that it is the universe or nothingness, that humanity’s meaning depends on our immortality. And so they start from this almost Nietzschean view of the universe that there’s no meaning, life means nothing. But their twist is to say, “But we can install meaning in the universe if we make ourselves permanent.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eSAkqM">
So if we achieve digital immortality, if we colonize the cosmos, we can put meaning into what was previously a godless vacuum, and we can even become kinds of gods ourselves. So the question of nihilism and overcoming nihilism through technology and through digital immortality is shot through contemporary extinction discourse.
</p>
<h4 id="ciGEeV">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CD8cEa">
There does seem to be something deeply religious about this. I mean, religious people have always been obsessed over the end of the world and our place in the cosmos, and this strikes me as a secular analog to that.
</p>
<h4 id="r1CndB">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="b2G2yO">
You know, people have been telling tales about the end of the world for as long as there have been human beings. You do see a shift in the late 18th, early 19th century to the first naturalistic, non-religious imaginations of human extinction. By naturalistic I mean human extinction not from a divine cause, but from a natural event or from technology. And yet even as that conversation becomes secular, there’s all sorts of religious holdovers that are suffused throughout this discourse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rvh7ZU">
I do think there’s a way that longtermism has become a kind of secular <a href="https://www.vox.com/religion">religion</a>. I mean, the stakes are as large in their telling as the stakes in something like the Bible. Both are dreaming of cosmic afterlife, of immortality and paradise and great things. And there is this sense of regaining the garden and creating a paradise that I think is deeply embedded in Silicon Valley, and also the alternatives of damnation in hell, extinction, or slavery from AI overlords. So there’s a lot of religious resonances for sure.
</p>
<h4 id="7yCdKB">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fcTizW">
Another point you make is that extinction panics are almost always elite panics. Why is that the case?
</p>
<h4 id="j68vFn">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7KTZc5">
Yeah, I think they tend to reflect the social anxieties of elite folks who are worried about changing positions in society, and that the future might not be one catered to them. So if you look at something like climate change, which again, I can’t emphasize enough, I take really seriously. But it’s hard to avoid noticing that for a certain kind of person, the panic of climate change is that I’m not going to be able to live in my suburban home with my two cars and my nice house and my vacations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RdKUfH">
And so it is kind of a middle- and upper-class anxiety often about changing fortunes in that they’re not going to have this luxurious lifestyle they’ve enjoyed thus far, even as the global poor are the primary victims of climate change.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oznS5g">
And there’s something similar with AI discourse where these elite tech bros are panicking and not buying 401(k)s and convinced we’re going to go the way of the dodo bird. Meanwhile, the people who are most impacted by AI are going to be the poor people put out of work after their jobs are automated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B96hJk">
Yeah, it is elites that tend to shape the discourse, and that’s the language I would use — “shaping.” Because it’s not that there’s no basis in reality to these concerns, but the narrative that forms around them tends to be one formed by elites.
</p>
<h4 id="Oc5ODT">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XxpZw2">
It seems like your basic advice is to worry, but not panic. How would you distinguish one from the other? What is the difference between worrying and panicking?
</p>
<h4 id="ZGAgNg">
Tyler Austin Harper
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7JfFRS">
Yeah, it’s a great question. I would define panicking as catastrophizing and adopting this fatalistic attitude. I think panic is predicated on certainty, the sense that I know what’s going to happen. When the history of science and technology tells us there’s a lot of uncertainty like there was in 1945, so many people were certain that the world was going to end in thermonuclear fire, and it didn’t.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7lBbXB">
And so I think worry is having a realistic sense that there are real challenges for our species and for our civilization, but at the same time, maybe I should invest in a 401(k). And maybe if I want children, I should think about having them. And not make sweeping life decisions at the individual level predicated on your certainty that the future’s going to look one way or the other.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D6Hr6d">
<em>To hear the rest of the conversation, </em><a href="https://podcasts.apple.com/us/podcast/a-brief-history-of-extinction-panics/id1081584611?i=1000646862560"><em>click here</em></a><em>, and be sure to follow </em><a href="https://www.vox.com/thegrayarea">The Gray Area</a><em> on </em><a href="https://podcasts.apple.com/gb/podcast/the-gray-area-with-sean-illing/id1081584611"><em>Apple Podcasts</em></a><em>, </em><a href="https://podcasts.google.com/search/vox%20conversations"><em>Google Podcasts</em></a><em>, </em><a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP"><em>Spotify</em></a><em>, </em><a href="https://www.pandora.com/podcast/the-gray-area-with-sean-illing/PC:30793"><em>Pandora</em></a><em>, or wherever you listen to podcasts.</em>
