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<title>25 March, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Concerns about data integrity of 30 randomized clinical trials from one author.</strong> -
<div>
Introduction In 2021, we learnt about the problems in studies on ivermectin and hydrocholoroquine in COVID-19. We noticed an appreciable number of unfunded randomised clinical trials (RCTs) on the treatment of COVID-19 conducted across three centres in Egypt (Tanta University, Assiut University, Ain-shams University) on COVID-19 patients with similar inclusion criteria and overlapping time frames. Dr Sherief M Abd-Elsalam ran seven such RCTs across these three centres; four of these RCTs have since been retracted. We therefore set out to systematically analyse the integrity of all RCTs (co-)authored by Dr Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. Methods We searched PubMed, Google Scholar, Scopus and clinical trial registries for RCTs published by Dr Sherief M Abd-Elsalam, affiliated with the Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt. We assessed trial registration, tables for identical data values, statistical errors, and improbable data trends. We assessed the probability of true randomization by assessing baseline characteristics through a Monte Carlo Analysis. Results We report on 30 published randomized control trials (RCTs) of Dr. Sherief Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. We found important issues in all RCTs examined. Of these 23 RCTs, 10 RCTs had substantial trial registration inconsistencies. Only one of these 10 RCTs has been retracted to date. We found nine RCTs with substantial statistical mistakes, five RCTs with similarities between tables unlikely to happen by chance, four RCTs with implausible Gaussian distributions, three RCTs in which almost all dichotomous variables had even values, while part of at least one study was plagiarized. Monte Carlo analysis indicated that the probability that distribution of baseline characteristics due to randomisation was 0.0000228. According to the trial registration, Dr. Abd-Elsalam is coordinating 76 clinical trials with 45 trials currently marked as ‘Recruiting’ and 17 trials marked as ‘Unknown Status’ as of November 2022. Interpretation We strongly recommend a thorough investigation of the data integrity of all RCTs by Dr Sherief M Abd-Elsalam by journal editors. Until the completion of such an investigation, we suggest that none of these studies are used to inform clinical practice.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/vjcnp/" target="_blank">Concerns about data integrity of 30 randomized clinical trials from one author.</a>
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<li><strong>False Information Literacy During the Covid-19 Pandemic</strong> -
<div>
The COVID-19 pandemic is a confusing time. Because COVID-19 was a new evolution of a virus, much of the information surrounding it was ever-evolving. Although a vaccine was quickly developed, and it was approved by the FDA for emergency use, people were still skeptical of its efficacy and safety. Malicious internet users chose to spread mis- and disinformation about the vaccine. An explosion of information literacy has accompanied the spread of misinformation. Specifically, people used the internet to combat misinformation and spread true information about both the virus and its corresponding vaccine. By using a case study of an article, I choose to explore the methods in which malicious users spread misinformation and specifically the language used to spread this misinformation. While doctors and other public health experts have used the internet to argue against misinformation, malicious users have also used their medical qualifications, applicable or otherwise, to demonstrate credibility. Similarly, arguments such as “believe science” or “trust the evidence” have been twisted to spread misinformation. Finally, visualizations showing a false relationship between otherwise-unrelated topics spread quickly. While information literacy is an important tool, malicious users have co-opted the language used to obtain credibility. Identifying the forms that this false information literacy takes is one step in understanding how to combat it.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/mdwrx/" target="_blank">False Information Literacy During the Covid-19 Pandemic</a>
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<li><strong>The COVID-19 impact on tuberculosis incidence notification in India- A comparative study (2017-2022)</strong> -
<div>
Abstract - Despite modern drugs treatment with 60 years of chemotherapy and 90 years of vaccination with various strategies to prevent and control tuberculosis (TB), globally TB ranks 13th in leading causes of mortality. In recent year 2021 Worldwide, TB ranks 2nd after COVID-19, in leading causes of infectious killer, killing about 1.6 million people in 2021 (including 187 000 people infected with HIV). During COVID-19 era 2020, very significant global reduction in TB incidence was detected, which suddenly reduced from 7.1 million in 2019, to 5.8 million in 2020 (–18 percent). Globally, India is listed among the top three countries accounting for 67percent of this global reduction in TB incidence, besides Indonesia and the Philippines. As per data of The World Bank, India’s annual TB incidence was falling continuously since 2000, rose again and reached 210/100,000 in 2021 from 204/100,000 in 2020. A modelling analysis study found that lockdown has induced 80 percent reduction in TB notification rates in India. India ranks fourth in infection and death from COVID-19; hence there is a possibility that slowing down of COVID-19 will unmask the TB cases and deaths leading to increase in the count of TB in future years. In spite of several similarities in manifestation and differences in aetiology, there is still lack of full knowledge about the epidemiological relationship between TB and COVID-19 .To know the real situation and scenario of TB cases this study was started with aim to alert policy maker for needful action to control TB effectively in time. This study aimed to know the impact of COVID-19 on annual TB notifications incidence in India. This is a cross-sectional, quantitative, retrospective, deductive study. This research study included all the 36 states and UTs of India. We performed a linear regression study of the existing data of pre pandemic years included in this study for calculating a counterfactual analysis in order to find out the possible real incidence of TB cases notifications, which may have been notified if the current natural intervention of COVID-19 had not taken place. The annual number of new (TB) cases detected during the pre-COVID-19 period as well as COVID-19 period of this study has shown similar trends separately. During both periods the number of new (TB) cases increased in consecutive years. Another significant finding of this study is that the number of new (TB) cases detected during the first two COVID-19 years i.e. 2020 and 2021 decreased in comparison to last pre-COVID-19 year i.e. 2019. The base year of this study i.e. 2017 are having least whereas the last year of this study i.e. 2022 are having the largest number of new (TB) cases detected in one individual year. There is an increase of 7.79 percent in TB case detection during the COVID-19 period of this study. This study revealed that during first COVID-19 year i.e. 2020 there is significant reduction in number of new (TB) cases detected by 580869 numbers or 24.29 percent in comparison to last pre-COVID-19 year i.e. 2019. The number of new (TB) cases detected increased continuously during pre-COVID-19 years by 29.59 percent in 2018 and 18.49 percent in 2019. The question arises from this study is that, is it possible to achieve the goal of NTEP by year 2025 in current scenario reality?
