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<title>26 March, 2023</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Longitudinal wastewater surveillance addressed public health priorities during the transition from “dynamic COVID-zero” to “opening up” in China: a population-based study</strong> -
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Background Wastewater surveillance provides real-time, cost-effective monitoring of SARS-CoV-2 transmission. We developed the first city-level wastewater warning system in mainland China, located in Shenzhen. Our study aimed to reveal cryptic transmissions under the “dynamic COVID-zero” policy and characterize the dynamics of the infected population and variant prevalence, and then guide the allocation of medical resources during the transition to “opening up” in China. Methods In this population-based study, a total of 1,204 COVID-19 cases were enrolled to evaluate the contribution of Omicron variant-specific faecal shedding rates in wastewater. After that, wastewater samples from up to 334 sites distributed in communities and port areas in two districts of Shenzhen covering 1.74 million people were tested daily to evaluate the sensitivity and specificity of this approach and were validated against daily SARS-CoV-2 screening. After the public health policy was switched to “opening up” in December 7, 2022, we conducted wastewater surveillance at wastewater treatment plants and pump stations covering 3.55 million people to estimate infected populations using model prediction and detect the relative abundance of SARS-CoV-2 lineages using wastewater sequencing. Findings In total, 82.4% of SARS-CoV-2 Omicron cases tested positive for faecal viral RNA within the first four days after the diagnosis, which was far more than the proportion of the ancestral variant. A total of 27,759 wastewater samples were detected from July 26 to November 30 in 2022, showing a sensitivity of 73.8% and a specificity of 99.8%. We further found that wastewater surveillance played roles in providing early warnings and revealing cryptic transmissions in two communities. Based on the above results, we employed a prediction model to monitor the daily number of infected individuals in Shenzhen during the transition to “opening up” in China, with over 80% of the population infected in both Futian District and Nanshan District. Notably, the prediction of the daily number of hospital admission was consistent with the actual number. Further sequencing revealed that the Omicron subvariant BA.5.2.48 accounted for the most abundant SARS-CoV-2 RNA in wastewater, and BF.7.14 and BA.5.2.49 ranked second and third, respectively, which was consistent with the clinical sequencing. Interpretation This study provides a scalable solution for wastewater surveillance of SARS-CoV-2 to provide real-time monitoring of the new variants, infected populations and facilitate the precise prediction of hospital admission. This novel framework could be a One Health system for the surveillance of other infectious and emerging pathogens with faecal shedding and antibiotic resistance genes in the future. Funding Sanming Project of Medicine in Shenzhen, Shenzhen Key Medical Discipline Construction Fund.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.25.23287563v1" target="_blank">Longitudinal wastewater surveillance addressed public health priorities during the transition from “dynamic COVID-zero” to “opening up” in China: a population-based study</a>
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<li><strong>Seventy Years of Mortality Transition in India 1950-2021</strong> -
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Mortality in India remains high by international standards. This paper analyses mortality transition in India during the 70 years since 1950 based on the annual estimates of age-specific probabilities of death prepared by the United Nations Population Division for the period 1950-2021. The analysis reveals that characterisation of mortality transition is sensitive to the summary index of mortality used. Mortality transition in India based on the geometric mean of the age-specific probabilities of death is found to be different from that based on the life expectancy at birth. The transition in mortality based on the geometric mean of age-specific probabilities of death accelerated during 2008-2019 but decelerated when based on the life expectancy at birth. The reason is that mortality transition in younger ages has been faster than mortality transition in older ages. The analysis also reveals that there were around 4.3 excess deaths associated with the COVID-19 epidemic in the country leading to a loss of around 3.7 years in the life expectancy at birth between 2019 and 2021.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.24.23287189v1" target="_blank">Seventy Years of Mortality Transition in India 1950-2021</a>
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<li><strong>The impact of the Covid-19 pandemic on young people from black and mixed-ethnic groups’ mental health: A qualitative study</strong> -
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Author Notes <strong>This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Dr Keri Ka-Yee Wong, keri.wong@ucl.ac.uk</strong> Abstract Objectives The Covid-19 pandemic has disproportionately impacted vulnerable groups’ physical and mental health, especially young people and minority ethnic groups, yet little is known about how this is taking place and what support they would like. To address this gap, this qualitative study aims to uncover the effect of the Covid-19 outbreak on young people with ethnic minority backgrounds’ mental health, how this changed since the end of lockdown and what support they need to cope with these issues. Setting and Participants Ten 20-minute in-person semi-structured interviews were conducted with young people aged 12 to 17 years old from black and mixed-ethnic groups who regularly attend a community centre in West London. Results Through Interpretative Phenomenological Analysis, results indicated that the participants’ mental health was negatively impacted by the Covid-19 pandemic, with feelings of loneliness being the most common experience. However, positive effects were concurrently observed including improved well-being and better coping strategies post-lockdown, which is a testament to the young people’s resilience. That said, it is clear that young people from minority ethnic backgrounds lacked support during the Covid-19 pandemic and would now need psychological, practical and relational assistance to cope with these challenges. Conclusions Whilst future studies would benefit from a larger ethnically-diverse sample, this is a start. Study findings have the potential to inform future government policies around mental health support and access for young people from ethnic minorities, notably prioritising support for grassroots initiatives during times of crisis. Strengths and limitations • This qualitative interview study during Covid-19 gives voice to the experiences of young people from black and mixed-ethnic backgrounds in the UK • The in-person quality of the interviews helped build rapport between the researcher and the young people and sharing of sensitive issues around mental health access and support, increasing the results’ validity • This is a convenient sample, with girls and those aged 15 years and above being disproportionately represented in our data as they provided most of the answers. • The small sample size and lack of ethnic diversity limits the generalisability of the study to individuals from other ethnic minority groups.
