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<title>07 August, 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>Diagnostic performance of LumiraDx SARS-CoV-2 rapid antigen test compared to PCR for diagnosis of COVID-19 in Liberia</strong> -
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Abstract Background: Diagnosis of SARS-CoV-2 infection in Liberia has primarily relied on polymerase chain reaction (PCR)-based testing at the country National Reference Laboratory. This centralized approach caused reporting delays, prompting evaluation of point-of-care antigen-based tests. We assessed the test performance of the LumiraDx SARS-CoV-2 Ag test (LumiraDx, London, UK) in this setting. Methods: We tested ambulatory individuals screened for enrollment into an observational cohort study of COVID-19 sequelae in Monrovia in 2021. We compared the results of LumiraDx testing of anterior nasal swab specimens to the results of PCR BioFire R2.1P (bioMerieux, Salt Lake City, Utah) on eluent from nasopharyngeal swabs. Results: We evaluated 348 individuals. Among the 274 persons with symptoms, 49.3% were PCR-positive and 36.5% were antigen-positive. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of LumiraDx in this group were 72.6% (95% CI: 64.3%-79.9%), 98.6% (95% CI: 94.9%-99.8%), 78.7% (CI: 71.9%-84.6%), and 98.0% (CI: 93.0%-99.8%), respectively. Among the 74 asymptomatic individuals, 12.2% were positive by PCR, and 5.5% by antigen testing, resulting in a sensitivity, specificity, NPV, and PPV of LumiraDx of 44.4% (95% CI: 13.7%-78.8%), 100% (95% CI: 94.5%-100%), 92.9% (CI: 84.1%-97.6%), and 100% (CI: 39.8%-100%), respectively. Conclusion: Although the specificity and PPV of LumiraDx for diagnosing SARS-CoV-2 were high among persons with and without symptoms, the sensitivity was unacceptably low in both groups, and much less than that reported by the manufacturer. Before new point-of-care diagnostics are adopted, test performance needs to be assessed in the local setting.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.01.23293521v1" target="_blank">Diagnostic performance of LumiraDx SARS-CoV-2 rapid antigen test compared to PCR for diagnosis of COVID-19 in Liberia</a>
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<li><strong>Work Attendance during Acute Respiratory Illness Before and During the COVID-19 Pandemic, United States, 2018-2022</strong> -
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza viruses can be transmitted by infected persons who are pre-symptomatic or symptomatic. To assess impact of the COVID-19 pandemic on work attendance during illness, we analyzed prospectively collected data from persons with acute respiratory illness (ARI) enrolled in a multi-state study during 2018-2022. Persons with prior experience working from home were significantly less likely than those without this experience to work onsite on the day before illness and during the first 3 days of illness; the effect was more pronounced for the COVID-19 pandemic period than the pre-pandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other ARIs. Among persons for whom positive COVID-19 test results were available by the second or third day of illness, few worked onsite. Work-from-home policies may reduce the likelihood of workplace exposures to respiratory viruses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.03.23293611v1" target="_blank">Work Attendance during Acute Respiratory Illness Before and During the COVID-19 Pandemic, United States, 2018-2022</a>
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<li><strong>Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative</strong> -
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Background: As SARS-CoV-2 has transitioned from a pandemic to endemic disease, the majority of new infections have been among previously infected individuals. To manage the risks and benefits of ongoing COVID-19 policies, it is important to understand whether prior infection modifies the severity of subsequent infections. Methods: We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative (N3C), a collection of health systems who provide de-identified electronic health records for research purposes. Our analysis was a sequential series of nested trial emulations. In the first of two analytic stages, we created a month-specific model of the probability of prior infection for each individual. In the second stage, we used an ordinal logistic regression with inverse probability weights calculated in the first stage to simulate a series of monthly trials comparing severity between the cohorts of first and second infections. In addition to cohort-wide effect estimates, we also conducted analyses among race/ethnicity, sex, and age subgroups. Results: From an initial cohort of 7,446,481 combined first and second infections, we identified a cohort of 2,227,484 infections, among which 7.6% were second infections. Ninety-four percent of patients with two recorded infections experienced mild disease for both. The overall odds ratio (OR) for more severe disease with prior infection was 1.06 (95% confidence interval [CI]: 1.03 to 1.10). Monthly point estimates of the OR ranged from 0.56 (95% CI: 0.37 to 0.84) in October 2020 to 1.64 (95% CI: 1.33 to 2.00) in February 2023. In most subgroups, the effect of prior infection was significant. In 8 out of 10 subgroups, the maximum monthly OR occurred after the minimum monthly OR, suggesting that protection has waned throughout the pandemic. Conclusion: Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.03.23293612v1" target="_blank">Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative</a>
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<li><strong>COVID-19 among migrants, refugees, and internally displaced persons: systematic review, meta-analysis and qualitative synthesis of the global empirical literature</strong> -
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Background: Pandemic response and preparedness plans aim at mitigating the spread of infectious diseases and protecting public health, but migrants are often side-lined. Evidence amounted early that migrants are disproportionately affected by the COVID-19 pandemic and its consequences. However, synthesised evidence is lacking that quantifies the inequalities in infection risk and disease outcomes, or contextualises the consequences of pandemic measures and their underlying mechanisms. Methods: Systematic review searching 25 databases and grey literature (12/2019 to 11/2021). We considered empirical articles covering migrants, refugees, asylum-seekers, and internally displaced persons reporting SARS-CoV-2 cases, hospitalisation, ICU admission, mortality, COVID-19 vaccination rates or health consequences of pandemic measures. Random-effects meta-analysis of observational studies and qualitative analysis were performed for evidence synthesis. A Protocol was registered with PROSPERO (CRD42021296952). Findings: Out of 6956 studies, we included 241 in the review. For the quantitative studies (n=46), meta-analysis with over 40 