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/wucgb/" target="_blank">The COVID-19 impact on tuberculosis incidence notification in India- A comparative study (2017-2022)</a>
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<li><strong>Obesity and Smoking: A Tale of 2 Risk Factors with Implications for the Next Pandemic</strong> -
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Background: In 1990, two risk factors that would figure prominently in the COVID-19 pandemic were on divergent paths in the US. The smoking rate was 23.5% and dropped to 13.5% in 2021, while the obesity rate was 11.5% and increased 186% to 33.0%. Objective: The study objective was to compare the global impact of those risk factors on COVID deaths to help prepare the US for future pandemics. Methods: Stata and Excel were used to regress global COVID deaths on obesity and smoking before and after vaccines were available, and US deaths/day were compared pre-and post-vaccines. Results: Obesity was associated with global COVID deaths, with R2 as high as 0.87 for cumulative data with slightly lower R2 and coefficients for post-vaccines. For 9 regressions of deaths on obesity, all P values (overall and coefficients) were &lt;0.05 while for regressions on smoking, no P values were &lt; 0.05. Of the 1.1 million US deaths, the death rate/day post-vaccines was 59% of that pre-vaccines. If the US obesity rate had remained 11.5%, estimates suggest 800,000+ lives could have been saved. US smoking rate was reduced 42% by multiple strategies using support from a 1998 multi-billion-dollar settlement between states and tobacco companies. Conclusion: Vaccines have limited ability to reduce total COVID deaths, with obesity remaining a key factor in death rates. Results suggest that lower obesity rates are needed to further reduce US COVID deaths, potentially saving thousands of lives in future pandemics. Lessons from reducing smoking rates might prove useful.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.23.23287630v1" target="_blank">Obesity and Smoking: A Tale of 2 Risk Factors with Implications for the Next Pandemic</a>
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<li><strong>Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study</strong> -
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Introduction: Three years into the pandemic, there remains significant uncertainty about the true infection and mortality burden of COVID-19 in the WHO-Africa region. High quality, population-representative studies in Africa are rare and tend to be conducted in national capitals or large cities, leaving a substantial gap in our understanding of the impact of COVID-19 in rural, low-resource settings. Here, we estimated the spatio-temporal morbidity and mortality burden associated with COVID-19 in a rural health district of Madagascar until the first half of 2021. Methods: We integrated a nested seroprevalence study within a pre-existing longitudinal cohort conducted in a representative sample of 1600 households in Ifanadiana District, Madagascar. Socio-demographic and health information was collected in combination with dried blood spots for about 6500 individuals of all ages, which were analysed to detect IgG and IgM antibodies against four specific proteins of SARS-CoV2 in bead-based multiplex immunoassay. We evaluated spatio-temporal patterns in COVID-19 infection history and its associations with several geographic, socio-economic and demographic factors via logistic regressions. Results: Eighteen percent of people had been infected by April-June 2021, with seroprevalence increasing with individuals age. COVID-19 primarily spread along the only paved road and in major towns during the first epidemic wave, subsequently spreading along secondary roads during the second wave to more remote areas. Wealthier individuals and those with occupations such as commerce and formal employment were at higher risk of being infected in the first wave. Adult mortality increased in 2020, particularly for older men for whom it nearly doubled up to nearly 40 deaths per 1000. Less than 10% of mortality in this period could be directly attributed to COVID-19 deaths given known infection fatality ratios and observed seroprevalence in the district. Conclusion: Our study provides a very granular understanding on COVID-19 transmission and mortality in a rural population of sub-Saharan Africa and suggests that the disease burden in these areas may have been substantially underestimated.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.24.23287674v1" target="_blank">Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study</a>
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<li><strong>“It’s no use saying it in English”: A qualitative study exploring community leaders’ perceptions of the challenges and opportunities with translating and interpreting COVID-19 related public health messaging to reach ethnic minorities in Australia</strong> -
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Background: The Australian Government implemented a range of public health response strategies and communication approaches to reduce the spread of COVID-19; however, concerns have been raised around a failure to consider culturally and linguistically diverse (CaLD) communities sufficiently in these processes. This research aimed to understand the factors that have impacted COVID-19 communication and engagement efforts during the pandemic from the perspective of key CaLD community stakeholders and community members. A further aim was to understand the processes that could be adopted to support future communication strategies, including the promotion of pandemic-related vaccines. Approach: This study included 29 key informant interviews with community and faith-based leaders in New South Wales, Australia. Results: The overwhelming message from community leaders was a sense of shared responsibility between their organisations and the government in communicating pertinent and accurate COVID-19 related information to CaLD communities. They expressed a sense of duty to keep their community members safe. While acknowledging this shared responsibility, community leaders and others shouldered significant costs related to resources and time that need to be acknowledged by governments in preparing for future disease outbreaks. They felt that governments should consider: 1) improving communication between governments and CaLD organisations; 2) responding to the specific CaLD needs with greater agility; 3) foregrounding social media in their communication strategy; 4) reinvesting in local public health units to know their population; 5) investing in a health ambassadors model program; 6) preparing a hybrid model of translators/interpreters to fill the gap; and, 7) reimagining vaccine information campaigns to better target CaLD communities. Conclusion: Given the technical details about the COVID-19 virus conveyed in government information campaigns and the media, ensuring the most vulnerable populations, including people from CaLD backgrounds, access clear, concise and timely public health messaging from both governments and community organisations requires further attention.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.23.23287618v1" target="_blank">“It’s no use saying it in English”: A qualitative study exploring community leaders’ perceptions of the challenges and opportunities with translating and interpreting COVID-19 related public health messaging to reach ethnic minorities in Australia</a>
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<li><strong>SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses</strong> -
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Mucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, little is known about the antibodies present on the nasal mucosal surfaces. In this study, we evaluated SARS-CoV-2 mucosal antibodies in response to infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 136 individuals, which include convalescent, vaccinated, or breakthrough infections. We detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. s-IgA binding antibodies showed significant correlation with neutralizing activity of nasal fluids against SARS-CoV-2 ancestral B.1 and Omicron-BA.5 variant, indicating that s-IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against both SARS-CoV-2 strains was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants. In summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates more potent binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.24.23287677v1" target="_blank">SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses</a>
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<li><strong>Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients</strong> -
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Objective. To evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases. Methods. We collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogrens syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry. Results. Most of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable. Conclusion. Rheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.22.23287597v1" target="_blank">Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients</a>
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<li><strong>Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial</strong> -
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Background: Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19. Methods: This phase 3, randomized, multicenter, open-label study tested non-inferiority of IM to IV administration using a 3.5% absolute non-inferiority margin. From June to August 2021, patients aged ≥12 years with COVID-19, not hospitalized or receiving supplemental oxygen, and at high risk for progression were randomized 1:1:1 to a single 500-mg IV sotrovimab infusion or 500-mg or 250-mg IM sotrovimab injection. The primary composite endpoint was progression to all-cause hospitalization for &gt;24 hours for acute management of illness or all-cause death through day 29. Results: Sotrovimab 500 mg IM was non-inferior to 500 mg IV: 10/376 (2.7%) participants in the sotrovimab 500-mg IM group versus 5/378 (1.3%) in the sotrovimab 500-mg IV group met the primary endpoint (absolute adjusted risk difference: 1.06% [95% confidence interval [CI]: −1.15%, 3.26%]). The CI upper limit was lower than the prespecified non-inferiority margin of 3.5%. 250-mg IM group enrollment was discontinued early because a greater proportion of hospitalizations was seen in that group versus the 500-mg groups. Serious adverse events occurred in &lt;1% to 2% of participants across groups. Four participants experienced serious disease related events and died (500 mg IM: 2/393 [&lt;1%]; 250 mg IM: 2/195 [1%]). Conclusions: Sotrovimab 500-mg IM injection was well tolerated and non-inferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.21.23287410v1" target="_blank">Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial</a>
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<li><strong>Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 antigen testing as a case study</strong> -
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In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multi-scale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing. Considering SARS-CoV-2 as a case study, we quantify the within-host dynamics using data from individuals with omicron variant infections. We demonstrate that regular antigen testing reduces, but may not eliminate, the outbreak risk, depending on characteristics of local transmission. In our baseline analysis, daily antigen testing reduces the outbreak risk by 45% compared to a scenario without antigen testing. Additionally, we show that accounting for heterogeneity in within-host dynamics between individuals affects outbreak risk estimates and assessments of the impact of antigen testing. Our results therefore highlight important factors to consider when using multi-scale models to design pre-emptive interventions against SARS-CoV-2 and other viruses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.23.23287633v1" target="_blank">Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 antigen testing as a case study</a>
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<li><strong>A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8</strong> -
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Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein in this context.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.04.510658v3" target="_blank">A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8</a>
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<li><strong>Bibliometric analysis of the Brazilian scientific response to the Zika epidemic: research pivots and thematic funding</strong> -
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In 2016, in face of the Zika virus outbreak, research funding was made available to study the virus and the scientific community directed its resources correspondingly. This resulted in several publications and increased understanding of the infection, the virus, its vector, associated syndromes and mechanisms. Brazil was particularly affected by the outbreak and at the same time had a prominent position in the global scientific production about the outbreak. In this study, we aim to characterize the researchers who engaged with Zika research in Brazil and how funding policy mediated the redirection of research towards particular themes. We performed a bibliometric assessment of the authors in Brazil who worked on Zika as a case study of how individual scientists respond to major changes in the macro research agenda. Using data from Web of Science, PubMed and the Lattes platform, we investigated (1) the pattern of researcher’s “pivots”, i.e. changes in research direction due to the Zika outbreak and (2) the correspondence between funding mandates and the research output. Our results show that while authors engaged with Zika research coming from more apparently distant fields - such as neuroscience -, most of the authors who studied Zika came from the expected fields and themes - infectious diseases or public health. Using a MeSH term-based classification, we also analyzed the output of a particular grant with an specific research agenda, finding a partial correspondence between the funding mandate and the output produced by the grantees. The results obtained are an important addition to our understanding of how research funding can contribute to preparedness policy - a need made more obvious with the COVID-19 pandemic - while opening up new questions and ways of studying the downstream effects of funding policies on individual scientists’ choices of research paths.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/metaarxiv/apj4c/" target="_blank">Bibliometric analysis of the Brazilian scientific response to the Zika epidemic: research pivots and thematic funding</a>
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<li><strong>Leveraging Machine Learning for Effective Public Health Policies: Lessons from the COVID-19 Pandemic and Future Directions in Global Health</strong> -
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The COVID-19 pandemic has exposed the vulnerabilities of global health systems and highlighted the need for rapid, data-driven decision-making in public health. Machine learning (ML) has the potential to provide valuable insights and contribute to improved health outcomes. In this paper, we aim to explore the role of ML in global health, identify its limitations, and discuss strategies to overcome these challenges while maximizing its benefits. We conduct a comprehensive literature review and analyze case studies from the COVID-19 pandemic. Our findings indicate that ML has played a significant role in the COVID-19 response, particularly in areas such as disease modeling, drug discovery, and resource allocation. However, several limitations, including data quality and accessibility, hinder the full potential of ML in global health. We propose strategies to overcome these limitations, such as promoting data-sharing collaborations, ensuring data privacy, and fostering interdisciplinary research. This paper contributes to the ongoing conversation on the applications and limitations of ML in global health, providing insights and recommendations for researchers, practitioners, and policymakers to effectively leverage ML for improved public health outcomes.
