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<title>07 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>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>
<li><strong>Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K</strong> -
<div>
During the continuing evolution of SARS-CoV-2, the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (Mpro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-Mpro) as free enzyme and in complex with the Mpro inhibitor, the alpha-ketoamide 13b-K, and we conducted enzymology, biophysical as well as theoretical studies to characterize the O-Mpro. We found that O-Mpro has a similar overall structure and binding with 13b-K; however, it displays lower enzymatic activity and lower thermal stability compared to the WT-Mpro (with "WT" referring to the original Wuhan-1 strain). Intriguingly, the imidazole ring of His132 and the carboxylate plane of Glu240 are in a stacked configuration in the X-ray structures determined here. The empirical folding free energy calculations suggest that the O-Mpro dimer is destabilized relative to the WT-Mpro due to the less favorable van der Waals interactions and backbone conformation in the individual protomers. The all-atom continuous constant pH molecular dynamics (MD) simulations reveal that His132 and Glu240 display coupled titration. At pH 7, His132 is predominantly neutral and in a stacked configuration with respect to Glu240 which is charged. In order to examine whether the Omicron mutation eases the emergence of further Mpro mutations, we also determined crystal structures of the relatively frequent P132H+T169S double mutant but found little evidence for a correlation between the two sites.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.04.583178v1" target="_blank">Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K</a>
</div></li>
<li><strong>A 10-valent composite mRNA vaccine against both influenza and COVID-19</strong> -
<div>
The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.05.583547v1" target="_blank">A 10-valent composite mRNA vaccine against both influenza and COVID-19</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>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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 <br/><b>Interventions</b>: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) <br/><b>Sponsors</b>: Selda Sarıkaya; Zonguldak Bulent Ecevit University <br/><b>Completed</b></p></li>
</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>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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Empowering SARS-CoV-2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides</strong> - With the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS-CoV-2 to host cell membranes and viral fusion. We developed pioneering IgG4-(HR2)(4) bifunctional antibodies by creating immunoglobulin…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Silico Evaluation of NO-Sartans against SARS-CoV-2</strong> - CONCLUSION: Based on our in silico studies, CLC-1280 (a Valsartan dinitrate) has the potential to be considered as an inhibitor of the SARS-CoV-2 virus. However, further in vitro and in vivo evaluations are necessary for the drug development process.</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>Immunomodulatory and anticytokine therapeutic potential of three Indian spices constituents and its hyaluronic acid conjugates for prevention and post COVID-19 complications: a computational modeling approach</strong> - Targeted drug delivery to SARS-CoV-2 host target proteins for preventing or blocking COVID-19 infection is making serious concern during COVID-19 pandemic and its consequent waves around the globe. People seek reliable, effective folkloric preventive medication for immediate and precautionary relief from COVID-19. These folkloric medicines were effective and saved many patients during the past COVID-19 pandemic. The current research study aims to deliver antiviral Indian spices phytocompounds…</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>Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis</strong> - Monocytes can develop an exhausted memory state characterized by reduced differentiation, pathogenic inflammation, and immune suppression that drives immune dysregulation during sepsis. Chromatin alterations, notably via histone modifications, underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we show altered DNA methylation throughout the genome of exhausted monocytes, including genes implicated in immune…</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>Targeting SIRT1 by Scopoletin to Inhibit XBB.1.5 COVID-19 Life Cycle</strong> - Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What kind of a problem is loneliness? Representations of connectedness and participation from a study of telepresence technologies in the UK</strong> - Loneliness is represented in UK policy as a public health problem with consequences in terms of individual suffering, population burden and service use. However, loneliness is historically and culturally produced; manifestations of loneliness and social isolation also require social and cultural analysis. We explored meanings of loneliness and social isolation in the UK 2020-2022 and considered what the solutions of telepresence technologies reveal about the problems they are used to address….</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>Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-kappaB and STAT3</strong> - CONCLUSIONS: We identified a significant metabolite, DCA, related to TGEV replication. It added TGEV replication in host cells by inhibiting phosphorylation of NF-κB and STAT3. This study provided novel insights into the metabolomic and transcriptomic alterations related to TGEV infection and revealed potential molecular and metabolic targets for the regulation of TGEV 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>Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease</strong> - Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary…</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>Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention</strong> - The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies…</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>Watching Super Tuesday Returns at Mar-a-Lago</strong> - Heading into the general election, the mood in Trump world is buoyant. - <a href="https://www.newyorker.com/news/dispatch/watching-super-tuesday-returns-at-mar-a-lago">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-bidens-last-campaign">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>Researchers use online opt-in surveys all the time. Should they?</strong> -
<figure>
<img alt="A man working on a laptop in a home office, sitting in front of a window in the daytime." src="https://cdn.vox-cdn.com/thumbor/m-Cz-9KVIZwGQGyQq2j7qiVWr4k=/555x0:4928x3280/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73188514/1229160021.0.jpg"/>
<figcaption>
Kira Hofmann/picture alliance via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Survey sites recruit respondents with the promise of a reward, which may lead to bogus answers. That doesn’t mean the data is unusable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bgUFdN">
Search around for ways to make a little extra money online, and you might find yourself at one of many sites that offer to pay you to take surveys.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UuffpK">
There’s Swagbucks, SurveyJunkie, InboxDollars, and KashKick, for instance. On each of these sites, users are paid small amounts of money for completing surveys, playing games, or making purchases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4Ew7xM">
The surveys on these sites are “opt-in” surveys, meaning that participants are actively choosing to take them, rather than researchers pulling a random sample of a population to poll, as professional pollsters do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yN9vK6">
Unsurprisingly, opt-in surveys can lead to some skewed results: earlier this week <a href="https://www.pewresearch.org/short-reads/2024/03/05/online-opt-in-polls-can-produce-misleading-results-especially-for-young-people-and-hispanic-adults/">Pew Research Center wrote</a> about their analysis of one such opt-in survey that found 20 percent of US adults under 30 believe that “The Holocaust is a myth.” Pew’s attempt to replicate this result via a random sampling of Americans found that just 3 percent of Americans under 30 agreed with an identically worded statement about the Holocaust — a percentage that was more or less the same across <em>all</em> age groups.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="94XHYl">
The analysis also included this incredible tidbit:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RMwwe0">
<em>“In a February 2022 survey experiment, we asked opt-in respondents if they were</em><a href="https://washstat.org/hansen/2022Kennedy.pdf"><em> licensed to operate a class SSGN (nuclear) submarine</em></a><em>. In the opt-in survey, 12% of adults under 30 claimed this qualification, significantly higher than the share among older respondents. In reality, the share of Americans with this type of submarine license rounds to 0%.” </em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Dv85Lw">
Oof, right?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qvzrTn">
The <a href="https://www.vox.com/google">Google</a> results for survey sites are filled with reviews from people who are mainly concerned with whether these sites are “legitimate” or scams. But the Pew analysis points to another question: just how good is the data collected for a survey when its participants are incentivized to speed through as many as possible in order to earn cash?
