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<title>08 March, 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>Who deserves economic relief - Preprint T Hilmar March 2024</strong> -
<div>
The economic shock of the Covid-19 crisis has disproportionately impacted small businesses and the self-employed. Around the globe, their survival during the pandemic often relied heavily on government assistance. This article explores how economic relief to business is understood through the lens of deservingness in the public. It examines the case of Germany, where the government has responded to the pandemic by implementing an extensive support program. Notably, in this context, the self-employed are typically outsiders to the state insurance system. Combining computational social science methods and a qualitative analysis, the article focuses on the debate about direct subsidies on the social media platform Twitter/X between March 2020 and June 2021. It traces variation in the patterns of claim making in what is a rich debate about pandemic state support, finding that this discourse is characterised by the concern that economic relief threatens to blur existing boundaries of worth in society. The reciprocity principle of deservingness theory is pivotal in asserting business identities in times of crisis, yet it also reveals a fundamentally ambiguous relationship with the principle of need. Additionally, the claim of justice-as-redress, as a novel dimension of reciprocity, surfaces as an important theme in this debate.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/swndy/" target="_blank">Who deserves economic relief - Preprint T Hilmar March 2024</a>
</div></li>
<li><strong>Protein design for evaluating vaccines against future viral variation</strong> -
<div>
Recurrent waves of SARS-CoV-2 infection, driven by the periodic emergence of new viral variants, highlight the need for vaccines and therapeutics that remain effective against future strains. Yet, our ability to proactively evaluate such therapeutics is limited to assessing their effectiveness against previous or circulating variants, which may differ significantly in their antibody escape from future viral evolution. To address this challenge, we develop a deep learning method to predict the effect of mutations on fitness and escape from neutralizing antibodies. We use this model to engineer 83 unique SARS-CoV-2 Spike proteins incorporating novel combinations of up to 46 amino acid changes relative to the ancestral B.1 variant. The designed constructs were infectious and evaded neutralization by nine well-characterized panels of human polyclonal anti-SARS-CoV-2 immune sera (from vaccinated, boosted, bivalent boosted, and breakthrough infection individuals). Designed constructs on contemporary SARS-CoV-2 strains displayed similar levels of antibody escape and similar antigenic profiles as variants seen subsequently (up to 12 months later) during the COVID-19 pandemic despite differences in exact mutations. Our approach provides targeted panels of antigenically diverse escape variants for an early evaluation of the protective ability of vaccines and therapeutics to inhibit not only currently circulating but also future variants. This approach is generalizable to other viral pathogens.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.08.561389v2" target="_blank">Protein design for evaluating vaccines against future viral variation</a>
</div></li>
<li><strong>Will Europe be forged in crises? The impact of the Covid-19 and Ukraine crises on EU actorness</strong> -
<div>
In this paper, we study the effect of crises on EU actorness, defined as the EU’s capacity to defend its interests and values at the global level. Our research focuses on two major crises, the Covid-19 crisis and the 2022 Russian invasion of Ukraine. Drawing on a process-tracing approach, we analyse four of the Union’s policy initiatives that were proposed, negotiated and implemented to respond to these crises: joint vaccine procurement, common gas purchases, and the COVAX and FARM initiatives. The paper assesses the outcomes of these four initiatives and discusses the extent to which these initiatives led to the development of EU actorness and the achievement of common objectives. The analysis identifies the degree of internal cohesion, and how it is influenced by specific crises, as a key factor in fostering or hampering EU actorness in different policy fields. It also shows that the formal distribution of competences between the EU and the member states in specific policy areas matters little in crisis times, as the EU can resort to emergency competences in such situations. The findings of this paper contribute to the literature on EU actorness and equally provide some insights on policy legacies and learning.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/c3zwt/" target="_blank">Will Europe be forged in crises? The impact of the Covid-19 and Ukraine crises on EU actorness</a>
</div></li>
<li><strong>Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae</strong> -
<div>
By largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct translation regulators, particularly the N6-methyladenosine (m6A) RNA methylase METTL3. These interactions with translation regulators implicated G9a in translational regulation of COVID-19. Inhibition of G9a activity suppressed SARS-CoV-2 replication in human alveolar epithelial cells. Accordingly, multi-omics analysis of the same alveolar cells identified SARS-CoV-2-induced changes at the transcriptional, m6A-epitranscriptional, translational, and post-translational (phosphorylation or secretion) levels that were reversed by inhibitor treatment. As suggested by the aforesaid chemoproteomic analysis, these multi-omics-correlated changes revealed a G9a-regulated translational mechanism of COVID-19 pathogenesis in which G9a directs translation of viral and host proteins associated with SARS-CoV-2 replication and with dysregulation of host response. Comparison of proteomic analyses of G9a inhibitor-treated, SARS-CoV-2 infected cells, or ex vivo culture of patient PBMCs, with COVID-19 patient data revealed that G9a inhibition reversed the patient proteomic landscape that correlated with COVID-19 pathology/symptoms. These data also indicated that the G9a-regulated, inhibitor-reversed, translational mechanism outperformed G9a-transcriptional suppression to ultimately determine COVID-19 pathogenesis and to define the inhibitor action, from which biomarkers of serve symptom vulnerability were mechanistically derived. This cell line-to-patient conservation of G9a-translated, COVID-19 proteome suggests that G9a inhibitors can be used to treat patients with COVID-19, particularly patients with long-lasting COVID-19 sequelae.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.583415v1" target="_blank">Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae</a>
</div></li>
<li><strong>MORTALITY-ASSOCIATED SARS-COV-2 GENOMIC VARIANTS FROM PATIENTS HOSPITALIZED FOR SEVERE PNEUMONIA IN AGUASCALIENTES, MEXICO FROM 2020 TO 2023</strong> -
<div>
The SARS-CoV-2 virus has caused a global health crisis, resulting in a significant loss of human lives. It is essential to report disease and mutation associations to provide ideas for public health interventions and preventive measures. In this study, to determine the association between genomic variants and the severity of pneumonia caused by SARS-CoV-2, a sequencing analysis of 150 patient samples with confirmed COVID-19 was conducted. These samples were collected between 2021 and 2023 and isolated in Aguascalientes, Mexico. The patient cohort had males and females ranging from 0 to 91 years old. Males accounted for 66% of the population analyzed. The Delta variant was the most prevalent lineage associated with deaths in 2021-2022, while the B.1.1.529 lineages emerged in mid-2022. Currently, the XBB lineage is the most commonly identified in Mexico. New mutations L95M and L46M in ORF 8 and ORF 9 were discovered in 30% and 20% of the sequences and are uniquely present in the studied population. These mutations are positively associated with patient death. This study provides valuable data to aid in understanding the evolution of SARS-CoV-2 in specific populations and explores the severity of the disease and mutation correlations.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583594v1" target="_blank">MORTALITY-ASSOCIATED SARS-COV-2 GENOMIC VARIANTS FROM PATIENTS HOSPITALIZED FOR SEVERE PNEUMONIA IN AGUASCALIENTES, MEXICO FROM 2020 TO 2023</a>
</div></li>
<li><strong>Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants</strong> -
<div>
The open reading frame 8 (ORF8), an accessory protein of SARS-CoV-2, is prone to deletions and mutations across different viral variants, which was first described in several Singapore variants. The reason why viral evolution favors loss or inactivation of ORF8 is not fully understood, although the effects of ORF8 on inflammation, immune evasion, and disease severity have been described. Here we show using clinical ORF8 deficient viral isolates, virus like particles (VLPs) and viral replicons that ORF8 expression dampens viral particle production. ORF8 physically interacts with the viral Spike protein and induces Golgi fragmentation, overall contributing to less virus particle production. Using systematic ORF8 deletions, we mapped the particle reducing function to its N terminal signal peptide. Interestingly, this part of ORF8 is severely truncated in the recent XBB.1.5 variant, and when restored, suppresses viral particle production in the context of the entire viral genome. Collectively, our data support the model that evolutionary pressure exists to delete ORF8 sequence and expression across SARS-CoV-2 variants to fully enable viral particle production.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583578v1" target="_blank">Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants</a>