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🖺 Full Text HTML: <a href="https://osf.io/f64cn/" target="_blank">Leveraging Machine Learning for Effective Public Health Policies: Lessons from the COVID-19 Pandemic and Future Directions in Global Health</a>
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<li><strong>Evaluating global interest in biodiversity and conservation</strong> -
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The first target of the Convention for Biological Diversity (Aichi target 1) was to increase public awareness towards the values of biodiversity and actions needed to conserve it - a key prerequisite for other conservation targets. Nevertheless, monitoring success in achieving this target at a global scale is difficult. However, the increased digitization of human life in recent decades offers an insight in people’s interests at an unprecedented scale, which allows a more comprehensive evaluation of success towards Aichi target 1 than previously attempted. Here, we used Google search volume data to evaluate global interest in biodiversity and its conservation, and investigated their correlates across countries. We found that during 2013-2020 global searches for biodiversity increased, driven mostly by searches for charismatic fauna. However, searches for conservation actions, driven mostly by searches for national parks, decreased since 2019 likely due to the COVID-19 pandemic. We further found that economic inequality was negatively correlated with interest in biodiversity and conservation, while purchasing power was indirectly positively correlated through increased education and research. Our results suggest partial success towards achieving Aichi target 1, in that interest in biodiversity has increased widely, but not for conservation. We suggest that increased outreach and education efforts towards neglected aspects of biodiversity and conservation are still needed. Popular topics in biodiversity and conservation could be leveraged to increase awareness of other topics, with attention to local socioeconomic contexts.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/vy65n/" target="_blank">Evaluating global interest in biodiversity and conservation</a>
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<li><strong>Adverse outcomes in SARS-CoV-2 infected pregnant mice are gestational age-dependent and resolve with antiviral treatment</strong> -
<div>
SARS-CoV-2 infection during pregnancy is associated with severe COVID-19 and adverse fetal outcomes, but the underlying mechanisms remain poorly understood. Moreover, clinical studies assessing therapeutics against SARS-CoV-2 in pregnancy are limited. To address these gaps, we developed a mouse model of SARS-CoV-2 infection during pregnancy. Outbred CD1 mice were infected at embryonic day (E) 6, E10, or E16 with a mouse adapted SARS-CoV-2 (maSCV2) virus. Outcomes were gestational age-dependent with greater morbidity, reduced pulmonary function, reduced anti-viral immunity, greater viral titers, and more adverse fetal outcomes occurring with infection at E16 (3rd trimester-equivalent) than with infection at either E6 (1st trimester-equivalent) or E10 (2nd trimester-equivalent). To assess the efficacy of ritonavir-boosted nirmatrelvir (recommended for pregnant individuals with COVID-19), we treated E16-infected dams with mouse equivalent doses of nirmatrelvir and ritonavir. Treatment reduced pulmonary viral titers, decreased maternal morbidity, and prevented adverse offspring outcomes. Our results highlight that severe COVID-19 during pregnancy and adverse fetal outcomes are associated with heightened virus replication in maternal lungs. Ritonavir-boosted nirmatrelvir mitigated adverse maternal and fetal outcomes of SARS-CoV-2 infection. These findings prompt the need for further consideration of pregnancy in preclinical and clinical studies of therapeutics against viral infections.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.23.533961v1" target="_blank">Adverse outcomes in SARS-CoV-2 infected pregnant mice are gestational age-dependent and resolve with antiviral treatment</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>Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>:   AccessBio, Inc.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Safety &amp; Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MIR 19 ®;   Combination Product: Standart therapy<br/><b>Sponsor</b>:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia<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>LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™;   Drug: Placebo<br/><b>Sponsors</b>:   Jose David Suarez, MD;   Sesderma S.L.;   Westchester General Hospital Inc. DBA Keralty Hospital Miami;   MGM Technology Corp<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>MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MP0420;   Drug: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Molecular Partners AG;   University of Minnesota<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>AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AZD7442;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   AstraZeneca;   University of Minnesota<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>PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: PF-07304814;   Drug: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Pfizer;   University of Minnesota<br/><b>Suspended</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>VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: VIR-7831;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Vir Biotechnology, Inc.;   GlaxoSmithKline;   University of Minnesota<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>BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BRII-196;   Biological: BRII-198;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Brii Biosciences Limited;   University of Minnesota<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>LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: LY3819253;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Eli Lilly and Company;   University of Minnesota<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>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>:   Norwegian University of Science and Technology;   University of Oslo<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>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: P1101 (Ropeginterferon alfa-2b);   Procedure: SOC<br/><b>Sponsor</b>:   National Taiwan University Hospital<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>:   WestVac 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>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Recombinant variant COVID-19 vaccine (Sf9 cell);   Biological: Recombinant COVID-19 vaccine (CHO cell);   Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>:   WestVac 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>Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>:   Post COVID-19 Condition<br/><b>Interventions</b>:   Other: Pursed lip breathing;   Other: Cognitive Behavior Therapy;   Other: Diaphragmatic breathing exercise;   Other: Kinesio tape<br/><b>Sponsor</b>:   Cairo University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Calcitriol;   Other: Placebo<br/><b>Sponsor</b>:   Universitas Sebelas Maret<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>Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models</strong> - One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently…</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>Protocol for an Implementation Science Evaluation of Roots of Hope: A Community Suicide Prevention Project</strong> - CONCLUSIONS: The evaluation results, including the identification of factors that facilitate and inhibit the implementation of RoH and adaptations to challenges, should be of use to the MHCC, current RoH communities and those who are considering adopting the RoH model.</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>Levels of Complement Components in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome</strong> - CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the complement system was associated with the pathogenesis of MIS-C and COVID-19 in children; complement inhibition could be further explored as a potential treatment option.</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 antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients</strong> - INTRODUCTION: With the emergence of SARS-CoV-2 mutant strains, especially the epidemic of Omicron, it continues to evolve to strengthen immune evasion. Omicron BQ. 1 and XBB pose a serious threat to the current COVID-19 vaccine (including bivalent mRNA vaccine for mutant strains) and COVID-19-positive survivors, and all current therapeutic monoclonal antibodies are ineffective against them. Older people, those with multimorbidity, and those with specific underlying health conditions remain at…</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>Dynamics of factors associated with rates of COVID-19 cases and deaths in African countries</strong> - CONCLUSION: In African countries, internal movement restrictions enacted to inhibit COVID-19, had the opposite effect and enabled COVID-19 spread. Low Education levels and high unemployment were associated with having higher death rates from COVID-19. More studies are needed to understand the impact of tourism on COVID-19 and other infectious diseases arising from other regions on African countries, in order to put in place adequate control protocols.