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🖺 Full Text HTML: <a href="https://osf.io/fe36p/" target="_blank">The impact of the Covid-19 pandemic on young people from black and mixed-ethnic groups’ mental health: A qualitative study</a>
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<li><strong>Intra-Host Mutation Rate of Acute SARS-CoV-2 Infection During the Initial Pandemic Wave</strong> -
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Background: Our understanding of SARS-CoV-2 evolution and mutation rate is limited. The rate of SARS-CoV-2 evolution is minimized through a proofreading function encoded by NSP-14 and may be affected by patient comorbidity. Current understanding of SARS-CoV-2 mutational rate is through population based analysis while intra-host mutation rate remains poorly studied. Methods: Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) [≥]0.25, [≥]0.5 and [≥]0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with ({Delta}NSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Results: Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI:90.8-96.4], 40.7 (95%CI:38.9-42.6) and 34.7 (95%CI:33.0-36.4) substitutions/genome/year at AF [≥]0.25, [≥]0.5, [≥]0.75 respectively. Mutation rate in {Delta}NSP-14 were significantly elevated at AF&gt;0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Discussion: Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.24.534062v1" target="_blank">Intra-Host Mutation Rate of Acute SARS-CoV-2 Infection During the Initial Pandemic Wave</a>
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<li><strong>Concerns about data integrity of 30 randomized clinical trials from one author.</strong> -
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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.
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🖺 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> -
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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.
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🖺 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> -
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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?
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🖺 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.
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🖺 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.
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🖺 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.
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🖺 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.
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🖺 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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🖺 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>
</div></li>
<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> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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.
</p>
</div>
<div class="article-link article-html-link">
🖺 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>
</div></li>
<li><strong>A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8</strong> -
<div>
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.
</div>
<div class="article-link article-html-link">
🖺 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>
</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>Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis</strong> - The “Thalidomide tragedy” is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, 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>Antiviral drugs block replication of highly immune-evasive Omicron subvariants ex vivo, but fail to reduce tissue inflammation</strong> - The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and antiviral drugs against clinical specimens for SARS-CoV-2 Omicron BA.4/BA.5, BF.7 and BQ.1.1 employing an immunofluorescence neutralization assay. Further we explored treatment of BA.4/BA.5 infections with efficient antiviral drugs and monoclonal…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332</strong> - PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (M^(pro)) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with M^(pro)s of various coronaviruses reveal their inhibitory mechanisms against different M^(pro)s. However, the structural information on the lower pathogenic coronavirus M^(pro) with PF-07321332 or PF-07304814 is currently scarce, which hinders our…</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>Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants</strong> - The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses</strong> - A variety of swine enteric coronaviruses (SECoVs) have emerged and are prevalent in pig populations, including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome (SADS)-CoV, a newly identified bat-origin CoV with zoonotic potential. Unfortunately, available traditional, inactivated and attenuated SECoV vaccines are of limited efficacy against the variants currently circulating in most pig…</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>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>
</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>
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<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
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<li><strong>How to foster your purpose wherever you are in life</strong> -
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<img alt="An overhead view of a maze of green shrubs on a sandy beach. Five people walk throughout the maze." src="https://cdn.vox-cdn.com/thumbor/MPgmC7HVRon-EuSfjsELSCLGw6Y=/131x0:5370x3929/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72116166/GettyImages_1308265260.0.jpg"/>
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Getty Images
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A non-stressful approach to figuring out what guides you.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ITUOHR">
It might have been a minute since you paused to consider your life’s purpose — if you ever have at all. It can be an overwhelming question, lofty and existential, and according to the people who study it, one that is frequently misunderstood.
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“‘Purpose’ is conflated with lots of other words,” says <a href="https://profiles.stanford.edu/william-damon">William Damon</a>, a professor of education at Stanford University, “like ‘meaning’ and ‘passion.’” Purpose, however, is something different — it’s broader than a goal, but it’s the guiding motivation that gives your life a sense of direction.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dXaBNv">
According to Damon, a life purpose has three components: It’s a long-term calling, act, or way of life that interests you; it’s something you have some competence in; and it makes a marginal difference in the world. Striving to be the best parent you can is a purpose — raising kids to become caring, respectful, and happy adults is your way of making a material impact — whereas wanting to make a lot of money with the sole intention of satisfying your every whim is not. It’s also common to have multiple purposes in life, Damon says: Your faith, your family, the satisfaction you get from your job are all common sources.
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Considering your purpose may seem like a project for the privileged, that you must have enough time and money to seriously consider your values. However, purpose can relate to practical matters, such as keeping your family safe, as well as the broader contours of your interests. You can work toward your purpose in incremental ways without sacrificing resources.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qu7MaJ">
If you struggle to define your purpose, to clearly articulate the thing — or things — you excel in that also leaves a mark on society, don’t fret. In his 20 years of research on life purpose, Damon finds most people falter for a bit before landing on the activity that lights their fire — about a quarter of participants in almost all of his studies did not have a purpose, he says. But gradually, he adds, over time, people do become more purposeful. “Out of all the things I’ve studied in terms of capacities and skills that young people develop,” Damon says, “purpose is the slowest one because it doesn’t really come to fruition until for most people until the late 20s, early 30s.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="frJ8i9">
Purpose isn’t fixed, either. As your life and values change, your purpose may, too. Throughout their lifespan, people’s purpose shifts according to their circumstances. Those parents who found purpose rearing their children may feel untethered and without meaning once they become empty-nesters. Or, an adult in their 40s may realize their creative hobby brings joy to an audience beyond their inner circle and decide to devote their time to sharing their talents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vJCxi4">
Having a purpose in life isn’t simply a fanciful pursuit. Research has found that having purpose can <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2734064">prolong life</a>, <a href="https://www.pnas.org/doi/10.1073/pnas.1814723116">reduce depressive symptoms</a>, and <a href="https://www.tandfonline.com/doi/abs/10.1080/17439760903271439">improve life satisfaction</a>. Whether you’re faltering or flourishing, you can cultivate a purpose — or align your interests to live more purposefully. All it takes is some mining of the soul.