</p>
<h3 id="V7gdfX">
The problems with opt-in surveys, explained
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9L2F6v">
I dug around and, surprise! It’s complicated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nRNNTr">
“Errors are introduced (and remediated) in the survey process at every step,” noted David Rothschild, an economist at Microsoft Research. The fact that a survey was conducted online for a small reward isn’t necessarily enough information to analyze data quality in a meaningful way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="74eQZ7">
As Pew noted in its analysis, the Holocaust denial survey used an agree/disagree format that can lead to “<a href="https://www.qualtrics.com/blog/avoiding-the-yes-bias/">acquiescence bias</a>” — a tendency for respondents to give an affirmative reply. This means that while the survey collection method might have been part of the problem, the question itself may have also led to inaccurate results.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OdNPT6">
“There are many types of opt-in online audiences; some have strong vetting to ensure the respondents are who they say they are and produce high quality responses, while others just accept whomever without any pre-response quality control,” Rothschild added.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZorGSu">
Here’s what you need to know.
</p>
<h3 id="r32Epx">
How do online survey sites work?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5ztSay">
Although there are a couple different models, the online survey sites we are talking about offer small rewards in exchange for survey participation. Most say they try to “match” users to relevant surveys based on the data they collect about their users, and generally speaking, you only get paid if you qualify to take the survey and complete each required question.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QCbwd4">
Typically, these sites pay users in points, which translate to small dollar amounts per survey, if they pass a set of screening questions and complete the entire survey. These points often do not translate to very much money: I created an account on Swagbucks and checked a list of available surveys. They included a 20-minute survey for 119 “Swagbucks,” which translates to … $1.19.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="13cgMY">
Longer surveys may offer more, while some surveys with a 10-minute time estimate offer less than a dollar. These are similar to the rates I saw on SurveyJunkie. On <a href="https://www.vox.com/amazon">Amazon</a>’s Mechanical Turk, a marketplace for work that includes survey taking, <a href="https://www.nytimes.com/interactive/2019/11/15/nyregion/amazon-mechanical-turk.html">a survey might pay less than 10 cents</a>.
</p>
<h3 id="9qdNKR">
Why would pollsters and researchers use sites like these to collect responses?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j9R9Fk">
In some applications like election polls, as Pew noted, opt-in surveys can perform similarly to random probability-based surveys. Which is great, because they are generally much cheaper to conduct.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4c87Ah">
“Lower cost survey pools are great for exploration” and when you don’t need a very precise outcome, said Rothschild. The results are generally faster, cheaper, and more convenient.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wJEUCW">
“Especially for research that’s being done on a close-to-shoestring budget, opt-in online surveys are a natural choice for scholars trying to study diverse aspects of social behavior,” added Thomas Gift, an associate professor of political science at University College London.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S3tNox">
Gift and another researcher studied the potential of fraudulent responses in online opt-in studies after using an opt-in study themselves to study a separate question. “It was only during the fielding of the experiment that large cohorts of respondents seemed to be giving suspicious answers about their backgrounds,” he said. “So we investigated further.”
</p>
<h3 id="Sps2OG">
Why, and when, are online surveys prone to bogus respondents?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jzPxDd">
Researchers can use a lot of tools, including screening questions, to weed out bad responses and end up with a set of usable data. But there are some instances, such as obscure beliefs or surveys where you need really precise data, where opt-in online surveys are going to be a problem.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rnYynQ">
Pew noted a few considerations here: based on their research over the years, online opt-in polls have a tendency to overestimate fringe beliefs (they gave the example of belief in conspiracy theories). That overrepresentation is more severe among younger respondents, and among Hispanic adults, they noted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g5lOSb">
Gift and his research partner hired a “nationally-recognized” marketing firm — which they left unnamed in their paper for liability reasons — to conduct a survey for them that collected respondents with experience in the Army. This firm, they said, distributed the survey to a number of sub-vendors that provided financial incentives for responses (these sub-vendors were also left anonymous).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uQri3I">
In order to detect whether respondents really did have experience in the Army or not, Gift used screening questions embedded in the survey. Respondents were asked about saluting protocol, and for specific information on their military background.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VXR2Xo">
<a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3957523">Based on their analysis of those screeners</a>, nearly 82 percent of respondents may have pretended to be associated with the Army in order to take the survey and get paid for it. About 36 percent of those respondents passed the knowledge screening test, but were identified as probably misrepresenting themselves based on their answers to the survey questions themselves.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5LcBRx">
And there was also evidence in the survey results that some respondents were taking the survey a bunch of times, giving nearly identical answers and tweaking their demographic data enough to pass as different people, presumably to get paid multiple times for the same survey.