</p></li>
<li><strong>The courts were never going to save America from Donald Trump</strong> -
<figure>
<img alt="Trump grimaces in a smile at Amy Coney Barrett." src="https://cdn.vox-cdn.com/thumbor/0MPecxz2QjEf4Hl5PAQapiw1gl8=/24x0:4189x3124/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73177533/1229490344.0.jpg"/>
<figcaption>
Then-president Donald Trump and Justice Amy Coney Barrett. | Ken Cedeno/CNP/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
No one is coming to save US democracy, except for ourselves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bChs2N">
The <a href="https://www.vox.com/scotus">Supreme Court</a> has ordered the most important of former <a href="https://www.vox.com/donald-trump">President Donald Trump</a>’s four criminal trials <a href="https://www.vox.com/scotus/2024/2/28/24086046/supreme-court-donald-trump-sabotage-delay-dc-trial-judge-chutkan">to be put on hold indefinitely</a>. It’s an extraordinary victory for Trump and a devastating blow to special counsel Jack Smith. The Court’s decision also raises serious doubts about whether these justices will allow a trial to take place before the November election.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PmEwjn">
Many Court observers, <a href="https://www.vox.com/scotus/2024/2/28/24086046/supreme-court-donald-trump-sabotage-delay-dc-trial-judge-chutkan">including myself</a>, were shocked by Wednesday’s order because it appeared to rest on the flimsiest of pretexts. The ostensible reason why the Court ordered Trump’s trial paused is so the justices could spend the next few months considering Trump’s argument that he is immune from prosecution for any “official acts” he engaged in while he was still president.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Jasgm">
This is an <a href="https://www.vox.com/scotus/2023/12/14/23998936/supreme-court-trump-crimes-jack-smith-election-theft-immunity-january-6">exceptionally weak legal argument</a>, with monstrous implications. Trump’s lawyers told one of the judges who ruled against this immunity claim that a former president could not be prosecuted, even if he <a href="https://www.washingtonpost.com/dc-md-va/2024/01/09/trump-immunity-appeals-court-arguments/">ordered “SEAL Team 6 to assassinate a political rival,”</a> unless the president was first successfully impeached and convicted (by lawmakers that, under Trump’s argument, the president could order killed if they attempted to impeach him).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zOwrfr">
There are, of course, historical examples of the Supreme Court behaving less deferentially toward presidents who thumb their nose at the law. The most well-known is <a href="https://supreme.justia.com/cases/federal/us/418/683/"><em>United States v. Nixon</em></a> (1974), the Court’s decision ordering President Richard Nixon to turn over tape recordings that implicated him in a crime, eventually leading to Nixon’s resignation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O8AjNl">
The decision to halt Trump’s trial, however, fits within a different judicial tradition, which is no less robust and no less prominent in the Supreme Court’s history. The judiciary is a weak institution, staffed by political officials who are often reluctant to stand against popular authoritarian policies or movements. Indeed, the justices themselves often belong to those movements.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CVBdx4">
This is the tradition of <a href="https://supreme.justia.com/cases/federal/us/323/214/"><em>Korematsu v. United States</em></a> (1944), where the Court stood side by side with a popular, wartime president who ordered tens of thousands of Americans sent to internment camps for the sin of having the wrong ancestors. And of <a href="https://supreme.justia.com/cases/federal/us/249/211/"><em>Debs v. United States</em></a> (1919), where the Court condemned a prominent <a href="https://www.vox.com/unions">union</a> leader and political candidate to 10 years in prison for giving a speech opposing the draft.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mWv1JP">
And it is the tradition of the <a href="https://supreme.justia.com/cases/federal/us/109/3/"><em>Civil Rights Cases</em></a> (1883), where the Court, at the very moment that white supremacists were consolidating an authoritarian regime that would rule the South for generations, declared that <a href="https://www.vox.com/congress">Congress</a> had done too much to protect Black people and that they should no longer treat freedmen as “the special favorite of the laws.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YvDKIl">
A written Constitution and the courts that are supposed to enforce it are weak guarantors of a liberal democratic society. The Supreme Court of the United States does not always align itself with authoritarian policies and movements, but it does so often enough that it cannot be counted on as an ally in a conflict between constitutional democracy and something more sinister.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8oHrLm">
And the Court is particularly ineffective in standing up against figures like Trump, who enjoy broad (if not necessarily majoritarian) political support.
