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<title>15 February, 2024</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Pooled PPIseq: screening the SARS-CoV-2 and human interface with a scalable multiplexed protein-protein interaction assay platform</strong> -
<div>
Protein-Protein Interactions (PPIs) are a key interface between virus and host, and these interactions are important to both viral reprogramming of the host and to host restriction of viral infection. In particular, viral-host PPI networks can be used to further our understanding of the molecular mechanisms of tissue specificity, host range, and virulence. At higher scales, viral-host PPI screening could also be used to screen for small-molecule antivirals that interfere with essential viral-host interactions, or to explore how the PPI networks between interacting viral and host genomes co-evolve. Current high-throughput PPI assays have screened entire viral-host PPI networks. However, these studies are time consuming, often require specialized equipment, and are difficult to further scale. Here, we develop methods that make larger-scale viral-host PPI screening more accessible. This approach combines the mDHFR split-tag reporter with the iSeq2 interaction-barcoding system to permit massively-multiplexed PPI quantification by simple pooled engineering of barcoded constructs, integration of these constructs into budding yeast, and fitness measurements by pooled cell competitions and barcode-sequencing. We applied this method to screen for PPIs between SARS-CoV-2 proteins and human proteins, screening in triplicate &gt;180,000 ORF-ORF combinations represented by &gt;1,000,000 barcoded lineages. Our results complement previous screens by identifying 74 putative PPIs, including interactions between ORF7A with the taste receptors TAS2R41 and TAS2R7, and between NSP4 with the transmembrane KDELR2 and KDELR3. We show that this PPI screening method is highly scalable, enabling larger studies aimed at generating a broad understanding of how viral effector proteins converge on cellular targets to effect replication.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580123v1" target="_blank">Pooled PPIseq: screening the SARS-CoV-2 and human interface with a scalable multiplexed protein-protein interaction assay platform</a>
</div></li>
<li><strong>Single-cell Masked Autoencoder: An Accurate and Interpretable Automated Immunophenotyper</strong> -
<div>
High-throughput single-cell cytometry data are crucial for understanding immune system's involvement in diseases and responses to treatment. Traditional methods for annotating cytometry data, specifically manual gating and clustering, face challenges in scalability, robustness, and accuracy. In this study, we propose a single-cell masked autoencoder (scMAE), which offers an automated solution for immunophenotyping tasks including cell type annotation. The scMAE model is designed to uphold user-defined cell type definitions, thereby facilitating easier interpretation and cross-study comparisons. The scMAE model operates on a pre-train and fine-tune approach. In the pre-training phase, scMAE employs Masked Single-cell Modelling (MScM) to learn relationships between protein markers in immune cells solely based on protein expression, without relying on prior information such as cell identity and cell type-specific marker proteins. Subsequently, the pre-trained scMAE is fine-tuned on multiple specialized tasks via task-specific supervised learning. The pre-trained scMAE addresses the shortcomings of manual gating and clustering methods by providing accurate and interpretable predictions. Through validation across multiple cohorts, we demonstrate that scMAE effectively identifies co-occurrence patterns of bound labeled antibodies, delivers accurate and interpretable cellular immunophenotyping, and improves the prediction of subject metadata status. Specifically, we evaluated scMAE for cell type annotation and imputation at the cellular-level and SARS-CoV-2 infection prediction, secondary immune response prediction against COVID-19, and prediction the infection stage in the COVID-19 progression at the subject-level. The introduction of scMAE marks a significant step forward in immunology research, particularly in large-scale and high-throughput human immune profiling. It offers new possibilities for predicting and interpretating cellular-level and subject-level phenotypes in both health and disease.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580114v1" target="_blank">Single-cell Masked Autoencoder: An Accurate and Interpretable Automated Immunophenotyper</a>
</div></li>
<li><strong>A spring-loaded and leakage-tolerant synthetic gene switch for in-vitro detection of DNA and RNA</strong> -
<div>
Nucleic acid tests (NATs) are essential for biomedical diagnostics. Traditional NATs, often complex and expensive, have prompted the exploration of Toehold-Mediated Strand Displacement (TMSD) circuits as an economical alternative. However, the wide application of TMSD-based reactions is limited by leakage-the spurious activation of the reaction leading to high background signals and false positives. Here we introduce a new TMSD cascade that recognizes a custom nucleic acid input and generates an amplified output. The system is based on a pair of thermodynamically spring-loaded DNA modules. The binding of a predefined nucleic acid target triggers an intermolecular reaction that activates a T7 promoter, leading to the perpetual transcription of a fluorescent aptamer that can be detected by a smartphone camera. The system is designed to permit the selective depletion of leakage byproducts to achieve high sensitivity and zero-background signal in the absence of the correct trigger. Using Zika virus (ZIKV)- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived nucleic acid sequences, we show that the assay generates a reliable target-specific readout. Native RNA can be directly detected under isothermal conditions, without requiring reverse transcription, with a sensitivity as low as 200 attomole. The modularity of the assay allows easy re-programming for the detection of other targets by exchanging a single sequence domain. This work provides a low-complexity and high-fidelity synthetic biology tool for point-of-care diagnostics and for the construction of more complex biomolecular computations.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.12.579921v1" target="_blank">A spring-loaded and leakage-tolerant synthetic gene switch for in-vitro detection of DNA and RNA</a>
</div></li>
<li><strong>Data mining antibody sequences for database searching in bottom-up proteomics</strong> -
<div>
Mass spectrometry (MS)-based proteomics allows identifying and quantifying thousands of proteins but suffers from challenges when measuring human antibodies due to their vast variety. The mainly used bottom-up proteomics approaches rely on database searches that compare experimental values of peptides and their fragments to theoretical values derived from protein sequences in a database. While the human body can produce millions of distinct antibodies, the current databases for human antibodies such as UniProtKB/Swiss-Prot are limited to only 1095 sequences (as of 2024 Jan). This limitation may hinder the identification of new antibodies using mass spectrometry. Therefore, extending the database for mass spectrometry is an important task for discovering new antibodies. Recent genomic studies have compiled millions of human antibody sequences publicly accessible through the Observed Antibody Space (OAS) database. However, this data has yet to be exploited to confirm the presence of these antibodies. In this study, we adopted this extensive collection of antibody sequences for conducting efficient database searches in publicly available proteomics data with a focus on the SARS-CoV-2 disease. Thirty million heavy antibody sequences from 146 SARS-CoV-2 patients in the OAS database were digested in silico to obtain 18 million unique peptides. These peptides were then used to create new databases for bottom-up proteomics. We used those databases for searching new antibody peptides in publicly available SARS-CoV-2 human plasma samples in the Proteomics Identification Database (PRIDE). This approach avoids false positives in antibody peptide identification as confirmed by searching against negative controls (brain samples) and employing different database sizes. We show that the found sequences provide valuable information to distinguish diseased from healthy and expect that the newly discovered antibody peptides can be further employed to develop therapeutic antibodies. The method will be broadly applicable to find characteristic antibodies for other diseases.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580076v1" target="_blank">Data mining antibody sequences for database searching in bottom-up proteomics</a>
</div></li>
<li><strong>Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020.</strong> -
<div>
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. A detailed analysis of the changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants that had the Y435F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early on during the outbreak. However, further introductions of the virus, with variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of the available viral genome data, we estimate that there were a minimum of about 17 separate examples of mink to human transmission of the virus in Denmark, using a conservative approach, but up to 60 such events (95% credible interval: (35-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using a Bayesian method. Using the latter approach, it was estimated that there were 136 jumps (95% credible interval: (112-164)) from humans to mink. Thus, transmission of these viruses from humans to mink, mink to mink, from mink to humans and between humans were all observed.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.13.580053v1" target="_blank">Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020.</a>
</div></li>
<li><strong>Evolving Trends in Neuropsychological Profiles of Post COVID-19 Condition: A 1-Year Follow-up in Individuals with Cognitive Complaints</strong> -
<div>
Background: Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. More longitudinal studies are needed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. Methods: 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results: Impacts on cognitive test scores remain stable across assessments. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Conclusions: Cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. An effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/bwgx8/" target="_blank">Evolving Trends in Neuropsychological Profiles of Post COVID-19 Condition: A 1-Year Follow-up in Individuals with Cognitive Complaints</a>
</div></li>
<li><strong>The Your COVID-19 Risk Assessment Tool and the Accompanying Open Access Data and Materials Repositories</strong> -
<div>