</div></li>
<li><strong>The Global Impact of COVID-19 on Tuberculosis: A Thematic Scoping Review, 2020-2023</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: This thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness. Data Sources: Publications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023. Study Selection: Our scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful––yet sometimes positive–– impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance. Data Extraction: Two authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction. Data Synthesis/Results: Of 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. Ten principal themes were established, which encompassed TB’s care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n=45; 26%); 2) diagnosis and laboratory systems (n=19; 10.7%) 3) prevention, treatment, and care (n=22; 12.2%); 4) telemedicine/telehealth (n=12; 6.8%); 5) social determinants of health (n=14; 8%); 6) airborne infection prevention and control (n=8; 4.6%); 7) health system strengthening (n=22; 13%); 8) mental health (n=13; 7.4%); 9) stigma (n=11; 6.3%); and 10) health education (n=10; 5.7%). Limitations: Heterogeneity of publications within themes. Conclusions: We identified ten globally generalizable themes of COVID-19’s impact on TB. These thematic areas will guide evidence-informed policies to strengthen comprehensive global responses, recovery for TB, and future airborne pandemic preparedness.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.04.24303743v1" target="_blank">The Global Impact of COVID-19 on Tuberculosis: A Thematic Scoping Review, 2020-2023</a>
</div></li>
<li><strong>Stress vulnerability and resilience in children facing COVID-19-related discrimination: a quasi-experimental study using polygenic, brain, and sociodemographic data</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
During the pandemic, perceived COVID-19-related discrimination aggravated children9s stress levels. The remaining question is to evaluate the individual variability in these effects and to identify vulnerable or resilient populations and why. Using the Adolescent Brain and Cognitive Development dataset (<i>N</i> = 1,116) and causal machine learning approach - Generalized Random Forest, we examined the average and individual treatment effects of perceived discrimination on stress levels immediately and six months later. Their variability and key factors were also assessed. We observed significant variability in the acute effects of perceived discrimination across children and pinpointed the frontotemporal cortical volume and white matter connectivity (streamline counts) as key factors of stress resilience and vulnerability. The variability of these neurostructural factors partially originated from the environmental and genetic attributes. The finding was replicated in held-out samples (<i>N</i> = 2,503). Our study has the potential for personalized prescriptive modeling to prevent children9s future psychopathology after the pandemic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.04.24303643v1" target="_blank">Stress vulnerability and resilience in children facing COVID-19-related discrimination: a quasi-experimental study using polygenic, brain, and sociodemographic data</a>
</div></li>
<li><strong>Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic was a significant shock to United States mortality, and it is important to understand how the pandemic impacted other causes of death. We estimated monthly excess mortality in the US by cause of death, age, and sex, for official deaths at ages 15 and older. Data come from the CDC Wonder Multiple Cause of Death database. We used a compositionally robust Generalized Additive Model (GAM) to estimate expected mortality counts in March 2020-December 2022 for eight causes of death: accidents, cardiovascular diseases, cancer, diabetes, influenza and pneumonia, substance-related (drugs and alcohol), suicide, and residual (including COVID-19 related deaths). Analyses were stratified by sex and 15-year age groups from 15-29 to 75+. Excess mortality was calculated as observed deaths minus expected deaths. From March 2020 to December 2022, we estimated 1 298 763 total excess deaths (95% CI: 1 226 542 to 1 370 804). While there were fewer deaths than expected due to some causes like flu/pneumonia and suicide, the largest number of excess deaths, excluding COVID-19, were attributed to cardiovascular diseases (115 765 deaths, 95% CI: 98 697 to 133 783) and substance use (86 637 deaths, 95% CI: 79 273 to 93 690). Percent excess substance-related mortality was high across all ages, while percent excess from cardiovascular diseases was highest at midlife ages. Some of these excess cardiovascular deaths were likely due to undercounted COVID-19 deaths, but others may reflect indirect impacts of the pandemic on healthcare utilization or longer-term effects of COVID-19 infections.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303783v1" target="_blank">Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic</a>
</div></li>
<li><strong>Learning from the COVID-19 pandemic: a systematic review of mathematical vaccine prioritization models</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As the world becomes ever more connected, the chance of pandemics increases as well. The recent COVID-19 pandemic and the concurrent global mass vaccine roll-out provides an ideal setting to learn from and refine our understanding of infectious disease models for better future preparedness. In this review, we systematically analyze and categorize mathematical models that have been developed to design optimal vaccine prioritization strategies of an initially limited vaccine. As older individuals are disproportionately affected by COVID-19, the focus is on models that take age explicitly into account. The lower mobility and activity level of older individuals gives rise to non-trivial trade-offs. Secondary research questions concern the optimal time interval between vaccine doses and spatial vaccine distribution. This review showcases the effect of various modeling assumptions on model outcomes. A solid understanding of these relationships yields better infectious disease models and thus public health decisions during the next pandemic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.04.24303726v1" target="_blank">Learning from the COVID-19 pandemic: a systematic review of mathematical vaccine prioritization models</a>
</div></li>
<li><strong>Mental illness and COVID-19 vaccination: a multinational investigation of observational &amp; register-based data</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Therefore, we aimed to investigate the association between mental illness and COVID-19 vaccination uptake, using data from five countries. Methods: Data from seven cohort studies (N=325,298), and the Swedish registers (8,080,234), were used to identify mental illness and COVID-19 vaccination uptake. Multivariable modified Poisson regression models were conducted to calculate the prevalence ratio (PR) and 95% CIs of vaccination uptake among individuals with v.s. without mental illness. Results from the cohort studies were pooled using random effects meta-analyses. Findings: Most of the meta-analyses performed using the COVIDMENT study population showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first (prevalence ratio [PR]: 0.98, 95% CI: 0.98-0.99, p&lt;0.001) and second dose among individuals with mental illness; the reduction was however greater among those not using pyschiatric medication (PR: 0.91, 95% CI: 0.91-0.91, p&lt;0.001). Conclusions: The high uptake of COVID-19 vaccination observed among individuals with most types of mental illness highlights the comprehensiveness of the vaccination campaign , however lower levels of vaccination uptake among subgroups of individuals with unmedicated mental illness warrants attention in future vaccination campaigns.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303691v1" target="_blank">Mental illness and COVID-19 vaccination: a multinational investigation of observational &amp;amp; register-based data</a>
</div></li>
<li><strong>XBB.1.5 mRNA COVID-19 Vaccination and Inpatient or Emergency Department Visits Among Adults Infected with SARS-CoV-2 JN.1 and XBB-Lineage Variants</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Within a multi-state viral genomic surveillance program, we conducted a case-control analysis comparing prior receipt of XBB.1.5-adapted mRNA vaccination between SARS-CoV-2-infected adults with inpatient/ED visits (proxy for severe illness) vs outpatient visits. Among 6,551 patients from September 2023-January 2024, 6.1% with inpatient/ED visits vs 12.0% with outpatient visits had received XBB.1.5 vaccination (aOR=0.41; 95% CI: 0.32-0.53). This protective association was weaker among JN.1 (aOR=0.62; 95% CI: 0.40-0.96) vs XBB-lineage (aOR=0.28; 95% CI: 0.18-0.43) variant infections (interaction, p=0.003). XBB.1.5 vaccination was also protective specifically compared to BA.4/BA.5-adapted mRNA vaccination (aOR=0.60; 95% CI: 0.45-0.79). XBB.1.5 vaccines protect against severe illness, but protection may be weaker against JN.1 vs XBB-lineage variants.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303796v1" target="_blank">XBB.1.5 mRNA COVID-19 Vaccination and Inpatient or Emergency Department Visits Among Adults Infected with SARS-CoV-2 JN.1 and XBB-Lineage Variants</a>