</p>
<h3 id="lR3mLa">
How can researchers minimize bogus responses and end up with useful data from an online survey?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iRK3VN">
Essentially, by testing the respondent. Online surveys use attention checks, IP tracking, anti-bot software, and monitoring the time it takes for someone to complete a survey in order to try to mitigate fraud. Asking respondents questions like the one Pew flagged about having a license to drive a submarine is a pretty good way to tell whether someone is just cruising through and answering questions as quickly as possible, or if they’re actually reading the questions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Nq3HGe">
Nothing is going to catch every single bogus response, and, as Rothschild noted, some low-quality responses will slip through attention checks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PbmY18">
There are also other models for collecting data online, Gift noted. Opt-in volunteer surveys “aren’t without their limitations,” but they create a different set of incentives for participants that don’t rely on a financial reward. Gift highlighted the work of the <a href="https://dlabss.harvard.edu/">Harvard Digital Lab for Social Sciences</a>, an online platform that allows people to volunteer to participate in social science research.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZJ5cyt">
While researchers might not be able to catch every single bad response, they can be transparent about how they collected their data, Rothschild noted. And it’s worth looking for that information the next time you see a shocking headline about a shocking belief held by The Youth.
</p></li>
<li><strong>Why did geologists reject the “Anthropocene” epoch? It’s not rock science.</strong> -
<figure>
<img alt="Scientists leaning over a sample from the lake. One person is chiseling into the sample." src="https://cdn.vox-cdn.com/thumbor/BogO7UvENNp6SA4nHeQevQ4bgRs=/221x0:3765x2658/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73188499/anthropocene.0.jpg"/>
<figcaption>
Francine McCarthy, center, of Brock University monitors core removal at Crawford Lake on April 12, 2023, in Ontario. McCarthy is a member of the Anthropocene Working Group. | Bonnie Jo Mount/The Washington Post via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The battle proves that time is political, any way you cut it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SkgT0d">
Scientists dealt a resounding blow this week in a long-running fight over one big question: Have humans messed up the Earth so badly that we’re now living in a new climate epoch?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sXUGnW">
For 15 years, an intrepid band of geologists has been trying to argue exactly that. They claimed that humanity has ushered in the Anthropocene, a new chapter in the Earth’s history borne of our impact on the planet. And they hunted all around the globe for proof.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7HKXga">
But it’s not easy to make the case that we’re in a new epoch. That’s a technical term that describes a chunk of time typically lasting a few million years (sounds like a lot, but it’s nothing compared to a geological “period” like the 54-million-year Jurassic or “era” like the 186-million-year Mesozoic). Scientists have to vote on whether the term “epoch” applies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="urZ5YU">
Now, a top body of Earth’s professional timekeepers has voted — <em>against </em>canonizing the Anthropocene.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HPOZUR">
And while this might just seem like a smackdown over semantics, the fight over “Anthropocene” is much more. It’s a deeply political fight over how to make meaning of what we humans are doing to the planet.
</p>
<h3 id="i5cYyR">
The case for the Anthropocene
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aacAvG">
Earth has gone through distinct geological epochs, chunks of time defined by changes in rock layers. To prove that the Anthropocene represents a new chunk, a group of geologists had to find a “golden spike” — a physical site where the rock, sediment, or ice clearly records the change from a previous chapter in time to a new one.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TZuPUC">
In 2009, they started scouring the planet and found a range of strong candidates, from a peat bog in Poland to a coral reef in Australia to the ice of Antarctica.
</p>
<aside id="NNRx6u">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vBug4c">
But the Anthropocene Working Group (AWG), as the group was called, wanted to pick a site where the rock record indisputably shows that we’ve left behind the Holocene epoch, which started 11,700 years ago when the last ice age ended.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ISAO2Q">
In 2023, <a href="https://www.vox.com/future-perfect/2023/7/11/23791629/anthropocene-climate-epoch-canada-lake-crawford">the geologists said they’d found their holy grail</a>: little Crawford Lake in Ontario, Canada.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sgkvAY">
There, the waters are so deep that whatever sinks to the floor usually remains without mixing with the upper layers of water, so it stays preserved, offering an amazingly good record of geological change.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n2Ts5i">
Since the middle of the 20th century, the sediment there has been inundated by the byproducts of human activity: plutonium isotopes from the nuclear bombs we’ve detonated, ash from the fossil fuels we’ve burned, and nitrogen from the fertilizer we’ve used.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FFgMmN">
That was also when we started to see major changes in phenomena like global warming, sea-level rise, ocean acidification, and the explosive growth of domestic animal populations. So the AWG said the Anthropocene began around 1950.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WknwwP">
That would prove controversial.
</p>
<h3 id="NBhXKz">
A golden spike, but not a silver bullet
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j9BYCT">
Some scientists argued that it doesn’t make sense to recognize our current interval as its own epoch, since it’s incredibly brief in geological time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fJM5sU">
If the previous epoch, the Holocene, lasted 11,700 years, does it make sense to give the same designation to an interval that hasn’t yet spanned 75 years?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J8VIfr">
But even among those who agreed that human activity had ushered in a new epoch, there was disagreement over when the epoch started.
</p>
<figure class="e-image">
<img alt="A lake surrounded by pine trees." src="https://cdn.vox-cdn.com/thumbor/nMD8f2F8p8TkhGx_SFebEU6baqI=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/25321983/GettyImages_1935927165__1_.jpg"/> <cite>Bonnie Jo Mount/The Washington Post via Getty Im</cite>
<figcaption>
Aerial view of Crawford Lake.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qJd2FQ">
Paul Crutzen, the atmospheric chemist who originally coined the term “Anthropocene,” <a href="https://www.nature.com/articles/415023a">said</a> it started in the late 18th century thanks to the greenhouse gas emissions that took off with the Industrial Revolution. Others looked further back to the colonial powers that ravaged the so-called New World. Still others said humans have been transforming the planet since the dawn of agriculture, so trying to pinpoint any later starting point would be arbitrary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kiVxIE">
Erle Ellis, an ecologist who’d been part of the AWG for 14 years, objected so strongly to its idea of drawing a bright line between pre- and post-1950 that he ultimately resigned.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0g1ZUU">
Carving up time that way “does real damage by denying the deeper history and the ultimate causes of Earth’s unfolding social-environmental crisis,” Ellis wrote in his <a href="https://anthroecology.org/why-i-resigned-from-the-anthropocene-working-group/">resignation letter</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MQreJ0">
“Are the planetary changes wrought by industrial and colonial nations before 1950 not significant enough to transform the planet? The political ramifications of such a misleading and scientifically inaccurate portrayal are clearly profound and regressive.”