In March 2020, the Your COVID-19 Risk tool was developed in response to the global spread of SARS-CoV-2. The tool is an online resource based on key behavioural evidence-based risk factors related to contracting and spreading SARS-CoV-2. This article describes the development of the tool, the produced resources, the associated open repository, and initial results. This tool was developed by a multidisciplinary research team consisting of more than 150 international experts. This project leverages knowledge obtained in behavioural science, aiming to promote behaviour change by assessing risk and supporting individuals completing the assessment tool to protect themselves and others from infection. To enable iterative improvements of the tool, tool users can optionally answer questions about behavioural determinants. The data and results are openly shared to support governments and health agencies developing behaviour change interventions. Over 60 000 users in more than 150 countries have assessed their risk and provided data.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/b8n5g/" target="_blank">The Your COVID-19 Risk Assessment Tool and the Accompanying Open Access Data and Materials Repositories</a>
</div></li>
<li><strong>Long-term cardiovascular safety of COVID-19 vaccination according to brand, dose and combinations: Cohort study of 46 million adults in England</strong> -
<div>
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Using longitudinal health records from 45.7 million adults in England followed for a year, our study compared the incidence of thrombotic and cardiovascular complications after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the first two years of the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273) These findings support the wide uptake of future COVID-19 vaccination programs.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302698v1" target="_blank">Long-term cardiovascular safety of COVID-19 vaccination according to brand, dose and combinations: Cohort study of 46 million adults in England</a>
</div></li>
<li><strong>Knowledge, Attitude, and Practices towards COVID-19 Infection and Prevention Measures among Medical Students</strong> -
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The COVID-19 pandemic has rapidly led to an unprecedented health threat worldwide. During this time, disease prevention is considered to be the best way for general health protection. This is achieved through public health education by extending proper knowledge, promoting an optimistic attitude, and keeping the public compliant with preventive measures. As components of the healthcare system, medical students should also play a role in disease prevention more so in the Philippines where the Department of Health has called upon medical graduates to render services in response to the national emergency. In this study, the knowledge, attitude, and practices (KAP) of medical students from Cebu Institute of Medicine (CIM) towards COVID-19 infection and preventive measures were assessed. Demographic factors, their respective effect size on KAP, as well as the relationship between KAP variables were determined. The revised questionnaire, drafted based on qualitative and quantitative validity tests, was then used for the pilot study to generate the final questionnaire. Responses from participants underwent descriptive and correlational analysis. The results showed that the majority of the medical students of CIM have adequate knowledge (78.24%), positive attitude (80.68%), and good practices (94.38%) towards COVID-19 infection and prevention measures. Females have a significant association (p-value = 0.03) with better practices than male counterparts. Knowledge (p-value = 0.004) and attitude (p-value = 0.003) also showed significant correlation with practices, implying that knowledge and attitude play a role in shaping compliance to health practices. Therefore, health interventions should aim to disseminate accurate, evidence-based information and improve attitude towards the implemented precautionary measures in order to increase effectiveness of policies.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302741v1" target="_blank">Knowledge, Attitude, and Practices towards COVID-19 Infection and Prevention Measures among Medical Students</a>
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<li><strong>SARS-CoV-2 virus in Raw Wastewater from Student Residence Halls with concomitant 16S rRNA Bacterial Community Structure changes</strong> -
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The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in sewage is well-established, but the concomitant changes in microbial compositions during the pandemic remain insufficiently explored. This study investigates the impact of the SARS-CoV-2 virus on microbial compositions in raw sewage, utilizing 16S rRNA sequencing to analyze wastewater samples collected from six dormitories over a one-year field trial at the University of Tennessee, Knoxville. The concentration of SARS-CoV-2 RNA was assessed using a reverse transcription-quantitative polymerase chain reaction. Significant variations in bacterial composition were evident across the six dormitories, highlighting the importance of independently considering spatial differences when evaluating the raw wastewater microbiome. Positive samples for SARS-CoV-2 exhibited a prominent representation of exclusive species across all dormitories, coupled with significantly reduced bacterial diversity compared to negative samples. The correlation observed between the relative abundance of enteric pathogens and potential pathogens at sampling sites introduces a significant dimension to our understanding of COVID-19, especially the notable correlation observed in positive SARS-CoV-2 samples. Furthermore, the significant correlation in the relative abundance of potential pathogens between positive and negative SARS-CoV-2 raw sewage samples may be linked to the enduring effects of microbial dysbiosis observed during COVID-19 recovery. These findings provide valuable insights into the microbial dynamics in raw sewage during the COVID-19 pandemic.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24302582v1" target="_blank">SARS-CoV-2 virus in Raw Wastewater from Student Residence Halls with concomitant 16S rRNA Bacterial Community Structure changes</a>
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<li><strong>Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis</strong> -
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Objective: To study body mass index (BMI) changes among individuals aged 18-99 years with and without SARS-CoV-2 infection. Subjects/Methods: Using real-world data from the OneFlorida+ Clinical Research Network of the National Patient-Centered Clinical Research Network, we compared changes over time in BMI in an Exposed cohort (positive SARS-CoV-2 test between March 2020 - January 2022), to a contemporary Unexposed cohort (negative SARS-CoV-2 tests), and an age/sex-matched Historical control cohort (March 2018 - January 2020). Body mass index (kg/m2) was retrieved from objective measures of height and weight in electronic health records. We used target trial approaches to estimate BMI at baseline and change per 100 days of follow-up for Unexposed and Historical cohorts relative to the Exposed cohort by categories of sex, race-ethnicity, age, and hospitalization status. Results: The study sample consisted of 44,436 (Exposed cohort), 164,118 (Unexposed cohort), and 41,189 (Historical cohort). Cumulatively, 62% were women, 21.5% Non-Hispanic Black, 21.4% Hispanic and 5.6% Non-Hispanic Other. Patients had an average age of 51.9 years (SD: 18.9). At baseline, relative to the Exposed cohort (mean BMI: 29.3 kg/m2 [95%CI: 29.0, 29.7]), the Unexposed (-0.07 kg/m2 [95%CI; -0.12, -0.01]) and Historical controls (-0.27 kg/m2 [95%CI; -0.34, -0.20]) had lower BMI. Relative to no change in the Exposed over 100 days (0.00 kg/m2 [95%CI; -0.03,0.03]), the BMI of those Unexposed decreased (-0.04 kg/m2 [95%CI; -0.06, -0.01]) while the Historical cohort9s BMI increased (+0.03 kg/m2 [95%CI;0.00,0.06]). BMI changes were consistent between Exposed and Unexposed cohorts for most population groups, except at start of follow-up period among Males and those 65 years or older, and in changes over 100 days among Males and Hispanics. Conclusions: In a diverse real-world cohort of adults, mean BMI of those with and without SARS-CoV2 infection varied in their trajectories. The mechanisms and implications of weight retention following SARS-CoV-2 infection remain unclear.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302697v1" target="_blank">Body mass index changes and their association with SARS-CoV-2 infection: a real-world analysis</a>
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<li><strong>Association between altitude and death from COVID-19 in subjects with diabetes mellitus during the first wave: cross sectional study of the National Death Index</strong> -
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Background. In high Andean areas, there is greater insulin sensitivity which may be a protective factor against complications in subjects with diabetes mellitus.  Objective: Determine the association between altitude of residence and death from COVID-19 in deaths with diabetes mellitus in Peru during the first wave.. Methods: We carried out a cross-sectional analysis of deaths registered in the National Death System of Peru (SINADEF in Spanish). We selected Peruvians with diabetes mellitus identified by presenting the diagnosis in any of the six boxes on the certificate. The dependent variable was death from COVID-19 as the basic cause of death, located in last place among causes A, B, C and D according to the Pan American Health Organization. The independent variable was the altitude of residence, categorized as less than 1 500 m a.s.l, 1 500 to 2 499 m  a.s.l. and greater than 2 500 m a.sl. Through a multilevel analysis by geographic region and using a Poisson regression, we obtained the risk ratios of death from COVID-19 according to the altitude of residence. We adjusted by individual and contextual variables. Results: We included 16 406 deaths with diabetes mellitus between March-December 2020. 34.3% died from Covid19 and 9.7% came from areas above 2 500 m. The proportion of deaths from COVID-19 of those with residence altitude above 2 500 m  was 20% lower compared to residents below 1 500 m (RR: 0.80; 95% CI: 0.70 – 0.91; p&lt;0.001), adjusted for individual and socioeconomic factors. Its influence is also shown as the altitude changes every 100, 250, 500 and 1000 m a.s.l., through multilevel analysis. Conclusion: A higher altitude of residence is associated with a lower proportion of deaths from COVID-19 in people with diabetes mellitus during the first wave in Peru. The study contribute to expanding knowledge of the effects of altitude with respect to mortality in people with diabetes mellitus in a context of a highly contagious and virulent infectious disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302726v1" target="_blank">Association between altitude and death from COVID-19 in subjects with diabetes mellitus during the first wave: cross sectional study of the National Death Index</a>
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<li><strong>Mathematical assessment of the role of human behavior changes on SARS-CoV-2 transmission dynamics</strong> -