</p>
<h3 id="Jb1kTJ">
How to cultivate purpose in your own life
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UjTgI9">
Thinking as broadly as possible, ask yourself some potentially challenging questions. What do you care about? What do you hope to accomplish? What difference do you want to make? What do you have to offer? What skills do you have that support the issues you’re passionate about? “It’s an ongoing process of reflecting on the things that you want to address in your life, the things you want to accomplish, or make progress toward in your life, and thinking about what you can uniquely contribute to that issue,” says <a href="https://www.cgu.edu/people/kendall-cotton-bronk/">Kendall Cotton Bronk</a>, a professor of psychology at Claremont Graduate University. “And it doesn’t happen overnight.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sxgeh5">
As counterintuitive as it may sound, purpose shouldn’t be something achievable, says <a href="https://artsci.wustl.edu/faculty-staff/patrick-hill">Patrick Hill</a>, an associate professor of psychological and brain sciences at Washington University in St. Louis. Goals, even long-term ones, are still more short-term than purpose, which is a lifelong framework under which to organize those goals, Hill says. “If your purpose in life was to perform on Broadway and the first time you perform on Broadway, you’ve succeeded,” he says. “Then it’s like, what do I do now?” Instead, take that specific goal, such as performing on Broadway, and think bigger. Instead, your purpose may be to share unique and diverse stories with a wider audience.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="afLQIk">
In a <a href="https://www3.nd.edu/~dlapsle1/Lab/Articles%20&amp;%20Chapters_files/Hill%20Burrow%20Brandenbeger%20et%20al%20%282010%29%20JADP.pdf">2010 study</a>, Hill developed four categories of life purposes: creative, prosocial, financial, and personal recognition. For example, people with creative purposes are fulfilled by various artistic pursuits throughout their lives — performing in school plays as a kid, writing for the college newspaper, or pursuing a career as a copywriter. Prosocially focused people have goals of helping others, people with financial purposes are motivated by economic well-being, and personal recognition orientation is marked by a desire for respect from colleagues and peers. While the means of living out your purpose changes depending on your age and circumstances, Hill found that the same motivation drives you. “Whatever your purpose in life is, you’re probably going to pursue it and progress towards it in different ways across the lifespan,” Hill says. “Which doesn’t necessarily mean your purpose has changed, but just the way that you engage with it changed.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PHyFu6">
One of Hill’s <a href="https://www.researchgate.net/publication/363917270_The_PATHS_to_Purpose_A_New_Framework_toward_Understanding_Purpose_Development">recent studies</a> outlined three ways people nurture their purpose. Some are proactive in their quest: they define a goal — to mentor others, for example — and work toward achieving it. Others stumble onto their raison d’être and upon deeper reflection, realize their actions have been serving their purpose all along. People also take inspiration from their peers and attempt to pursue a passion in the same manner. While these frameworks aren’t necessarily prescriptive in nature, Cotton Bronk says, intentional thinking may lead you down one of these paths of discovery.
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<h3 id="YCdzQX">
Your job can be purposeful, but not your sole purpose
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6RsuR7">
One of the most common ways of living out purpose is through work. This isn’t inherently a bad thing: When people pursue their passions, they tend to end up in jobs they enjoy and <a href="https://www.bbc.com/worklife/article/20220902-the-search-for-meaning-at-work">give them meaning</a>. But because <a href="https://www.cnbc.com/2022/01/26/work-is-the-most-important-way-of-proving-your-worth-in-the-us-says-professor.html">American society values work</a> above leisure, art, and community, people tend to lose themselves in labor. “If your job is your sole source of meaning and identity, and you lose it, what’s left?” says Simone Stolzoff, author of the forthcoming book <a href="https://www.penguinrandomhouse.com/books/704142/the-good-enough-job-by-simone-stolzoff/"><em>The Good Enough Job: Reclaiming Life from Work</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dMBawX">
Untangling work from purpose can be difficult. For instance, if your purpose is to support your family, working an unfulfilling yet well-paying job is still meeting your purpose, Damon says. You should never feel ashamed for trying to get by. But if you can, try to foster purpose during non-working hours. Stolzoff stresses the importance of engaging in meaningful activities outside of work: coffee dates with friends, tending to a community garden, playing on a recreational sports league, exploring your faith. Regardless if your job gives you purpose or if it’s simply a way of funding the rest of your life, you can meet your need for passion (which is not the same as purpose, but is good to have) outside of work through enjoyable hobbies, like reading, knitting, or playing music — all energizing activities, but ones you do for yourself, and not for the greater good.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pFGdna">
It is possible to tie your job to a greater purpose. In a <a href="https://positiveorgs.bus.umich.edu/wp-content/uploads/Crafting-a-Job_Revisioning-Employees.pdf">study of cleaners in a hospital</a>, those who saw themselves as integral to the patients’ healing process found more meaning in their jobs than those who did not. “Connecting what you do to a greater sense of ‘why’ can often make the daily tasks and fluctuations of your job more pleasurable,” Stolzoff says. “Just be clear about why you care about what you’re doing, and how those values are reflected in your behaviors, and how you choose to spend your time.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="39Q1aW">
Because many people do find purpose in their work, retirement or periods of unemployment can be unmooring. During this phase of life, think back on the core purpose your job fulfilled — perhaps educating people — and find ways to achieve that elsewhere, Damon says, like substitute teaching, babysitting grandchildren, or volunteering at a youth organization.
</p>
<h3 id="5G6njd">
Ways to pursue purpose regardless of your circumstances
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XOqa8N">
So how do you nurture purpose when life is always changing? If you’re in the middle of a major move, in an unfulfilling job, or are dealing with new circumstances — like parenthood or retirement — living purposefully can seem like a daunting task. Hill recommends paying attention to the activities in your day-to-day life that motivate you, excite you, or make you feel goal-oriented. “Organize your life in a way that allows for you to make those things more habitual,” Hill says. “Ultimately, that can be a way to help people think about developing a purpose from the ground up, eventually.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pABHlv">
If you struggle to identify anything that enlivens you at work or at home, take it as a sign that you may not have purpose in this domain, Hill says. You shouldn’t quit your job if you find no excitement in it, but how can you manufacture motivation in other areas of your life? Maybe that means joining an activist organization that fights for systemic change or teaching piano lessons to neighborhood kids.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kKgmrD">
Since purpose tends to materialize well into adulthood, Damon suggests looking back on previous moments in your life when you had a sense of fulfillment: when you were captain of the basketball team, when you helped a lost tourist find their hotel, when you tutored your cousin in math. “It gives them clues about the kinds of experiences that offer them this satisfaction and what they’re capable of,” Damon says. How can you recreate these circumstances where you thrive within your current life?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vjmuS3">
Clearly defining the areas where you make the most impact can be difficult. Enlisting the help of trusted friends or loved ones gives you an objective view of your strengths, Cotton Bronk says. Try asking five people — mentors, colleagues, friends, family — three questions, she suggests: “What do you think I do particularly well?” “What do you think I really enjoy doing?” and “How do you think I will leave my mark?” Often, those in your inner circle can more easily identify your talents and passions than you can.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U3TQDC">
Cultivating a purpose and marching on the path of progress looks different for everyone. What you value and excel in will be unique to you and the various seasons of your life. Just make sure your purpose is what matters to <em>you</em>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bbQn8H">
“The important part is that you’re actively choosing,” Stolzoff says. “Opposed to, as is all too often the case, inheriting the values of the institutions that we’re a part of. We start climbing ladders that we don’t actually want to be on, or playing games we don’t actually want to win because we haven’t taken the time to think critically about, what is it that I actually value?”