</p>
<h3 id="fngb67">
Time is political, any way you cut it
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="saKIoL">
The thing is, carving up time is inherently political, because scientists are not the only ones who use geological labels. The public uses them too. They feature in our school textbooks, our museum exhibits, and even our music.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DDijPm">
The term “Anthropocene” is already widely used and understood — in 2020, the musician Grimes even released an album dubbed <em>Miss Anthropocene</em>. The term has become a way to get people to take climate change more seriously.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8wSgSp">
While some scientists were <a href="https://www.nytimes.com/2022/12/17/climate/anthropocene-age-geology.html">uncomfortable</a> with the idea of using the “Anthropocene” label to make a political statement about what humanity is doing to the planet, other scholars embraced that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Vrneuj">
The geologist Emlyn Koster, for example, <a href="https://www.nytimes.com/2022/12/17/climate/anthropocene-age-geology.html#:~:text=Ten%20thousand%20years%20after%20our,Anthropocene%2C%20the%20age%20of%20humans.">told</a> the New York Times in 2022 that geologists shouldn’t think of defining the Anthropocene as solely the AWG’s business. “I always saw it not as an internal geological undertaking,” he said, “but rather one that could be greatly beneficial to the world at large.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jp1Y0E">
Now that the Subcommission on Quaternary Stratigraphy, the body in charge of recognizing geological time units, has rejected “Anthropocene” as a new epoch, some scientists are at pains to emphasize that humans are still screwing up badly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SbV1Xz">
“We are in the Anthropocene, irrespective of a line on the time scale,” <a href="https://www.nytimes.com/2024/03/05/climate/anthropocene-epoch-vote-rejected.html#:~:text=Francine%20M.G.,%2C%E2%80%9D%20Dr.%20McCarthy%20said.">said</a> Francine McCarthy, an earth scientist at Canada’s Brock University who participated in the AWG. “And behaving accordingly is our only path forward.”
</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>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bZwgNI">
</p></li>
<li><strong>How Nvidia beat everyone else in the AI race</strong> -
<figure>
<img alt="A close-up of an Nvidia-made computer chip with its name and logo printed on it." src="https://cdn.vox-cdn.com/thumbor/idto3H4hU1r9hS-Dg-Awi5h3bNc=/198x0:3347x2362/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/73188457/GettyImages_1251437220.0.jpg"/>
<figcaption>
Nvidia, founded in California in 1993, originally made chips mainly used for gaming. | Jakub Porzycki/NurPhoto via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The company you might not have heard of is now worth $2 trillion — more than Google or Amazon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="69v4Cs">
Only four companies in the world are worth over $2 trillion. <a href="https://www.vox.com/apple">Apple</a>, <a href="https://www.vox.com/microsoft">Microsoft</a>, the oil company Saudi Aramco — and, as of 2024, Nvidia. It’s understandable if <a href="https://www.bloomberg.com/news/newsletters/2023-08-25/how-do-you-say-nvidia-despite-its-growth-pronunciation-bedevils-people">the name doesn’t ring a bell</a>. The company doesn’t exactly make a shiny product attached to your hand all day, every day, as Apple does. Nvidia designs a chip hidden deep inside the complicated innards of a computer, a seemingly niche product more are relying on every day.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TbvtWN">
Rewind the clock back to 2019, and Nvidia’s market value was hovering around <a href="https://www.sec.gov/Archives/edgar/data/1045810/000104581020000010/nvda-2020x10k.htm">$100 billion</a>. Its incredible speedrun to 20 times that already enviable size was really enabled by one thing — the <a href="https://www.vox.com/2023/4/28/23702644/artificial-intelligence-machine-learning-technology">AI</a> craze. Nvidia is arguably the biggest winner in the AI industry. ChatGPT-maker OpenAI, which catapulted this obsession into the mainstream, is currently worth around <a href="https://www.nytimes.com/2024/02/16/technology/openai-artificial-intelligence-deal-valuation.html">$80 billion</a>, and according to market research firm <a href="https://www.grandviewresearch.com/industry-analysis/artificial-intelligence-ai-market">Grand View Research</a>, the entire global AI market was worth a bit under $200 billion in 2023. Both are just a paltry fraction of Nvidia’s value. With all eyes on the company’s jaw-dropping evolution, the real question now is whether Nvidia can hold on to its lofty perch — but here’s how the company got to this level.