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The COVID-19 pandemic has not only presented a major global public health and socio-economic crisis, but has also significantly impacted human behavior towards adherence (or lack thereof) to public health intervention and mitigation measures implemented in communities worldwide. The dynamic nature of the pandemic has prompted extensive changes in individual and collective behaviors towards the pandemic. This study is based on the use of mathematical modeling approaches to assess the extent to which SARS-CoV-2 transmission dynamics is impacted by population-level changes of human behavior due to factors such as (a) the severity of transmission (such as disease-induced mortality and level of symptomatic transmission), (b) fatigue due to the implementation of mitigation interventions measures (e.g., lockdowns) over a long (extended) period of time, (c) social peer-pressure, among others. A novel behavior-epidemiology model, which takes the form of a deterministic system of nonlinear differential equations, is developed and fitted using observed cumulative SARS-CoV-2 mortality data during the first wave in the United States. Rigorous analysis of the model shows that its disease-free equilibrium is locally-asymptotically stable whenever a certain epidemiological threshold, known as the control reproduction number (denoted by R_C) is less than one, and the disease persists (i.e., causes significant outbreak or outbreaks) if the threshold exceeds one. The model fits the observed data, as well as makes a more accurate prediction of the observed daily SARS-CoV-2 mortality during the first wave (March 2020 -June 2020), in comparison to the equivalent model which does not explicitly account for changes in human behavior. Of the various metrics for human behavior changes during the pandemic considered in this study, it is shown that behavior changes due to the level of SARS-CoV-2 mortality and symptomatic transmission were more influential (while behavioral changes due to the level of fatigue to interventions in the community was of marginal impact). It is shown that an increase in the proportion of exposed individuals who become asymptomatically-infectious at the end of the exposed period (represented by a parameter r) can lead to an increase (decrease) in the control reproduction number (R_C) if the effective contact rate of asymptomatic individuals is higher (lower) than that of symptomatic individuals. The study identifies two threshold values of the parameter r that maximize the cumulative and daily SARS-CoV-2 mortality, respectively, during the first wave. Furthermore, it is shown that, as the value of the proportion r increases from 0 to 1, the rate at which susceptible non-adherent individuals change their behavior to strictly adhere to public health interventions decreases. Hence, this study suggests that, as more newly-infected individuals become asymptomatically-infectious, the level of positive behavior change, as well as disease severity, hospitalizations and disease-induced mortality in the community can be expected to significantly decrease (while new cases may rise, particularly if asymptomatic individuals have higher contact rate, in comparison to symptomatic individuals).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24302662v1" target="_blank">Mathematical assessment of the role of human behavior changes on SARS-CoV-2 transmission dynamics</a>
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<li><strong>Temporal variations in international air travel: implications for modelling the spread of infectious diseases</strong> -
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Background The international flight network creates multiple routes by which pathogens can quickly spread across the globe. In the early stages of infectious disease outbreaks, analyses using flight passenger data to identify countries at risk of importing the pathogen are common and can help inform disease control efforts. A challenge faced in this modelling is that the latest aviation statistics (referred to as contemporary data) are typically not immediately available. Therefore, flight patterns from a previous year are often used (referred to as historical data). We explored the suitability of historical data for predicting the spatial spread of emerging epidemics. Methods We analysed monthly flight passenger data from the International Air Transport Association to assess how baseline air travel patterns were affected in outbreaks of MERS, Zika, and SARS-CoV-2 over the past decade. We then used a stochastic discrete time SEIR metapopulation model to simulate global spread of different pathogens, comparing how epidemic dynamics differed in simulations based on historical and contemporary data. Results We observed local, short-term disruptions to air travel from South Korea and Brazil for the MERS and Zika outbreaks we studied, whereas global and longer-term flight disruption occurred during the SARS-CoV-2 pandemic. For outbreak events that were accompanied by local, small, and short-term changes in air travel, epidemic models using historical flight data gave similar projections of timing and locations of disease spread as when using contemporary flight data. However, historical data were less reliable to model the spread of an atypical outbreak such as SARS-CoV-2 in which there were durable and extensive levels of global travel disruption. Conclusions The use of historical flight data as a proxy in epidemic models is an acceptable practice except in rare, large epidemics that lead to substantial disruptions to international travel.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.12.24302682v1" target="_blank">Temporal variations in international air travel: implications for modelling the spread of infectious diseases</a>
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<li><strong>Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology</strong> -
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Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti- interferon (IFN) autoantibodies. We found that older age correlated with an increased SARS-CoV- 2 viral load at the time of admission, and with delayed viral clearance over 28 days. This contributed to an age-dependent increase in type I IFN gene expression in both the respiratory tract and blood. We also observed age-dependent transcriptional increases in peripheral blood IFN-gamma, neutrophil degranulation, and Toll like receptor (TLR) signaling pathways, and decreases in T cell receptor (TCR) and B cell receptor signaling pathways. Over time, older adults exhibited a remarkably sustained induction of proinflammatory genes (e.g., CXCL6) and serum chemokines (e.g., CXCL9) compared to younger individuals, highlighting a striking age-dependent impairment in inflammation resolution. Augmented inflammatory signaling also involved the upper airway, where aging was associated with upregulation of TLR, IL17, type I IFN and IL1 pathways, and downregulation TCR and PD-1 signaling pathways. Metatranscriptomics revealed that the oldest adults exhibited disproportionate reactivation of herpes simplex virus and cytomegalovirus in the upper airway following hospitalization. Mass cytometry demonstrated that aging correlated with reduced naïve T and B cell populations, and increased monocytes and exhausted natural killer cells. Transcriptional and protein biomarkers of disease severity markedly differed with age, with the oldest adults exhibiting greater expression of TLR and inflammasome signaling genes, as well as proinflammatory proteins (e.g., IL6, CXCL8), in severe COVID-19 compared to mild/moderate disease. Anti-IFN autoantibody prevalence correlated with both age and disease severity. Taken together, this work profiles both host and microbe in the blood and airway to provide fresh insights into aging-related immune changes in a large cohort of vaccine-naïve COVID-19 patients. We observed age-dependent immune dysregulation at the transcriptional, protein and cellular levels, manifesting in an imbalance of inflammatory responses over the course of hospitalization, and suggesting potential new therapeutic targets.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.02.11.24301704v1" target="_blank">Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology</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>Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood.</strong> - <b>Conditions</b>: Covid-19 <br/><b>Interventions</b>: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) <br/><b>Sponsors</b>: Vachira Phuket Hospital <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease <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; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH <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>Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) <br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France <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>ADJUVANT TREATMENT TO REDUCE CARDIOVASCULAR RISK IN PATIENTS WITH LONG COVID: HIGH-DEFINITION TRANSCRANIAL DIRECT CURRENT STIMULATION (HD-TDCS) AND CHLORELLA PYREINOIDOSA</strong> - <b>Conditions</b>: Cardiovascular Diseases; Long Covid19 <br/><b>Interventions</b>: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyreinodosa <br/><b>Sponsors</b>: Federal University of Paraíba; City University of New York <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>SGB for COVID-induced Parosmia</strong> - <b>Conditions</b>: COVID-19-Induced Parosmia <br/><b>Interventions</b>: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection <br/><b>Sponsors</b>: Washington University School of Medicine <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>Investigating the Effectiveness of Vimida</strong> - <b>Conditions</b>: Long COVID; Post COVID-19 Condition <br/><b>Interventions</b>: Behavioral: vimida <br/><b>Sponsors</b>: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock <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>Effects of Physiotherapy Via Video Calls in Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function <br/><b>Interventions</b>: Behavioral: Exercise training <br/><b>Sponsors</b>: Chulabhorn Hospital <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>Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: Exercise session; Behavioral: Control session <br/><b>Sponsors</b>: University of Nove de Julho <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reducing Respiratory Virus Transmission in Bangladeshi Classrooms</strong> - <b>Conditions</b>: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection <br/><b>Interventions</b>: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units <br/><b>Sponsors</b>: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh <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>SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19</strong> - <b>Conditions</b>: Anxiety; COVID-19 Pandemic <br/><b>Interventions</b>: Behavioral: Mindfulness <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International <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 Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus</strong> - <b>Conditions</b>: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus <br/><b>Interventions</b>: Behavioral: Nutritional Intervention <br/><b>Sponsors</b>: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo <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>A Study to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults</strong> - <b>Conditions</b>: Influenza, Human; SARS-CoV-2 Infection; COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo <br/><b>Sponsors</b>: Pfizer <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>The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management</strong> - <b>Conditions</b>: Trauma; COVID-19 Pandemic <br/><b>Interventions</b>: Other: epidemyolojical <br/><b>Sponsors</b>: Bakirkoy Dr. Sadi Konuk Research and Training Hospital <br/><b>Completed</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post-COVID-19 pulmonary fibrosis</strong> - CONCLUSION: ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.