</p></li>
<li><strong>How the March for Our Lives activists see the country now</strong> -
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<img alt="" src="https://cdn.vox-cdn.com/thumbor/q6sgxsY30nLCPMlyeCWtONqepYs=/317x0:5324x3755/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72116109/1249070097.0.jpg"/>
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US Representative Maxwell Frost speaks during a news conference on bicameral gun violence legislation outside the US Capitol in Washington, DC, on March 22, 2023. | Stefani Reynolds/AFP via Getty Images
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</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Five years later, David Hogg and Rep. Maxwell Frost reflect on the impact of the March for Our Lives demonstration in Washington, DC.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xuIaoa">
Last week marked the fifth anniversary of the 2018 <a href="https://www.vox.com/policy-and-politics/2018/3/26/17160646/march-for-our-lives-crowd-size-count">March for Our Lives</a> demonstration in Washington, DC.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rEWM48">
The student-led demonstration brought the issue of mass shootings to the forefront of American conversation and reignited a longstanding debate on what to do about the pervasive issue of gun violence across the country.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4TlyFw">
Now, five years later, its first national organizing director, <a href="https://www.vox.com/podcasts/2022/11/29/23482867/maxwell-frost-florida-midterm-elections-2022-gen-z-congress">Maxwell Frost</a>, is a first-term Congress member representing Florida’s 10th District.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mNDYx8">
<a href="https://www.vox.com/today-explained-podcast"><em>Today, Explained</em></a> hosts <a href="https://www.vox.com/authors/noel-king">Noel King</a> and <a href="https://www.vox.com/authors/sean-rameswaram">Sean Rameswaram</a> sat down with Frost and <a href="https://www.vox.com/videos/2018/4/19/17253324/strikethrough-parkland-student-david-hogg-beats-critics">David Hogg</a>, a co-founder of March for Our Lives. Hogg and Frost are part of America’s increasingly politically influential Gen Z generation. They shared what they think their generation cares about when it comes to gun violence, climate change, and the 2024 presidential election. Plus, Rep. Frost walks us through the details of a new bill he co-introduced with Sen. Chris Murphy, which would create the first federal office dedicated to gun violence prevention.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xQ6o3H">
<em>Below is an excerpt of the conversation, edited for length and clarity. There’s much more in the full podcast, so find </em>Today, Explained<em> on </em><a href="https://podcasts.apple.com/us/podcast/today-explained/id1346207297"><em>Apple Podcasts</em></a><em>, </em><a href="https://open.spotify.com/show/3pXx5SXzXwJxnf4A5pWN2A"><em>Spotify</em></a><em>, </em><a href="https://www.stitcher.com/podcast/vox/today-explained"><em>Stitcher</em></a><em>, or </em><a href="https://link.chtbl.com/todayexplainedpod"><em>wherever you listen.</em></a>
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<hr class="p-entry-hr" id="gdKNyE"/>
<h4 id="mDNb1p">
Sean Rameswaram
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AgqSOq">
How are you feeling right now about the five-year anniversary of the March for Our Lives?
</p>
<h4 id="I8qy9N">
David Hogg
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l7tXbC">
Complicated. I wouldn’t say that I’m always hopeful by any means, considering what happens every day in this country with this issue. But I also am not entirely pessimistic either. How could you be? We were a group of high school students that started out five years ago, who many people said would never do anything and would never amount to anything. But now I’m sitting in this room with you all five years later, with the first member of Congress from our organization to be elected as the youngest member of Congress.
</p>
<h4 id="oJxcdT">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xDcSIp">
You want to organize on the ground, but you want a movement that permeates the culture, bridges the gap between cool and consciousness, and builds an environment where people want to do it because it’s the thing to do or it’s cool or whatever. And that’s really what March for Our Lives did, especially that whole year. It was cool to go to the march. I remember going to mine and seeing a ton of people I didn’t see in a long time. They were like, “Yeah, I just felt like I had to be here. Like it’s the moment.” And that’s why I always say, the way you know the strength of a movement, it’s what they’re doing when no one gives a shit, when it’s not in the news, when no one cares. Because when it is on the news and people care, the way you organize the infrastructure you built, that’s what matters. And so that’s what we see March for Our Lives doing today,
</p>
<h4 id="TPDGlL">
Noel King
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IPNQk5">
What was the objective five years ago? I mean, you have, as you say, millions of young people out in the streets. But at that point, you also need them to do something. What was it you were trying to get out of this moment?
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<h4 id="8KdIVd">
David Hogg
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JfijdS">
One, it enabled us to help register voters. Two, it helped set the tone for a generation and a cultural shift in that generation to say, this is who we are. I think one of the most important things the marches have done is offer survivors solidarity and in knowing that they’re not alone. I think that’s one of the really hard things about this is survivors, because of the guilt that they feel, put so much pressure on themselves that they have to solve this that it crushes the movement because those people end up not being able to take care of themselves and they end up feeling crushed. When you’re there with your friends and your allies and you make new friends, you know that you’re not alone and you know that you can have the permission to step back when you need to rest. And it’s not reliant on any single one of us.
</p>
<h4 id="FKbQd0">
Noel King
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ImxDrp">
March for Our Lives sent me and Sean this very tantalizing fact, which is that this movement has won the passage of 250-plus gun laws since it began. That’s an extraordinary number. What are those laws and where would we see them out in the wild?
</p>
<h4 id="ZxYtjl">
David Hogg
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IBusBR">
One of the laws that we did pass after Parkland was the thing called an extremist protection order or a red flag law that enables you to disarm somebody that is a risk to themselves or others. An instance where this was actually used was for my own mom. Somebody threatened to kill my mom and sent her a death threat that said F with the NRA and you’ll be DOA. We used the law that we passed after Parkland to disarm that individual that lived, I think, only like 20 minutes away from us. That law has now been used at least, last I checked, I think it was around 9,000 times. There’s a lot of people, the detractors out there say, well, you know, gun laws don’t work. But the reality is no law is perfect. I will fully admit that. But, you know, that law may have helped prevent me from having to bury my own mom.