million study participants showed that compared to non-migrants, migrants have an elevated risk of infection (RR = 2.33; 95%-CI: 1.88-2.89) but similar risk for hospitalisation (RR = 1.05; 0.80-1.37), while the likelihood of ICU admission was higher (RR = 1.36; 1.04-1.78). Among those hospitalised, migrants had a lower risk of mortality (RR = 0.47; 0.30-0.73), while their population-based excess mortality tended to be higher (RR = 1.31; 0.95-1.80). The qualitative synthesis (n=44) highlighted the complex interplay of social and COVID-19-related factors at different levels. This involved increased exposure, risk, and impact of pandemic measures that compromised the health of migrants. Interpretation: Even in the advanced stages of the pandemic, migrants faced higher infection risks and disproportionately suffered from the consequences of COVID-19 disease, including deaths. Population-level interventions in future health emergencies must better consider socio-economic, structural and community-level exposures to mitigate risks among migrants and enhance health information systems, to close coverage gaps in migrant groups.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.03.23293586v1" target="_blank">COVID-19 among migrants, refugees, and internally displaced persons: systematic review, meta-analysis and qualitative synthesis of the global empirical literature</a>
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<li><strong>Impact of Adjustment for Differential Testing by Age and Sex on Apparent Epidemiology of SARS-CoV-2 Infection in Ontario, Canada</strong> -
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Background: Surveillance of communicable diseases typically relies on case counts for estimates of risk, and counts can be strongly influenced by testing rates. In the Canadian province of Ontario, testing rates varied markedly by age, sex, geography and time over the course of the SARS-CoV-2 pandemic. We applied a standardization-based approach to test-adjustment to better understand pandemic dynamics from 2020 to 2022, and to better understand when test-adjustment is necessary for accurate estimation of risk. Methods: SARS-CoV-2 case counts by age, sex, public health unit and week were obtained from Ontarios Case and Contact Management system (CCM), which includes all SARS-CoV-2 cases from March 2020 to August 2022. Complete data on testing volumes was obtained from the Ontario Laboratory Information System (OLIS). Case counts were adjusted for under-testing using a previously published standardization-based approach that estimates case numbers that would have been expected if the entire population was tested at the same rate as most-tested age and sex groups. Logistic regression was used to identify threshold testing rates beyond which test-adjustment was unnecessary. Results: Testing rates varied markedly by age, sex, public health unit and pandemic wave. After adjustment for under-testing, overall case counts increased threefold. Adjusted epidemic curves suggested, in contrast to reported case counts, that the first two pandemic waves were equivalent in size, and that there were three distinct pandemic waves in 2022, due to the emergence of Omicron variants. Under-reporting was greatest in children and young males, and varied significantly across public health units, with variation explained partly by testing rates and prevalence of multigenerational households. Test adjustment resulted in little change in the epidemic curve during pandemic waves when testing rates were highest; we found that test-adjustment did not increase case counts once weekly per capita testing rates exceeded 6.3%. Conclusions: Standardization-based adjustment for differential testing by age and sex, and for dynamic changes in testing over time, results in a different picture of infection risk during the SARS-CoV-2 pandemic in Ontario; test-adjusted epidemic curves are concordant with observed patterns of mortality during the pandemic and have face validity. This methodology offers an alternative to sero-epidemiology for identification of true burden of infection when reinfection, sero-reversion, and non-specificity of serological assays make sero-epidemiology challenging.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.01.23293449v1" target="_blank">Impact of Adjustment for Differential Testing by Age and Sex on Apparent Epidemiology of SARS-CoV-2 Infection in Ontario, Canada</a>
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<li><strong>COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records</strong> -
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Background: The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities. Method and findings: In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (&lt;80 years old, BP &lt;=140/90mmHg; 80 or more years old: &lt;=150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using 9blood pressure control9 (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively. The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control. Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value&lt;0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value&lt;0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value&lt;0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value&lt;0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study. Conclusion: The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.02.23293505v1" target="_blank">COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records</a>
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<li><strong>OUTCOME OF COVID-19 PATIENTS ON STEROID THERAPY: A LONGITUDINAL STUDY</strong> -
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ABSTRACT: Introduction: SARS-CoV-2 is responsible for global pandemic that originates from Wuhan, China (1). Patients presentation van be varied from asymptomatic to severe ARDS and multiorgan dysfunction likely due the dysregulated systemic inflammation (2). Glucocorticoids inhibits the inflammation by down streaming of cytokine receptor and promote resolution (3). The role of corticosteroid in COVID-19 still remains controversial. Corticosteroids associated with many long terms side effects. Previous MARS outbreak had experienced avascular necrosis with corticosteroid use (4). Objectives: The aim of the study was to evaluate the outcome of covid-19 patients on the corticosteroid therapy and estimate mortality rate with corticosteroid therapy and investigate potential long-term adverse events associated with its use. Methods: We did a longitudinal follow up study at the AIIMS Rishikesh to assess the side effects of corticosteroids in COVID-19 patients. Patients with moderate to severe COVID-19 pneumonia requiring the oxygen support were included in the study. According to the institutional protocol patients received conventional dose steroids versus pulse dose steroids. (Based on CT/ X-ray findings). Patients were followed up in the hospital till discharge/death for assessment of adverse events due to corticosteroids and all other biochemical parameters (Inflammatory markers) and SOFA score were obtained during hospitalisation till discharge. And at the 6 month follow up patient was assessed for infection and avascular necrosis of the femur. Results: A total of 600 patients were screened out of which 541 patients who received corticosteroids were included in this study. 