</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>Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses</strong> - Great interest exists towards the discovery and development of broad-spectrum antivirals. This occurs due to the frequent emergence of new viruses which can also eventually lead to pandemics. A reasonable and efficient strategy to develop new broad-spectrum antivirals relies on targeting a common molecular player of various viruses. Heparan sulfate is a sulfated glycosaminoglycan present on the surface of cells which plays a key role as co-receptor in many virus infections. In previous work,…</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>[Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19</strong> - This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is…</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>Cystic fibrosis transmembrane conductance regulator modulators attenuate platelet activation and aggregation in blood of healthy donors and COVID-19 patients</strong> - Cystic fibrosis transmembrane conductance regulator (CFTR) modulators reduce agonist-induced platelet activation and function. CFTR modulators, such as ivacaftor, present a promising therapeutic strategy in thrombocytopathies, including severe COVID-19. https://bit.ly/3HJykdt</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>Intravenous ravulizumab in mechanically ventilated patients hospitalised with severe COVID-19: a phase 3, multicentre, open-label, randomised controlled trial</strong> - BACKGROUND: The complement pathway is a potential target for the treatment of severe COVID-19. We evaluated the safety and efficacy of ravulizumab, a terminal complement C5 inhibitor, in patients hospitalised with severe COVID-19 requiring invasive or non-invasive mechanical ventilation.</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>Diphenyl Diselenide and SARS-CoV-2: <em>in silico</em> Exploration of the Mechanisms of Inhibition of Main Protease (M<sup>pro</sup>) and Papain-like Protease (PL<sup>pro</sup>)</strong> - The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (M^(pro)) and the papain-like protease (PL^(pro)) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe)(2) which is an archetypal model of diselenides and a renowned potential therapeutic agent. The in vitro inhibitory concentration of (PhSe)(2) against…</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>New workflow predicts drug targets against SARS-CoV-2 via metabolic changes in infected cells</strong> - COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication</strong> - ER-phagy is a form of autophagy that is mediated by ER-phagy receptors and selectively degrades endoplasmic reticulum (ER). Coronaviruses have been shown to use the ER as a membrane source to establish their double-membrane vesicles (DMVs). However, whether viruses modulate ER-phagy to drive viral DMV formation and its underlying molecular mechanisms remains largely unknown. Here, we demonstrate that coronavirus subverts ER-phagy by hijacking the ER-phagy receptors FAM134B and ATL3 into p62…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A cell-free platform to measure coronavirus membrane fusion</strong> - Here we present a protocol to measure coronavirus-mediated membrane fusion, an essential event in coronavirus cell entry. The approach uses nanoluciferase (Nluc) “HiBiT”-tagged corona virus-like particles (VLPs) and Nluc “LgBiT”-containing extracellular vesicles (EVs) as proxies for virus and cell, respectively. VLP-EV membrane fusion allows HiBiT and LgBiT to combine into measurable Nluc, which signifies virus fusion with target cell membranes. We highlight assay utility with methods to assess…</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 Comprehensive Effects of Carassius auratus Complex Formula against Lipid Accumulation, Hepatocarcinogenesis, and COVID-19 Pathogenesis via Stabilized G-Quadruplex and Reduced Cell Senescence</strong> - Carassius auratus complex formula (CACF) is a traditional Chinese medicine known for its antidiabetic effects. Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, and there are currently no effective therapies for advanced HCC. This study explores the comprehensive effects and possible mechanisms of CACF on HCC. The results show that CACF reduces the viability of hepatoma cells in vitro, while benefiting normal hepatocytes. In addition, CACF inhibits hepatoma cell…</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 novel Nsp9-interacting host factor H2BE promotes PEDV replication by inhibiting endoplasmic reticulum stress-mediated apoptosis</strong> - Porcine epidemic diarrhoea (PED) caused by porcine epidemic diarrhoea virus (PEDV) has led to significant economic losses in the swine industry worldwide. Histone Cluster 2, H2BE (HIST2H2BE), the main protein component in chromatin, has been proposed to play a key role in apoptosis. However, the relationship between H2BE and PEDV remains unclear. In this study, H2BE was shown to bind and interact with PEDV nonstructural protein 9 (Nsp9) via immunoprecipitation-mass spectrometry (IP-MS). Next, we…</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>Trolled by Trump, Again</strong> - Thoughts after a week of waiting and waiting for the indictment that the former President promised. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/trolled-by-trump-again">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Secret Joke at the Heart of the Harvard Affirmative-Action Case</strong> - A federal official wrote a parody of Harvard’s attitude toward Asian Americans and shared it with the dean of admissions. Why did a judge try to hide that from the public? - <a href="https://www.newyorker.com/news/our-columnists/the-secret-joke-at-the-heart-of-the-harvard-affirmative-action-case">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Advice for Alvin Bragg from Former Trump Prosecutors</strong> - The Manhattan District Attorney faces huge legal and political challenges, but the former President’s antics could help the prosecution’s case. - <a href="https://www.newyorker.com/news/daily-comment/advice-for-alvin-bragg-from-former-trump-prosecutors">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Should Latinos Be Considered a Race?</strong> - A proposed change to the census faces opposition from Afro-Latino groups, and exposes conflicts among Latino communities. - <a href="https://www.newyorker.com/news/daily-comment/should-latinos-be-considered-a-race">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Jia Tolentino on the Ozempic Weight-Loss Craze</strong> - A drug designed to treat diabetes is changing how celebrities—and maybe the rest of us—will look. Plus, D. T. Max on the Latino author who fabricated his very identity. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/jia-tolentino-on-the-ozempic-weight-loss-craze">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Utah’s social media for kids law could be coming to a state near you</strong> -
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<img alt="A teen girl looking at her phone." src="https://cdn.vox-cdn.com/thumbor/hmikcZriMrqolqAXev0Vmjk1zys=/0x0:5973x4480/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72113609/GettyImages_1445186465.0.jpg"/>
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Utah’s kids will have a very different social media experience next year. It might not be a better one. | Georgijevic/Getty Images
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Utah’s strict new social media laws have some scary implications for the whole country.
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If everything goes according to the government of Utah’s plan, around this time next year, there will be some big changes on social media platforms for the state’s residents. Especially — but not exclusively — for the younger ones. They may also, possibly, have an effect on social media users beyond Utah’s borders.
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In a ceremony on Thursday, Utah Gov. Spencer J. Cox <a href="https://www.youtube.com/watch?v=uda6JYMOKrQ&amp;ab_channel=Gov.SpencerJ.Cox">signed two bills</a> regulating minors’ use of social media, denoting how important and significant he believes these <a href="http://socialmedia.utah.gov">two pieces of legislation</a> are. Combined, the new laws call for social media platforms to verify all users’ ages. Those under 18 will have special rules for their online activity, including curfews; more privacy from advertisers but less from their parents or guardians; and the ability to sue platforms over certain harms, including addiction.
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The laws are the first in the country to place such restrictions on kids’ usage of social media. They likely won’t be the last, however, as other states and the federal government <a href="https://www.axios.com/2023/02/14/congress-kids-online-safety">are increasingly considering legal restrictions</a> in the name of protecting minors as the potential for harm those platforms pose gets more attention. But opponents of such laws say they will have unintended consequences for the free speech and privacy of people of all ages.
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Both laws, which are collectively known as the Social Media Regulation Act, are set to take effect on March 1, 2024. The first, <a href="https://le.utah.gov/~2023/bills/static/SB0152.html">SB 152</a>, requires social media companies to verify the age of any Utah resident with an account on their services. Those under 18 will have to get their parent or guardian’s permission to sign up for an account and to access it at all between the hours of 10:30 pm and 6:30 am, and social media companies can’t advertise to or collect data on minors. The second, <a href="https://le.utah.gov/~2023/bills/static/HB0311.html">HB 311</a>, requires social media companies to ensure that they are not designed to cause minors to become addicted to them, and gives Utah’s minors the right to sue social media companies if they believe they’ve become addicted to or otherwise somehow harmed by a social media platform they have an account on.
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At the signing, Cox <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407706/">cited</a> <a href="https://mitsloan.mit.edu/ideas-made-to-matter/study-social-media-use-linked-to-decline-mental-health">studies</a> that <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2749480">showed</a> how poor mental health in young people can be caused or exacerbated by their use of social media platforms.
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“I think we need to do something,” the governor said. “These are first-of-their-kind bills in the United States. That’s huge.”