</p>
<h3 id="hJ6CY4">
From games to crypto mining to AI
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XojKWO">
In 1993, long before uncanny AI-generated art and amusing AI chatbot convos took over our social media feeds, three Silicon Valley electrical engineers launched a startup that would focus on an exciting, fast-growing segment of personal computing: <a href="https://www.nytimes.com/1993/09/16/nyregion/video-violence-it-s-hot-it-s-mortal-it-s-kombat-teen-agers-eagerly-await.html">video games</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4lW14T">
Nvidia was founded to design a specific kind of chip called a graphics card — also commonly called a GPU (graphics processing unit) — that enables the output of fancy 3D visuals on the computer screen. The better the graphics card, the more quickly high-quality visuals can be rendered, which is important for things like playing games and video editing. In the <a href="https://d18rn0p25nwr6d.cloudfront.net/CIK-0001045810/e198721c-58f6-4772-8633-cb95ca474654.pdf">prospectus</a> filed ahead of its initial public offering in 1999, Nvidia noted that its future success would depend on the continued growth of computer applications relying on 3D graphics. For most of Nvidia’s existence, game graphics were Nvidia’s raison d’etre.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PL5ODt">
Ben Bajarin, CEO and principal analyst at the tech industry research firm Creative Strategies, acknowledged that Nvidia had been “relatively isolated to a niche part of computing in the market” until recently.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QuUoYV">
Nvidia became a powerhouse selling cards for video games — now an entertainment industry juggernaut making <a href="https://www.latimes.com/entertainment-arts/business/story/2023-08-21/global-gaming-industry-report-2023-league-of-legends-activision-electronic-arts-nintendo-mobile-gaming-mario-bros">over $180 billion in revenue</a> last year — but it realized it would be smart to branch out from just making graphics cards for games. Not all its experiments panned out. Over a decade ago, Nvidia made a failed gambit to become a major player in the <a href="https://www.reuters.com/article/idUSN30427294/">mobile chip market</a>, but today <a href="https://www.counterpointresearch.com/insights/global-smartphone-ap-market-share/">Android phones use a range of non-Nvidia chips</a>, while iPhones use Apple-designed ones.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5hpBUk">
Another play, though, not only paid off, it became the reason we’re all talking about Nvidia today. In 2006, the company released a programming language called CUDA that, in short, unleashed the power of its graphics cards for more general computing processes. Its chips could now do a lot of heavy lifting for tasks unrelated to pumping out pretty game graphics, and it turned out that graphics cards could multitask even better than the CPU (central processing unit), what’s often called the central “brain” of a computer. This made Nvidia’s GPUs great for calculation-heavy tasks like machine learning (and, crypto mining). 2006 was the same year <a href="https://www.vox.com/amazon">Amazon</a> launched its cloud computing business; Nvidia’s push into general computing was coming at a time when massive data centers were popping up around the world.
</p>
<div class="c-float-right">
<aside id="0vucfE">
<q>Nvidia has joined the ranks of tech titans designated the “Magnificent Seven”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oHvnLq">
That Nvidia is a powerhouse today is especially notable because for most of Silicon Valley’s history, there already was a chip-making goliath: Intel. Intel makes both CPUs and GPUs, as well as other products, and it manufactures its own semiconductors — but after a <a href="https://www.vox.com/2016/4/20/11463818/intel-iphone-mobile-revolution">series of missteps</a>, including not investing into the development of AI chips soon enough, the rival chipmaker’s preeminence has somewhat faded. In 2019, when Nvidia’s market value was just over the $100 billion mark, <a href="https://www.intc.com/filings-reports/annual-reports/content/0000050863-20-000011/0000050863-20-000011.pdf">Intel’s value</a> was double that; now Nvidia has joined the ranks of tech titans designated <a href="https://www.cnbc.com/2024/02/19/magnificent-7-profits-now-exceed-almost-every-country-in-the-world-should-we-be-worried.html">the “Magnificent Seven”</a>, a cabal of tech <a href="https://www.vox.com/stock-market">stocks</a> with a combined value that exceeds the entire stock market of many rich G20 countries.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="u9Wp8x">
“Their competitors were asleep at the wheel,” says Gil Luria, a senior analyst at the financial firm D.A. Davidson Companies. “Nvidia has long talked about the fact that GPUs are a superior technology for handling accelerated computing.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OZzGSL">
Today, Nvidia’s four main markets are gaming, professional visualization (like 3D design), data centers, and the automotive industry, as it provides chips that train self-driving technology. A few years ago, its gaming market was still the biggest chunk of revenue at about <a href="https://www.sec.gov/Archives/edgar/data/1045810/000104581020000010/nvda-2020x10k.htm">$5.5 billion</a>, compared to its data center segment, which raked in about $2.9 billion. Then the pandemic broke out. People were spending a lot more time at home, and demand for computer parts, including GPUs, shot up — gaming revenue for the company in fiscal year 2021 jumped a whopping 41 percent. But there were already signs of the coming AI wave, too, as Nvidia’s data center revenue soared by an <a href="https://www.sec.gov/Archives/edgar/data/1045810/000104581021000010/nvda-20210131.htm">even more impressive 124 percent</a>. In 2023, its revenue was <a href="https://www.cnbc.com/2024/02/21/nvidias-data-center-business-is-booming-up-over-400percent-since-last-year-to-18point4-billion-in-fourth-quarter-sales.html">400 percent</a> higher than the year before. In a clear display of how quickly the AI race ramped up, data centers have overtaken games, even in a gaming boom.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="thZ1GJ">
When it went public in 1999, Nvidia had <a href="https://www.wsj.com/articles/SB917224371262043000">250 employees</a>. Now it has over <a href="https://media.iprsoftware.com/219/files/202311/corporate-nvidia-in-brief-pdf-december-3056300-r2-2.pdf?Signature=j%2FonafsYJugHfH6cXe%2FdwO6g%2Bns%3D&amp;Expires=1709842242&amp;AWSAccessKeyId=AKIAJX7XEOOELCYGIVDQ&amp;versionId=Kg1wCZP.LuqFtUOJi3dAakvjMU.DGF27&amp;response-content-disposition=attachment">27,000</a>. Jensen Huang, Nvidia’s CEO and one of its founders, has a personal net worth that currently hovers around $70 billion, an over 1,700 percent increase <a href="https://www.forbes.com/profile/jensen-huang-1/?sh=5edc5583a6c4">since 2019</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iG3rOo">
It’s likely you’ve already brushed up against Nvidia’s products, even if you don’t know it. Older gaming consoles like the <a href="https://www.cnet.com/tech/tech-industry/nvidia-to-work-on-playstation-3-chip/">PlayStation 3</a> and the <a href="https://www.techpowerup.com/gpu-specs/xbox-gpu.c1866">original Xbox</a> had Nvidia chips, and the current Nintendo Switch uses an Nvidia mobile chip. Many mid- to high-range laptops come packed up with an Nvidia graphics card as well.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8KgNkY">
But with the AI bull rush, the company promises to become more central to the tech people use every day. <a href="https://finance.yahoo.com/news/tesla-ceo-elon-musk-were-using-a-lot-of-nvidia-hardware-174620935.html">Tesla cars’ self-driving feature</a> utilizes Nvidia chips, as do practically all major tech companies’ cloud computing services. These services serve as a backbone for so much of our daily internet routines, whether it’s streaming content on <a href="https://www.vox.com/netflix">Netflix</a> or using office and productivity apps. To train ChatGPT, OpenAI harnessed tens of thousands of <a href="https://www.bloomberg.com/news/articles/2023-03-13/microsoft-built-an-expensive-supercomputer-to-power-openai-s-chatgpt">Nvidia’s AI chips</a> together. People underestimate <a href="https://www.youtube.com/watch?v=YsZ-lx_3eoM">how much they use AI</a> on a daily basis, because we don’t realize that some of the automated tasks we rely on have been boosted by AI. Popular apps and social media platforms are adding new AI features seemingly every day: TikTok, <a href="https://www.vox.com/instagram-news">Instagram</a>, X (formerly <a href="https://www.vox.com/twitter">Twitter</a>), even <a href="https://www.vox.com/pinterest">Pinterest</a> all boast some kind of AI functionality to toy with. <a href="https://www.vox.com/slack">Slack</a>, a messaging platform that many workplaces use, recently <a href="https://slack.com/blog/transformation/how-we-designed-slack-ai">rolled out the ability to use AI</a> to generate thread summaries and recaps of Slack channels.