</p>
<h4 id="UVb2TU">
Sean Rameswaram
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NA80AU">
How do you go about taking credit for 250 laws when there’s been this preexisting movement for decades?
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<h4 id="aFrBbQ">
David Hogg
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M7fcnF">
I would say that we are part of it and helping to reignite a movement that was already there before us, especially a movement pioneered by Black women in places like Jamaica, Queens, in New York City, like Erica Ford. I like to think that part of the change that March for Our Lives helped bring, from really the beginning when we started this work, was about making sure it’s not just about Parkland, it’s not just about Sandy Hook, or any community that goes through mass shootings. It’s about communities that go through all forms of gun violence, and not speaking for them, but making sure that people understand that they have always been in this conversation and they have to be part of the conversation. It can’t just be about how we stop gun violence inside of schools.
</p>
<h4 id="G6lZkc">
Noel King
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kwfqb7">
Rep. Frost, I hear that you’re getting ready to introduce your first piece of legislation. Can you tell us what’s in it?
</p>
<h4 id="4GNioD">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9VnBCk">
We’re releasing a piece of legislation that’s bicameral, introduced in both the Senate and the House, with Sen. Chris Murphy, who I’ve known for a long time from my work going to the Sandy Hook vigils and everything. This is a piece of legislation that’s pretty simple. What it does is it creates a federal Office of Gun Violence Prevention, which is really important for many different reasons. Number one, the federal government does not have a coordinated approach to ending gun violence. And so what this would do is have a coordinating office department that works with DHS, ATF, HHS, all these different agencies to provide a coordinated response to ending gun violence that’s both preventative and reactionary and looks at the root causes and provides data for members of Congress. Most of the data and research that comes from this issue does not come from our government. It comes from outside organizations, third-party organizations, nonprofits. That’s important work but [government work is needed] for an issue that takes 100 lives a day. In this country, right now, the leading cause of death for children is gun violence. So this would be a federal coordinated approach to ending gun violence, looking at the causes, providing real data after these horrible situations happen. So that way members of Congress, state legislatures, municipal governments have real data from the government, so that way they can act upon it.
</p>
<h4 id="ODBRJX">
Sean Rameswaram
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2liAX4">
Do you have any idea how this is going to land?
</p>
<h4 id="8wIjt2">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xMdTLE">
I think we have a really good opportunity to get this done, whether it’s through Congress or through executive action, because the president can also create the office himself. So we’re hoping that one of the two will end up happening.
</p>
<h4 id="xbkWZF">
Sean Rameswaram
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LGEoIR">
What else is on Gen Z’s agenda?
</p>
<h4 id="IeL0j7">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NxSbUF">
I don’t think Gen Z cares about different values or issues more than other Americans, right? If you were to ask people of past generations about moments that were defining for their generation, no matter who they are, you hear about the moon landing, post 9/11. Where the country came together for our generation, you ask them and you’re gonna hear Parkland, Pulse, George Floyd, Breonna Taylor, death, death, death, trauma. It really changes the way a generation thinks about the issues because we’re kind of confused, like why are we still dealing with these issues? And we want to be a part of the solution. We’re not here to play the blame game.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a5DSod">
I think we care about the existential climate crisis that we’re seeing the effects of. We care about ending gun violence because we see that young people are really at the front lines of this issue a lot of the time, especially when it comes to, yes, mass shootings, but also, unfortunately, what many folks call daily gun violence, that’s in a lot of our communities — especially Black and brown communities, that stems from underinvestment in our communities, poverty, and the economic status of a lot of our people. I think the age of the single-issue voter is kind of dying because young people really see things holistically and they really care about everything because they know everything is connected.
</p>
<h4 id="DcECZR">
Noel King
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="poIBC4">
In order to enact the agenda that you are talking about, a Democrat needs to be president of this country. Right now, two of the biggest threats to that happening in 2024 come from your home state — former President Donald Trump and Gov. Ron DeSantis — who, Maxwell, you have accused of engaging in, um, fascism.
</p>
<h4 id="XtO9SL">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sDtQM8">
Number one, I think Ron DeSantis is the greatest threat to democracy in this country right now. This governor took the New College of Florida, a small liberal arts college, less than 1,000 students, and he wants to make an example of them. So he abused his power as governor and completely took out the board of trustees, put a bunch of conservative lap dogs on it, fired the president of the university, and installed a new interim president who is the former Republican speaker of the House, who is not qualified to be the president of the university. DeSantis also changed the salary from $200,000 to $699,000 a year. Then the state allocated $15 million in like a few days to this university for “institutional changes,” which they’re going to use to market to a lot more conservative areas to change the demographics of the students. I say that to say, this is not something that governors do. He’s using his power to close down businesses and attack teachers. There’s this atmosphere of fear in, not just in Orlando, but across the entire state, because of what he’s doing.
</p>
<h4 id="IcPz1l">
Sean Rameswaram
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dJ6i7d">
What does it say to you guys that this individual you define as a fascist is exceedingly popular?
</p>
<h4 id="4saHdT">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a0X1dH">
We have to realize that a lot of these polls poll likely voters who are not the entire population of a state. I’m not saying he’s not super popular in the state of Florida, but there’s a difference between policy and politics. When you have enough money and when there’s voids in democratic organizing in a state, you’re able to shift the narrative. Most people would hear about permitless carry and over 70 percent of Floridians say, “No, that’s a stupid idea. We don’t want that.” But then a lot of the same people would say, “Yes, I want to vote for DeSantis.” It’s because he’s effective at separating those two things.
</p>
<h4 id="3ZaJCh">
David Hogg
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VV60Sc">
What’s happening is Republicans are doubling down on their efforts to fuel voter suppression to change who can vote, to change who the voters are instead of changing their policies. It’s going to backfire on them eventually when those demographics that they’re relying on die out because they are inherently older and our generation can come in to start replacing them.
</p>
<h4 id="PybLrr">
Noel King
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sr8IEa">
But Joe Biden does not represent your generation per se. Joe Biden is not a young progressive, and young progressives have argued he’s not even that progressive. We’re looking at a situation in which potentially the Democratic nominee is in his 80s. You are both in your 20s. Should Joe Biden run again or is it time for someone new, someone younger?