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<img alt="Utah governor Spencer J. Cox speaks at an event with President Joe Biden." src="https://cdn.vox-cdn.com/thumbor/W3MHL-PnXdeQLoLRWkyrFR7TfOI=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24534875/GettyImages_1247057614.jpg"/> <cite>Nathan Howard/Getty Images</cite>
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Utah Governor Spencer J. Cox entertains President Biden at a recent dinner. Biden is a fellow proponent of laws regarding social media platforms and children.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OLpiIv">
There are a lot of things that can happen in the year before most of the legislation’s provisions take effect, including courts striking them down in part or entirely, as the companies or platform users affected by the laws are sure to take legal action to prevent them. The new laws also don’t totally spell out how platforms are supposed to verify users’ ages, as those details will be hammered out in consultation with the companies affected. But it’s pretty clear that they’ll go much further than the easily bypassable age verification services social media platforms currently use to comply with COPPA, the federal children’s privacy law, which depends on underage users telling the truth about their age.
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This is a problem for privacy advocates, who <a href="https://www.eff.org/deeplinks/2023/03/age-verification-mandates-would-undermine-anonymity-online">point out</a> that identity verification rules take away consumers’ rights to use these services anonymously, while companies get to collect even more of their data than before. And that goes for users of all ages, as the only way to prove you aren’t a child subject to these rules is to verify that you’re an adult. The provisions allowing parents to see everything their child posts and messages are a clear privacy issue as well. The laws are also a problem for free speech advocates, who believe the lack of anonymity will suppress everyone’s speech. That may include children in abusive situations or LGBTQ children who could be harmed if their parents snooped on their online activities.
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“These bills radically undermine the constitutional and human rights of young people in Utah, but they also just don’t really make any sense,” Evan Greer, the director of digital rights advocacy group Fight for the Future, told Vox.
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Defenders of Utah’s new laws, including some children’s <a href="https://www.commonsensemedia.org/press-releases/statement-on-the-signing-of-utahs-social-media-regulation-act">advocacy groups</a>, believe that social media platforms are harmful to children and their mental health and that the tools those platforms have implemented willingly aren’t enough. That’s a complaint we’ve been hearing a lot more of lately, especially after Meta whistleblower Frances Haugen <a href="https://www.vox.com/recode/2021/10/3/22707940/frances-haugen-facebook-whistleblower-60-minutes-teen-girls-instagram">revealed</a> that the company knew its platforms harmed minors’ mental health but didn’t do enough to prevent it. In <a href="https://www.vox.com/recode/2022/3/1/22957507/biden-state-of-the-union-social-media-mental-health-children-accountability-frances-haugen">his</a> <a href="https://www.vox.com/recode/2023/2/15/23599879/congress-children-safety-online-big-tech">two</a> State of the Union addresses, President Biden has said that social media platforms are “experimenting” on children. <a href="https://www.vox.com/recode/2022/3/14/22971618/earn-it-sesta-fosta-children-safety-internet-laws">Several</a> <a href="https://www.hawley.senate.gov/new-hawley-introduces-two-bills-protect-kids-online-fight-back-against-big-tech#:~:text=The%20MATURE%20Act%20would%3A,a%20private%20right%20of%20action.">bills</a> aimed at children and online services, including social media, have been introduced in recent Congresses. None have passed, but they have bipartisan support, and it appears that both houses of the current Congress are <a href="https://www.vox.com/recode/2023/2/15/23599879/congress-children-safety-online-big-tech">determined</a> to get something over the finish line. Several members of Congress in the recent <a href="https://www.vox.com/technology/23653884/tiktok-hearing-shou-chew-winners-losers">hearing about TikTok</a> stressed the dangers of all social media platforms on children.
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“I suspect that you will see lots of bills like these, and of course we are working with our federal partners as well,” Cox said. “This is one of those rare areas today where we see broad agreement amongst both Republicans and Democrats.”
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Indeed, several states are considering children’s social media laws, including <a href="https://arkansasadvocate.com/briefs/arkansas-governor-backed-bill-would-require-social-media-age-verification/">Arkansas</a>, <a href="https://www.ctinsider.com/politics/article/social-media-children-ct-parents-17777585.php">Connecticut</a>, <a href="https://www.njspotlightnews.org/2023/03/nj-lawmakers-seek-to-protect-children-from-social-media-addiction/">New Jersey</a>, and <a href="https://www.chron.com/news/houston-texas/article/texas-social-media-law-17648942.php">Texas</a>. California <a href="https://www.gov.ca.gov/2022/09/15/governor-newsom-signs-first-in-nation-bill-protecting-childrens-online-data-and-privacy/">passed a law</a> last year that would increase privacy protections for children online. It takes effect July 1 of next year. And Louisiana <a href="https://www.marketplace.org/shows/marketplace-tech/louisiana-law-requiring-proof-of-id-for-porn-site-access-has-privacy-advocates-worried/">has a law</a> that requires websites that have a certain amount of pornographic content on them to verify that users are at least 18 before they can view it.
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So even if you don’t live in Utah, you should prepare yourself for the possibility that the state you do live in — or even the federal government — will pass something similar. That seems especially likely if Utah’s law survives the inevitable court challenges. There is also a chance that some of these platforms apply Utah’s rules to the entire country, as the borderless nature of the internet makes it difficult to set rules for just one state (see: how several companies have applied provisions of California’s <a href="https://www.vox.com/recode/2019/12/30/21030754/ccpa-2020-california-privacy-law-rights-explained">online privacy laws</a> to all Americans).
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TikTok and Snapchat did not respond to a request for comment about Utah’s new laws. Meta didn’t say if it intends to challenge the law or if it would simply stop offering its services in Utah to avoid having to comply with it. Instead, the company noted that it already has “<a href="https://about.instagram.com/safety">more than 30 tools</a> to support teens and families, including tools that let parents and teens work together to limit the amount of time teens spend on Instagram, and age verification technology that helps teens have age-appropriate experiences” and that it will “continue to work closely with experts, policymakers and parents on these important issues.”
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Greer believes that “very real harms” are caused by social media companies with business models based on the collection of data, but that there are other, better ways to deal with those harms.
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“Rather than pushing for legislation that actually weakens kids’ online safety and security, lawmakers should focus on passing comprehensive privacy legislation,” Greer said. “The FTC and state regulators should crack down on predatory design practices like autoplay and infinite scroll, the use of personal data for algorithmic recommendations, and intrusive notifications.”
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<li><strong>If your AI model is going to sell, it has to be safe</strong> -
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<img alt="A hand holding a phone in front of a screen with the OpenAI logo and the term GPT-4." src="https://cdn.vox-cdn.com/thumbor/3tBuiqHpMhzvuB5c6SnkYjHX-gA=/0x0:4000x3000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72113519/GettyImages_1249183770.0.jpg"/>
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CFOTO/Future Publishing via Getty Images
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OpenAI’s GPT-4 shows the competitive advantage of putting in safety work.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BddTSg">
On March 14, OpenAI released the successor to ChatGPT: GPT-4. It <a href="https://www.vox.com/2023/3/15/23640640/gpt-4-chatgpt-openai-generative-ai">impressed</a> observers with its markedly improved performance across reasoning, retention, and coding. It also <a href="https://www.vox.com/future-perfect/2023/3/18/23645013/openai-gpt4-holden-karnofsky-artificial-intelligence-ai-safety-existential-risk">fanned fears around AI safety,</a> around our ability to control these increasingly powerful models. But that debate obscures the fact that, in many ways, GPT-4’s most remarkable gains, compared to similar models in the past, have been around safety.
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According to the company’s <a href="https://arxiv.org/pdf/2303.08774.pdf">Technical Report</a>, during GPT-4’s development, OpenAI “spent six months on safety research, risk assessment, and iteration.” OpenAI <a href="https://openai.com/product/gpt-4">reported</a> that this work yielded significant results: “GPT-4 is 82% less likely to respond to requests for disallowed content and 40% more likely to produce factual responses than GPT-3.5 on our internal evaluations.” (ChatGPT is a slightly tweaked version of GPT-3.5: if you’ve been using ChatGPT over the last few months, you’ve been interacting with GPT-3.5.)