71.3% were male and 26.6 % were females. Most prevalent comorbidity was systemic hypertension (38.8%) followed by diabetes mellitus (38%). Most common presenting symptoms was dyspnoea followed by fever and cough. Majority patients received dexamethasone (95%). 65.8 % patients received conventional dose while 34.2% of patients received pulse dose. Mortality was more associated with pulse dose (44%) then a conventional dose (30%) (p-value 0.0015). the median duration of the corticosteroids was 10 days with an IQR of 7-13 days. During the hospitalisation 142 patients (26.2%) develops hyperglycaemia. Hyperglycaemia was more prevalent in the pulse dose steroid group (16.8% versus 9.4%). One patient develops pancreatitis. There was a significant reduction in the levels of inflammatory markers (p&lt;0.005) after steroid initiation. At the 6th month of follow patients were assessed for AVN and suspected infection. 25 patients (8.25%) had infection out of which 19 received pulse dose. Out of 25 patients cultures was available for 7 patients and 2 patients grows pathogenic organism in the urine (pseudomonas and E. coli). 02 patients develop non-specific joint pain at 6 months. No patient had AVN during the follow up.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.03.23293425v1" target="_blank">OUTCOME OF COVID-19 PATIENTS ON STEROID THERAPY: A LONGITUDINAL STUDY</a>
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<li><strong>Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England</strong> -
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Background: Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative. Methods: Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients. Results: The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate, respectively. Conclusions: Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.03.23293543v1" target="_blank">Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England</a>
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<li><strong>The post-COVID-19 population has a high prevalence of crossreactive antibodies to spikes from all Orthocoronavirinae genera</strong> -
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The Orthocoronaviridae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 (COVID-19) pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly crossreactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, betacoronaviruses including Middle Eastern respiratory syndrome coronavirus (MERS CoV), and extending to alpha-, gamma- and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these crossreactive antibodies, they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.01.23293522v1" target="_blank">The post-COVID-19 population has a high prevalence of crossreactive antibodies to spikes from all Orthocoronavirinae genera</a>
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<li><strong>Impact of the COVID-19 Pandemic on International Business Travel and Associated Health Issues: A Survey of Japanese Public Companies</strong> -
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Objectives: Compared to long-term expatriates, the health issues of short-term international business travellers are less clear. Particularly, there are no reports on the impact of the COVID-19 pandemic. We explored the changes in health challenges faced by Japanese international business travellers owing to the COVID-19 pandemic. Design: Cross-sectional survey research using questionnaires Setting: We surveyed 3,845 listed public companies in Japan in September 2021. Participants: A total of 251 companies responded (response rate: 6.5%), of which 131 (52%) had foreign travel requirements for their business. Primary and secondary outcome measures: The survey included questions regarding company size, business type, necessity for foreign travel, destination and number of trips, common health issues that arise, and the importance of business travel before and after the COVID-19 pandemic. Results: Among the companies, 44% replied that they could not predict the number of foreign business trips after the pandemic. However, 64% of companies responded that business travel would continue to be important in the future. Before the COVID-19 pandemic, the most important health concerns faced by business travellers were illness during travel (42%), followed by the prevention of infectious diseases and lifestyle disease management. Post-pandemic, 48% of the responses were for infectious diseases, including COVID-19, followed by 40% for travel-related diseases, and 25% for lifestyle-related diseases. Conclusions: Owing to global economic and social activities, business travel will continue to be necessary in the post-COVID-19 era. Comprehensive health management including prevention of infectious diseases is desirable for business travel.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293302v1" target="_blank">Impact of the COVID-19 Pandemic on International Business Travel and Associated Health Issues: A Survey of Japanese Public Companies</a>
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<li><strong>Racial/Ethnic Differences in COVID-19-Traumatic Symptoms, Sleep, Coping Outcomes in a Group of New-Yorkers</strong> -
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Background: Little research has examined within/between group predictors and mediators of race/ethnic differences or disparities in mental and sleep health outcomes arising from the experience of the COVID-19 pandemic. Objectives: This study sought to evaluate the effect of COVID-19 experiences on trauma-related symptoms and sleep quality among a multiracial/ethnic sample in New York. Method: This is a cross-sectional study conducted online among multiethnic adults (n=541) who experienced the pandemic in New York from September to November 2020. Comparisons of characteristics and mean scores by race/ethnicity status were conducted using one-way ANOVA and independent samples t-tests for continuous variables and chi-square tests for categorical variables. Multilinear regression was used for associations between social determinants of health and/or SES, trauma-related symptoms, coping, and sleep. Results: Compared to Whites [Mean (SD)= (24.1(7.6)] and other group [Mean (SD)=24.9(8.2), Blacks [Mean (SD)=(26.3(6.4)] and Hispanics [Mean(SD)=(27.2(8.2)] reported higher level of peritraumatic distress [ df= 3; F=4273; p=0.005). The prevalence of clinically significant PTSD symptoms was 21.4%(n=113): [Whites=31(16.3%); Blacks=28(25.7%); Hispanics=24(25%); and other groups=30(22.4%); x2 =4.93; p=0.177]. This rate doubled [48.3%(257)] when it comes to the overall clinically significant depression level. Compared to all subcategories, [Blacks=52(47.7%); Hispanics =62(64.6%); other group=66(49.3%)], depression symptoms were lower among Whites [77(39.9%; x2 =15.71; p=0.001]. We found a prevalence of insufficient sleep &lt;6 hours of 41%(198): [Whites=69(39.4%); Blacks=43(41.7%); Hispanics=46(52.3%); other groups=40(34.2%); x2=12.21; p=0.057]. Several unique demographic predictors of PTSD emerged for distinct racial/ethnic groups. Among Blacks, sex [β = −0.22; p &lt; .01] and employment [β = −0.159; p &lt; .05] emerged as significant predictors for PTSD, but for no other racial/ethnic group. Interestingly, among Hispanics [β = −0.144; p = .064] and Blacks [β = −0.174; p = .0.076], coping strategies did not mitigate PTSD or depressive symptoms. Conclusion: As New York and the rest of the world are trying to bounce back from the COVID-19 consequences, mental health outcomes are devastating, particularly among historically marginalized communities. This study provides insight into the emergency for policymakers to invest in racial justice programs and provide free access to culturally responsive mental health care for the most vulnerable groups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293452v1" target="_blank">Racial/Ethnic Differences in COVID-19-Traumatic Symptoms, Sleep, Coping Outcomes in a Group of New-Yorkers</a>
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<li><strong>Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection</strong> -
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Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293337v1" target="_blank">Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection</a>
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<li><strong>Healthcare resource utilization and costs associated with COVID-19 among pediatrics managed in the community or hospital setting in England: a population-based cohort study</strong> -
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Background Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial healthcare resource burden. This study aimed to describe healthcare resource utilization (HCRU) and costs associated with COVID-19 in pediatrics aged 1-17 years in England. Methods A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care (HES APC) secondary care data. HCRU and associated costs to the National Health Service (NHS) were stratified by age, risk of severe COVID-19, and immunocompromized status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). Results This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those aged 1-4 years (face-to-face: 4.3%; telephone: 6.0%) compared to those aged 5-11 (2.0%; 2.1%) and 12-17 years (2.2%; 2.5%). In the hospitalized cohort, mean [SD] length of stay was longer (5.0 [5.8] days) among those aged 12-17 years (n=24) than those aged 1-4 (n=15; 1.8 [0.9] days) and 5-11 years (n=21; 2.8 [2.1] days). Conclusions Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those aged 12-17 years. Our results may help optimize the management and resource allocation of COVID-19 in this population.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293335v1" target="_blank">Healthcare resource utilization and costs associated with COVID-19 among pediatrics managed in the community or hospital setting in England: a population-based cohort study</a>
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<li><strong>Systematic Review and Meta-Analysis Protocol of the Efficacy and Safety of COVID-19 Drug Candidates Targeting Host Enzymes Involved in Immune Response</strong> -
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COVID-19 is a rapidly spreading infectious disease caused by the SARS-CoV-2 virus. Although several therapeutic interventions have been developed, the mortality rate of the disease remains high, and effective treatment options are urgently needed. Host-directed therapies targeting enzymes involved in the immune response represent a promising strategy for the development of novel therapeutics against COVID-19. This study aims to conduct a systematic review and meta-analysis of the literature to evaluate the potential of drug candidates targeting host enzymes involved in the immune response for the treatment of COVID-19. We will conduct a systematic search of electronic databases including PubMed, Embase, and Cochrane Library, as well as preprint servers and clinical trial registries for relevant studies. We will include randomized controlled trials, observational studies, and preclinical studies evaluating the efficacy of drug candidates targeting host enzymes involved in the immune response in COVID-19. Two reviewers will independently screen articles, extract data, and assess study quality. The primary outcome will be the effect of drug candidates on mortality, while secondary outcomes will include time to recovery, adverse events, and changes in immune markers. A meta-analysis will be performed to estimate pooled effect sizes of the interventions, and a narrative synthesis will be conducted for studies that are not amenable to quantitative analysis. This study will provide a comprehensive evaluation of the potential of host-directed therapies targeting enzymes involved in the immune response for the treatment of COVID-19. The results of this study may guide the development of novel therapeutics against COVID-19 and inform clinical practice.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293338v1" target="_blank">Systematic Review and Meta-Analysis Protocol of the Efficacy and Safety of COVID-19 Drug Candidates Targeting Host Enzymes Involved in Immune Response</a>
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<li><strong>Vaccine effectiveness against hospitalisation and comparative odds of hospital admission and severe outcomes with BQ.1, CH.1.1. and XBB.1.5 in England.</strong> -
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Background Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity. Methods A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Findings There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5 to 56.0%), 29.7% (95% C.I.; 7.5 to 46.6%) and 52.7% (95% C.I.; 24.6 to 70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5 to 9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77 to 0.99) and 0.88 (95% C.I.; 0.75 to 1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71 to 1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44 to 1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Interpretation Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. Funding None.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293333v1" target="_blank">Vaccine effectiveness against hospitalisation and comparative odds of hospital admission and severe outcomes with BQ.1, CH.1.1. and XBB.1.5 in England.</a>