</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>Methotrexate Inhibits the Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Receptor Binding Domain to the Host-Cell Angiotensin-Converting Enzyme-2 (ACE-2) Receptor</strong> - As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus mutates, finding effective drugs becomes more challenging. In this study, we use ultrasensitive frequency locked microtoroid optical resonators in combination with in silico screening to search for COVID-19 drugs that can stop the virus from attaching to the human angiotensin-converting enzyme 2 (hACE2) receptor in the lungs. We found 29 promising candidates that could block the binding site and selected four of them that…</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>Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies</strong> - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recognized for their analgesic and anti-inflammatory properties. Amidst the SARS-CoV-2 pandemic, the role of NSAIDs in modulating viral and bacterial infections has become a critical area of research, sparking debates and necessitating a thorough review. This review examines the multifaceted interactions between NSAIDs, immune responses, and infections. Focusing on the immunomodulatory mechanisms of NSAIDs in SARS-CoV-2 and their…</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>Molecular docking of bioactive compounds extracted and purified from selected medicinal plant species against covid-19 proteins and in vitro evaluation</strong> - Bioactive compounds are secondary metabolites of plants. They offer diverse pharmacological properties. Peganum harmala is reported to have pharmaceutical effects like insecticidal, antitumor, curing malaria, anti-spasmodic, vasorelaxant, antihistaminic effect. Rosa brunonii has medicinal importance in its flower and fruits effective against different diseases and juice of leaf is reported to be applied externally to cure wounds and cuts. Dryopteris ramosa aqueous leaf extract is used to treat…</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>Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK</strong> - Immunostaining in lungs of patients who died with COVID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase (Arylsulfatase B; ARSB). To explain these findings, human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain (SPRBD) and transcriptional mechanisms were investigated. Phospho-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD, and their inhibition…</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>Investigating vulnerability of the conserved SARS-CoV-2 spike’s heptad repeat 2 as target for fusion inhibitors using chimeric miniproteins</strong> - Inhibition of SARS-CoV-2 membrane fusion is a highly desired target to combat COVID-19. The interaction between the spike’s heptad repeat (HR) regions 1 (HR1) and 2 (HR2) is a crucial step during the fusion process and these highly conserved HR regions constitute attractive targets for fusion inhibitors. However, the relative importance of each subregion of the long HR1-HR2 interface for viral inhibition remains unclear. Here, we designed, produced, and characterized a series of chimeric…</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>TYPE I INTERFERON PATHWAY GENETIC VARIANTS IN SEVERE COVID-19</strong> - Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. According to the World Health Organization (WHO), there have been over 760 million reported cases and over 6 million deaths caused by this disease worldwide. The severity of COVID-19 is based on symptoms presented by the patient and is divided as asymptomatic, mild, moderate, severe, and critical. The manifestations are interconnected with genetic variations. The innate immunity is the quickest response mechanism…</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>Inhibition of CD40L with Frexalimab in Multiple Sclerosis</strong> - CONCLUSIONS: In a phase 2 trial involving participants with multiple sclerosis, inhibition of CD40L with frexalimab had an effect that generally favored a greater reduction in the number of new gadolinium-enhancing T1-weighted lesions at week 12 as compared with placebo. Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with multiple sclerosis. (Funded by Sanofi; ClinicalTrials.gov number, NCT04879628.).</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>Hyperacetylated microtubules assist porcine deltacoronavirus nsp8 to degrade MDA5 via SQSTM1/p62-dependent selective autophagy</strong> - The microtubule (MT) is a highly dynamic polymer that functions in various cellular processes through MT hyperacetylation. Thus, many viruses have evolved mechanisms to hijack the MT network of the cytoskeleton to allow intracellular replication of viral genomic material. Coronavirus non-structural protein 8 (nsp8), a component of the viral replication transcriptional complex, is essential for viral survival. Here, we found that nsp8 of porcine deltacoronavirus (PDCoV), an emerging…</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>An isothermal calorimetry assay for determining steady state kinetic and enzyme inhibition parameters for SARS-CoV-2 3CL-protease</strong> - This manuscript describes the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL ^(pro) from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL ^(pro) is the main protease that plays a crucial role of producing the whole array of proteins necessary for the viral infection that caused the spread of COVID-19, responsible for millions of deaths worldwide as well as global…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of new pharmacophore against SARS-CoV-2 spike protein by multi-fold computational and biochemical techniques</strong> - COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2’s spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Calpain-2 mediates SARS-CoV-2 entry via regulating ACE2 levels</strong> - Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (M^(pro)), which plays an essential role in processing viral polyproteins. In this study, we found that calpain inhibitors potently inhibited the infection of a…</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>Combination of Polygonatum Rhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON<sub>3</sub> -induced mitochondrial damage and endoplasmic reticulum stress in A549 cells</strong> - CONCLUSION: SP inhibits proliferation of lung cancer A549 cells by downregulating PON(3) -induced apoptosis in the mitochondrial and ER pathways.</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>Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study</strong> - There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Trauma of Giving Birth in Gaza</strong> - An obstetrician who just returned from the war zone describes what the Israeli bombardment has meant for maternal care. - <a href="https://www.newyorker.com/news/q-and-a/the-trauma-of-giving-birth-in-gaza">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is the Media Prepared for an Extinction-Level Event?</strong> - Ads are scarce, search and social traffic is dying, and readers are burned out. The future will require fundamentally rethinking the press’s relationship to its audience. - <a href="https://www.newyorker.com/news/the-weekend-essay/is-the-media-prepared-for-an-extinction-level-event">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Friendship Challenge</strong> - How envy destroyed the perfect connection between two teen-age girls. - <a href="https://www.newyorker.com/magazine/2024/02/12/the-friendship-challenge">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Art World Before and After Thelma Golden, by Calvin Tomkins</strong> - When Golden was a young curator in the nineties, her shows, centering Black artists, were unprecedented. Today, those artists are the stars of the art market. - <a href="https://www.newyorker.com/magazine/2024/02/12/the-art-world-before-and-after-thelma-golden">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Teen’s Fatal Plunge Into the London Underworld</strong> - After Zac Brettler mysteriously plummeted into the Thames, his grieving parents were shocked to learn that he’d been posing as an oligarch’s son. Would the police help them solve the puzzle of his death? - <a href="https://www.newyorker.com/magazine/2024/02/12/a-teens-fatal-plunge-into-the-london-underworld">link</a></p></li>
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<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
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<li><strong>In The Book of Love, Kelly Link shows that the best romances are ghost stories too</strong> -
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<img alt="The cover of “The Book of Love” by Kelly Link has a red background and a pattern of gold moons in phases of waxing and waning." src="https://cdn.vox-cdn.com/thumbor/mRlzxM9rcJn6cv2fv0TDrl1tC9Y=/0x0:1847x1385/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73141204/9780812996586.0.jpg"/>
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<em>The Book of Love</em> by Kelly Link. | Random House
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The first novel by the acclaimed short-story writer is magical, strange, and just a tad too slow.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GPiVla">
<a href="https://go.skimresources.com?id=1025X1701643&amp;xs=1&amp;url=https%3A%2F%2Fbookshop.org%2Fp%2Fbooks%2Fthe-book-of-love-kelly-link%2F20099222%3Fean%3D9780812996586"><em>The Book of Love</em></a>, Kelly Link’s first novel, is a love story, yes. It’s also a ghost story, and a coming-of-age story, and a portrait of a small town. It’s about magic and music and morality. It’s about how annoying siblings are, and how much you need them. It is a book that contains many books, that is bigger than the sum of its many parts. It is also, perhaps, a book that should have been a touch smaller.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bWeCOf">
<em>The Book of Love</em> begins with three teenagers back from the dead: Type A Laura, eternal elder brother Daniel, inquisitive Mo. They have been in some strange limbo, “a blotted, attenuated, chilly nothingness,” for almost a year. They can’t remember how they died. They don’t understand how they happened to come back.
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Their old music teacher, the enigmatic Mr. Anabin, seems to have some answers, but he’s not willing to tell them much. Instead, he puts them through a series of trials, informing them that if they don’t complete their tasks successfully, they will doubtless find themselves back in limbo. Helpfully, Mr. Anabin also enchants all the revenants’ friends and families so that they believe them to have been studying abroad instead of dead — although Susannah, Laura’s rebellious sister and Daniel’s ex-girlfriend, seems to cherish some suspicions despite all the magic.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wccjcf">
The mystery of what happened to the three teenagers provides Link with the skeleton of a plot, but she is almost palpably uninterested in solving it. Link, <a href="https://www.vox.com/culture/23672639/white-cat-black-dog-kelly-link-review">a MacArthur “genius” grant recipient and Pulitzer finalist for her short stories</a>, seems to be most invested in atmosphere and character work, and she’s developed an ideal showcase for both skills with her setting for <em>The Book of Love</em>: the small town of Lovesend.