</p>
<h4 id="ufsuTi">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4jOw5g">
I always have the same answer to this because I truly believe this. If the president wants to run again, which it seems like he does, I’m gonna support him. Do I agree with him on everything? No, I worked for Bernie Sanders in the primary. I’m definitely to the left of the president. But I’m very pleasantly surprised. The president just took this executive action on gun violence. He signed into law the bipartisan Safer Communities Act. Is it everything that we need to end gun violence? No, but it’s going to save lives. You look at something like Build Back Better — the fact that the president put that forward, free universal tuition, free college, two-year college for all of our people, free child care for all of our people. Everything that was in Build Back Better, I think if we would have passed it, Democrats would still have the House right now. I think we’ve seen a president that’s really surprised me as a young progressive. Do we agree on everything? No, but I’ll support him.
</p>
<h4 id="gm0iE8">
Sean Rameswaram
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="92yind">
When you see President Biden approving new oil drilling in Alaska, do you feel like you can come out and speak out against him? Or is the race in 2024 too fragile to risk speaking ill of the sitting president?
</p>
<h4 id="1jg7lm">
Maxwell Frost
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WSaNOF">
I spoke out against the Willow project, and a lot of times in life, you have to hold multiple truths, especially in politics. The president who signed the law, the most money ever going to defeating the climate crisis, also approved a drilling project, which is going to be really bad for our environment. Both things are true, at the same time in our reality. It’s just something we have to hold and we figure out, how do we move forward? Does it mean we don’t work to hold them accountable? No. I talked about the fact that part of the reason Gen Z turned out is because of the president’s bold vision on the climate crisis and ending it and so I was honest about that. But that’s not to the detriment of 2024.
</p>
<h4 id="gnrhuk">
David Hogg
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ffen9C">
I think there’s two ways that you can look at this. You can either look at what’s going on in Florida as, “Oh my gosh, everything’s turning back and we’re losing,” which is what they want us to believe, that there was absolutely nothing that we as people can do to stand up for the founding principles of our country. Granted, the men who talked about them are very, very, very deeply flawed. Nonetheless, I still think that most of us agree on those principles of life, liberty, and the pursuit of happiness. It means that all of us can succeed together because we all know and care about each other, not as Democrats or Republicans, but as Americans that want a better future for all of us, because we know the best is ahead and not behind us.
</p></li>
<li><strong>America’s hypersonic arms race with China, explained</strong> -
<figure>
<img alt="Fiscal Year 2024 Request for the Department of Defense" src="https://cdn.vox-cdn.com/thumbor/qfmPaluvckD_FCm_rg2f2n7TieE=/0x0:7081x5311/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72114745/1249137364.0.jpg"/>
<figcaption>
Gen. Mark Milley, chairman of the Joint Chiefs of Staff, testifies during the House Appropriations Subcommittee on Defense hearing titled Fiscal Year 2024 Request for the Department of Defense, March 23. | Tom Williams/CQ-Roll Call, Inc via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Without treaties to rein in their use, a dangerous escalation between countries becomes much more likely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tGoEJS">
The US Department of Defense is pouring money into hypersonic weapons after years of defense officials’ warnings that China is gaining superiority in that arena. But a 21st-century arms race is a major risk, especially without a full picture of Chinese weapons development and amid the increasingly poor relationship between the two nations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tabm79">
Hypersonic weapons, or vehicles and missiles that travel faster than Mach 5, or five times the speed of sound, aren’t new; the US has been developing and testing those weapons since the 1950s. But there’s been relatively little US<strong> </strong>investment in these systems in recent decades, while China and Russia have developed their hypersonics programs. Russia even <a href="https://www.nytimes.com/2023/03/09/world/europe/hypersonic-missiles-russia-ukraine.html">used six of its hypersonic Kinzhal missiles in Ukraine earlier this month</a>, the largest number the country has deployed in one strike in the war. Other countries including Australia, Iran, both North and South Korea, Brazil, Germany, Israel, India, and Japan are developing hypersonic programs. However, the increase in funding and tempo of the US program comes as relations between the US and China are the worst they’ve been in decades.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ha3NiJ">
The DoD’s proposed budget for Army and Air Force hypersonics development and requisition for the years 2023 through 2027 sits at $15 billion, according to a January report from the <a href="https://www.cbo.gov/publication/58924#:~:text=DoD's%20Current%20Hypersonic%20Missile%20Programs,-The%20Department%20of&amp;text=In%20its%20latest%20five%2Dyear,%242%20billion%20for%20procuring%20missiles.">Congressional Budget Office</a>. That figure doesn’t include the Navy’s hypersonics development program, which in February announced a $1.1 billion contract with the defense manufacturer <a href="https://news.lockheedmartin.com/2023-02-17-Lockheed-Martin-Awarded-1-1-Billion-Initial-Contract-to-Provide-Nations-First-Sea-Based-Hypersonic-Strike-Capability">Lockheed Martin</a> to add a hypersonic system to Zumwalt-class destroyers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QfeHws">
<a href="https://www.nytimes.com/2021/10/27/us/politics/china-hypersonic-missile.html">Defense officials</a> have been arguing for years that the US is “behind” China in its hypersonic weapons development, and that may be true. China fielded <a href="https://www.ft.com/content/ba0a3cde-719b-4040-93cb-a486e1f843fb">a test in 2021</a> of a hypersonic, nuclear-capable weapon which at the time took many in the defense community by surprise and showed astounding development in China’s hypersonics capabilities.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SpNbE3">
“Once, American technological predominance was regarded as all but unassailable, and China tended to be dismissed as a copycat that was unlikely to close the gap,” Elsa Kania, an adjunct senior fellow with the Technology and National Security Program at the Center for a New American Security, told Vox in an email. “Today, recognition of China’s potential to lead in new frontiers and strategic technologies is heightening the urgency behind U.S. efforts and programs on several fronts.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kXGljM">
Worryingly, there are no multilateral or bilateral treaties regarding the use of hypersonic weapons — a situation which, as <a href="https://thebulletin.org/2022/10/sixty-years-after-the-cuban-missile-crisis-how-to-face-a-new-era-of-global-catastrophic-risks/?utm_source=Google&amp;utm_medium=Ad&amp;utm_campaign=SearchAds&amp;utm_content=NuclearRisk_CMCnewera_10132022&amp;gclid=Cj0KCQjwt_qgBhDFARIsABcDjOdtYl-YM_pEQvWLioD7Fi9Tq5ckT0nYWG006YNULw_SNoHKgEhkGUwaApD9EALw_wcB">the Cuban Missile Crisis</a> demonstrated in October 1962, can lead to global panic or even catastrophe. And there’s no current indication that any such treaty or agreement is on the table, given that the major players in the hypersonic space are on the outs with little desire to negotiate on much of anything, much less a burgeoning battlefield threat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EiSmFd">
Still, that hasn’t stopped US defense officials, legislators, and <a href="https://www.fool.com/earnings/call-transcripts/2023/01/24/lockheed-martin-lmt-q4-2022-earnings-call-transcri/">weapons manufacturers</a> from pushing ahead with lobbying for hypersonic technology — and as of now, the government is ready to pour money into the project.