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</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>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>:   Asfendiyarov Kazakh National Medical 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>Effects of Exercise Training on Patients With Long COVID-19</strong> - <b>Condition</b>:   Long COVID-19<br/><b>Intervention</b>:   Behavioral: Exercise training<br/><b>Sponsor</b>:   Guangdong Provincial People’s Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</strong> - <b>Conditions</b>:   Vaccination; Infection;   COVID-19<br/><b>Intervention</b>:   Biological: Comirnaty<br/><b>Sponsor</b>:   Radboud University Medical Center<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 2/3 Open-Label Study to Evaluate the Safety and Immunogenicity of an XBB.1.5 (Omicron Subvariant) SARS CoV-2 rS Vaccine.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: XBB.1.5 Vaccine (Booster);   Biological: XBB.1.5 Vaccine (single dose)<br/><b>Sponsor</b>:   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: mRNA-CR-04 vaccine 10μg;   Biological: mRNA-CR-04 vaccine 30μg;   Biological: mRNA-CR-04 vaccine 100μg;   Drug: Placebo<br/><b>Sponsor</b>:   GlaxoSmithKline<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 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine;   Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>:   Novavax<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hyperbaric on Pulmonary Functions in Post Covid -19 Patients.</strong> - <b>Condition</b>:   Post COVID-19 Patients<br/><b>Interventions</b>:   Device: hyperbaric oxygen therapy;   Device: breathing exercise;   Drug: medical treatment<br/><b>Sponsor</b>:   Cairo University<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>Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome</strong> - <b>Conditions</b>:   Post-Acute COVID-19 Syndrome;   Fatigue<br/><b>Interventions</b>:   Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome;   Other: Attention Control<br/><b>Sponsor</b>:   University of Maryland, Baltimore<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>Non-ventilated Prone Positioning in the COVID-19 Population</strong> - <b>Conditions</b>:   COVID-19;   Proning;   Oxygenation;   Length of Stay<br/><b>Interventions</b>:   Other: Proning group;   Other: Control group<br/><b>Sponsor</b>:   Baylor St. Luke’s Medical Center<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>HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19</strong> - <b>Conditions</b>:   COVID-19;   Delirium;   Critical Illness<br/><b>Interventions</b>:   Combination Product: Active HD-tDCS;   Combination Product: Sham HD-tDCS<br/><b>Sponsors</b>:   Suellen Andrade;   City University of New York<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>RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms</strong> - <b>Conditions</b>:   Long COVID-19;   Long COVID<br/><b>Interventions</b>:   Drug: Paxlovid 25 day dosing;   Drug: Paxlovid 15 day dosing;   Drug: Control<br/><b>Sponsor</b>:   Kanecia Obie Zimmerman<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 Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Biological: CV0701 Bivalent High dose;   Biological: CV0701 Bivalent Medium dose;   Biological: CV0701 Bivalent Low dose;   Biological: CV0601 Monovalent High dose;   Biological: Control vaccine<br/><b>Sponsors</b>:   GlaxoSmithKline;   CureVac<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>RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>:   Long COVID;   Long Covid19;   Long Covid-19<br/><b>Interventions</b>:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham<br/><b>Sponsor</b>:   Duke 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>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>:   Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>:   Drug: Beclomethasone;   Other: Placebo;   Device: Microsponge<br/><b>Sponsor</b>:   Duke 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>RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>:   Long COVID;   Long Covid19;   Long Covid-19<br/><b>Interventions</b>:   Other: BrainHQ/Active Comparator Activity;   Other: BrainHQ;   Other: PASC CoRE;   Device: tDCS-active;   Device: tDCS-sham<br/><b>Sponsor</b>:   Duke University<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of the Tyrosine-Based Sorting Signals of the ORF3a Protein of SARS-CoV-2 on Intracellular Trafficking, Autophagy, and Apoptosis</strong> - The open reading frame 3a (ORF3a) is an accessory transmembrane protein that is important to the pathogenicity of SARS-CoV-2. The cytoplasmic domain of ORF3a has three canonical tyrosine-based sorting signals (YxxΦ; where x is any amino acid and Φ is a hydrophobic amino acid with a bulky -R group). They have been implicated in the trafficking of membrane proteins to the cell plasma membrane and to intracellular organelles. Previous studies have indicated that mutation of the ^(160) YSNV ^(163)…</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>Discovery of Hybrid Thiouracil-Coumarin Conjugates as Potential Novel Anti-SARS-CoV-2 Agents Targeting the Virus’s Polymerase “RdRp” as a Confirmed Interacting Biomolecule</strong> - The coronavirus (COVID-19) pandemic, along with its various strains, has emerged as a global health crisis that has severely affected humankind and posed a great challenge to the public health system of affected countries. The replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly depends on RNA-dependent RNA polymerase (RdRp), a key enzyme that is involved in RNA synthesis. In this regard, we designed, synthesized, and characterized hybrid thiouracil and coumarin…</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>Transfer and biotransformation of the COVID-19 prodrug molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-placenta barrier</strong> - BACKGROUND: Molnupiravir is an orally bioavailable prodrug of the nucleoside analogue β-D-N4-hydroxycytidine (NHC) and is used to treat coronavirus disease 2019 (COVID-19). However, the pharmacokinetics and transplacental transfer of molnupiravir in pregnant women are still not well understood. In the present study, we investigated the hypothesis that molnupiravir and NHC cross the blood-placenta barrier into the fetus.</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>Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19</strong> - PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters</strong> - ABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with…</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>Novel computational and drug design strategies for inhibition of monkeypox virus and <em>Babesia microti</em>: molecular docking, molecular dynamic simulation and drug design approach by natural compounds</strong> - CONCLUSION: These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo…</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>Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic</strong> - The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, 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>Inhibition by components of <em>Glycyrrhiza uralensis</em> of 3CLpro and HCoV-OC43 proliferation</strong> - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen</strong> - The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains 3 linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein. It