</p>
<h3 id="85mU1k">
Constitutional rights and other legal safeguards are worthless in the face of a sufficiently powerful political movement
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9xBd9W">
For 49 years, the right to an <a href="https://www.vox.com/abortion">abortion</a> was a constitutional right, affirmed <a href="https://www.law.cornell.edu/supremecourt/text/410/113">over</a> and <a href="https://www.law.cornell.edu/supremecourt/text/505/833">over</a> and <a href="https://supreme.justia.com/cases/federal/us/579/15-274/">over</a> again by the Supreme Court. And then, one early summer morning, the right disappeared.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SzXwHI">
The American people woke up on June 24, 2022, with their right to an abortion intact. <a href="https://www.supremecourt.gov/opinions/21pdf/19-1392_6j37.pdf">Before noon, it was gone</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rvRvKK">
This did not happen because of any substantive change to the Constitution. The Constitution in 2022, when <a href="https://www.vox.com/2022/5/3/23055125/roe-v-wade-abortion-rights-supreme-court-dobbs-v-jackson"><em>Roe v. Wade</em></a> was overruled, was identical to the Constitution in 1973, when <em>Roe</em> was first handed down (save for a <a href="https://constitutioncenter.org/the-constitution/amendments/amendment-xxvii">minor, irrelevant amendment</a> concerning congressional pay).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p6mev8">
Rather, Roe fell because the <a href="https://news.gallup.com/poll/321143/americans-stand-abortion.aspx#:~:text=When%20asked%20about%20the%20legality,and%20third%20(70%25)%20trimesters.">minority of Americans who oppose abortion</a> organized. They took over one of America’s two major political parties. And then they <a href="https://www.vox.com/scotus/2023/7/8/23784320/supreme-court-2022-term-affirmative-action-religion-voting-rights-abortion">installed their operatives</a> on the Supreme Court of the United States.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bogD74">
In fairness, one plausible explanation for <em>Roe</em>’s fall is that it <a href="https://www.vox.com/policy-and-politics/23219138/supreme-court-roe-wade-substantive-due-process-samuel-alito">rested on a debatable interpretation</a> of the Constitution’s text. The Constitution protects both enumerated (meaning that they are laid out explicitly in the document’s text) and unenumerated rights, and the Ninth Amendment <a href="https://constitution.congress.gov/constitution/amendment-9/">explicitly forbids courts</a> from construing the Constitution to deny the existence of unenumerated rights. But the fact that the Constitution does not specifically mention abortion has always given <em>Roe</em>’s opponents a powerful rhetorical argument against it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q6baD3">
Do not think, however, that a right is secure because it is explicitly protected by the Constitution. Certainly, <a href="https://www.vox.com/the-highlight/23066920/democracy-juneteenth-in-america-is-a-rigged-game">nothing in African American history supports this Pollyanna-ish assumption</a>. And the Supreme Court’s history is riddled with cases giving the back of the hand to rights specifically enumerated in the Constitution.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hsf0xo">
The <a href="https://www.law.cornell.edu/constitution/amendmentxv#:~:text=The%20right%20of%20citizens%20of,or%20previous%20condition%20of%20servitude.">15th Amendment</a>, for example, was ratified in 1870, five years after Union forces defeated a separatist rebellion dedicated to the cause of slavery. It provides that “the right of citizens of the United States to vote shall not be denied or abridged by the United States or by any state on account of race, color, or previous condition of servitude.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TmuQ6y">
But this amendment ceased to function the minute popular support for Reconstruction faded. Black people’s right to vote, at least in states that were determined to deny them that right, <a href="https://www.vox.com/2015/3/6/8163229/voting-rights-act-1965">lay dormant until 1965</a>, when Congress passed the Voting Rights Act. And in the long century between these two legal reforms, the Supreme Court often made itself complicit in white supremacy by <a href="https://supreme.justia.com/cases/federal/us/189/475/">giving its blessing to Jim Crow voter suppression</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gvs54Q">
Indeed, the Court aligned itself with Southern racists even before Reconstruction collapsed as <a href="https://www.rbhayes.org/hayes/betrayal-of-the-freedman-rutherford-b.-hayes-and-the-end-of-reconstruction/">part of a corrupt deal</a> to install President Rutherford B. Hayes in the White House in 1877. Two years earlier, in <a href="https://www.law.cornell.edu/supremecourt/text/92/542"><em>United States v. Cruikshank</em></a> (1875), the justices tossed out the criminal convictions of several members of a white supremacist mob that used guns and a cannon to kill a rival Black militia defending the right of freedmen to elect their own leaders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w4bJFr">
Black people, the Court said in a decision that should send shivers down the spine of anyone familiar with the history of the US South, “must look to the States” to protect constitutional rights such as the right to vote or the right to peacefully assemble.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S4gCoc">
Nor is the Supreme Court’s haphazard approach to constitutional rights limited to the rights of Black people. The Constitution says quite explicitly that no one may be denied “<a href="https://www.law.cornell.edu/constitution/amendmentxiv">the equal protection of the laws</a>,” and it forbids “<a href="https://www.law.cornell.edu/constitution/fourth_amendment">unreasonable searches and seizures</a>.” That didn’t stop <em>Korematsu</em> from holding that American citizens could be incarcerated solely for having Japanese ancestry.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M23wdM">
Or witness nearly the entire history of the First Amendment, which was often powerless, not just <a href="https://www.vox.com/2019/11/12/20957868/unionized-journalist-labor-first-amendment-nlrb-general-counsel">against federal suppression of wartime speech</a>, but against something as mundane as people who don’t like nude art. For much of the late 19th and early 20th century, art and literature depicting <a href="https://www.vox.com/politics/23678636/supreme-court-anthony-comstock-abortion-mifepristone-matthew-kacsmaryk">human sexuality was a frequent subject of criminal prosecution</a> under the federal Comstock Act — a law, it is worth noting, that is still on the books — or under similar state laws.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XTpzzt">
In one case, an art gallery owner was successfully prosecuted for selling reproductions of Alexandre Cabanel’s masterpiece <em>The</em> <em>Birth of Venus.</em>
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/bATHII8qxFFELX98GpHhgEWPlW4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24577369/Alexandre_Cabanel___The_Birth_of_Venus___Google_Art_Project_2.jpg"/> <cite>Public domain via Wikipedia</cite>
<figcaption>
Alexandre Cabanel’s <em>The</em> <em>Birth of Venus</em>, one of many works of art censored during the Comstock era.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HhyTEW">
So the idea that Donald Trump, and the MAGA movement he leads, would crumble simply because there’s a law saying that his actions are forbidden was always naïve. When powerful political movements conflict, the Court honors the law maybe some of the time. And it is just as likely to align itself with an authoritarian faction as it is to choose the rule of law.