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This demonstrates a broader point: For AI companies, there are significant competitive advantages and profit incentives for emphasizing safety. The key success of ChatGPT over other companies’ large language models (LLMs) — apart from a nice user interface and remarkable word-of-mouth buzz — is precisely its safety. Even as it <a href="https://blog.gitnux.com/chat-gpt-statistics/#:~:text=Chat%20GPT%20has%20secured%20100,word%2Dof%2Dmouth%20marketing.">rapidly grew</a> to over 100 million users, it hasn’t had to be taken down or significantly tweaked to make it less harmful (and less useful).
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Tech companies should be investing heavily in safety research and testing for all our sakes, but also for their own commercial self-interest. That way, the AI model works as intended, and these companies can keep their tech online. ChatGPT Plus is <a href="https://www.itpro.com/business/business-strategy/369989/openai-launches-chatgpt-plus-greater-revenue">making money</a>, and you can’t make money if you’ve had to take your language model down. OpenAI’s reputation has been increased by its tech being safer than its competitors, while other tech companies have had their reputations hit by their tech being unsafe, and even having to take it down. (Disclosure: I am listed in the acknowledgments of the GPT-4 System Card, but I have not shown the draft of this story to anyone at OpenAI, nor have I taken funding from the company.)
</p>
<h3 id="kRthUr">
The competitive advantage of AI safety
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hiajpo">
Just ask Mark Zuckerberg. When Meta released its large language model BlenderBot 3 in August 2022, it immediately <a href="https://www.theguardian.com/technology/2022/aug/10/meta-ai-facebook-blenderbot-3-chatbot">faced problems</a> of making inappropriate and untrue statements. Meta’s Galactica was only up for three days in November 2022 before <a href="https://www.technologyreview.com/2022/11/18/1063487/meta-large-language-model-ai-only-survived-three-days-gpt-3-science/">it was withdrawn</a> after it was shown confidently ‘hallucinating’ (making up) academic papers that didn’t exist. Most recently, in February 2023, Meta irresponsibly released the full weights of its latest language model, LLaMA. As many experts predicted would happen, it <a href="https://www.theverge.com/2023/3/8/23629362/meta-ai-language-model-llama-leak-online-misuse">proliferated to 4chan</a>, where it will be used to mass-produce disinformation and hate.
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I and my co-authors warned about this five years ago in a 2018 report called “<a href="https://arxiv.org/abs/1802.07228">The Malicious Use of Artificial Intelligence</a>,” while the Partnership on AI (Meta was a founding member and remains an active partner) had a great <a href="https://partnershiponai.org/paper/responsible-publication-recommendations/">report</a> on responsible publication in 2021. These repeated and failed attempts to “move fast and break things” have probably exacerbated Meta’s trust problems. In <a href="https://www.jair.org/index.php/jair/article/view/12895/26701">surveys</a> from 2021 of AI researchers and the US public on trust in actors to shape the development and use of AI in the public interest, “Facebook [Meta] is ranked the least trustworthy of American tech companies.”
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But it’s not just Meta. The original misbehaving machine learning chatbot was Microsoft’s Tay, which was <a href="https://www.theverge.com/2016/3/24/11297050/tay-microsoft-chatbot-racist">withdrawn 16 hours after it was released</a> in 2016 after making racist and inflammatory statements. Even Bing/Sydney had some very erratic responses, including <a href="https://www.nytimes.com/2023/02/16/technology/bing-chatbot-transcript.html">declaring</a> its love for, and then threatening, a journalist. In response, Microsoft limited the number of messages one could exchange, and Bing/Sydney no longer answers questions about itself.
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We now know Microsoft based it on OpenAI’s GPT-4; Microsoft invested $11 billion into OpenAI in return for OpenAI running all their computing on Microsoft’s Azure cloud and <a href="https://news.microsoft.com/2019/07/22/openai-forms-exclusive-computing-partnership-with-microsoft-to-build-new-azure-ai-supercomputing-technologies/">becoming</a> their “preferred partner for commercializing new AI technologies.” But it is unclear why the model responded so strangely. It could have been an early, not fully safety-trained version, or it could be due to its connection to search and thus its ability to “read” and respond to an article about itself in real time. (By contrast, GPT-4’s training data only runs up to <a href="https://platform.openai.com/docs/models/gpt-4">September 2021</a>, and it does not have access to the web.) It’s notable that even as it was heralding its new AI models, Microsoft recently <a href="https://www.theverge.com/2023/3/13/23638823/microsoft-ethics-society-team-responsible-ai-layoffs">laid off</a> its AI ethics and society team.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oIzsOw">
OpenAI took a different path with GPT-4, but it’s not the only AI company that has been putting in the work on safety. Other leading labs have also been making clear their commitments, with <a href="https://www.anthropic.com/index/core-views-on-ai-safety">Anthropic</a> and <a href="https://www.alignmentforum.org/posts/a9SPcZ6GXAg9cNKdi/linkpost-some-high-level-thoughts-on-the-deepmind-alignment">DeepMind</a> publishing their safety and alignment strategies. These two labs have also been safe and cautious with the development and deployment of <a href="https://www.anthropic.com/index/introducing-claude">Claude</a> and <a href="https://www.deepmind.com/blog/building-safer-dialogue-agents">Sparrow</a>, their respective LLMs.
</p>
<h3 id="61w3F2">
A playbook for best practices
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Tech companies developing LLMs and other forms of cutting-edge, impactful AI should learn from this comparison. They should adopt the best practice as shown by OpenAI: Invest in safety research and testing before releasing.
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What does this look like specifically? GPT-4’s <a href="https://cdn.openai.com/papers/gpt-4-system-card.pdf">System Card</a> describes four steps OpenAI took that could be a model for other companies.
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First, prune your dataset for toxic or inappropriate content. Second, train your system with reinforcement learning from human feedback (RLHF) and rule-based reward models (RBRMs). RLHF involves human labelers creating demonstration data for the model to copy and ranking data (“output A is preferred to output B”) for the model to better predict what outputs we want. RLHF produces a model that is sometimes overcautious, refusing to answer or hedging (as some users of ChatGPT will have noticed).
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RBRM is an automated classifier that evaluates the model’s output on a set of rules in multiple-choice style, then rewards the model for refusing or answering for the right reasons and in the desired style. So the combination of RLHF and RBRM encourages the model to answer questions helpfully, refuse to answer some harmful questions, and distinguish between the two.