</p>
<h3 id="W3bFAc">
Hypersonic weapons are pricey, but they do have some advantages
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IxjT13">
The US military began working on hypersonic systems back in the 1960s, mostly looking at <a href="https://www.popsci.com/technology/hypersonic-weapon-milestones/">hypersonic flight capabilities</a> for carrying people, not necessarily just weapons. But in the 1980s, that began to change, as Popular Science reported last year. That’s when the Air Force tested the Maneuvering Reentry Vehicle (MaRV), showing that missiles going at Mach 5 or faster as they re-entered Earth’s atmosphere could be maneuvered to hit a target. The US started pursuing hypersonic weapons development in earnest in the early 2000s, as part of its <a href="https://sgp.fas.org/crs/nuke/R41464.pdf">conventional prompt global strike program</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jLH2FX">
There are two main hypersonic weapons system concepts — the <a href="https://sgp.fas.org/crs/natsec/IF11459.pdf">glide vehicle </a>and<a href="https://sgp.fas.org/crs/natsec/IF11459.pdf"> </a><a href="https://www.airforce-technology.com/projects/hypersonic-air-breathing-weapon-concept-hawc-usa/">air-breathing missile</a> — that the US is developing. While the weapons systems themselves are conventional, or non-nuclear, China is developing nuclear-capable missiles, as the 2021 tests showed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qOZAR4">
“China has been seeking ways to counter US missile defense systems for decades; China’s always felt that US missile defense systems undermine China’s nuclear deterrence,” Lyle Morris, fellow for foreign policy and national security at Asia Society Policy Institute’s Center for China Analysis told Vox in an interview. Starting in the early 2000s, China ramped up its hypersonics development in response to the dissolution of the <a href="https://www.armscontrol.org/factsheets/abmtreaty">Anti-Ballistic Missile treaty</a>, originally signed by the US and the Soviet Union. With anti-ballistic systems development now unfettered, China felt the need for a different kind of deterrent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SioAhr">
Glide-type weapons, which China has tested, are launched from a ballistic missile, Timothy Heath, a senior international defense researcher at the RAND Corporation, explained. “The way their system works is you launch a ballistic missile with this hypersonic glider sitting on top of it. At a certain point, the glider separates from the ballistic missile and goes on this hypersonic trajectory, which is in the atmosphere, unlike a ballistic missile, and travels at hypersponic speeds, maneuvers, and strikes its target primarily using inertia from the launch.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NQRpSz">
According to Heath, China says they’re ready to deploy their hypersonic weapons, which is “a step or two beyond where the US program is right now, we are still in the testing phase of hypersonic missiles, so the Chinese do appear to have made faster progress than the US.” China’s ballistic missile program is<strong> </strong>also<strong> </strong>highly sophisticated; given that, and the US’s concurrent underinvestment in ballistic missiles, it’s not surprising that China was able to outpace the US in developing these weapons.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CglenU">
Where hypersonic weapons really differ from ballistic weapons aren’t necessarily their speed, but their maneuverability in flight and their ability to evade missile detection and defense systems <a href="https://www.reuters.com/world/europe/what-is-patriot-missile-defense-system-2022-12-21/">like the Patriot</a>, one of the US’s most advanced missile defense system which is also used in 17 other countries besides the US. They <a href="https://www.scientificamerican.com/article/hypersonic-weapons-cant-hide-from-new-eyes-in-space/#:~:text=They%20use%20aerodynamic%20lift%20to,used%20to%20track%20ballistic%20missiles">evade detection</a> during parts of their journey by exiting or nearly exiting the earth’s atmosphere, and by shifting their course during flight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kn9byI">
“In the near term, hypersonic weapons systems are expected to have the potential to overcome even the most sophisticated air and missile defense systems,” Kania told Vox.
</p>
<h3 id="F8zgI7">
There are serious consequences to a new arms race
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K2vABA">
Given China’s successful hypersonics testing and the hostile mood between Beijing and Washington, it’s reasonable to be concerned about the acceleration in both weapons development and hostile rhetoric. But in reality, there are several roadblocks to widespread use of these weapons in battle, given how expensive they are — <a href="https://www.cbo.gov/publication/58924">about $15 million to $18 million per missile</a>, according to the Congressional Budget Office — and the reality of the battlefield, where basics like <a href="https://www.nytimes.com/2023/03/24/us/politics/military-weapons-ukraine-war.html">artillery</a> are much more useful.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fEJZUi">
Some experts, including Morris and Heath, expressed doubt about the actual utility of hypersonics on the battlefield; according to a February report from the <a href="https://sgp.fas.org/crs/weapons/R45811.pdf">Congressional Research Service</a>, critics of the US’s hypersonics development program say the weapons “lack defined mission requirements, contribute little to US military capability, and are unnecessary for deterrence.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UQmJDj">
Of course, there’s also the concern that China could share technology with US adversaries like North Korea and Iran, and particularly Russia all of whom are standing up their own hypersonics programs. “As China and Russia seem to be on track to expand defense and technological cooperation, at least covertly, the transfer or sharing of data or research related to hypersonics development would be unsurprising,” Kania told Vox. “Certainly, Beijing has more leverage at this point and strong interest in learning from Russia’s experiences in Ukraine.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4whFXF">
Part of the concern about China’s hypersonics program in particular is the idea that the US is being caught flat-footed, and that looking anything less than absolutely dominant is a problem for US defense. That concern was particularly evident in 2021, after China’s successful hypersonic missile tests. Gen. Mark Milley, the chairman of the joint chiefs of staff, referred to the tests as <a href="https://www.nytimes.com/2021/10/27/us/politics/china-hypersonic-missile.html">a precursor to China’s “Sputnik moment,”</a> comparing the test to <a href="https://history.nasa.gov/sputnik.html">the Soviet Union’s launch of the first artificial Earth-orbiting satellite</a> in 1957.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XvhBzs">
If there were a conflict between the US and China or another adversary with hypersonic weapons, Heath said, hypersonics wouldn’t be the deciding factor “given that the US has such an advantage in other military technologies like stealth aircraft, long-range bombers, aircraft carriers, submarines — all of these conventional capabilities that allow the US to deploy forces far from the US and fight and dominate their adversaries without the need for long-range missiles.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="djGtQp">
Still, as the US pours money into hypersonics, and other nations develop their capabilities, it’s critically important to find a way to agree on how these weapons should be used in battle. That’s not likely to happen, Morris said, until there’s a major escalatory event — China’s military and the US defense apparatus are in a particularly touchy phase, and that lack of communication increases the risk of misunderstanding and miscalculation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yoZ5nk">
Furthermore, most major weapons agreements have been between the US and Russia or the Soviet Union; since <a href="https://www.csis.org/analysis/russia-suspends-new-start-and-increases-nuclear-risks">Russia pulled out of the New START</a>, the last remaining major nuclear arms control treaty, the possibility of any kind of agreement to limit defense technologies is probably a pipe dream.