</p>
<h3 id="hIdFEh">
It’s not even clear that the Supreme Court is capable of standing up for the rule of law in the face of a sufficiently determined opposition
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EI4R7w">
Even before the US Constitution was ratified, one of the early Republic’s greatest statesmen <a href="https://avalon.law.yale.edu/18th_century/fed78.asp">saw that the courts are a paper tiger</a>. The judiciary, Alexander Hamilton wrote in the Federalist Papers, “has no influence over either the sword or the purse; no direction either of the strength or of the wealth of the society; and can take no active resolution whatever.” It doesn’t even have the authority to enforce its own decisions, and “must ultimately depend upon the aid of the executive arm even for the efficacy of its judgments.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="302UUh">
The Court’s two most famous decisions — one its most celebrated, and one its most reviled — confirm that Hamilton was correct. The courts are weak, and it is far from clear that they can stand up to a strong political movement even when they want to.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pAbQ5X">
Consider <a href="https://supreme.justia.com/cases/federal/us/60/393/"><em>Dred Scott v. Sanford</em></a><em> </em>(1857), the odious pro-slavery decision that declared that Black people are “beings of an inferior order” with “no rights which the white man was bound to respect.” This decision is now widely viewed by scholars as an attempt to resolve sectional tensions over slavery by handing down a sweeping, comprehensive judicial declaration of the rights (or lack thereof) of enslaved people.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LvqAL6">
And wow did the Court fail in this mission. As the historian Robert McCloskey wrote about the period following <em>Dred Scott</em>, “the tempest of malediction that burst over the judges seems to have stunned them; far from extinguishing the slavery controversy, they had fanned its flames and had, moreover, deeply <a href="https://books.google.com/books?id=N4XPCwAAQBAJ&amp;pg=PA62&amp;lpg=PA62&amp;dq=%22The+tempest+of+malediction+that+burst+over+the+judges+seems+to+have+stunned+them;+far+from+extinguishing+the+slavery+controversy%22&amp;source=bl&amp;ots=hRJU3bX_YT&amp;sig=ACfU3U0znX5A6kP1iOH6UjyozegVR_O8vA&amp;hl=en&amp;sa=X&amp;ved=2ahUKEwjA2JGNltGEAxVpEGIAHcyRB2AQ6AF6BAgHEAM#v=onepage&amp;q=%22The%20tempest%20of%20malediction%20that%20burst%20over%20the%20judges%20seems%20to%20have%20stunned%20them%3B%20far%20from%20extinguishing%20the%20slavery%20controversy%22&amp;f=false">endangered the security of the judicial arm of government</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xa8pCg">
In the very next presidential election, the nation elected President Abraham Lincoln, a man whose commitment to abolitionism developed only gradually, but whose contempt for <em>Dred Scott</em> was apparent in his very first act as president. In his <a href="https://avalon.law.yale.edu/19th_century/lincoln1.asp">first inaugural address</a>, Lincoln revealed his intent to openly defy the Court’s decision:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZTFb9w">
[I]f the policy of the Government upon vital questions affecting the whole people is to be irrevocably fixed by decisions of the Supreme Court, the instant they are made in ordinary litigation between parties in personal actions the people will have ceased to be their own rulers, having to that extent practically resigned their Government into the hands of that eminent tribunal.