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Third, provide <a href="https://www.governance.ai/post/sharing-powerful-ai-models">structured access</a> to the model through an API. This allows you to filter responses and monitor for poor behavior from the model (or from users). Fourth, invest in moderation, both by humans and by automated moderation and content classifiers. For example, OpenAI used GPT-4 to create rule-based classifiers that flag model outputs that could be harmful.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yh6SWB">
This all takes time and effort, but it’s worth it. Other approaches can also work, like Anthropic’s rule-following <a href="https://www.anthropic.com/index/measuring-progress-on-scalable-oversight-for-large-language-models">Constitutional AI</a>, which leverages RL from AI feedback (RLAIF) to complement human labelers. As OpenAI acknowledges, their approach is not perfect: the model still hallucinates and can still sometimes be tricked into providing harmful content. Indeed, there’s room to go beyond and <a href="https://time.com/6247678/openai-chatgpt-kenya-workers/">improve upon OpenAI’s approach</a>, for example by providing more compensation and career progression opportunities for the human labelers of outputs.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ezcdTy">
Has OpenAI become less open? If this means less open source, then no. OpenAI adopted a “<a href="https://arxiv.org/abs/1908.09203">staged release</a>” strategy for GPT-2 in 2019 and an <a href="https://openai.com/blog/openai-api">API</a> in 2020. Given Meta’s 4chan experience, this seems justified. As Ilya Sutskever, OpenAI chief scientist, noted to <a href="https://www.theverge.com/2023/3/15/23640180/openai-gpt-4-launch-closed-research-ilya-sutskever-interview">The Verge</a>: “I fully expect that in a few years it’s going to be completely obvious to everyone that open-sourcing AI is just not wise.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mwpPMc">
GPT-4 did have less information than previous releases on “architecture (including model size), hardware, training compute, dataset construction, training method.” This is because OpenAI is concerned about <a href="https://cdn.openai.com/papers/gpt-4-system-card.pdf">acceleration risk</a>: “the risk of racing dynamics leading to a decline in safety standards, the diffusion of bad norms, and accelerated AI timelines, each of which heighten societal risks associated with AI.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sY8LTo">
Providing those technical details would speed up the overall rate of progress in developing and deploying powerful AI systems. However, AI poses many unsolved governance and technical challenges: For example, the <a href="https://www.nist.gov/itl/ai-risk-management-framework/roadmap-nist-artificial-intelligence-risk-management-framework-ai">US</a> and <a href="https://artificialintelligenceact.eu/standard-setting/">EU</a> won’t have detailed safety technical standards for high-risk AI systems ready until early 2025.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L4uAAF">
That’s why I <a href="https://www.vox.com/future-perfect/23619354/openai-chatgpt-sam-altman-artificial-intelligence-regulation-sydney-microsoft-ai-safety">and others</a> believe we shouldn’t be speeding up progress in AI capabilities, but we should be going full speed ahead on safety progress. Any reduced openness should never be an impediment to safety, which is why it’s so useful that the System Card shares details on safety challenges and mitigation techniques. Even though OpenAI seems to be coming around to this view, they’re still at the forefront of pushing forward capabilities, and should provide more information on how and when they envisage themselves and the field slowing down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="COh2ji">
AI companies should be investing significantly in safety research and testing. It is the right thing to do and will soon be required by regulation and safety standards in the EU and USA. But also, it is in the self-interest of these AI companies. Put in the work, get the reward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="09vgFt">
<em>Haydn Belfield has been </em><a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__twitter.com_HaydnBelfield&amp;d=DwMGaQ&amp;c=7MSjEE-cVgLCRHxk1P5PWg&amp;r=mTM0ruyioL3vFpq5GgUZftnxirsFoCe5-UZtYwnKki8&amp;m=fafNoDRYchktF6CmyLmwtRE1Dt1uZmJeDTqC_-94paSKyG8-WBBDyvzsCPMMphux&amp;s=8wpMbuaRp27Bl2ciP_ieN5e9ac-s3eWypajx66fqlFk&amp;e="><em>academic project manager</em></a> <em>at the University of Cambridge’s Centre for the Study of Existential Risk (CSER) for the past six years. He is also an associate fellow at the Leverhulme Centre for the Future of Intelligence.</em>
</p></li>
<li><strong>Would Trump’s indictment help or hurt his 2024 campaign?</strong> -
<figure>
<img alt="A person in a Trump mask waves an “America first” flag." src="https://cdn.vox-cdn.com/thumbor/Y-9-QPg0I0JCVmvrZ8LH8YThi2k=/333x0:3000x2000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72113395/1475120264.0.jpg"/>
<figcaption>
Justin Nezarez shows his support for former President Donald Trump near his Mar-a-Lago home on March 21, 2023. in Palm Beach, Florida | Joe Raedle/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
We asked four political strategists and pollsters about what could come next.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PM97gX">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vQmDCT">
Before heading to Waco, Texas, for the first rally of his 2024 campaign Saturday, former President Donald Trump spent more than a week signaling he thinks being indicted on falsifying records charges related to hush money payments to the porn star Stormy Daniels will be good for him politically. So much so that he reportedly <a href="https://www.theguardian.com/us-news/2023/mar/22/trump-wants-to-be-handcuffed-for-court-appearance-in-stormy-daniels-case-sources-say">wanted to be seen in handcuffs</a>. But it’s not clear he’s right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wcEMtq">
Trump’s indictment, which at this point appears to be <a href="https://www.nbcnews.com/politics/donald-trump/live-blog/trump-news-grand-jury-indictment-new-york-live-updates-rcna76239">delayed</a> until at least next week, could strengthen support among the Republican base for his 2024 reelection campaign. But it could<strong> </strong>also turn off voters who have come to see Trump as a liability given his refusal to accept his 2020 election loss, the resulting fallout of the January 6, 2021, insurrection at the US Capitol, and the bevy of additional <a href="https://www.nytimes.com/article/trump-investigations-civil-criminal.html">criminal and civil investigations</a> he’s facing. Those include probes into his business dealings, interference in the 2020 election in Georgia, withholding of classified documents after he left office, and his role in inciting the insurrection, which could lead to additional indictments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SwPlc2">
Even if an indictment earns him votes over his Republican Party challengers in the primary, it’s unclear whether the same would be true in the general election. The news has already splintered his own party, with some of his political opponents, including Florida Gov. Ron DeSantis, invoking it in their lines of attack; others have rushed to the former president’s defense in the face of what they frame as a politically motivated case.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cFUWVW">
We spoke with pollsters and political strategists from both parties about what they think an indictment could mean in the months ahead.
</p>
<h3 id="A0OtaG">
The case that an indictment may help Trump
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6tRZaA">
<strong>Robert Cahaly, senior strategist and pollster at the Trafalgar Group and former Republican political consultant:</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l8TZz8">
With all the stuff that’s out there brewing that could turn into some kind of legal action against Trump, this is probably the weakest case. I think it’s very beneficial for Trump that something so superficial and silly is the first example.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7GrcWe">
It’s one thing when OJ [Simpson] is in the headlines, and everybody thinks that what he did was horrible. It’s another thing when somebody’s in the headlines and everybody doesn’t think going after them is fair. Trump’s best role has always been a conservative martyr. And this falls right in that … Literally, I can see them selling millions of T-shirts with his mug shot as a badge of honor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c9d1qH">
There are a lot of people who really like Trump, but they just don’t think he can win. They just think they need somebody different. This is taking some of those people off the sidelines and making them consider Trump even now in the primary … Whoever’s galvanizing your opposition the most is most likely someone that your fans are going to rally behind.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sNWkzy">
<strong>Whit Ayres, ​​founder and president of the polling firm North Star Opinion Research and adviser to GOP congressional and gubernatorial candidates: </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jV9TOC">
Anything I say is rank speculation completely uninformed by data or evidence. We’re talking about something that has never ever occurred before in American history. There is no data on the political implications of indictment of a former president and leading presidential candidate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZEItAk">
I am skeptical that a charge about a years-old event that everybody has already known about for years is likely to have much impact on anything, other than it will probably rally Republicans and supporters of Trump around him, at least in the short term. This would be a very easy case to frame as a partisan political indictment. Much easier to frame that way than, say, the Georgia voting case or the classified documents or January 6.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gyevyL">
It will force every other Republican candidate to react to it, which of course, keeps Trump directly in the spotlight — as he usually is.
</p>
<h3 id="r4t7wD">
The case that an indictment hurts Trump (and his party)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ega4tc">
<strong>Simon Rosenberg, a Democratic strategist among the few who correctly </strong><a href="https://www.vox.com/policy-and-politics/2022/11/27/23475262/midterm-elections-2022-results-red-wave-democrats"><strong>predicted the results of the 2022 midterms</strong></a><strong>:</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cTg978">
I think it will help [Trump] in the Republican primary, but will continue to degrade him with the broader electorate. MAGA has underperformed in three consecutive elections, and we know it doesn’t work in the battlegrounds. And if the Republicans present themselves as the party all for MAGA in 2024, they’re gonna have a very, very hard time winning the presidency.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2HdKex">
Trump coming in as the nominee, having been indicted potentially two or three times — there’s no scenario where that’s helpful to him in a national election. It perhaps will help him crowd out DeSantis and other challengers in the primary. But of course, that would be a disaster for the Republican Party. I’d much rather be us than them heading into this next election.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EOyp23">
<strong>Matt Dole, an Ohio-based Republican strategist: </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PTuT8G">
Trump faced an uphill battle before this for the nomination. I think [his indictment] probably just adds to that. A lot of folks in the Republican coalition want an option that espouses [Trump’s] policies without bringing the antics. Ron DeSantis, obviously, is the model for that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1onFVn">
Over the long term, I think this probably helps Trump’s opponents in the Republican primary. There’s certainly a lot to be said for political attacks on President Trump. But I think throughout the entire Republican coalition, this probably hurts him more than it would help.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oDSDAK">
There is a subset of Republicans who are going to support Donald Trump to the very end. And they are loud. And they are well-covered by the media. There will certainly be blowback. But again, all of this is feeding into the fatigue about Donald Trump. So I could personally believe that this is a politically motivated indictment. And I could also believe that it’s just another thing to add to the long list of things that I’m tired of having to defend and deal with as a Republican.”