</div></li>
<li><strong>Amino acid profiling of COVID-19 patients blood serum</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Main objectives of this study were to analyse metabolomic profile features of patients with COVID-19 using mass spectrometry techniques while taking into account the clinical and laboratory history, and to study the relationship between the severity of COVID-19 symptoms and the concentration of primary metabolites, primarily amino acids. We used frozen blood serum samples of 935 COVID-19 patients from the City Hospital No. 40 biobank collection. Metabolomic profile was studied by HPLS-MS/MS method. R programming language was used for statistical data processing. The difference of metabolic profile of patients with COVID-19 depending on the severity of the disease was revealed based on the performed analysis - for 52 out of 84 detected compounds there were differences with reliability p&lt;0,01. Statistically significant differences in concentration were recorded for organic acids, amino acids and their derivatives. Using samples from the biobank collection, a metabolomic study of the biomaterial of patients hospitalised with the diagnosis of COVID-19 was carried out. According to the results obtained, kynurenine, phenylalanine and acetylcarnitine were associated with the severity of COVID-19 infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.03.05.24303773v1" target="_blank">Amino acid profiling of COVID-19 patients blood serum</a>
</div></li>
<li><strong>Yeast-based production platform for potent and stable heavy chain-only antibodies</strong> -
<div>
Monoclonal antibodies are the leading drug of the biopharmaceutical market because of their high specificity and tolerability, but the current CHO-based manufacturing platform remains expensive and time-consuming leading to limited accessibility, especially in the case of diseases with high incidence and pandemics. Therefore, there is an urgent need for an alternative production system. In this study, we present a rapid and cost-effective microbial platform for heavy chain-only antibodies (VHH-Fc) in the methylotrophic yeast Komagataella phaffii (aka Pichia pastoris). We demonstrate the potential of this platform using a simplified single-gene VHH-Fc fusion construct instead of the conventional monoclonal antibody format, as this is more easily expressed in Pichia pastoris. We demonstrate that the Pichia-produced VHH-Fc fusion construct is stable and that a Pichia-produced VHH-Fc directed against the SARS-CoV-2 spike has potent SARS-CoV-2 neutralizing activity in vitro and in vivo. We expect that this platform will pave the way towards faster and cheaper development and production of broadly neutralizing single-chain antibodies in yeast.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.580093v1" target="_blank">Yeast-based production platform for potent and stable heavy chain-only antibodies</a>
</div></li>
<li><strong>Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein</strong> -
<div>
Filopodia are dynamic, actin-rich cellular protrusions, increasingly linked to cellular mechanotransduction. However, how dynamic filopodia translate external mechanical cues remains poorly understood. Recent studies show that the SARS-CoV-2 spike (S) protein binds the ACE2 receptor on airway multicilia and that cilia are required for viral infection(1) and sufficient to induce filopodial extension and viral binding. To test if spike protein is sufficient to induce filopodial expansion, we employed live-cell single-particle tracking with quantum dots targeting ACE2, to reveal a robust filopodia extension and virus binding mechanism requiring the enzymatic activity of ACE2. Using time-lapse imaging, we reveal that spike protein binding to filopodia is associated with intracellular actin remodeling, alterations in bulk cell stiffness, and an elevation in intracellular calcium levels linked to actin-rearrangement, filopodia initiation, and persistence. We propose the activation of ACE2 creates an active signaling and mechanosensory environment within adherent cells and airway epithelial cells that allows the remodeling of actin in filopodia to trap virus and potentially organize viral exit from cells.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.01.581813v1" target="_blank">Filopodial Mechanotransduction is regulated by Angiotensin-Converting Enzyme 2 (ACE2) and by SARS-CoV-2 spike protein</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>COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) <br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp &amp; Dohme LLC <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>An E-health Psychoeducation for People With Bipolar Disorders</strong> - <b>Conditions</b>: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic <br/><b>Interventions</b>: Other: e-health psychoeducation <br/><b>Sponsors</b>: University of Cagliari; Alessandra Perra <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>Sulfureous Water Therapy in Viral Respiratory Diseases</strong> - <b>Conditions</b>: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water <br/><b>Sponsors</b>: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl <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>Phase 3 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</b>: Novavax <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety &amp; Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of a Nasal Spray on Viral Respiratory Infections</strong> - <b>Conditions</b>: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold <br/><b>Interventions</b>: Device: Nasal Spray HSV Treatment <br/><b>Sponsors</b>: CEN Biotech; Urgo Research, Innovation &amp; Development <br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: GS-441524; Drug: Placebo <br/><b>Sponsors</b>: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc <br/><b>Not yet recruiting</b></p></li>
</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>Effects of Lamiaceae family plants and their bioactive ingredients on coronavirus-induced lung inflammation</strong> - Coronaviruses (CoVs) are a family of viruses that cause infection in respiratory and intestinal systems. Different types of CoVs, those responsible for the SARS-CoV and the new global pandemic of coronavirus disease 2019 in people, have been found. Some plants were used as food additives: spices and dietary and/or medicinal purposes in folk medicine. We aimed to provide evidence about possible effects of two Lamiaceae family plants on control or treatment of CoVs-induced inflammation. The…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deregulation of interferon-gamma receptor 1 expression and its implications for lung adenocarcinoma progression</strong> - Interferon-gamma (IFN-γ) plays a dual role in cancer; it is both a pro- and an antitumorigenic cytokine, depending on the type of cancer. The deregulation of the IFN-γ canonic pathway is associated with several disorders, including vulnerability to viral infections, inflammation, and cancer progression. In particular, the interplay between lung adenocarcinoma (LUAD) and viral infections appears to exist in association with the deregulation of IFN-γ signaling. In this mini-review, we investigated…</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 role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial</strong> - N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. 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>Metabolic profiling of milk thistle different organs using UPLC-TQD-MS/MS coupled to multivariate analysis in relation to their selective antiviral potential</strong> - CONCLUSION: This study valorizes the importance of different S. marianum organs as wealthy sources of selective and effective antiviral candidates. This approach can be extended to unravel potentially active constituents from complex plant matrices.</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>Role of Microbiota-Derived Corisin in Coagulation Activation during SARS-CoV-2 Infection</strong> - CONCLUSION: The microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial and monocytic cells.</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>Risks of infection and severity of coronavirus disease 2019 in kidney transplant recipients: A single-center cohort study</strong> - CONCLUSION: In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking &gt;5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection.</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>Metabolic regulation of neutrophil functions in homeostasis and diseases</strong> - Neutrophils are the most abundant leukocytes in humans and play a role in the innate immune response by being the first cells attracted to the site of infection. While early studies presented neutrophils as almost exclusively glycolytic cells, recent advances show that these cells use several metabolic pathways other than glycolysis, such as the pentose phosphate pathway, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, which they modulate to perform their functions….