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5cTy2t">
And Lincoln <a href="https://www.vox.com/21549641/obamacare-supreme-court-case-amy-coney-barrett-california-texas-biden-departmentalism">followed through on this threat</a>. His State Department issued a passport to a Black man, flouting the Court’s declaration that Black people cannot be citizens. More significantly, he also signed legislation banning slavery in US territories, mocking <em>Dred Scott</em>’s conclusion that enslaved people do not escape from bondage after entering a free territory.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3ZGlY0">
It should go without saying that Lincoln is the hero in this narrative and the justices who joined the <em>Dred Scott</em> decision are the villains. Elected officials should not have deferred to such a monstrous decision, and the American people were right to elect a leader who would defy it. Rather, my point is that, when the judiciary took a firm stand on the most contentious issue facing the nation in 1857, it had no ability to sustain its decision against a powerful political movement that found that decision repugnant.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D2BYrv">
A similar narrative played out nearly a century later, with the Supreme Court taking the opposite side. In <a href="https://supreme.justia.com/cases/federal/us/347/483/"><em>Brown v. Board of Education</em></a> (1954), the Supreme Court famously held that racially segregated public schools are “inherently unequal,” placing a unanimous Court in opposition to the Southern racial apartheid that characterized that region ever since the 15th Amendment ceased to function.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NkQIG7">
But <em>Brown </em>was enforced unreliably in its first decade on the books, and enforcing it required extraordinary resources that were far beyond the judiciary. President Dwight Eisenhower had to <a href="https://www.eisenhowerlibrary.gov/research/online-documents/civil-rights-little-rock-school-integration-crisis#:~:text=When%20Governor%20Faubus%20ordered%20the,the%20Supreme%20Court%20were%20upheld.">send the 101st Airborne Division</a> to protect Black students attending a historically white high school in Little Rock.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yv5HbB">
At least initially, moreover, <em>Brown</em> <a href="https://www.vox.com/2022/6/25/23181976/case-against-the-supreme-court-of-the-united-states">accomplished virtually nothing</a> in the states most determined to resist it. As legal historian Michael Klarman has documented, only 40 of North Carolina’s 300,000 Black students attended an integrated school five years after the Court’s decision. In Nashville, just 42 of the city’s 12,000 Black students were integrated six years after <em>Brown</em>. By <em>Brown</em>’s 10th anniversary, only one in 85 Black children in the South attended an integrated school.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="t2vscz">
<em>Brown</em> most likely made life worse for African Americans in the South, at least in the short term, by reinvigorating terrorist groups like the Ku Klux Klan. A major reason why no one even filed a lawsuit seeking to integrate a Mississippi grade school, until eight years after <em>Brown,</em> is that anyone who agreed to be the plaintiff in such a lawsuit <a href="https://www.thenation.com/article/archive/brown-v-board-education-didnt-end-segregation-big-government-did/">risked being murdered</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kmSDwB">
The landscape did shift in 1964, but not because of anything the Supreme Court did. That was the year <a href="https://www.vox.com/2022/6/25/23181976/case-against-the-supreme-court-of-the-united-states">Congress passed legislation</a> permitting the Justice Department to sue segregated schools, and also permitting the federal government to withhold funds from schools that refused to desegregate. Two years after this bill became law, the number of Southern Black students in integrated schools increased fivefold. By 1973, 90 percent of these same students were in desegregated facilities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kDTj7s">
So the Court was unable to achieve integration in the face of a powerful white supremacist political movement in the South. It was only after a more powerful movement gained the sympathy of the federal government, and enlisted Congress and the Executive in the fight against segregation, that Jim Crow began to crumble.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RcMs3A">
There is a lesson here for all who hope to defeat Trump’s authoritarian movement.
</p>
<h3 id="O38cs1">
No one is coming to save us from Donald Trump. We have to do it ourselves.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6rNvSx">
It’s sometimes difficult to look at the rematch lining up this November without despair. Trump literally incited an insurrection that attacked the US Capitol and tried to overthrow the nation’s democratically elected government. <a href="https://www.vox.com/joe-biden">President Joe Biden</a>, meanwhile, is an 81-year-old man whose polls suggest that he could lose to Trump.
</p>
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And so we are now hearing a cacophony of calls for some kind of deus ex machina — or, at least, some way to up the odds that American voters will not make the kind of mistake that is not easily reversed.
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What if the Democrats <a href="https://www.nytimes.com/2024/02/16/opinion/ezra-klein-biden-audio-essay.html">simply replace Biden at the DNC</a>, presumably with some as-yet-unidentified savior who is simultaneously younger, more popular, and more capable of uniting the party’s disparate factions? Or maybe the 14th Amendment, with its provision <a href="https://www.vox.com/scotus/2024/1/3/24022580/supreme-court-donald-trump-ballot-insurrection-fourteenth-amendment-colorado-anderson">forbidding insurrectionist former officials from seeking high office</a>, will neutralize Trump’s candidacy — as if the 14th Amendment has ever been a reliable bulwark against autocracy.
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Or perhaps Trump would be criminally prosecuted, and a conviction would so disqualify the former president, in the eyes of the electorate, that democracy would be saved. But after the Supreme Court’s decision on Wednesday, we can’t count on that outcome either. We can’t even be sure that there will be a trial.
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No one is coming to save us — not the courts, not the Constitution, and certainly not a process for choosing candidates that has not been used since the 1960s.
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Donald Trump will be defeated, if at all, in November at the ballot box. The only thing his opponents can do to make that happen is to vote for Joe Biden, and to encourage others to do the same.
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There is no other solution.