</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>IPL 2023 | Lack of Pant, Indian pace bowling firepower remains a concern for Delhi Capitals</strong> - While Mitchell Marsh and Kuldeep Yadav’s form will boost DC’s morale, not being able to find an ideal Indian replacement for Pant will certainly give the think tank sleepless nights.</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>Delhi hopes to cash in on ‘Kapp impact’</strong> - Ours is such a well-balanced side and credit has to go to the people who have put together this team, says South African star</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>NZ vs SL 1st ODI | Shipley’s five-for sinks Sri Lanka in New Zealand’s 198-run win</strong> - Chasing 275 for victory, Sri Lanka were bundled out for 76 in the 20th over as Henry Shipley’s 5 for 31 scripted a big win for New Zealand in the 1st ODI</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>Piquet ordered to pay $950,000 for racist, homophobic comments</strong> - A Brazil court ordered the three-time F1 champion to pay a fine in moral damages for his comments on Lewis Hamilton</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>Afghanistan beats Pakistan for first time in a T20</strong> - Afghanistan overcame falling to 45-4 in the 10th over to cruise home at 98-4 and win by six wickets with more than two overs to spare</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>AAP alleges Hassan officers failed to act against BJP MLA</strong> - Preetham Gowda has been distributing gifts to lure voters in the name of religious programme, says AAP candidate</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>Mandya: Election control rooms set up in all segments</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>Mehrauli killing | Court gives ‘last opportunity’ to Poonawala’s advocate to respond to arguments on charges</strong> - Meanwhile, the court also allowed the application of the victim’s father and complainant Vikas Walkar to attend the court proceedings through video conferencing.</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>Current COVID-testing levels insufficient as compared to WHO standards in some states: Health Ministry</strong> - India continues to register sustained increase in trajectory of COVID-19 cases</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>SC gives States, UTs and High Courts three months to set up online RTI portals</strong> - ‘Though the Act was enacted in October 2005, after a lapse of 17 years, online web portals are still to be operationalised by some of the High Courts,’ the apex court noted in its order</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>Ukraine war: Battle for Bakhmut ‘stabilising’, says commander</strong> - Despite Russia spending months trying to take the city, Ukrainian officials say they are holding on.</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>King Charles’s France visit postponed after pension protests</strong> - Emmanuel Macron says the trip could not go ahead because of pension protests during the trip.</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>Europe migrant crisis: Dozens missing off Tunisian coast</strong> - The boat, which was trying to reach Italy, is the fifth to capsize in two days in the Mediterranean.</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>Deutsche Bank share slide reignites worries among investors</strong> - Worries over the financial strength of the sector persist, with Deutsche Bank down 14% at one point.</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>Do Kwon: Fugitive ‘cryptocrash’ boss arrested in Montenegro</strong> - Terraform Labs’ Do Kwon has also been charged with fraud by US prosecutors.</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>The fight to expose corporations’ real impact on the climate</strong> - Most carbon emissions caused by businesses are hidden from sight. - <a href="https://arstechnica.com/?p=1926799">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Garmin’s Forerunner 955 review: Still king for runners and cyclists</strong> - Garmin proves once again that it’s the only choice for serious athletes. - <a href="https://arstechnica.com/?p=1872046">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rising seas will cut off many properties before they’re flooded</strong> - Along the US coasts, many properties will lose access to essential services. - <a href="https://arstechnica.com/?p=1926888">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fallout 4 mod uses voice AI to add sensible reactions, more RPG-like choices</strong> - More than 300 lines added for cannibals, lunkheads, and other role-players. - <a href="https://arstechnica.com/?p=1926831">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two more dead as patients report horrifying details of eye drop outbreak</strong> - EzriCare and Delsam products have been recalled, but outbreak is expected to grow. - <a href="https://arstechnica.com/?p=1926844">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>Classic Catholic Joke, “The Son of a Bitch”</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I’ve been Catholic all of my life, and this is one of my favorite jokes of all time.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One of the parish priests from the Cathedral went on a fishing trip. On the last day of his trip he hooked a monster fish &amp; proceeded to reel it in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The guide, holding a net, yelled, “Look at the size of that Son of a Bitch!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The priest looks shocked, “My son! Such language is uncalled for from a child of God!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The guide, thinking quickly as he did not want to offend the priest, says, “No, Father, that’s what kind of fish it is - a Son of a Bitch fish!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Really?” The priest says, “Well then, help me land this Son of a Bitch!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After a long struggle, the priest and the guide finally get the fish in the boat. As they marveled at the size of the monster, the guide says, “Father, that’s the biggest Son of a Bitch I’ve ever seen! You must bring it home and cook it. You’ll never eat anything as good as Son of a Bitch!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Elated, the priest headed home to the rectory. While unloading his gear &amp; his prize catch, Sister Mary inquired about his trip.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Sister! You simply <em>must</em> take a look at this big Son of a Bitch I caught!” he exclaimed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sister Mary gasped, “Father!” made the sign of the cross, and clutched her rosary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The priest shook his head, “Fear not, Sister! That’s what kind of fish it is, a Son of a Bitch fish!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sister Mary informed the priest that the Pope was making a surprise visit to the Cathedral, and that they should fix the Son of a Bitch for his dinner. Humble as ever, she said, “Father, it would be the greatest privilege of my life if you’d give me the honor of cleaning the Son of a Bitch.” And of course the priest consented.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As she was cleaning the huge fish, the Bishop walked in. “What are you doing Sister?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Father wants me to clean this big Son of a Bitch for the Pope’s Dinner!” she replied.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Sister Mary!” The bishop exclaimed, “If you’re that upset, I can clean it for you! There is no need for such vulgar language!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No, your Eminence,” the Nun replied, bowing, “It’s called a Son of a Bitch fish!” “Really?” said the Bishop, “Well, in that case, I shall fix up a delicious meal to go with it, and that Son of a Bitch can be the main course! Let me know when you’ve finished cleaning.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Now, on the night of the Pope’s visit, everything was <em>perfect</em>. The Bishop had prepared an excellent meal. The wine was fine, and the fish was just as succulent as the fishing guide had promised.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Pope said, “What a wonderful fish, where did you get it?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I caught that Son of a Bitch!” said the priest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I cleaned the Son of a Bitch!” said the nun.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I cooked that Son of a Bitch!” said the Bishop.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Pope looked around at each of them. A big smile crept across his face as he said, “Well I sure as hell liked eating that son of a bitch. You mother fuckers are my kind of people!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Azrael_The_Bold"> /u/Azrael_The_Bold </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12102bo/classic_catholic_joke_the_son_of_a_bitch/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12102bo/classic_catholic_joke_the_son_of_a_bitch/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My girlfriend dressed up as a policewoman and told me I was under arrest for suspicion of being good in bed.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After 2 minutes, all charges were dropped due to lack of evidence.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/yomommafool"> /u/yomommafool </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/120ix4b/my_girlfriend_dressed_up_as_a_policewoman_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/120ix4b/my_girlfriend_dressed_up_as_a_policewoman_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Don’t challenge Death to a pillow fight..</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
..if you’re not willing to deal with the reaper cushions.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/AcidBathVampire"> /u/AcidBathVampire </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1212buc/dont_challenge_death_to_a_pillow_fight/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1212buc/dont_challenge_death_to_a_pillow_fight/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My wife was very disappointed when I told her that I got “I love you” tattooed on my penis.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She just shook her head and said, “There you go again, always trying to put words in my mouth.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/yomommafool"> /u/yomommafool </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/120iyj2/my_wife_was_very_disappointed_when_i_told_her/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/120iyj2/my_wife_was_very_disappointed_when_i_told_her/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What did the sign on the door of the brothel say?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Beat it, we’re closed.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/sorry_cant_find"> /u/sorry_cant_find </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1216efm/what_did_the_sign_on_the_door_of_the_brothel_say/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1216efm/what_did_the_sign_on_the_door_of_the_brothel_say/">[comments]</a></span></p></li>
</ul>
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