</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>Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice</strong> - CONCLUSIONS: These findings suggest that 2DG has a systemic impact that varies across organs, potentially affecting multiple pathways and functions. The study provides insights into the potential therapeutic benefits of 2DG across different diseases and highlights the importance of understanding its systemic effects for future research and clinical applications.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of SARS-CoV-2 compounds against Marburg Virus using MD simulation, mm/GBSA, PCA analysis, and free energy landscape</strong> - The significant mortality rate associated with Marburg virus infection made it the greatest hazard among infectious diseases. Drug repurposing using in silico methods has been crucial in identifying potential compounds that could prevent viral replication by targeting the virus’s primary proteins. This study aimed at repurposing the drugs of SARS-CoV-2 for identifying potential candidates against the matrix protein VP40 of the Marburg virus. Virtual screening was performed where the control…</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>Natural products as a source of Coronavirus entry inhibitors</strong> - The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate…</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>Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023</strong> - CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be…</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>Glycan-directed SARS-CoV-2 inhibition by leek extract and lectins with insights into the mode-of-action of Concanavalin A</strong> - Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies. Given the high genetic plasticity of SARS-CoV-2 and the rapid emergence of immune escape variants, targeting the glycan shield…</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>Structural Relationships to Efficacy for Prazole-Derived Antivirals</strong> - Here, an in vitro characterization of a family of prazole derivatives that covalently bind to the C73 site on Tsg101 and assay their ability to inhibit viral particle production is presented. Structurally, increased steric bulk on the 4-pyridyl of the prazole expands the prazole site on the UEV domain toward the β-hairpin in the Ub-binding site and is coupled to increased inhibition of virus-like particle production in HIV-1. Increased bulk also increased toxicity, which is alleviated by…</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>BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase inhibitor, inhibits SARS-CoV-2 variants of concern and exerts synergistic antiviral activity in combination with remdesivir</strong> - Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC(50) = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe…</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 PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association</strong> - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of…</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>What’s Left of Reagan Republicanism After the Demise of Nikki Haley’s Campaign?</strong> - Old-style free-market conservatism lives on at think tanks and among the G.O.P.’s donor class, but Donald Trump’s grip on the Party’s voters is viselike. - <a href="https://www.newyorker.com/news/our-columnists/whats-left-of-reagan-republicanism-after-the-demise-of-nikki-haleys-campaign">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Forty-three Mexican Students Went Missing. What Really Happened to Them?</strong> - One night in 2014, a group of young men from a rural teachers’ college vanished. Since then, their families have fought for answers. - <a href="https://www.newyorker.com/magazine/2024/03/11/what-really-happened-to-the-forty-three">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lucy Prebble’s Dramas of High Anxiety</strong> - In plays such as “The Effect” and TV shows such as “I Hate Suzie” and “Succession,” the writer has become an expert at getting deep inside worried characters’ heads. - <a href="https://www.newyorker.com/magazine/2024/03/11/lucy-prebbles-dramas-of-high-anxiety">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Joe Biden’s Last Campaign</strong> - Trailing Trump in polls and facing doubts about his age, the President voices defiant confidence in his prospects for reëlection. - <a href="https://www.newyorker.com/magazine/2024/03/11/joe-biden-profile-re-election-campaign-donald-trump">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Legacy of RuPaul’s “Drag Race”</strong> - The drag star brought the form mainstream, and made an empire out of queer expression. Now he fears “the absolute worst.” - <a href="https://www.newyorker.com/magazine/2024/03/11/rupaul-doesnt-see-how-thats-any-of-your-business">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Are Biden and the Democrats finally turning on Israel?</strong> -
<figure>
<img alt="US President Joe Biden with Israeli Prime Minister Benjamin Netanyahu in Tel Aviv in October 2023." src="https://cdn.vox-cdn.com/thumbor/ueRkBtVjbxHvtlPmuod1BXguwrE=/92x0:1148x792/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73191138/1730842169.0.jpg"/>
<figcaption>
“It’s not you, it’s me.” | GPO/Handout/Anadolu/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Biden’s new plan to build a pier on the Gaza coast seems to say yes. The continued military aid to Israel says otherwise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c5xjQS">
For years, there <a href="https://www.vox.com/22440197/us-israel-democrats-alliance-partisanship-gaza">have been signs</a> that the Democratic Party’s historic support for <a href="https://www.vox.com/israel">Israel</a> might be wavering. <a href="https://www.vox.com/joe-biden">Joe Biden</a>’s staunch support for Israel after October 7 seemed to suggest that this theory was overblown — that when push came to shove, Democrats would always revert to the centrist pro-Israel position they had taken for decades.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Bh1eQl">
But in the past few days, it’s started to feel like the winds might be shifting again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qdKKK0">
Both in <a href="https://twitter.com/BarakRavid/status/1765053398636752934">public</a> and <a href="https://www.axios.com/2024/03/05/israel-gaza-aid-benny-gantz-white-house">private</a>, Biden and his deputies have fumed about Israel blocking aid from entering the <a href="https://www.vox.com/2018/11/20/18080046/gaza-palestine-israel">Gaza Strip</a>. Administration officials told reporter Barak Ravid that last week, when over 100 people were killed <a href="https://www.vox.com/world-politics/2024/2/29/24087031/gaza-humanitarian-aid-israel">outside an aid convoy,</a> was (in his words) <a href="https://twitter.com/BarakRavid/status/1765052806417748013">a “turning point</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Da8rPc">
Of course, the White House can complain all it wants (and <a href="https://www.nbcnews.com/news/investigations/biden-disparages-netanyahu-private-hasnt-changed-us-policy-israel-rcna138282">has done so before</a>): It’s meaningless unless accompanied by actions to push Israel toward changing course.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jurY3i">
They started down that road earlier this year by imposing serious sanctions on violent Israeli settlers <a href="https://www.theatlantic.com/international/archive/2024/03/israel-sanctions-settlers-biden-netanyahu/677647/">in the West Bank</a>. Then during last night’s State of the Union, President Biden ordered the US military to establish a port in Gaza that would bypass Israeli-controlled land crossings and thus allow humanitarian aid to flow more freely into the Strip.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KzUbMO">
And it’s not just the administration — or even just the party’s <a href="https://www.nytimes.com/2024/03/06/us/politics/uncommitted-biden-washington-state.html">clearly furious left flank</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="koXfp4">
A recent letter <a href="https://www.axios.com/2024/03/06/biden-israel-rafah-house-democrats">signed by 37 Congressional Democrats</a>, including prominent and mainstream figures like Rep. Jamie Raskin (MD), argued that the <a href="https://www.nbcnews.com/news/world/live-blog/israel-hamas-war-live-updates-rcna139428">planned Israeli assault</a> on the overcrowded city of Rafah would likely violate international law. This, they argue, should trigger a cutoff of military aid to Israel — a threat that has yet to be proven credible, but one that <a href="https://www.washingtonpost.com/opinions/2024/03/06/biden-rafah-attack-israel-hamas-gaza-war/">knowledgeable observers take seriously</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B1JABP">
It does seem like something is starting to change in the Democratic Party’s approach to the Gaza war, and maybe Israel more broadly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6FKIsn">
But nothing is real until it actually happens, and there are still plenty of good reasons for skepticism.