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<li><strong>How to master the art of small talk</strong> -
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<img alt="An illustration of two pairs of hands gesturing as in conversation while holding cocktails." src="https://cdn.vox-cdn.com/thumbor/kdTU4-vtM1P4oZ5Y7xzBwnqqSxA=/0x0:4358x3269/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73177463/GettyImages_132075518.0.jpg"/>
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Getty Images
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A guide to having actually interesting conversations with strangers.
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Andy Lowe was not naturally blessed with the gift of gab. But even he, a self-described shy, introverted person, understands its functions. Lowe works at a technology public relations firm where chitchat with clients and journalists is just another part of the job. As a previous user of dating apps (Lowe is happily partnered now), he realized banter reigned supreme. He also plays bass in bands in Seattle; meeting other collaborators involves some amount of introductory small talk.
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So he decided to get better. To improve his small talk, Lowe says he paid closer attention to his conversation partners to discover “what makes them tick, what drives them,” he explains. He’ll ask what books people are reading or <a href="https://www.vox.com/movies">movies</a> or <a href="https://www.vox.com/tv">television</a> they enjoy. “Then just making sure that when you go into those situations,” Lowe says, “you are more interested in the person that you’re talking to than talking about yourself.”
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<a href="https://www.vox.com/the-highlight/23191522/small-talk-friendship-how-to">Small talk gets a bad rap</a> for being too surface-level, too rote, a throwaway filler conversation. But casual chat can be the on-ramp to deeper connection. After all, most of us wouldn’t introduce ourselves to a stranger with a question about their biggest fears. Small talk is an opportunity to build trust and to learn about others, and to become a more curious person, says <a href="https://www.georgienightingall.co.uk/">Georgie Nightingall</a>, a conversation specialist and human connectivity researcher. “Being genuinely curious, that always helps,” she says. “You can actually realize that you do want to know more rather than having that sense of like, I’m just asking for the sake of asking.”
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Even if you find your small talk game lacking, with some practice you can improve. To ensure you’re leading with curiosity, experts and small talk enthusiasts offer their best advice to strike up a conversation with strangers and familiar faces alike, without relying on stereotypical openers.
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View small talk as an opportunity, not an annoyance
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Many people bemoan small talk because they “get stuck” in it, Nightingall says, without moving on to deeper conversation. “One of the key elements of small talk,” she says, “is having the mindset that actually this is not where we’re going to end up.” Consider all the relationships that began as banter or the <a href="https://www.nytimes.com/2019/05/06/smarter-living/why-you-need-a-network-of-low-stakes-casual-friendships.html">job opportunities that came from acquaintances</a>. There is potential for small talk to bloom into something bigger.
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However, you should avoid viewing chitchat as solely transactional. <a href="https://www.vox.com/even-better/23670005/small-acts-kindness-matter-liking-gap">Research shows</a> people enjoy and appreciate talking with strangers or acquaintances, and these brief interactions contribute to well-being. While these conversations have the potential to be awkward, <a href="https://gilliansandstrom.com/">Gillian Sandstrom</a>, a senior lecturer in the psychology of kindness at the University of Sussex, has <a href="https://www.sciencedirect.com/science/article/pii/S0022103122000750?via%3Dihub">found in research</a> that most introductory small talk with strangers does in fact go well. As people engage in these chats with greater frequency, the more confident they are in their abilities to talk to strangers, according to the study. “That’s enough to allow you to be in the moment more instead of in panic mode,” Sandstrom says.
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What to talk about instead of your job
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Popular scripts dominate small talk: comments about traffic and the weather, the questions “So, what do you do?” and “How are you?” Often, people give unengaging or throwaway answers that don’t give the other person much to respond to. Instead, lead with inquiries related to your interests, says <a href="https://www.smileyposwolsky.com/">Adam Smiley Poswolsky,</a> a workplace belonging expert and author of <a href="https://www.hachettebookgroup.com/titles/adam-smiley-poswolsky/friendship-in-the-age-of-loneliness/9780762472260/?lens=running-press"><em>Friendship in the Age of Loneliness: An Optimist’s Guide to Connection</em></a>. Consider asking a barista at your neighborhood cafe about their favorite beverage or if a friend of a friend at a party has also watched the newest season of <em>Love Is Blind</em>. If you want to feel a little more prepared, Poswolsky suggests having a list of five or so questions at the ready that are topical and feel authentic to you — just be sure to refresh your list every few weeks. Maybe your talking points include asking if someone has an upcoming vacation or if they tried any new restaurants recently.
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Or instead of questioning your conversation partner, try a statement or observation. Something as simple as “This line is taking forever,” or “[Mutual friend’s name] makes the best cheese boards,” or “You have the cutest dog I have ever seen” can be an effective entrée to small talk. <a href="https://myscp.onlinelibrary.wiley.com/doi/abs/10.1002/jcpy.1387">Research has found</a> that making an observation about a product or item another person has chosen to display — like a band T-shirt or a colorful hat — is a better conversation starter than discussing the weather. Initiating a chat with someone wearing a shirt from your alma mater is easier than attempting to find common ground with nothing to go on. “Those conversations tend to go better,” says the study’s lead author, <a href="https://www.albany.edu/business/faculty/hillary-wiener">Hillary Wiener</a>, an assistant professor of marketing at the University at Albany, “because it’s on something that both people involved might actually care about.” The products that were most successful at launching a conversation “suggested a point of commonality between the asker and the person wearing, using a product,” she says. For example, try approaching someone in a Taylor Swift shirt if you too love Taylor Swift or sharing a hiking story with someone who is drinking out of a water bottle from Yosemite National Park.