was…</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-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation</strong> - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…</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>Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease</strong> - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Crystal structures of main protease (M<sup>pro</sup>) mutants of SARS-CoV-2 variants bound to PF-07304814</strong> - There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (M^(pro)) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 M^(pro) with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment…</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>Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo</strong> - COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles’ ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five…</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>Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model</strong> - Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury</strong> - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The War on Cities</strong> - For nearly two decades, Washington, D.C., had been carefully revising its criminal code. It took a month to blow it all up. - <a href="https://www.newyorker.com/news/annals-of-crime/the-war-on-cities">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trump’s Subdued Courtroom Appearance</strong> - At his arraignment on Thursday, the former President sat fragile and meek in the defendant’s seat. - <a href="https://www.newyorker.com/news/dispatch/trumps-subdued-courtroom-appearance">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Former Federal Prosecutor Explains the Latest Trump Indictment</strong> - The case will hinge on proving whether the former President truly believed that the election was stolen as he attempted to overturn it. - <a href="https://www.newyorker.com/news/q-and-a/a-former-federal-prosecutor-explains-the-latest-trump-indictment">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Death of a Ukrainian Writer</strong> - Victoria Amelina was a gifted novelist who put fiction aside to devote herself to documenting the atrocities of Putin’s war. - <a href="https://www.newyorker.com/news/daily-comment/the-death-of-a-ukrainian-writer-victoria-amelina">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What the Webb Space Telescope Will Show Us Next</strong> - The astrophysicist Jane Rigby talks about the beauty of space, the possibility of life on other planets, and how the Webb sees hidden parts of the universe. - <a href="https://www.newyorker.com/news/the-new-yorker-interview/what-the-webb-space-telescope-will-show-us-next">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The White House should admit that student debt forgiveness isn’t happening</strong> -
<figure>
<img alt="Two activists, holding blue signs bordered in white with white text reading “Cancel student debt now!,” stand in front of the US Supreme Court building." src="https://cdn.vox-cdn.com/thumbor/ariw2WgNJ-23zNYs8RaE_hC9A1A=/0x0:5276x3957/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72520413/1505800929.0.jpg"/>
<figcaption>
Student debt relief activists participate in a rally at the US Supreme Court on June 30, 2023, in Washington, DC. | Kevin Dietsch/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
There’s still time to help student debtors before loan repayment begins — but it means changing course.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZGtO2O">
When Chief Justice John Roberts <a href="https://www.vox.com/2023/6/22/23769890/supreme-court-student-loan-debt-relief-forgiveness-ruling">vaporized</a> Joe Biden’s half-trillion-dollar student loan forgiveness plan in June, he used some dramatically non-legal words to explain why. Writing for the Supreme Court’s six-member conservative majority in the case of <em>Biden v. Nebraska, </em>Roberts declared that the truly offensive and unacceptable thing about the Biden plan, which would have wiped out the loan balances of nearly <a href="https://www.whitehouse.gov/briefing-room/statements-releases/2022/08/24/fact-sheet-president-biden-announces-student-loan-relief-for-borrowers-who-need-it-most/">20 million people</a>, was the sheer size of it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qxf3OG">
The economic and political significance of the scheme was “staggering by any measure,” wrote Roberts, and thus ran afoul of the Court’s radical new doctrine of limiting presidential power.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="peWg97">
Later that day, an angry Biden responded from the White House. His administration had been accused of being unprepared for other seismic court actions, like the <em>Dobbs </em>decision overturning <em>Roe v. Wade. </em>This time was different. The president announced that the Department of Education would immediately begin <a href="https://www.vox.com/23762367/student-loan-forgiveness-supreme-court-biden-cancellation">re-implementing the loan forgiveness plan</a> using a different legal rationale. Progressive lawmakers and grassroots activists, who had been pressing the administration to continue the fight, cheered in response.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="frQl0f">
But Biden’s so-called <a href="https://www.vox.com/23762367/student-loan-forgiveness-supreme-court-biden-cancellation">“Plan B” for mass loan cancellation</a> comes at a perilous moment for student borrowers. For the last three and a half years, federal student loan payments and interest charges have been <a href="https://www.vox.com/22839890/student-loan-payments-restart-february">suspended</a> because of the pandemic. Under the terms of the last-minute debt ceiling deal struck between the White House and congressional Republicans in June, the Department of Education is required to turn the loan repayment system back on in September. Monthly payments are due starting in October.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mXOMKa">
Meanwhile, some of the same scholars who laid the legal groundwork for the original mass cancellation plan are saying that the Supreme Court will likely kill the new plan, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TZRJqA">
The Biden administration is urging people to start paying their loans this fall. But it has also announced a year-long “on-ramp” to making payments that works much like the grace period borrowers face after leaving school, while simultaneously telling millions of borrowers their loans will be entirely forgiven by “Plan B.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7lOfJI">
The resulting confusion, stoked by student loan advocates who demand mass loan forgiveness with no compromises, could wreck the administration’s efforts to successfully restart the student loan collection system. By pushing a politically potent but legally dubious mass forgiveness strategy, President Biden may well be setting a debt trap for the same vulnerable borrowers he is trying to help.