</p>
<h3 id="y4T1dP">
A crisis between Democrats and Israel has been long in the making
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eIZUJc">
The tension between Israel and the Democrats really started emerging in 2009.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EI3aLx">
That year, President Barack Obama pushed Israeli Prime Minister <a href="https://www.vox.com/23910085/netanyahu-israel-right-hamas-gaza-war-history">Benjamin Netanyahu</a> to freeze <a href="https://www.vox.com/2018/11/20/18080034/west-bank-israel-palestinians">West Bank</a> settlement construction as part of a push toward a peace agreement. Netanyahu dragged his feet and even outright thumbed his nose at the administration. During a 2010 visit from then-Vice President Biden, Israel announced the construction of <a href="https://www.nytimes.com/2010/03/10/world/middleeast/10biden.html">1,600 new housing units</a> in contested East Jerusalem.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a9wxG7">
The conflict between Obama and Netanyahu only intensified after that, as Netanyahu began acting as if Israel’s future would be best secured by allying itself with the Republican Party specifically rather than the US writ large.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZT7gnv">
He all-but-openly campaigned against Obama in 2012, worked with Republicans to coordinate opposition to the <a href="https://www.vox.com/iran">Iran</a> deal in <a href="https://www.vox.com/congress">Congress</a> in 2015, and then hugged Trump as tightly as possible from 2016 onward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hqFHxW">
From the outside, this strategy seems nuts: Why would you intentionally stoke conflict with one of the two major parties in your most important ally? The answer is that Netanyahu has — correctly! — identified <a href="https://www.vox.com/22440197/us-israel-democrats-alliance-partisanship-gaza">fundamental ideological tension</a> between Democrats and his right-wing vision for Israel.
</p>
<aside id="VGjENG">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l17F0V">
As a party that counts young people and racial minorities as key constituencies, Democrats were not likely (in the long run) to countenance indefinite Israeli occupation of the West Bank and blockade of Gaza. Netanyahu saw bolstering Republicans as the best way to protect American support without having to make concessions to <a href="https://www.vox.com/palestine">Palestinians</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zzyQGq">
Netanyahu’s theory may have become something of a self-fulfilling prophecy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PlG972">
By aligning with Republicans, he turned both <a href="https://www.vox.com/2014/10/29/7089853/obama-netanyahu-chickenshit-us-israel">elite</a> and <a href="https://news.gallup.com/poll/472070/democrats-sympathies-middle-east-shift-palestinians.aspx">rank-and-file</a> Democrats against his government far more rapidly than they might have otherwise. After Netanyahu traveled to Washington to give a speech to Congress opposing the Iran deal in 2015, his approval rating among Democrats <a href="https://news.gallup.com/poll/181916/americans-views-netanyahu-less-positive-post-visit.aspx">fell from 32 percent to 17 percent</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zPaa0k">
The divergence between Democrats and Israel has been on increasingly sharp display during the Gaza war. Biden’s “unconditional” support for Israel after October 7 has given way to open feuding about the postwar plan for Gaza. The US has called for Palestinian Authority rule over the Strip and a two-state solution; Netanyahu has unveiled a <a href="https://www.vox.com/world-politics/2024/2/23/24081543/israel-postwar-plan-gaza-two-state-netanyahu">pseudo-plan that basically amounts to indefinite Israeli occupation</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tS6jsV">
This is hardly the only example. In a column titled “<a href="https://www.haaretz.com/israel-news/2024-03-05/ty-article/.premium/the-u-s-finally-realized-netanyahu-broke-an-unbreakable-alliance/0000018e-0df1-dc37-a9ae-dffba1cf0000">The US finally realized: Netanyahu broke an unbreakable alliance</a>,” former Israeli diplomat Alon Pinkas lists off points of conflict between the allies — which, he concludes, are producing a fundamental rethink on the American side.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cgfS4E">
“Once the United States became convinced that Netanyahu was not being cooperative, not being a considerate ally, behaving like a crude ingrate and has been focused only on his political survival after the October 7 debacle, the time was ripe to try a new political course,” he writes.
</p>
<h3 id="zeoKxZ">
But is anything <em>really </em>changing?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EndiWl">
By all accounts, President Biden still holds <a href="https://www.reuters.com/world/us/i-am-zionist-how-joe-bidens-lifelong-bond-with-israel-shapes-war-policy-2023-10-21/">a relatively old-school Democratic view of Israel</a> — one that’s deeply sympathetic to the country and its security interests.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JuCOu5">
As frustrated as he may be with Netanyahu’s brutish <a href="https://www.vox.com/policy">policies</a> and rank partisanship, it’s far from obvious that he is willing to start putting real pressure on Israel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RR046y">
Most of Biden’s actual policies have involved giving Israel what it wants, like <a href="https://www.aljazeera.com/news/2024/2/20/us-vetoes-another-un-security-council-resolution-urging-gaza-war-ceasefire">vetoing two UN resolutions calling for a ceasefire</a>. Perhaps most importantly, the US has made <a href="https://www.washingtonpost.com/national-security/2024/03/06/us-weapons-israel-gaza/">over 100 arms sales to Israel since the war began</a>, many of which were structured in such a way that they could escape congressional and public oversight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HXbhfP">
For this reason, hearing about the administration’s frustration with Israel can feel a bit like hearing about <a href="https://www.washingtonpost.com/lifestyle/media/republicans-anonymous-private-concerns-media/2020/12/10/301e98a6-2e75-11eb-bae0-50bb17126614_story.html">Republican frustration with Trump</a>. They’re perfectly happy to complain to reporters in private so long as they don’t have to actually do anything about it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MyMxgJ">
Yet at the same time, events appear to be moving toward a breaking point. Biden’s personal views on Israel are crashing on the shoals of <a href="https://www.vox.com/24055522/israel-hamas-gaza-war-strategy-netanyahu-strategy-morality">Israel’s terrible war policy</a> and long-brewing tension within his own political coalition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YRQZbo">
We may soon find out whether the long-predicted crisis in US-Israel relations is truly here — or once again delayed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yH5b6A">
<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 world’s mental health is in rough shape — and not getting any better, a new report finds</strong> -
<figure>
<img alt="An illustration of a person’s head with the top opened on a hinge. A globe hovers over the opening." src="https://cdn.vox-cdn.com/thumbor/z8UKVdxKj5i0QOnBCw_Hr2YEdUE=/0x1266:7000x6516/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73191124/GettyImages_1308460514.0.jpg"/>
<figcaption>
Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Guess where the US ranks?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N6Dlxm">
While running a microfinance company working across rural India in 2014, neuroscientist Tara Thiagarajan had a free Sunday, a portable EEG headset, and a question: What is modernization doing to our brains?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="07BTFl">
In a DIY experiment using herself and colleagues as baselines, they <a href="https://sapienlabs.org/about-us/#:~:text=Our%20Founding%20Story,and%20small%20towns%20in%20India">found striking differences</a> in brain activity between their urban brains with lifelong exposure to modernity, and those who’ve spent their lives in small Indian villages. At the time, a criticism of studies on <a href="https://www.vox.com/mental-health">mental health</a> was that they were mostly based on findings from <a href="https://www.cambridge.org/core/journals/behavioral-and-brain-sciences/article/abs/weirdest-people-in-the-world/BF84F7517D56AFF7B7EB58411A554C17">small samples of Western college students</a> — a poor experimental design to figure out how differential exposure to modernization and technology affects mental well-being across the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xUFbks">
By 2020, she had founded a nonprofit called <a href="https://sapienlabs.org/">Sapien Labs</a>, built a survey that reached 49,000 people across eight English-speaking countries, and published Sapien’s first <a href="https://sapienlabs.org/wp-content/uploads/2021/03/Mental-State-of-the-World-Report-2020-1.pdf">Mental State of the World (MSW) report</a>, which measures what they call the “<a href="https://sapienlabs.org/mhq/">mental health quotient</a>,” or mental well-being score, of respondents. The findings weren’t great. Compared to responses from 2019, the 2020 mental well-being score (which notably captured the pandemic onset) dropped 8 percent. Forty-four percent of young adults reported clinical level risk, compared with only 6 percent of adults 65 and over.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4IXH2y">
Monday, Sapien released its fourth annual <a href="https://mentalstateoftheworld.report/">Mental State of the World report</a> with data from more than 400,000 respondents in 13 languages across 71 countries. The bottom line: Our modern minds do not appear to be recovering from that drop in the early pandemic years.