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Lovesend is a seaside town in Massachusetts. The local club is built out of a plane hangar on the cliffs made iconic for its indoor carousel; the food is mediocre. The coffee shop is called What Hast Thou Ground, and its owner has a policy of cultivating good coffee and a bad atmosphere so people don’t linger too long. Music always seems to be playing somewhere, as though Lovesend is Prospero’s Island. The place is already a little strange, a little unearthly, long before magic arrives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v0K55A">
After that, statues start climbing off their plinths and walking around and people start climbing onto the plinths and turning into statues. There’s a boy who turns into moths and seagulls. There’s a cat who, grooming itself, begins to swallow its leg, and then keeps going, swallowing its whole body until it has swallowed even its smile, “rosy wet gullet snapping together like a fanged coin purse,” a kind of nightmarishly fleshy Cheshire Cat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BNsXrg">
As wonders and horrors fight their way across the page, Link moves from character to character. Each chapter of this novel is given an almost biblical “book of” title — The Book of Laura, the Book of Susannah, the Book of Lovesend. The bulk of the novel is given over to the book of the main characters, but Link periodically turns the pages to the books of some of the other citizens of Lovesend, like a man who’s been turned into a tiger or a teen lesbian on whom Laura is madly crushing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jwy73J">
Most beautiful and effective of all is The Book of Maryanne, Mo’s grandmother, a rushing kaleidoscope of a chapter that follows Maryanne throughout her life. We see her early career as a Black romance novelist writing white heroines under a pen name, her successes and her failures, the loss of her daughter and the arrival of Mo. “Time,” thinks Maryanne, “is a row of small and hateful stitches.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0kZpJe">
It’s hard not to think, looking at The Book of Maryanne, of a very brief and strange and beautiful short story, the kind at which Link excels. She’s been writing for decades now, but <em>The Book of Love</em> is her first novel. Chapters like The Book of Maryanne make me wonder if <em>The Book of Love</em> would not have felt a little more beautiful and more magical as a novel in stories rather than the sprawling 625-page saga Link has delivered us. Occasionally, you feel a little stab of discomfort with the form as you go.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E9fsH8">
This is a slow-moving book. It takes 89 pages for Mo, Laura, and Daniel to make their way through their first night back from the dead, and 125 pages after that for a single character to discover any answers about the central mysteries. Then that character promptly gets their memory magically revised, a move Link repeats so often that it starts to feel almost comical.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hzOBoC">
At times the slow place works as a way of exploring this richly textured small town, these deeply realized love stories. At other times it feels willfully slow, information withheld for no reason until it becomes time for exposition to be dumped inelegantly onto the page. For a writer of Link’s gifts, such clumsiness is jarring. If you’re new to Link’s work, it might be worth checking out her intricate and twisting short stories, a form over which she has full mastery, before you come to this odd novel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="beFz3c">
Nonetheless, Link’s gifts are fairly extraordinary on their own. If <em>The Book of Love</em> is flawed, it’s also something strange and beautiful and shimmering.
</p></li>
<li><strong>Trump’s big day in court</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/wqrVMr8cPmb20BfpZ1E2iXEcmOA=/246x0:3446x2400/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73141190/GettyImages_1925057776.0.jpg"/>
<figcaption>
Former US President Donald Trump sits in the courtroom during his civil fraud trial at New York Supreme Court on January 11, 2024, in New York City. | Jefferson Siegel/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We’re about to learn how imperiled two of Trump’s prosecutions are.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uCuBS6">
Prosecutors in all four of the cases against Donald Trump are racing against time to try to get to trial before Election Day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RKggPa">
But to do so, they each have to clear <a href="https://www.vox.com/politics/24055503/trump-trials-fani-willis-jack-smith-alvin-bragg">a series of legal and procedural hurdles</a> — and soon, we’ll get a better idea of which, if any, will make it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vseIXj">
Today, two of those prosecutions will go in the spotlight via high-stakes hearings where we’ll get a sense of how seriously judges are taking Trump’s efforts to get indictments thrown out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DS3My4">
In Fulton County, District Attorney Fani Willis’s prosecution of Trump for trying to steal Georgia’s 2020 election has been sidetracked by allegations about Willis’s personal life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="npdL1b">
Embarrassingly, a judge will hear testimony on exactly when Willis’s relationship with Nathan Wade, a prosecutor she’d brought on to the case, began. One of Trump’s co-defendants has asserted that Willis improperly financially benefited from the prosecution because she’s been paying Wade’s attorney fees, and he’s paid for vacations they took together. Trump <a href="https://abcnews.go.com/US/trump-joins-motion-seeking-disqualify-da-fani-willis/story?id=106686320">wants Willis disqualified</a> from the case.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HMUVUW">
Meanwhile, in Manhattan, where District Attorney Alvin Bragg has charged Trump with falsifying business records related to hush money paid to Stormy Daniels, a judge will assess whether to move forward with a planned March 25 trial — or throw the charges out entirely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JRUYFt">
The New York case is the least substantively important of the four Trump cases, but it’s lately seemed likely to go to trial first because of <a href="https://www.vox.com/politics/24055503/trump-trials-fani-willis-jack-smith-alvin-bragg">procedural delays in the federal cases</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y675xJ">
But there have been questions about whether Bragg’s rationale for charging Trump with felonies will survive court scrutiny — and on Thursday, we’ll get to hear what that case’s judge thinks about those arguments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5iRkYL">
Thursday, in short, could be a make-or-break day for the two state-level prosecutions against the former president.
</p>
<h3 id="RfitCt">
In Georgia, we’ll soon learn whether Fani Willis stays on the case
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RlKpt3">
When Willis had Trump and 18 co-defendants indicted last August, her case was widely hailed as the most sweeping effort to hold him and his allies to account for the attempted 2020 election theft. Four of those defendants have already pleaded guilty.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JPuWjQ">
But another defendant, Michael Roman — a former Trump <a href="https://www.washingtonpost.com/national-security/2024/02/02/mike-roman-trump-georgia-election-case-fani-willis/">campaign opposition research specialist</a> — struck back in a <a href="https://www.documentcloud.org/documents/24352568-roman-motion-to-dimiss-010824">filing from his attorney</a> arguing that Willis should be removed from the case.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RK4Wix">
Roman’s attorney asserted that Willis and Wade had a “clandestine personal relationship,” and argued that was inappropriate for a few reasons: asserting Wade was unqualified for the job, that Willis overpaid him, and that she benefited financially from his hiring when he paid for vacations they took together.
</p>
<aside id="rpxu1y">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kqDfO6">
In response, Willis’s office claimed there was no impropriety. Wade said in an affidavit that he’d indeed “developed a personal relationship” with Willis — but only after he joined the investigation in 2022. (Roman’s attorney fired back by saying she had a witness who would testify otherwise.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EVeFFs">
On Monday, Judge Scott McAfee gave some insight into how he’d approach the topic. “I think it’s possible that the facts alleged by the defendant could result in disqualification,” he said. But, he went on, Wade’s qualifications for the job weren’t relevant. The key question, in his view, was whether “a personal relationship resulted in a financial benefit to the district attorney.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m13ACf">
To assess that, he said, he wanted to determine when the relationship between Willis and Wade formed and whether it is still ongoing. If McAfee does decide to remove Willis’s office from the case, the Prosecuting Attorneys’ Council of Georgia would get to choose her replacement — and the case’s future would hinge on whom they choose.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wbULlJ">
So the high-minded case about the sanctity of elections, which will take place Thursday and likely Friday, may now hinge on tawdry testimony about the district attorney’s love life and travel.