</p>
<h3 id="gQOgG9">
Nvidia’s chips continue to sell out — for now
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UwIaQl">
For Nvidia’s customers, the problem with sizzling demand is that the company can charge eye-wateringly high prices. The chips used for AI data centers cost tens of thousands of dollars, with the top-of-the-line product sometimes <a href="https://www.cnbc.com/2023/04/14/nvidias-h100-ai-chips-selling-for-more-than-40000-on-ebay.html">selling for over $40,000</a> on sites like Amazon and eBay. Last year, some clients clamoring for Nvidia’s AI chips were <a href="https://www.trendforce.com/news/2024/02/28/news-nvidias-h100-ai-chip-no-longer-out-of-reach-inventory-pressure-reportedly-forces-customers-to-resell/">waiting as much as 11 months</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zYTeOq">
Just think of Nvidia as the <a href="https://www.cnn.com/style/hermes-birkin-bag-origins-cost/index.html">Birkin bag</a> of AI chips. A comparable offering from another chipmaker, AMD, is reportedly being sold to customers like Microsoft for <a href="https://seekingalpha.com/news/4061277-amds-35b-ai-guidance-is-sandbagged-citi-say">about $10,000 to $15,000</a>, just a fraction of what <a href="https://www.reuters.com/technology/nvidia-chases-30-billion-custom-chip-market-with-new-unit-sources-2024-02-09/">Nvidia charges</a>. It’s not just the AI chips, either. Nvidia’s gaming business continues to boom, and the price gap between its high-end gaming card and a similarly performing one from AMD has been <a href="https://www.theverge.com/2022/11/16/23462949/nvidia-amd-rtx-4080-rdna-3-7900-xt-price-size">growing wider</a>. In its last financial quarter, Nvidia reported a gross margin of <a href="https://nvidianews.nvidia.com/news/nvidia-announces-financial-results-for-fourth-quarter-and-fiscal-2024">76 percent</a>. As in, it cost them just 24 cents to make a dollar in sales. AMD’s most recent gross margin was only <a href="https://ir.amd.com/news-events/press-releases/detail/1180/amd-reports-fourth-quarter-and-full-year-2023-financial">47 percent</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mGOOdp">
Nvidia’s fans argue that its yawning lead was earned by making an early bet that AI would take over the world — its chips are worth the price because of its superior software, and because so much of AI infrastructure has already been built around Nvidia’s products. But Erik Peinert, a research manager and editor at the American Economic Liberties Project who helped put together a <a href="https://www.economicliberties.us/our-work/reshoring-and-restoring-chips-implementation-for-a-competitive-semiconductor-industry/">recent report</a> on competition within the chip industry, notes that Nvidia has gotten a price boost because TSMC, the biggest semiconductor maker in the world, has <a href="https://www.reuters.com/technology/tsmc-q4-profit-falls-19-beats-market-expectations-2024-01-18/">struggled for years to keep up</a> with demand. A recent <a href="https://www.wsj.com/tech/ai/nvidia-ceo-jensen-huang-vision-company-f05db212">Wall Street Journal</a> report also suggested that the company may be throwing its weight around to maintain dominance; the CEO of an AI chip startup called Groq claimed that customers were scared Nvidia would punish them with order delays if it got wind they were meeting with other chip makers.