</p>
<h3 id="WEQzXc">
The new Biden student debt relief plan — and why it’s doomed to fail
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jnvjai">
While the White House has been short on details, all signs suggest that its next push for expansive forgiveness is essentially the same as the court-nullified Plan A, but based on statutory authority from a different law. The plan thrown out by the Supreme Court was based on the 2003 HEROES Act, which gives the Secretary of Education authority to waive or modify student loans during a national emergency, like a pandemic. The plan would have subtracted $10,000 from the balance of nearly every outstanding federal student loan. Women and people of color in particular would have benefited because they are more likely to borrow, and an additional $10,000 in relief would have gone to low-income students.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jiuFJy">
Plan B will be based on the Higher Education Act (HEA), which was first enacted in 1965 and is the main law governing federal college grants and loans. The HEA gives the Secretary of Education the authority to “compromise” or “modify, waive, or release” student debt obligations. These are collectively called “settlement authorities.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B4HqpR">
To block Plan B, Biden’s opponents will need legal standing to sue. <em>Biden v. Nebraska </em>began with the court deciding that the state of Missouri had that standing. Missouri’s argument was <a href="https://www.nytimes.com/2023/05/26/opinion/student-debt-relief.html">weak</a>, but the Court accepted it anyway, as courts do when they like a plaintiff’s case. Which means the same plaintiffs would very likely have standing to oppose the new Biden plan.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xJxmN9">
Biden’s lawyers will then have to grapple with the so-called “<a href="https://www.vox.com/scotus/23791610/supreme-court-major-questions-doctrine-nebraska-biden-student-loans-gorsuch-barrett">major questions doctrine</a>,” a legal standard that has been brewing in conservative jurisprudence for several decades and was fully conjured into existence barely a year ago in the case of <em>West Virginia v. EPA. </em>The doctrine says it’s unconstitutional for federal agencies to do things of vast economic and political significance without clear congressional authorization — “vast” and “clear” meaning whatever the court wants them to mean. <a href="https://www.vox.com/scotus/2023/6/30/23779903/supreme-court-student-loan-biden-nebraska-john-roberts">Critics</a> have called this a “fake” doctrine with “no basis in any law or any provision of the Constitution,” and Justice Elena Kagan excoriated the majority’s reasoning in her dissent. But Roberts et al disagreed. That’s where the “staggering by any measure” part comes in. The Biden plan was too big to not fail.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r0zXHJ">
Which means the outcome of the next lawsuit will hinge less on the exact meaning of the Higher Education Act and more on whether the plan once again offends Justice Roberts’s sense of inappropriate vastness. And the White House has given every indication that vast is exactly what it has in mind. Perhaps anticipating Plan B, Roberts even made a point of declaring that the HEA only authorizes loan forgiveness in “certain limited circumstances,” which is pretty much the opposite of “subtract $10,000 from every loan.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NBB6Hx">
Legal experts say the major questions doctrine is an enormous barrier for Biden to overcome. While studying for a PhD at Yale Law School, Luke Herrine wrote an influential 2020 <a href="https://digitalcommons.law.buffalo.edu/buffalolawreview/vol68/iss2/1/">law review article</a> arguing that the Secretary of Education could use the settlement authority granted by the Higher Education Act for mass debt cancellation. Herrine also served as legal director of the Debt Collective, a student loan forgiveness advocacy group, before joining the law faculty at the University of Alabama.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3yVED1">
In the wake of <em>Biden v. Nebraska, </em>he now says, “The Supreme Court has given every indication that it’s not inclined to look favorably on novel uses of the HEA’s settlement authorities” to cancel student debt.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xP3ike">
In other words, Plan B will almost certainly meet the same fate as Plan A.