</p>
<h3 id="3oFA3X">
In New York, we’ll soon learn whether Bragg’s charges survive
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YzUiCX">
Manhattan DA Bragg was the first prosecutor to have Trump indicted back in March of last year, but his case was quickly superseded in the public discourse by the election-stealing and classified documents cases, which were more substantively important. Now, though, it may be the case with the best odds of a speedy trial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0lZM3P">
To recap: In October 2016, Trump attorney Michael Cohen paid hush money to Stormy Daniels so she wouldn’t come forward alleging a sexual encounter with Trump. Trump later reimbursed Cohen through the Trump Organization, with payments he categorized as legal expenses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jgd7Hj">
This, Bragg asserts, violated state law against falsifying business records (because they were hush money payments, not legal fees). Some legal commentators questioned Bragg’s rationale for charging these as felony counts rather than misdemeanors. To do so, Bragg had to argue that Trump falsified these records with the intent of committing or concealing another crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xsmnVW">
For some time, though, it wasn’t totally clear <a href="https://www.vox.com/politics/24055503/trump-trials-fani-willis-jack-smith-alvin-bragg">even to prosecutors on the case</a> which crime would fit the bill, with some fearing judges could throw out the charges before trial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QVJzmL">
So on Thursday, Judge Juan Merchan is set to finally weigh in on these questions. Most legal commentators expect him to let the charges stand, but we won’t know for sure until we hear it from him (and Trump may appeal afterward).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rN6IFm">
Merchan is also expected to let us know whether he’ll stick to the March 25 trial date in the case. If he lets both the charges and the date stand, then unless Trump wins a quick appeal, the former president will face his first criminal trial next month.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eVMEmD">
Which means the question of whether Trump will run for office as a convicted felon may hinge on the simultaneously tawdry yet technical matter of whether reimbursements for hush money covering up a sex scandal abided by New York bookkeeping law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VCmOJL">
<em>This story appeared originally in </em><a href="https://www.vox.com/today-explained-podcast"><em><strong>Today, Explained</strong></em></a><em>, Vox’s flagship daily newsletter. </em><a href="https://www.vox.com/pages/today-explained-newsletter-signup"><em><strong>Sign up here for future editions</strong></em></a><em>.</em>
</p></li>
<li><strong>The Supreme Court will decide if the government can seize control of YouTube and Twitter</strong> -
<figure>
<img alt="DeSantis gestures with both hands while holding a press conference, standing in front of a US flag." src="https://cdn.vox-cdn.com/thumbor/9B17ykygBvvUAPcQutphhuRtVdM=/180x0:4020x2880/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73141174/1251934515.0.jpg"/>
<figcaption>
Florida Gov. Ron DeSantis, who signed one of the unconstitutional laws before the Supreme Court in the <em>NetChoice</em> cases. | Paul Hennessy/SOPA Images/LightRocket via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We’re about to find out if the Supreme Court still believes in capitalism.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r8rN5u">
In mid-2021, about a year before he began his <a href="https://www.vox.com/23036427/ron-desantis-disney-first-amendment-constitution-supreme-court">longstanding feud with the biggest employer in his state</a>, Florida’s <a href="https://www.vox.com/ron-desantis">Republican Gov. Ron DeSantis</a> signed legislation <a href="https://www.vox.com/scotus/2023/9/22/23883888/supreme-court-social-media-first-amendment-netchoice-paxton-murthy-missouri-twitter-facebook">attempting to seize control of content moderation</a> at major social media platforms such as <a href="https://www.vox.com/youtube">YouTube</a>, <a href="https://www.vox.com/facebook">Facebook</a>, or <a href="https://www.vox.com/twitter">Twitter</a> (now called X by <a href="https://www.vox.com/elon-musk">Elon Musk</a>). A few months later, Texas Gov. Greg Abbott, also a Republican, <a href="https://www.washingtonpost.com/technology/2021/09/09/govgregabbott-social-media-censorship-bill/">signed similar legislation in his state</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mmoUCf">
Both laws are <a href="https://www.vox.com/scotus/2023/9/22/23883888/supreme-court-social-media-first-amendment-netchoice-paxton-murthy-missouri-twitter-facebook">almost comically unconstitutional</a> — the First Amendment does not permit the government to order <a href="https://www.vox.com/media">media companies</a> to publish content they do not wish to publish — and neither law is currently in effect. A federal appeals court <a href="https://casetext.com/case/netchoice-llc-v-attorney-gen">halted the key provisions of Florida’s law</a> in 2022, and the <a href="https://www.vox.com/scotus">Supreme Court</a> <a href="https://www.vox.com/2022/5/31/23149183/supreme-court-texas-social-media-ruling-netchoice-paxton">temporarily blocked Texas’s law shortly thereafter</a> (though the justices, somewhat ominously, split 5-4 in this later case).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i90ICn">
Nevertheless, the justices have not yet weighed in on whether these two unconstitutional laws must be permanently blocked, and that question is now before the Court in a pair of cases known as <a href="https://www.scotusblog.com/case-files/cases/moody-v-netchoice-llc/"><em>Moody v. NetChoice</em></a> and <a href="https://www.scotusblog.com/case-files/cases/netchoice-llc-v-paxton/"><em>NetChoice v. Paxton</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FSx0bY">
The stakes in both cases are quite high, and the Supreme Court’s decision is likely to reveal where each one of the Republican justices falls on the GOP’s internal conflict between old-school free market capitalists and a newer generation that is eager to pick cultural fights with business.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hAnkFU">
Proponents of the two laws have not hidden that they were enacted entirely because Republican lawmakers in Texas and Florida believed that social media websites must do more to elevate conservative voices. As DeSantis said of his state’s law, it exists to fight supposedly “biased silencing” of “<a href="https://casetext.com/case/netchoice-llc-v-attorney-gen">our freedom of speech as conservatives … by the ‘big tech’ oligarchs in Silicon Valley</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yVNdXV">
So, if the Supreme Court were to uphold these laws, it would give Republican policymakers sweeping and unprecedented ability to control what many American voters read about our elections and our political debates. More broadly, the <em>NetChoice</em> cases are a test of how this Supreme Court, with its 6-3 Republican supermajority, views free market capitalism in an era when many of the justices’ fellow partisans view corporate America as the enemy in a culture war.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BmBN40">
DeSantis, in particular, is one of the GOP’s leading voices for a kind of reactionary anti-capitalism that is eager to use the government’s authority to suppress voices that disagree with conservative orthodoxy — often when those voices are associated with big businesses — while elevating opinions DeSantis finds more congenial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZV2jSq">
DeSantis famously signed legislation <a href="https://www.vox.com/23036427/ron-desantis-disney-first-amendment-constitution-supreme-court">retaliating against the Walt Disney Corporation</a> after <a href="https://www.vox.com/disney">Disney</a> denounced Florida’s “Don’t Say Gay” law — a law that is itself an <a href="https://www.vox.com/2022/3/15/22976868/dont-say-gay-florida-unconstitutional-ron-desantis-supreme-court-first-amendment-schools-parents">unconstitutional attempt to suppress speech</a>. He’s also signed legislation seeking to <a href="https://www.flgov.com/2023/05/02/governor-ron-desantis-signs-legislation-to-protect-floridians-financial-future-economic-liberty/">limit investment strategies DeSantis views as too “woke.”</a> DeSantis said he endorsed former <a href="https://www.vox.com/donald-trump">President Donald Trump</a> bid to return to the White House because <a href="https://www.vox.com/policy-and-politics/2023/2/14/23599194/nikki-haley-donald-trump-2024-presidential-campaign">Nikki Haley</a>, Trump’s final rival for the GOP presidential nomination, embodies a “<a href="https://www.tallahassee.com/story/news/politics/2024/01/21/read-transcript-of-statement-from-desantis-suspending-campaign/72304820007/">repackaged form of warmed-over corporatism</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pwzXe9">
This anti-capitalist Republicanism, moreover, is hardly limited to DeSantis. Among other things, it’s penetrated deep into the Federalist Society — the powerful legal organization that plays an enormous role in selecting Republican appointees to the federal bench. During the <a href="https://www.vox.com/joe-biden">Biden administration</a>, the Federalist Society’s annual conventions have featured an <a href="https://www.vox.com/2021/11/18/22783108/federalist-society-capitalism-woke-corporations-milton-friedman-supreme-court-judiciary-judges">array of paranoid speakers making grandiose claims about corporate America</a>, such as “massive corporations are pursuing a common and mutually agreed upon agenda to destroy American freedom.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nR2O9w">
The social media laws at issue in the two <em>NetChoice</em> cases place the GOP’s internal conflict between free market traditionalists and MAGA-aligned culture warriors in stark relief. Again, these laws seek to use the power of the government to seize control of private media companies’ editorial decisions. That’s not simply an attack on the “marketplace of ideas” protected by the First Amendment; it’s a direct attack on the market itself.
</p>
<h3 id="ZQ4mtd">
Social media companies moderate content and ban users because they want to make money
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qxqAAg">
Before we dive into the details of the social media laws at issue in the <em>NetChoice</em> cases, it’s helpful to understand why social media companies often delete content they deem to be offensive, dangerous, or simply unwelcome on their site.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WgDNvQ">
The premise underlying both Texas’s and Florida’s laws, which put strict limits on these companies’ power to remove such speech or ban users who engage in it, is that there is, in Abbott’s words, a “dangerous movement by social media companies to silence conservative viewpoints and ideas,” and that the government must step in to quell this supposed movement.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5JsgDn">
In reality, there is little evidence that companies like Facebook or <a href="https://www.vox.com/google">Google</a> (which owns YouTube) are engaged in any kind of systematic effort to suppress conservative content — right-leaning posts <a href="https://www.vox.com/recode/2020/7/29/21347128/big-tech-antitrust-hearing-facebook-zuckerberg-amazon-bezos-apple-cook-google-pichai">tend to perform quite well on social media</a>. But it is true that some viewpoints associated with the political right, such as <a href="https://www.vox.com/recode/2021/6/4/22519076/trump-facebook-two-years-oversight-board">support for the January 6 insurrection</a>, tend to be frowned upon by many social media moderators.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JFTjgV">
The best explanation for such content moderation, however, is not that <a href="https://www.vox.com/mark-zuckerberg">Mark Zuckerberg</a> is secretly determined to elect Democrats by quieting conservative voices. It’s that social media companies depend on advertisers to make money, and those advertisers demand “<a href="https://www.vox.com/scotus/2023/10/27/23929468/supreme-court-social-media-twitter-free-speech-content-moderation">brand safety</a>” — meaning that they don’t want to advertise on a site that will list their product next to a swastika, a rant against <a href="https://www.vox.com/coronavirus-covid19">Covid-19</a> vaccines, or some other content that is likely to offend many potential customers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BQWuwV">
As the Verge’s Nilay Patel <a href="https://www.theverge.com/2022/10/28/23428132/elon-musk-twitter-acquisition-problems-speech-moderation">colorfully explained</a>, running a profitable social media company “means you have to ban racism, sexism, transphobia, and all kinds of other speech that is totally legal in the United States but reveals people to be total assholes.” These sorts of assholes also apparently have many friends in the Florida and Texas state legislatures.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ROEhZc">
Patel’s thesis was recently tested in a very unusual real-world experiment. After billionaire Elon Musk purchased Twitter, he declared that the company would move in a more “free speech absolutist” direction, and restored the accounts of thousands of users who were suspended or banned by Twitter’s previous management. That included the accounts of <a href="https://www.vox.com/technology/2023/2/16/23603155/elon-musk-twitter-worse-degrading-quality-glitches-superbowl-boost-feed">several prominent neo-Nazis and QAnon conspiracy theorists</a>, as well as <a href="https://www.vox.com/recode/2022/11/19/23468634/trump-twitter-elon-musk-ban-allowed-back-president-2024">Trump’s infamous Twitter account</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mZRzRU">
This move away from moderating far-right content <a href="https://www.pcmag.com/news/twitter-traffic-on-downward-trend-since-elon-musks-takeover">proved disastrous for Twitter</a>. According to an estimate by the data and analytics company Similarweb, which was released last fall, “in September, global web traffic to twitter.com was down -14%, year-over-year, and traffic to the ads.twitter.com portal for advertisers was down -16.5%.” Other reporting <a href="https://www.nytimes.com/2023/11/24/business/x-elon-musk-advertisers.html">shows advertisers fleeing the site</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EIx8hY">
In fairness, Musk’s management of Twitter has been so comprehensively awful that it is hard to attribute the site’s falling fortunes solely to the reactivation of many previously banned right-wing users. Among other things, Musk’s Twitter tweaked the site’s algorithms in ways that <a href="https://www.vox.com/technology/2023/2/16/23603155/elon-musk-twitter-worse-degrading-quality-glitches-superbowl-boost-feed">elevated low-quality content</a> produced by people who signed up for Twitter’s new $8-a-month subscription service. And he’s <a href="https://www.vox.com/recode/2022/11/16/23461217/elon-musk-twitter-fired-employees-free-speech-contradictions-joke">retaliated against users who’ve mocked him online</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DWNPIe">
Nevertheless, all of these examples of Musk’s poor management support the thesis that a social media company’s profitability rises and falls based on how well the company moderates its content to attract both high-quality users and advertisers. And that means that companies that hope to remain profitable will ban some users who share some opinions that are common within the Republican Party — for reasons that have nothing to do with politics and everything to do with capitalism.