</p>
<figure class="e-image">
<img alt="Ranking of the top six and bottom six countries from the fourth annual mental state of the world report. Countries like the Dominican Republic an Tanzania are on top, while the UK, Australia, And Uzbekistan are at the bottom." src="https://cdn.vox-cdn.com/thumbor/ubdXysnMWAcGud3SU2LuRxlWeTM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25323557/Final_2.png"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uI2XUl">
The mental well-being report is part of a larger effort, the <a href="https://sapienlabs.org/global-mind-project/">Global Mind Project</a>, where Sapien Labs uses its survey data — which runs continuously throughout the year (you can fill out the <a href="https://sapienlabs.org/mhq/">assessment here</a>; it takes about 15 minutes to complete) — to gauge not only the mental state of affairs but to look for causal factors.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mBBOBy">
If “modernization” is harming our minds as Thiagarajan suspects, what exactly is doing the damage? “The Global Mind Project allows for very quick understanding at a very large scale, which has not been possible before,” said Thiagarajan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z1OQhG">
Along with their annual overview of mental well-being, the project publishes more targeted reports that home in on different possible scourges of modernity, like <a href="https://sapienlabs.org/wp-content/uploads/2023/05/Sapien-Labs-Age-of-First-Smartphone-and-Mental-Wellbeing-Outcomes.pdf">access to smartphones</a> at younger and younger ages, <a href="https://sapienlabs.org/wp-content/uploads/2023/09/Sapien_Processed-Food-Rapid-Report_2023-2.pdf">ultra-processed foods</a>, and the <a href="https://sapienlabs.org/wp-content/uploads/2023/06/Family-Relationships-and-Mental-Wellbeing.pdf">breakdown of family relationships</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UwJ0ld">
“Greater wealth and economic development does not necessarily lead to greater mental wellbeing, but instead can lead to consumption patterns and a fraying of social bonds that are detrimental to our ability to thrive,” the report cautions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZI0Sca">
A number of <a href="https://ourworldindata.org/">Our World in Data</a> graphs show how economic growth <a href="https://ourworldindata.org/what-is-economic-growth">still tracks really well with human prosperity</a> in the long run. The evidence that economic growth tracks with goods and services that enable human prosperity is compelling, but as my colleague <a href="https://www.vox.com/the-highlight/23862090/subjective-wellbeing-wealth-philanthropy-gdp-happiness-givewell">Sigal Samuel reports</a>, figuring out how best to approximate human well-being is still an ongoing and lively discourse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f2EE5g">
Thiagarajan takes a nuanced approach, arguing against a simple binary choice between growth or <a href="https://www.vox.com/future-perfect/22408556/save-planet-shrink-economy-degrowth">degrowth</a>. Instead, she argues that what matters is how wealth is created and toward what ends it’s used. Or, as the economist Mariana Mazzucato often puts it, what matters is the “<a href="https://www.ucl.ac.uk/bartlett/public-purpose/sites/bartlett_public_purpose/files/mazzucato_perez_2022_redirecting_growth-inclusive_sustainable_and_innovation-led.pdf">direction</a>” of growth and whether it’s angled at the <a href="https://www.ucl.ac.uk/bartlett/public-purpose/publications/2023/oct/governing-economics-common-good">common good</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mlu5Iq">
“At the moment, growth is causing harm,” Thiagarajan said. “But there are different types of growth.”
</p>
<h3 id="iqVk2M">
How to measure mental well-being
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yhdVlG">
There is, as of yet, no exact science of mental well-being, let alone a perfect cross-cultural survey. “People commonly conflate things like mental well-being with happiness,” said Thiagarajan. But if you compare the findings from their mental well-being survey to the <a href="https://worldhappiness.report/ed/2023/world-happiness-trust-and-social-connections-in-times-of-crisis/#ranking-of-happiness-2020-2022">World Happiness Report</a> (WHR), a publication by Oxford’s <a href="https://wellbeing.hmc.ox.ac.uk/">Wellbeing Research Centre</a>, much of the results are inverted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6OPYiL">
The Dominican Republic and Sri Lanka have the highest average mental well-being scores on the Mental State of the World list. On the World Happiness Report, they rank 73rd and 112th, respectively. Tanzania is third on the MSW and 128th on the WRH. What’s going on?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5Bciv7">
The World Happiness Report <a href="https://worldhappiness.report/ed/2023/world-happiness-trust-and-social-connections-in-times-of-crisis/#ranking-of-happiness-2020-2022">leans on</a> capturing what Thiagarajan described as “feeling.” That includes respondents rating their life satisfaction on a scale from one to 10 and daily measures of whether they felt laughter, enjoyment, or interest the day before. But you could feel<em> </em>great and still be functioning poorly in the world. Following the World Health Organization’s <a href="https://www.who.int/news-room/fact-sheets/detail/mental-health-strengthening-our-response">definition of mental health</a>, which includes the capacity to function productively and contribute to society, Thiagarajan wanted the Global Mind Project to capture functioning, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bY0DOY">
To build their measure, the mental health quotient, Thiagarajan and her team found 126 different kinds of assessments used across academia and clinical environments, and then boiled those down to 47 aspects of mental health. Then, rather than asking about frequency, like “How many times did you feel sad yesterday,” the MHQ sets its questions along a life impact scale, based on the idea that it’s easier to report how impactful something is to your life than how many times you drank water or laughed the day before (I couldn’t tell you either of those for yesterday).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xUqloS">
Their results produce a number along a 300-point scale that ranges from “distressed” at the low end to “thriving” at the high end.
</p>
<figure class="e-image">
<img alt="A 300 point scale that runs from “distressed” to “thriving,” showing the average score from 71 countries in 2023 at 65, in the territory marked “managing.”" src="https://cdn.vox-cdn.com/thumbor/4-D57pFlBXaoxURuPyAP1dG2KDQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25323545/report_graphs_02.jpg"/> <cite>Global Mind Project / 4th Annual Mental State of the World Report</cite>
<figcaption>
The average mental health quotient score measured in 2023, which was nearly identical to the previous year.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xU5nU2">
For 2023, across the 71 countries they received data from, the global average was 65, indicating that we’re all “managing,” and doing so just a few hairs above “enduring.”
</p>
<h3 id="JV5Tiz">
The problems: Smartphones, ultra-processed foods, and crumbling families
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2cUtgA">
There’s a theory going around that, as former neuroscientist and author Erik Hoel <a href="https://www.theintrinsicperspective.com/p/what-the-heck-happened-in-2012">put it</a>, the modern world was invented in 2012. For social psychologist Jonathan Haidt, 2012 also <a href="https://www.persuasion.community/p/haidt-the-teen-mental-illness-epidemic">marks the beginning</a> of the teen mental illness epidemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A4jzdZ">
Findings across the four years of the MHQ agree. Prior to 2010, young people <a href="https://www.pnas.org/doi/10.1073/pnas.1003744107">tended to top</a> surveys of happiness, mood, and outlook. But from 2019 until this year’s report, the most persistent trend observed has been declining mental well-being across the “internet-enabled” youth (because the survey requires internet access) of every country measured, from Africa to Asia, Europe to the Americas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zAqRAa">
The youth, once the peak of reported happiness, have dropped to the absolute bottom, while others, like those 65 or older, have remained basically the same.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UbKuKi">
To be more precise: For the eight English-speaking countries with data collected since 2019, those aged 18–24 and 25–34 dropped by 14–17 percent. That decline gradually flattens out as you move up the age brackets.