</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>Satwik-Chirag win Swiss Open title</strong> - Playing the Chinese pair for the first time, Satwik and Chirag turned up the heat at the right moments.</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>Rishabh Pant must take his time to heal properly: Ganguly</strong> - Former India captain Mr. Ganguly said that the Delhi Capitals franchise will definitely miss the wicketkeeper-batter in the upcoming Indian Premier League</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 way Shubman Gill is playing, I’ll pick him ahead of myself: Shikhar Dhawan</strong> - Shubman Gill has been in sublime form in all three formats this season, even as Mr. Dhawan finds himself out of favour due to a dip in form</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>Half-centuries from Madhevere, Ballance help Zimbabwe beat Netherlands by 7 wickets, clinch ODI series 2-1</strong> - This 2-1 series win helped Zimbabwe finish the Super League in 12th place, with 65 points in their kitty.</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>No Haaland as Spain beats Norway; Wales draws with Croatia</strong> - Best known until now for coaching Spain’s youth teams, Mr. De la Fuente didn’t have to deal with Norway’s striker Erling Haaland, who missed the game with a groin injury</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>Modern Supplyco supermarkets will be started across the State: Minister</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>Kerala to soon attain self-sufficiency in milk production: Minister</strong> - She inaugurates a Milma food truck at Kollam KSRTC depot</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>Here are the big stories from Tamil Nadu today</strong> - Welcome to the Tamil Nadu Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Lalitha Ranjani.</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>Complaint against film producer Prashanth Sambaragi for derogatory posts on Deve Gowda, Kumaraswamy</strong> - The Bigg Boss contestant had recently launched the “Jhatka Cut” campaign against Halal meat</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>Those who weaken democracy can’t observe ‘Satyagraha’: Adityanath’s dig at Congress</strong> - Gandhiji made an appeal for this which is called ‘Satyagraha’, CM Adityanath said</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>No Ukraine offensive without more weapons – Zelensky</strong> - There has been talk for some weeks of Ukraine launching a spring offensive against Russian forces.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Putin: Russia to station nuclear weapons in Belarus</strong> - The US Defense Department says it does not believe Russia is preparing to use the nuclear weapons.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>French police clash with water reservoir protesters</strong> - The unrest follows weeks of protests against President Emmanuel Macron’s pension reforms.</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>Finland election: Sanna Marin fights for survival</strong> - Polls suggest she is in a tight race with centre-right Petteri Orpo and right-wing populist Riikka Purra.</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>
</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>Your grocery bag might not have been recycled</strong> - Laws encourage recycling plastics, but verifying recycled content relies on tricky math. - <a href="https://arstechnica.com/?p=1926872">link</a></p></li>
<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>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An old fellow walking down the road and sees a frog sitting in the grass. The frog says…</strong> - <!-- SC_OFF --></p>
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“Hey there if you kiss me I will turn into a beautiful woman for ya.”<br/> The old man picks up the frog and puts it in his shirt pocket and keeps on down the road. About a mile down the road the frog looks up at him and says “Aren’t you going to kiss me?” The old man says “No I don’t think so.” The frog says“Dont you want a beautiful woman?” The old man responds “At my age I would rather have a talking frog.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Traditional-Bad-2627"> /u/Traditional-Bad-2627 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1222jj8/an_old_fellow_walking_down_the_road_and_sees_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1222jj8/an_old_fellow_walking_down_the_road_and_sees_a/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>If a blind girl says you have a big willy…</strong> - <!-- SC_OFF --></p>
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She’s probably just pulling your leg.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Goatmanthealien"> /u/Goatmanthealien </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1227e4o/if_a_blind_girl_says_you_have_a_big_willy/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1227e4o/if_a_blind_girl_says_you_have_a_big_willy/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I just watched a documentary on marijuana.</strong> - <!-- SC_OFF --></p>
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I think all documentaries should be watched this way.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/cloudswarm"> /u/cloudswarm </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/121lj5f/i_just_watched_a_documentary_on_marijuana/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/121lj5f/i_just_watched_a_documentary_on_marijuana/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>On the first day of my flying lessons, I looked down nervously and asked my instructor, “What are all these buttons for?” He explained calmly…</strong> - <!-- SC_OFF --></p>
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“Those are to keep your shirt closed.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/madazzahatter"> /u/madazzahatter </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/122ir0v/on_the_first_day_of_my_flying_lessons_i_looked/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/122ir0v/on_the_first_day_of_my_flying_lessons_i_looked/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I bet a guy $50 that I could jump higher than a house.</strong> - <!-- SC_OFF --></p>
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So we went outside and stood by a house. Mustering all my strength, I managed to jump about 18 inches off the ground.
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“Ha! Is that as high as you can jump?”
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“Hold on, let’s see how high the house jumps.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/prlugo4162"> /u/prlugo4162 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/1221oj3/i_bet_a_guy_50_that_i_could_jump_higher_than_a/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/1221oj3/i_bet_a_guy_50_that_i_could_jump_higher_than_a/">[comments]</a></span></p></li>
</ul>
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