</p>
<h3 id="WGvRop">
Texas and Florida’s laws are ham-handed, incompetently drafted, and almost laughably unconstitutional
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1P48mY">
Both <a href="https://www.supremecourt.gov/DocketPDF/22/22-277/295796/20240116135803764_NetChoice%20Final%20to%20file.pdf">Florida</a> and <a href="https://www.supremecourt.gov/DocketPDF/22/22-555/295811/20240116145554309_22-555%20Brief%20for%20Respondent.pdf">Texas</a> frame their laws as anti-discrimination regimes intended to prevent social media companies from treating certain opinions differently than others. The core provision of Texas’s law prohibits the major social media companies from moderating content based on “<a href="https://capitol.texas.gov/tlodocs/872/billtext/html/HB00020S.htm">the viewpoint of the user or another person</a>” or on “the viewpoint represented in the user’s expression or another person’s expression.” Florida’s law, meanwhile, has a similar provision requiring the biggest social media sites to moderate content “<a href="https://casetext.com/case/netchoice-llc-v-attorney-gen">in a consistent manner among its users on the platform</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JEJdQ1">
If taken seriously, however, a ban on viewpoint discrimination wouldn’t just make moderation of offensive political content impossible. It would effectively forbid major social media platforms from taking the most basic steps to sanction rude behavior that is likely to drive away users.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TBfORF">
Suppose, for example, that a woman’s stalker ex-boyfriend harasses her on Twitter, creating multiple accounts that bombard her with tweets calling her “ugly” and “stupid.” Under Texas’s law (and most likely under Florida’s more vaguely worded law), Twitter may not ban this stalker, or otherwise take action against his online harassment, unless it also takes identical action against someone who labels the same woman “beautiful” or “intelligent.” Only banning users who express negative opinions about this woman would amount to viewpoint discrimination.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6D0JvU">
Now consider how these provisions will operate in the political context. Facebook cannot ban someone who calls for a MAGA revolution that overthrows the United States government and installs the Trump family as an absolute hereditary monarchy, unless it also bans people who support the US Constitution. Twitter cannot delete tweets claiming someone can cure Covid-19 by <a href="https://www.vox.com/2020/4/24/21234427/trump-coronavirus-bleach-injection-ultraviolet-light-treatment">injecting themselves with bleach</a>, unless it also deletes tweets by doctors and <a href="https://www.vox.com/public-health">public health</a> officials warning people not to do this. YouTube cannot ban a literal Nazi who posts videos calling for the extermination of all Jewish people, unless it also bans people who express the opposite viewpoint — that is, the view that Jews should not be exterminated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ytbhim">
In case there is any doubt, the First Amendment does not allow the government to force media outlets to publish Nazis, quack medical theories, monarchal revolutionaries, stalkers, or anyone else, for that matter. To understand why, it’s helpful to understand four principles of First Amendment law.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0n3Q0F">
<strong>First</strong>, this amendment protects against both government censorship and government actions that attempt to force someone to speak against their will. As the Supreme Court said in <a href="https://caselaw.findlaw.com/court/us-supreme-court/547/47.html"><em>Rumsfeld v. Forum for Academic and Institutional Rights</em></a> (2006), “freedom of speech prohibits the government from telling people what they must say.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MQs5TH">
<strong>Second</strong>, the First Amendment protects corporations. This idea became controversial after the Court’s decision in <a href="https://www.law.cornell.edu/supct/html/08-205.ZS.html"><em>Citizens United v. FEC</em></a> (2010) held that the First Amendment permits corporations to spend unlimited sums of money to influence elections, but it’s impossible to imagine free speech or a free press enduring unless the First Amendment extends to corporate speech. After all, media companies like Vox Media, the New York Times, and the Washington Post are all corporations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TgOGbs">
<strong>Third</strong>, the First Amendment protects the right of traditional media companies such as newspapers to choose what they want to print. As the Court held in <a href="https://caselaw.findlaw.com/us-supreme-court/418/241.html"><em>Miami Herald v. Tornillo</em></a> (1974), a news outlet’s “choice of material to go into a newspaper” is subject only to the paper’s “editorial control and judgment,” and “it has yet to be demonstrated how governmental regulation of this crucial process can be exercised consistent with First Amendment guarantees of a free press.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WvTiIO">
<strong>Finally</strong>,<strong> </strong>the same rules apply to internet-based media as apply to traditional outlets. Though the Supreme Court acknowledged in <a href="https://supreme.justia.com/cases/federal/us/521/844/"><em>Reno v. ACLU</em></a> (1997) that online media is distinct from other mediums because it “can hardly be considered a ‘scarce’ expressive commodity” — that is, unlike a newspaper or magazine, there is no physical limit on how much content can be published on a website. Nevertheless, <em>Reno</em> concluded that “our cases provide no basis for qualifying the level of First Amendment scrutiny that should be applied to this medium.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o8iAAa">
Together, these four principles establish that YouTube, and not the government, gets to decide what videos will appear on YouTube — just as CNN gets to decide which guests appear on its network, and which news stories it will emphasize, without government coercion.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7Nd1kD">
This conclusion, moreover, is bolstered by the Supreme Court’s decision last June in <a href="https://www.supremecourt.gov/opinions/22pdf/21-476_c185.pdf"><em>303 Creative v. Elenis</em></a>, which held that an <a href="https://www.vox.com/lgbtq">anti-LGBTQ</a> website designer could refuse to do business with same-sex couples — even if her state’s law forbids such discrimination — because “the government may not compel a person to speak its own preferred messages.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yIQoGO">
If the Supreme Court were to hold that religious conservatives have a First Amendment right to defy anti-discrimination laws, at least in the context of online speech, but that Republican states can forbid major media outlets from “discriminating” against insurrectionists and anti-vaxxers — well, it’s hard to see how anyone could take this Court seriously as a nonpartisan institution after such a decision.