</p>
<div class="c-float-right">
<aside id="V9cxx2">
<q>“The biggest challenge for Nvidia is that their customers want to compete with them”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SMweuQ">
It’s undeniable that Nvidia put in the investment into courting the AI industry well before others started paying attention, but its grip on the market isn’t unshakable. An army of competitors are on the march, ranging from <a href="https://www.nytimes.com/2024/01/29/technology/ai-chips-nvidia-amazon-google-microsoft-meta.html">smaller startups to deep-pocketed opponents</a>, including Amazon, <a href="https://www.vox.com/meta">Meta</a>, Microsoft, and <a href="https://www.vox.com/google">Google</a>, all of which currently use Nvidia chips. “The biggest challenge for Nvidia is that their customers want to compete with them,” says Luria.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bBU1HQ">
It’s not just that their customers want to make some of the money that Nvidia has been raking in — it’s that they can’t afford to keep paying so much. Microsoft “went from spending less than 10 percent of their capital expenditure on Nvidia to spending nearly 40 percent,” Luria says. “That’s not sustainable.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B4iOOx">
The fact that <a href="https://fortune.com/2024/02/22/what-does-nvidia-do-chips-ai-jensen-huang/">over 70 percent of AI chips</a> are bought from Nvidia is also cause for concern for <a href="https://www.vox.com/antitrust">antitrust</a> regulators around the world — the <a href="https://www.vox.com/european-union">EU</a> recently started <a href="https://www.bloomberg.com/news/articles/2023-09-29/eu-begins-early-stage-probe-into-ai-chip-market-abuses-that-nvidia-dominates">looking into the industry</a> for potential antitrust abuses. When Nvidia <a href="https://nvidianews.nvidia.com/news/nvidia-to-acquire-arm-for-40-billion-creating-worlds-premier-computing-company-for-the-age-of-ai">announced in late 2020</a> that it wanted to spend an eye-popping $40 billion to buy Arm Limited, a company that designs a chip architecture that most modern smartphones and newer Apple computers use<a href="https://nvidianews.nvidia.com/news/nvidia-to-acquire-arm-for-40-billion-creating-worlds-premier-computing-company-for-the-age-of-ai">,</a> <a href="https://www.ftc.gov/legal-library/browse/cases-proceedings/2110015-nvidiaarm-matter">the FTC blocked the deal</a>. “That acquisition was pretty clearly intended to get control over a software architecture that most of the industry relied on,” says Peinert. “The fact that they have so much pricing power, and that they’re not facing any effective competition, is a real concern.”
</p>
<h3 id="kdWWJf">
Will the AI love affair cool off?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="asFFEh">
Whether Nvidia will sustain itself as a $2 trillion company — or rise to even greater heights — depends, fundamentally, on whether both consumer and investor attention on AI can be sustained. Silicon Valley is awash with newly founded AI companies, but what <a href="https://www.wsj.com/tech/ai/ais-costly-buildup-could-make-early-products-a-hard-sell-bdd29b9f">percentage of them will take off</a>, and how long will funders keep pouring money into them?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HcM7WR">
Widespread AI awareness came about because ChatGPT was an easy-to-use — or at least easy-to-show-off-on-social-media — novelty for the general public to get excited about. But a lot of AI work is still focusing on AI training rather than what’s called AI inferencing, which involves using trained AI models to solve a task, like the way that ChatGPT answers a user’s query or facial recognition tech identifies people. Though the AI inference market is growing (and maybe <a href="https://www.wsj.com/tech/ai/how-a-shifting-ai-chip-market-will-shape-nvidias-future-f0c256b1">growing faster than expected</a>), much of the sector is still going to be spending a lot more time — and money — on training. For training, Nvidia’s first-class chips will likely remain the most coveted, at least for a while. But once AI inferencing explodes, there will be less of a need for such high-performance chips, and Nvidia’s primacy could slip.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DPmGs1">
Some financial analysts and industry experts have expressed wariness over <a href="https://apolloacademy.com/the-current-ai-bubble-is-bigger-than-the-1990s-tech-bubble/">Nvidia’s stratospheric valuation</a>, suspecting that AI enthusiasm will slow down and that there may already be <a href="https://www.ft.com/content/dc47c5f3-9bd4-4da0-a5cb-c795efd14c9c">too much money going toward</a> making AI chips. Traffic to <a href="https://www.reuters.com/technology/chatgpt-traffic-slips-again-third-month-row-2023-09-07/">ChatGPT has dropped off</a> since last May and some investors are <a href="https://www.theinformation.com/articles/some-ai-startups-find-the-moneys-no-longer-so-easy">slowing down the money hose</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ar2FGy">
“Every big technology goes through an adoption cycle,” says Luria. “As it comes into consciousness, you build this huge hype. Then at some point, the hype gets too big, and then you get past it and get into the trough of disillusionment.” He expects to see that soon with AI — though that doesn’t mean it’s a bubble.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7LAFXe">
Nvidia’s revenue last year was about <a href="https://nvidianews.nvidia.com/news/nvidia-announces-financial-results-for-fourth-quarter-and-fiscal-2024">$60 billion</a>, which was a 126 percent increase from the prior year. Its high valuation and stock price is based not just on that revenue, though, but for its predicted continued growth — for comparison, Amazon currently has a lower market value than Nvidia yet made almost <a href="https://ir.aboutamazon.com/news-release/news-release-details/2024/Amazon.com-Announces-Fourth-Quarter-Results/">$575 billion in sales</a> last year. The path to Nvidia booking large enough profits to justify the <a href="https://fortune.com/2024/02/22/nvidia-stock-price-earnings-investors-outlook/">$2 trillion valuation looks steep</a> to some experts, especially knowing that the competition is kicking into high gear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E9k1es">
There’s also the possibility that Nvidia could be stymied by how fast microchip technology can advance. It has moved at a blistering pace in the last several decades, but there are signs that the pace at which more transistors can be fitted onto a microchip — making them smaller and more powerful — is <a href="https://www.wsj.com/articles/tech-progress-is-slowing-down-b7fcaee0">slowing down</a>. Whether Nvidia can keep offering meaningful hardware and software improvements that convince its customers to buy its latest AI chips could be a challenge, says Bajarin.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OB4I2I">
Yet, for all these possible obstacles, if one were to bet whether Nvidia will soon become as familiar a tech company as Apple and Google, the safe answer is yes. AI fever is why Nvidia is in the rarefied club of trillion-dollar companies — but it may be just as true to say that AI is so big because of Nvidia.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="F7Cwwa">