</p>
<figure class="e-image">
<img alt="Trends in mental well-being by age group. 18 – 24 and 25 – 34 had the steepest declines, while the decrease flattens out at older age groups." src="https://cdn.vox-cdn.com/thumbor/faPxSkrC8Kg6KZZBMXu7oDb5jXg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25323585/report_graphs_04.jpg"/> <cite>Global Mind Project / 4th Annual Mental State of the World Report.</cite>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cGXj8t">
According to the Global Mind Project’s <a href="https://sapienlabs.org/wp-content/uploads/2023/05/Sapien-Labs-Age-of-First-Smartphone-and-Mental-Wellbeing-Outcomes.pdf">report on smartphone use</a> in May, the <a href="https://www.theatlantic.com/magazine/archive/2017/09/has-the-smartphone-destroyed-a-generation/534198/">smartphone hypothesis</a> — which has been advocated for by psychologists like <a href="https://psychology.sdsu.edu/people/jean-twenge/">Jean Twenge</a> — holds up. “The younger you get your smartphone, the worse off you are as an adult,” said Thiagarajan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8F5kBq">
The more you break down the demographics, the more you find that the consequences of smartphone use are concentrated on young females. But looking at another potential causal factor they recently published on, the <a href="https://sapienlabs.org/wp-content/uploads/2023/09/Sapien_Processed-Food-Rapid-Report_2023-2.pdf">consumption of ultra-processed foods</a>, those effects are universal across all demographics. “It affects everything, every aspect of mental functioning,” said Thiagarajan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GONlKg">
Their report notes the complexities involved in defining ultra-processed foods (UPFs) and provides a simple rule of thumb: food with substances you would rarely find in a home kitchen (it’s worth noting that the entire category of UPFs is still under scrutiny, particularly for targeting plant-based foods). Even after trying to control for the indirect effects of exercise frequency or income, they found that those who eat UPFs several times a day have a threefold increased risk for serious mental health issues.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bWLdCg">
There are plenty of other possible confounding variables, like frequency of cooking or sharing meals, but their findings are large: “We’re looking at when you rule out all the other 100 things that we can capture data on,” Thiagarajan said, “and ultra-processed foods seem to account for at least a third of the global burden of mental health that we see.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UkPRE9">
The last culprit she singled out was family relationships. And yes, <a href="https://sapienlabs.org/wp-content/uploads/2023/06/Family-Relationships-and-Mental-Wellbeing.pdf">there’s a report</a> for that too, which finds the breakdown of family relationships across the modern world as a major factor in the decline of youth mental well-being. Families with less exposure to the institutions and technologies of modernity, the report argues, tend to have stronger and more numerous family bonds, which tracks closely with better mental well-being.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7ob1uV">
Thiagarajan explained how when they got their first MHQ results, they wondered why countries like Venezuela and Tanzania came out on top. “But it’s these factors,” she said. “They can’t afford all the westernized ultra-processed foods so they don’t import them. They don’t give smartphones to their kids so young. And they have large families that stay together.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p8Fpxi">
She noted that given the speed and scale of “the issue” — that issue being, well, modernity — we’re forced to take action on imperfect knowledge. Part of the goal of the Global Mind Project, across the MHQ and its more targeted reports, is to help figure out the most effective places to aim policy efforts, particularly regulations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4I4kH5">
“If it’s a free-for-all,” she said, “people will take the easiest shortcut to short-term profits at the expense of mental health.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KZhgJK">
<em>A version of this story originally appeared in the </em><a href="https://www.vox.com/future-perfect"><em><strong>Future Perfect</strong></em></a><em> newsletter. </em><a href="https://www.vox.com/pages/future-perfect-newsletter-signup"><em><strong>Sign up here!</strong></em></a>
</p></li>
<li><strong>Biden’s State of the Union got one big thing right</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/WXU1DGuCfdB-MgxeJ_fX2o3y4IY=/0x0:5333x4000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73190904/2059264750.0.jpg"/>
<figcaption>
President Joe Biden during the State of the Union address at the US Capitol in Washington, DC, on March 7, 2024. | Shawn Thew/EPA/Bloomberg via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The president dodged the “norms trap” by going straight after Trump on democracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yU27uU">
During Thursday night’s State of the Union address, <a href="https://www.vox.com/joe-biden">President Joe Biden</a> issued an unmistakable warning about the threat <a href="https://www.vox.com/donald-trump">Donald Trump</a> poses to American democracy. The speech also implicitly made a more subtle point about democracy: that defending it can require uncomfortably blunt talk.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mk2QxB">
One of democracy’s core premises is that elections are not like armed conflict, where either you win or you die. Since all parties accept the basic rules of the game, like competitive elections and free speech, the stakes of elections are not existential. Political opponents are less enemies than rivals; disagreement isn’t disaster.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZEcNEz">
Authoritarian populists like Donald Trump win by attacking this foundational democratic norm.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tHTWY4">
They demonize their opponents, arguing repeatedly that their opponents are not rivals but rather monsters bent on the country’s destruction. They claim that the system is in the enemy’s corrupt hands and not to be trusted, that their faction and our leader deserve absolute power (“<a href="https://www.theatlantic.com/politics/archive/2016/07/trump-rnc-speech-alone-fix-it/492557/">I alone can fix it</a>,” as Trump said in 2016). The nefarious plans of the domestic enemy must be resisted by any means necessary, even ones that might seem extreme.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LducNa">
“We fight like hell. And if you don’t fight like hell, you’re not going to have a country anymore,” Trump said, infamously, in his <a href="https://www.npr.org/2021/02/10/966396848/read-trumps-jan-6-speech-a-key-part-of-impeachment-trial">speech on the morning of the January 6 attack</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1T8pew">
For those committed to democracy, this kind of radical attack might seem to pose a dilemma. If you ignore or downplay your opponents’ rhetoric, you fail to alert the public to the danger. But if you correctly point out that it threatens democracy, you risk coming across as a hypocrite: demonizing your opponents in the same way they’re demonizing you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dT3WkT">
But this supposed dilemma is no dilemma at all.<strong> </strong>The reason is deceptively simple: There is no hypocrisy in defending truth against lies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i8JNPT">
When Trump says the <a href="https://www.vox.com/2020-presidential-election">2020 election</a> was stolen, he is lying to create a pretext to overthrow a legitimate election. When Biden calls Trump’s behavior a threat to democracy, warning that the former president seeks “to bury the truth of January 6,” he is telling the truth about Trump’s lies and the dangers they pose to American democracy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hafxOq">
Fail to appreciate this distinction and you risk falling into what I call the “norms trap:” prioritizing the appearance of respecting democracy’s principles over acting in those principles’ defense.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tziWCv">
At the State of the Union, Biden recognized this trap and avoided it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CEm7Xb">
When he warned of the ongoing threat to American democracy, saying, “My predecessor and some of you here seek to bury the truth of January 6th,” he did indeed sound an unusually partisan note for the typically staid affair. This might seem like a violation of democratic norms, and some <a href="https://twitter.com/marcthiessen/status/1765931302140723376">conservatives</a> attempted to <a href="https://twitter.com/bdomenech/status/1765934660909928710">cast</a> it as such. This was the theme of <a href="https://www.foxnews.com/politics/bidens-sotu-blasted-nakedly-partisan-campaign-speech-utter-disgrace?intcmp=tw_fnc">one of Fox News’ top stories after the speech</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Y5hov">
This is hard to take seriously as a good faith objection, especially given <a href="https://www.vox.com/2020/2/5/21123597/rush-limbaugh-medal-of-freedom-trump-racist-sexist">Trump’s State of the Union track record</a>. As a rhetorical tactic, though, it’s a powerful distraction: an attempt to shift focus away from the substance of Biden’s warning about the rising threat to democracy, onto a disingenuous debate over whether Biden himself is behaving undemocratically.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ovvx8U">
Yes, it’s rare for a president to in essence campaign during the State of the Union. But it’s also unusual for the president’s opponent to be someone who has a stated desire to be a “<a href="https://www.youtube.com/watch?v=aX0iAmz9iLM">dictator on day one</a>,” with<a href="https://www.justsecurity.org/92714/american-autocracy-threat-tracker/"> a host of policies</a> that could bring that vision frighteningly close to fruition. The State of the Union is supposed to highlight grave national concerns; this is clearly one of them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1Xy5lk">
This is not to say that Biden can do or say whatever he wants to fight Trump. He should not break the law or take actions that meaningfully weaken American democracy (which Democrats are <a href="https://www.vox.com/policy-and-politics/2018/12/14/18140773/new-jersey-democrats-gerrymandering-2018">entirely capable of doing</a>).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DhJYjU">
But in a world where American democracy is facing an unprecedented threat from one of two major political parties, it’s reasonable to risk a too-partisan speech in order to safeguard it. It’s good that Biden recognized this and devoted a good chunk of the State of the Union to telling the truth.