</p>
<h3 id="a2OPvX">
Someone has to have the final word on what content appears online, and this authority must not be given to the government
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JNi5KM">
Having laid out these constitutional principles, it’s important to acknowledge that social media companies do not always make responsible decisions about what content should appear online. <a href="https://www.amnesty.org/en/latest/news/2022/09/myanmar-facebooks-systems-promoted-violence-against-rohingya-meta-owes-reparations-new-report/">Just ask the Rohingya people</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OMDrAl">
But the fact that social media platforms sometimes make bad decisions does not mean that we should trust the government to override those decisions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zKTD6L">
Ordinarily, we trust government officials to regulate business because they are more likely to act in the public’s interest than executives at a for-profit company. EPA regulators do not always reach the right conclusions, but they are more likely to strike the right balance between economic growth and environmental protection than the CEO of Exxon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9szkSp">
But this dynamic is reversed in the free speech context — which is why the First Amendment exists in the first place. If Texas Republicans are allowed to regulate political speech, they will likely elevate speech that benefits Republicans and suppress speech that elevates Democrats.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MsvAxU">
Ultimately, someone needs to decide what content will appear online. And leaving these decisions to the free market means that they won’t be made by the most self-interested people in the world: elected officials who are more likely to hold onto their jobs if they can manipulate what information is seen by voters.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C6VupM">
Nor is it a solution to give this power to unelected officials. Federal judges, and especially Supreme Court justices, are political appointees who are typically vetted by the White House to ensure that they support the incumbent president’s political goals. Government agencies are also normally run by political appointees chosen, at least in part, because they are loyal Democrats or Republicans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fSXe7Y">
So there’s no government agency that can be trusted to regulate speech in a politically neutral way. The only choice is to either let the social media companies run their own platforms or to give that power to the government. And, in the <em>NetChoice</em> cases, giving that power to the government means placing control over what information voters will see in the hands of men like Ron DeSantis and Greg Abbott.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D6KlIf">
It is right to be uncomfortable with Mark Zuckerberg or, for God’s sake, Elon Musk wielding the kind of power they wield over public discourse. But few things are more dangerous to democracy than a government that can override editorial decisions made by a free press.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Zz25z0">
More broadly, the <em>NetChoice </em>cases will show us which members of the Supreme Court’s six-justice Republican majority still believe in traditional Republican ideas about the free market and capitalism, and which of them agree with DeSantis that the power of the government should be used to reshape our culture — and that corporations that do not align with the rightward side of a culture war should be forced to do so against their will.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Man United’s 2022-2023 squad the most expensive ever in Europe: UEFA report</strong> - The Premier League had nine teams in the top-20 earning clubs, with an average revenue of €323 million.</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>Daily Quiz | On traditional games</strong> - India has several traditional games and sports, most of which have been played for thousands of years. Here is a quiz on some of them</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>Champions League | Bayern Munich beaten 1-0 at Lazio to pile pressure on Tuchel</strong> - Lazio captain Ciro Immobile converted a penalty kick when Bayern was reduced to 10 men midway through the second half</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>Rahul Dravid to remain India’s head coach till T20 World Cup: Jay Shah</strong> - The BCCI secretary said he held an initial talk with Dravid before arriving at the decision to retain the former captain’s services till the T20 World Cup in June</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ind vs Eng 3rd Test | Rohit, Jadeja lead India’s robust recovery against England on Day 1</strong> - Rohit and Jadeja cashed in on a batting-friendly surface, which had provided early troubles to India’s youngsters in the first session.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Banking on discontent within the ruling Congress, BJP fields a Rajya Sabha candidate from Himachal Pradesh</strong> - Despite its 40 MLAs in a 68-member House, Congress is facing internal anger for fielding ‘outsider’ Abhishek Singhvi, instead of State veteran Anand Sharma; “high chance of cross-voting”, says senior leader</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>Electoral bonds brought for transparency in poll funding, we respect Supreme Court verdict: BJP</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>Watch | Supreme Court verdict on electoral bonds scheme</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>TSRTC-hire bus driver dies after suffering heart attack while driving</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>Pre-KG, additional bilingual sections to be started in government schools in Karnataka from 2024-25 academic year to encourage English medium education from primary level</strong> - Government wants to encourage English medium education right from the primary level and to strengthen the learning ability of children in government schools</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deadly attack on Russian shopping centre near border</strong> - At least five people are reported killed in an air attack on the city of Belgorod, close to Ukraine.</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>Ukraine battles frostbite and shell shortage in ruined town</strong> - After months of heavy fighting, Russian forces appear close to surrounding the ruins of Avdiivka.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Spain triple murder suspect held for prison killing</strong> - A man facing trial for the murder of three elderly siblings is suspected of killing his cellmate.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>French migration row engulfs island in Indian Ocean</strong> - The island of Mayotte becomes the latest battleground in France over the laws on immigration.</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>Putin expresses preference for Biden over Trump</strong> - It’s a change in tune for the Russian leader, who praised Mr Trump during his first presidential run.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can you sanitize the inside of your nose to prevent COVID? Nope, FDA says.</strong> - There are a lot of COVID nasal sprays for sale, but little data to show they work. - <a href="https://arstechnica.com/?p=2003503">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asahi Linux project’s OpenGL support on Apple Silicon officially surpasses Apple’s</strong> - Newest driver supports the latest versions of OpenGL and OpenGL ES. - <a href="https://arstechnica.com/?p=2003456">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deep Rock Galactic: Survivor is a fine entry point into the auto-shooting depths</strong> - This fleshed-out Early Access version could convert first-timers to the genre. - <a href="https://arstechnica.com/?p=2003379">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Musk’s X sold checkmarks to Hezbollah and other terrorist groups, report says</strong> - X (aka Twitter) accused of violating sanctions by taking payment from terrorists. - <a href="https://arstechnica.com/?p=2003423">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>USPTO says AI models can’t hold patents</strong> - Inventors must be human, but there’s still a condition where AI can officially help. - <a href="https://arstechnica.com/?p=2003310">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An overweight guy is watching TV.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A commercial comes on for a program that guarantees weight loss of 10 pounds in a week, so the guy signs up for it. The next morning an incredibly beautiful woman is standing at his door in nothing but a pair of running shoes and a sign around her neck that reads “If you catch me, you can have me.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As soon as he sees her, she takes off running. He tries to catch her but is unable. This continues for a week, at the end of which, the man has lost 10 pounds.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After this, he tries the next weight loss plan - 15 pounds in a week. The next morning an even more beautiful woman is standing at the door, in similar conditions. The same happens with her as the first woman, except he almost catches her. This continues for a week, at the end of which, he weighs 15 pounds less. Excited about this success, he decides to do the 20 pounds master program.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Before he signs up, he is required to sign a waiver and is warned about the intensity of the plan. Still, he signs up. The next morning, waiting at the door, is a hulking 300 pound muscle man with nothing but a pair of running shoes, a raging erection, and a sign around his neck that says, “If I catch you, you’re mine!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/JustOurKind"> /u/JustOurKind </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1ar43jo/an_overweight_guy_is_watching_tv/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1ar43jo/an_overweight_guy_is_watching_tv/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Boss: “How good are you at PowerPoint?” - Me: “I Excel at it.” - Boss: “Was that a Microsoft Office pun?”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Me: “Word”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Town-Hoarse278"> /u/Town-Hoarse278 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1arb9lk/boss_how_good_are_you_at_powerpoint_me_i_excel_at/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1arb9lk/boss_how_good_are_you_at_powerpoint_me_i_excel_at/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I had never tried drugs before.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
But now I’m up to speed.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/KairuSmairukon"> /u/KairuSmairukon </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1ar69ms/i_had_never_tried_drugs_before/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1ar69ms/i_had_never_tried_drugs_before/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clive went to see his doctor for a routine check up. (Long)</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Upon inspecting Clive, the doctor seemed perplexed and insisted on carrying out some tests. Following the initial tests, again the doctor has a furrowed brow and a look of concern on his face.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What’s the issue doctor? Is there something wrong?” asked Clive.<br/> The doctor claimed he had a sinking suspicion but wanted to perform a few more tests.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Eventually the results came back and the doctor sat Clive down for a serious chat.<br/> “I’m going to be honest with you Clive, it’s not good news I’m afraid. It seems you have a very rare disease known in the medical field as ‘Yellow 84’. Only 84 people have ever been known to have the disease and every single one of them turned yellow just before they died. I regret to inform you that you don’t have long left so it would be a wise decision to start making preparations”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Clive walked out of the doctors office, determined not to let this information bog him down and for his illness to ruin his life, he purchases a scratch card as after all he doesn’t have much to lose. To his surprise, he wins £10,000. He then buys a lottery ticket for that night and leaves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He runs home to give his wife the good and bad news, that they have just won a pot of money however their time together is now limited. They agree that life really is too short and decide to make the most of the short time they have left. Whilst planning on how they will spend their time, the lottery numbers are announced and Clive has won the Jackpot of £5 million.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
With their new wealth, Clive and his wife plan holidays and cruise trips to all of the places they’d discussed but never managed to see. They spend a couple of months travelling, taking in the wonders of the world and enjoying their time together. Clive also buys his wife a new car, pays off the mortgage and makes sure that his wife will have everything she will need in life following his imminent passing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After their long trips and they have returned back to normal life, they decide to head to the bingo one night. Whilst there, Clive manages to win the first line, the second line, and a full house. In fact, he ended up winning every prize on off that night.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He ventures up to the window to collect his winnings and the prize master looks at him and says “I know you! You’re becoming pretty famous! First off you win £10k on a scratch card, that same day you win a further £5m on the lottery and you’ve just won every prize in this bingo hall tonight. You must be the luckiest man alive!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
At this, Clive narrows his brow and yells “LUCKY?! You think I’m lucky?! I’ll have you know, I have Yellow 84!”. The end of his shouting echoing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Prize Master lowers his head for a second and snaps it back up in an instant, his eyes wide and says
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“did you say you have Yellow 84? Congratulations! You’ve won the raffle as well”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Papa_Wolf5"> /u/Papa_Wolf5 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1arbbo9/clive_went_to_see_his_doctor_for_a_routine_check/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1arbbo9/clive_went_to_see_his_doctor_for_a_routine_check/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My deaf girlfriend just told me “I think we need to talk.”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
That’s not a good sign.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Candidate-Amusing757"> /u/Candidate-Amusing757 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1aqw425/my_deaf_girlfriend_just_told_me_i_think_we_need/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1aqw425/my_deaf_girlfriend_just_told_me_i_think_we_need/">[comments]</a></span></p></li>
</ul>
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