</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>Golden Neil and Earth catch the eye</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>Aldgate, Promiseofthefuture, True Punch and Martha impress</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>Sanjeet goes down to Aibek Oralbay</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>Daily Quiz | On Ravichandran Ashwin</strong> - A quiz on R. Ashwin and his many milestones as he gears up for his 100th 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>Marais Erasmus draws curtain on umpiring career</strong> - The 60-year-old Erasmus, whose long career as an umpire began in 2006, on March 7 announced his decision to retire from Emirates ICC Elite Panel of Umpires.</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>Collaboration to deal with zero-value plastics in Coonoor announced</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>Explore Mysuru on tonga, Karanji lake will be linked with zoo and Regional Museum of Natural History in Swadesh Darshan initiative</strong> - The project will enhance the experience of people visiting Mysuru and provide a good look into the city’s abundant natural beauty</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>Sharad Pawar says BJP is ‘washing machine’ which people facing graft charges can join and become clean</strong> - He accused the Centre of targeting the chief ministers of non BJP-ruled states.</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>Plan to promote aromatic crops in the State through ‘Aroma Mission’</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>MHA designates Mohammad Qasim Gujjar as ‘individual terrorist’</strong> - The MHA said that he is presently residing in PoK and belongs to Lashkar-e-Taiba (LeT), a terrorist outfit</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>‘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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two Brighton fans stabbed before Roma match</strong> - Two Brighton &amp; Hove Albion fans have since been discharged from hospital.</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 world’s largest robots are setting sail</strong> - Ocean-going vessels with no-one on board - a vision of the future that’s coming faster you think.</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>Explosions hit Odesa as Zelensky meets Greek PM</strong> - Ukraine’s navy says five people have been killed after missile strikes in the southern port city.</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>Navalny’s widow urges Russians to protest on election day</strong> - Yulia Navalnaya urges opponents of Vladimir Putin to form long queues at polling stations at the same time.</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>Russia’s next-generation rocket is a decade old and still flying dummy payloads</strong> - Russia’s heavy-lift Angara A5 rocket is about to launch on its fourth test flight. - <a href="https://arstechnica.com/?p=2008459">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Some teachers are now using ChatGPT to grade papers</strong> - New AI tools aim to help with grading and lesson plans—but they may have serious drawbacks. - <a href="https://arstechnica.com/?p=2008453">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Microsoft accused of selling AI tool that spews violent, sexual images to kids</strong> - It looks like Microsoft may be filtering violent AI outputs flagged by engineer. - <a href="https://arstechnica.com/?p=2008483">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Samsung is making it harder to know what type of OLED TV you’re getting</strong> - QD-OLED or classic WOLED? Samsung reportedly won’t tell. - <a href="https://arstechnica.com/?p=2008256">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“It‘s kind of depressing”: WB Discovery pulls indie game for “business changes”</strong> - Developer makes <em>Small Radios Big Televisions</em> free to download in response. - <a href="https://arstechnica.com/?p=2008282">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>Steve dies and goes to Heaven, where St Peter informs him that he’ll have to share apartment with someone else.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“You see, it’s getting a bit crowded up here”, St Peter explains.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What kind of roommate will I get?” Steve asks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“A gentleman from 14th century Mexico.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Medieval Mexico?!” Steve exclaims. “But I’m from 21st century Britain! We’ll have nothing in common!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I’m sure you’ll find something to talk about if you try”, says St Peter.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So Steve is shown to his heavenly home and is introduced to a shy, skinny fellow whom he’s supposed to share it with.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“So what did you work as?” asks Steve.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Peasant”, says the Mexican.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“How was that?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Hard.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I was a web designer.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What’s that?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I don’t know how to explain it to you, sorry. Did you have hobbies? Mine was old cars.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I don’t understand.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Thus the conversation continues, both men struggling to keep it going, both fearing an eternity of awkwardness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Then the Mexican asks: “How did you die?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well…” Steve hesitates. “To be honest, I died because my life had become too difficult for me to handle.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Why had it become so difficult?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I fell for a pyramid scheme. You see, my heart was stolen by someone who only wanted to use me.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Mexican beams with relief. “What a coincidence!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/OskarTheRed"> /u/OskarTheRed </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b7yytf/steve_dies_and_goes_to_heaven_where_st_peter/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b7yytf/steve_dies_and_goes_to_heaven_where_st_peter/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s brown and rhymes with snoop?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Dr. Dre
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Conehead1"> /u/Conehead1 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b8ebxc/whats_brown_and_rhymes_with_snoop/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b8ebxc/whats_brown_and_rhymes_with_snoop/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How do we know Steve Irwin didn’t wear sunscreen?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sunscreen protects you from harmful rays.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/PrinceBarin"> /u/PrinceBarin </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b8g2y5/how_do_we_know_steve_irwin_didnt_wear_sunscreen/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b8g2y5/how_do_we_know_steve_irwin_didnt_wear_sunscreen/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>As the blonde licked my balls, I wondered …</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Was this her first tennis lesson?
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Comfortable_Fly_3050"> /u/Comfortable_Fly_3050 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b8qw3o/as_the_blonde_licked_my_balls_i_wondered/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b8qw3o/as_the_blonde_licked_my_balls_i_wondered/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A teacher asks her class for some examples of medicines they know</strong> - <!-- SC_OFF --></p>
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Little Harry promptly raises his hands and says, “Tylenol! For headaches!”
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The teacher says, “Very good, Harry, anyone else?”
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Little Jenny answers from the back, “Um, Ambien, my Mom tells me it helps her sleep…?”
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The teacher smiles at her and says, “Good job, Jenny,” then turns to her class and goes on, “Listen here children, always be careful with medicines at home, okay? Now, does anyone else have another example?”
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Little Johnny raises his hands slowly and says, “Viagra? For diarrhea?”
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The teacher freezes for a second, before the rest of his statement hits her and she stammers out, “F-for diarrhea?”
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Little Johnny explains, “Yeah, my Mom keeps telling my dad to take it, it’ll harden his shit up.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/fudgemental"> /u/fudgemental </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1b899i7/a_teacher_asks_her_class_for_some_examples_of/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1b899i7/a_teacher_asks_her_class_for_some_examples_of/">[comments]</a></span></p></li>
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