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However, don’t feel like you must write off meteorological small talk. Discussing the weather is ample conversation fodder for my colleague <a href="https://www.vox.com/authors/miles-bryan">Miles Bryan</a>, a senior producer and reporter (and the self-appointed Philly Bureau Chief) for <a href="https://www.vox.com/pages/today-explained"><em>Today, Explained</em></a>. “It’s such a shared experience between everybody I’m talking to,” he says. “It’s a way to connect with somebody else without a lot of pressure on the conversation.” Luxuriating in small talk is thoughtful, Bryan says: “Small talk is empathetic.”
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To be better at small talk, actually listen
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Making the most of small talk — and elevating the conversation to large talk — involves active listening. If someone mentions the city they grew up in, you can use that detail for follow-up questions. What did they like the most about that city? What did they dislike? Why did they move? You can even offer a personal anecdote, Nightingall says, maybe mentioning a trip you may have taken there. “Whenever someone shares anything with you, they’re sharing a tiny dot in a web of hugeness,” Nightingall says. “Our job is to find out what makes this person different, interesting. What makes their life unique?”
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The more curious you are about another person’s experiences or perspectives, the more likely the other party will be interested in continuing the conversation, Poswolsky says. The other person, in turn, will readily offer more information, furthering the discussion.
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Just don’t make it weird
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With any interaction, there is a risk of coming on too strong or rubbing your conversation partner the wrong way. For small talk with strangers, especially, a well-meaning question may not be taken as intended or they may suspect you of trying to flirt with them. Small talk is warm and introductory, with no ulterior motives. It can surely blossom into a more flirtatious exchange but you should lead with curiosity and friendliness. “You can’t realistically be sitting next to someone on the plane and say, ‘Hi, what’s your favorite superpower,’” Wiener says. “That doesn’t work on a human interaction level.” Starting with an observation about how packed the flight is or asking whether the person is traveling for work might be more of a context-appropriate introduction.
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Wiener also suggests avoiding making small talk about someone’s physical appearance or religious wear. Never make assumptions about or comment on someone’s background, income level, sexuality, political stance, or other personal identifier.
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Try not to sound accusatory either, Sandstrom says. One of her go-to opening lines is “What are you doing?” “I saw someone who was leaning over a bush and lifting up a leaf,” she says “and I’m like, ‘What’s going on here?’ They taught me some stuff about bugs.” But do your best to keep the mood playful — you’re asking out of curiosity, not suspicion.
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Every once in a while, someone might bristle at your attempts at small talk or appear confused as to why you’re talking to them, and that’s okay. Sandstrom finds explicitly stating “I’m just being friendly” helps ease some of the awkwardness.
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What to do if you get stuck
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Every conversation, including small talk, inevitably encounters roadblocks. Whether you find yourself giving one-word answers or the discussion veers toward potentially contentious territory, there are ways of deftly navigating. For chats that are veering on boring, feel free to direct the conversation to another topic or ask a random question. (Conversations aren’t linear anyway, Nightingall notes.)
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If you find the discussion isn’t going anywhere after a few exchanges, don’t force it, Poswolsky says. Either politely excuse yourself (“I’ve got to run to the bathroom” is a great exit) if you’re at a social gathering or simply drop the chitchat if you’re mingling with a stranger on public transit. For talks that become prejudiced or offensive, Sandstrom suggests saying “This conversation is making me uncomfortable.” Just remember, both people need buy-in for small talk to be productive.
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“If zero people are excited, it’s over,” Poswolsky says. “If one person is excited, you can see where you’re heading. What you’re looking for, and this is rare, is when two people are [having] a back-and-forth. There’s active listening happening on both parties. There are decent questions happening.”
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Small talk is what you make it. It can be a delightful way to spend a few minutes with a stranger while in line at the grocery store, it can be your superpower at a party, or it can lead to your next career move. Or, if you’re like Bryan, it can simply be uplifting banter about precipitation.
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“If it looks like rain, and you’ve got more to say about it, and you’re interested in what your partner has to say, just stay with it,” he says. “The big stuff will come. But you don’t need to rush it. It’s okay to stay small.”