</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>French Open badminton | Fighting Sindhu loses epic battle against Olympic champion Chen</strong> - The last time Sindhu had beaten the world no. 2 Chen was en route to her 2019 World Championships gold.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>World Olympic boxing qualifier | Nishant eases past Eskerkhan, enters pre-quarters</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>Shubman Gill completes 4,000 international runs during Dharamsala Test</strong> - A solid unbeaten partnership of 160 runs between Rohit Sharma and Gill gave an upper hand to India in the first session of the ongoing fifth Test match</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>Nishant Dev enters pre-quarterfinals of World Olympic Boxing Qualifiers</strong> - The Indian won by a unanimous 5-0 margin against Tokyo Olympics quarterfinalist Eskerkhan</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 5th Test | India reach 473/8 on Day 2, lead by 255 runs</strong> - Rohit, Gill put India in driver’s seat despite late batting collapse</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>Here are the big stories from Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.</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>Extension of trains on main line comes as a surprise to commuters</strong> - The Railway Board has asked the Southern Railway and South-Western Railway to extend the Mysore-Mayiladuthurai-Mysore Express train to Cuddalore Port</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>Health Minister envisions global recognition for health education and medical tourism in Telangana</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>I feel like I’m still in jail: Acquitted former professor G.N. Saibaba</strong> - Thanking his lawyers for fighting the case, he said one of them fought his case without any fees.</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>Nitin Gadkari’s name will be first in list of BJP candidates from Maharashtra, says Devendra Fadnavis</strong> - Devendra Fadnavis was responding to Shiv Sena (UBT) chief Uddhav Thackeray’s offer to give Union Minister Nitin Gadkari a ticket to contest the Lok Sabha elections representing the Maha Vikas Aghadi</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>Singapore sting: How spies listened in on German general</strong> - Berlin said human error was to blame for the intercept of conversations between top military officers.</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>Far-right ex-football pundit shakes up Portuguese vote</strong> - André Ventura made his name as a sports pundit. Now, his far-right Chega party is third in the polls.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Polls open on Ireland’s family and care referendum</strong> - Voters are being asked if they wish to amend two articles of the Irish constitution.</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>Sweden formally joins Nato military alliance</strong> - Sweden joins Nato, becoming the military alliance’s second new member since Russia’s full-scale invasion of 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>‘We know what’s coming’: East Ukraine braces for Russian advance</strong> - Russian troops are advancing in eastern Ukraine. Residents must choose - flee, or risk occupation.</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>Ghouls, gulpers, and general mayhem abound in Fallout official trailer</strong> - “Everyone wants to save the world. They just disagree on how.” - <a href="https://arstechnica.com/?p=2008809">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>visionOS 1.1 tries to make Personas less unsettling, plus other Apple OS updates</strong> - Apple starts picking low-hanging fruit in visionOS; other OSes see minor improvements. - <a href="https://arstechnica.com/?p=2008833">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>US lawmakers vote 50-0 to force sale of TikTok despite angry calls from users</strong> - Lawmaker: TikTok must “sever relationship with the Chinese Communist Party.” - <a href="https://arstechnica.com/?p=2008851">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Attack wrangles thousands of web users into a password-cracking botnet</strong> - Ongoing attack targeting thousands of sites, continues to grow. - <a href="https://arstechnica.com/?p=2008817">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>After Astra loses 99 percent of its value, founders take rocket firm private</strong> - First you burn the cash, then comes the crash. - <a href="https://arstechnica.com/?p=2008812">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 engineer comes to work one day with a new bike.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His friend says “Cool bike. Where did you get it?”<br/> First guy says “I was walking home through the park. A beautiful woman on a bike rode up, jumped off the bike, stripped naked, and told me to take whatever I wanted. I took the bike.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Good call” says the friend. “The clothes probably wouldn’t have fit anyway.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/BobT21"> /u/BobT21 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9brk9/an_engineer_comes_to_work_one_day_with_a_new_bike/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9brk9/an_engineer_comes_to_work_one_day_with_a_new_bike/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tea is an evil substance. It is much more dangerous than beer. I discovered this last night. I drank 15 beers up until 3 am in the pub while my wife was just at home drinking tea.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
You should have seen how mad and violent she was when I got home. She threw the chair at me and kept screaming at the top of her lungs. On the other hand, I was quiet and peaceful and silently made my way to bed. But she kept cursing and shouting through the night and well into the next morning.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Please friends, if you can’t handle your tea, you should not be drinking it. Please avoid drinking tea.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9lyzj/tea_is_an_evil_substance_it_is_much_more/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9lyzj/tea_is_an_evil_substance_it_is_much_more/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>If bigger shoes means a bigger penis, and bigger car means a smaller penis. Well…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
… I think I know why people are afraid of clowns.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/TheBlank16"> /u/TheBlank16 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9gb6v/if_bigger_shoes_means_a_bigger_penis_and_bigger/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9gb6v/if_bigger_shoes_means_a_bigger_penis_and_bigger/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The biggest dick of Brazil</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In Brazil, there’s a legend about a guy from Pernambuco (a brazilian state) famous for two things. First, he’s the biggest patriot of his land, fiercely proud of its culture and flag. The second reason is his gigantic penis. So grand, in fact, that he decided to tattoo a message along the hefty shaft of the organ. His friends, with a mix of jest and curiosity, immediately went:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Come on, you’ve got to show us!” After some persuasion, he gives in, “Alright, alright, I’ll show it.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He unzips his pants, and from the fly unfurls that meaty staff, rolling out onto the table: A tattoo with bold, large letters proclaiming: “Welcome to Nabuco.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Stunned, his friends, bewildered, exclaim, “Damn! That’s not a human dick, that belongs on a horse!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“But wait,” interrupts one, scratching his head, “what the hell is ‘Nabuco’? Never heard of it.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
With a grin, the man explains, “Ah, you see, i am a little nervous, it’s limp, wrinkled, and shrunken.” He stretches the skin. “When it’s in its on its peak form, it proudly reads: ‘Welcome to the glorious state of Pernambuco’.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Cine81"> /u/Cine81 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9fk8r/the_biggest_dick_of_brazil/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b9fk8r/the_biggest_dick_of_brazil/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Man: Last year, my brother ran for Congress.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Two friends meet after a long time….
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Man: two year ago, my brother ran for Congress.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Friend: What does he do now?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Man: Nothing — he got elected!
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/brideofrocknroll"> /u/brideofrocknroll </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b985po/man_last_year_my_brother_ran_for_congress/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b985po/man_last_year_my_brother_ran_for_congress/">[comments]</a></span></p></li>
</ul>
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