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<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</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>Marlboro Man shines</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>India climb to top spot in World Test Championship standings</strong> - With five wins, two losses and one draw, India have 62 points in 8 matches, while the Black Caps have 36 from five matches and have a point-percentage of 60</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>Liverpool is exhausted, injury-hit and relying on youngsters. They keep on winning for Klopp</strong> - No English Premier League win by the Reds has been sealed as late as the one at Nottingham Forest on March 2</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Morning Digest | Mahagathbandhan to hold its first mega joint rally in Bihar on March 3; HP rebel MLAs say more Congress legislators in touch with them, and more</strong> - Here is a select list of stories to start the day</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ranji Trophy Semifinal | Tamil Nadu pays the price for batting first on a pitch with a tinge of green</strong> - When former cricketer Vijay Dhaiya, who conducted the toss, suggested it was a brave call to Sai Kishore, the skipper said, “I looked at the wicket and didn’t know much. I didn’t decide what I am going to do. Felt like I should bat on this wicket,” said the 27-year-old.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</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>Watch | Sandeshkali violence | How it will impact 2024 Lok Sabha polls</strong> - In this episode of Talking Politics, we discuss how the arrest of Mr. Shahjahan will impact the 2024 Lok Sabha polls</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>Dindigul Reader’s Mail</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>Lac bangles from Hyderabad secure GI tag</strong> - The GI tag gives the identity as provenance and gives the lac bangles an edge over similar products manufactured in Rajasthan and Uttar Pradesh.</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>Tirunelveli Reader’s Mail</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>2024 Lok Sabha polls | Gujarat’s former Deputy CM Nitin Patel withdraws candidature for Mehsana Lok Sabha constituency</strong> - Nitin Patel said that the name of the candidate from Mehsana is yet to be finalised</p></li>
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<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>France to enshrine abortion right in constitution</strong> - Macron’s popular move is expected on Monday - but critics say he is using the issue for a political advantage.</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>Russia says 38 Ukrainian drones intercepted in Crimea</strong> - Reports say a fuel depot was hit during the attack on the town of Feodosiya on the occupied peninsula.</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>Girl, 7, dies in English Channel crossing attempt</strong> - A boat carrying 16 migrants capsized in French waters a few kilometres from the coast, local officials 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>Norway king flies home after Malaysia hospital stay</strong> - King Harald, 87, was fitted with a pacemaker after falling ill whilst on holiday.</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>Russia publishes German army meeting on Ukraine</strong> - German chancellor promises probe after leak of officers discussing the supply of long-range missiles.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How melting Arctic ice leads to European drought and heatwaves</strong> - Fresh, cold water from Greenland ice melting upsets North Atlantic currents. - <a href="https://arstechnica.com/?p=2007381">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>2024 Porsche 911 S/T review: Threading the needle</strong> - The S/T celebrates the 60th anniversary of the 911 and is limited to just 1963 examples. - <a href="https://arstechnica.com/?p=2007258">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Researchers create AI worms that can spread from one system to another</strong> - Worms could potentially steal data and deploy malware. - <a href="https://arstechnica.com/?p=2007366">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CDC ditches 5-day COVID isolation, argues COVID is becoming flu-like</strong> - The agency released a unified “practical” guidance for respiratory viruses. - <a href="https://arstechnica.com/?p=2007434">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Report: Boeing may reacquire Spirit at higher price despite hating optics</strong> - Spirit was initially spun out from Boeing Commercial Airplanes in 2005. - <a href="https://arstechnica.com/?p=2007384">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>What’s the difference between a Porsche and a porcupine?</strong> - <!-- SC_OFF --></p>
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A porcupine has the pricks on the outside
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/man_teats"> /u/man_teats </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b59gc3/whats_the_difference_between_a_porsche_and_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b59gc3/whats_the_difference_between_a_porsche_and_a/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I’m told that women prefer guys with massive dicks….</strong> - <!-- SC_OFF --></p>
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Well, I may not have 12 inches, but it kinda smells like a foot
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/dustaknuckz"> /u/dustaknuckz </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b5bedw/im_told_that_women_prefer_guys_with_massive_dicks/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b5bedw/im_told_that_women_prefer_guys_with_massive_dicks/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A study of over 1500,00 men finds that people with a lower IQ are likely to have a larger penis</strong> - <!-- SC_OFF --></p>
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The study goes on to say it found a strong coruhlashin between IQ and penis size saying the results had a stastisticly sigfignicant negitiv coruhlashin. With a study size of over 1500,00 mails, sientists say these results are cunclewsiv
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/FatLoadShooter"> /u/FatLoadShooter </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b4or7z/a_study_of_over_150000_men_finds_that_people_with/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b4or7z/a_study_of_over_150000_men_finds_that_people_with/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My old girlfriend can count the number of guys she’s been intimate with on one hand.</strong> - <!-- SC_OFF --></p>
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If she’s holding a calculator.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/old_farmer"> /u/old_farmer </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b4tvo1/my_old_girlfriend_can_count_the_number_of_guys/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b4tvo1/my_old_girlfriend_can_count_the_number_of_guys/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Doctor: You’ve tested positive for opiates.</strong> - <!-- SC_OFF --></p>
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Patient: Oh I had a bagel with poppy seeds earlier.<br/> Doctor: Yes well you also tested positive for cannabis, LSD, and cocaine.<br/> Patient: …It was an everything bagel.
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