</p>
<h3 id="rvvMWt">
The debt forgiveness trap
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GpLexj">
For student loan advocates, a loss in the Supreme Court is no reason to give up the fight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sdKLqd">
Mass student loan cancellation is a case study in how grassroots activism can move a social justice idea from the ideological fringe to the halls of power. With roots in the Occupy movement and a critical boost from Bernie Sanders’s insurgent 2016 presidential campaign, advocates used a combination of old-fashioned politicking and modern social media to shove debt cancellation into the center of the 2020 Democratic primary debate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eWlvSU">
Biden was reluctant. His official <a href="https://twitter.com/JoeBiden/status/1241869418981920769">position</a> as a candidate was that he’d support a plan to forgive the first $10,000 of people’s loans if it came in the form of a bill passed by Congress. But when Democratic control of the Senate was still in doubt in the months after the election, advocates immediately began pressing for unilateral executive action on loans, and they never let up. Indebted college-educated millennial voters had been a key to victory, they argued, and the White House risked alienating them without bold action on loans. When Biden announced his mass cancellation plan in August 2022 and the midterms went relatively well for Democrats shortly thereafter, the strategy seemed vindicated.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VU3KdY">
But the plan itself had been doomed since at least September 18, 2020, when Ruth Bader Ginsburg died in time for Donald Trump to seat a sixth conservative on the Supreme Court. The lawsuits from Biden opponents were inevitable, and all hopes that the same court that willfully discarded decades of precedent in recent decisions on abortion and affirmative action would approach the loan question with mercy and restraint came to naught.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mehQ7Z">
For student loan activists, the post-defeat course was clear: press onward with the same uncompromising tactics that had driven their success. Activists worked closely with the White House to push for the original mass forgiveness plan and to make sure that Plan B would be immediately launched in the wake of a Supreme Court defeat. The extent of their influence over Biden administration policy is well-represented in this recent Politico <a href="https://www.politico.com/newsletters/west-wing-playbook/2023/03/16/the-other-plan-b-00087488">article</a>, in which former Sanders campaign staffer and founder of the loan activist group <a href="https://www.cancelstudentdebt.org/">We, the 45 Million</a> Melissa Byrne says of former White House chief of staff Ron Klain, “We all loved Ron. He was personally invested.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LNNSp0">
Now Byrne is <a href="https://twitter.com/mcbyrne/status/1678524021275598850?s=20">telling</a> her followers, “No one needs to make a payment until October 2024 thanks to the on-ramp. Literally no one pay.” The Debt Collective <a href="https://twitter.com/StrikeDebt/status/1680029128337006593?s=20">says</a>, “Student debt strike begins Oct 1.” It’s a strategy that Astra Taylor, a filmmaker and co-founder of the Debt Collective, has described as “<a href="https://www.vox.com/policy-and-politics/22383450/student-debt-forgiveness-biden-astra-taylor">economic disobedience</a>.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mr571p">
When asked for comment, Byrne invited this author to “Go shill for student loan companies elsewhere.” (Under reforms implemented during the Obama administration, companies haven’t made federal student loans since 2010.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ChwoKM">
The Biden administration is officially telling people to start making the payments that stopped in March 2020. But it is simultaneously telling those very same people that their loan payments are soon going to be reduced or, in the case of nearly 20 million people below the $10,000 and $20,000 thresholds, eliminated entirely. And thanks to the recently announced Department of Education “on-ramp” policy that Byrne cites, people who don’t make payments won’t be penalized or reported to credit agencies for at least another year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vlflal">
For borrowers, this is enormously confusing. Payments are due, but there is no penalty for not paying, and you might be paying down a loan balance that is going to be forgiven under a Plan B whose terms have yet to be announced and might not happen — or might, depending on who you believe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OnJy34">
For loan advocates, the critical thing is to continue the struggle. Mike Pierce, a lawyer and the executive director of the Student Borrower Protection Center, says no one can know for sure how the Supreme Court will treat Plan B and that the normal rules of crafting policies based on the likelihood of them being thrown out in court no longer apply.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="byD30b">
“We’re at an inflection point with this administration’s relationship to a corrupt and unethical right-wing court,” he says, arguing that obstructionist Supreme Courts in the past have eventually bent to public pressure. To Pierce, Biden backing away from mass debt cancellation would amount to “unilateral disarmament.”
</p>
<h3 id="Qm0UPm">
It’s time to get the loan system ready for repayment
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2ep88e">
The pandemic wasn’t the first time federal student loan payments have been paused. In 2017, payments were automatically suspended for borrowers living in <a href="https://studentaid.gov/announcements-events/disaster">areas affected by wildfires and hurricanes</a>. When the pause ended the following year, federal officials who monitor the loan program began to notice a troubling pattern.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ln43Br">
When people miss a student loan payment, they descend into a kind of limbo called “delinquency.” If they miss nine months’ worth of payments, they fall down another level into default, where their wages, tax refunds, and even Social Security checks can be garnished. When the disaster-area borrowers were required to start making payments again in 2018, the number of delinquencies began to rise. This continued for nine months and was immediately followed by an <a href="https://fsapartners.ed.gov/knowledge-center/library/electronic-announcements/2020-01-03/federal-student-aid-posts-new-reports-fsa-data-center">increase in the number of defaults</a>. Some people may have fallen out of contact with the loan system and didn’t know they owed money again, or they couldn’t afford it or had lost the habit of making monthly payments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rpA5qH">
The risk now is a similar default crisis on a massive scale. About two-thirds of undergraduates use debt to pay for their degrees. Over 5 million people have left college since 2020 who have never made a single payment on their loans. They may have changed addresses, switched phone numbers, or given loan servicers college email addresses that are now defunct. A recent <a href="https://www.nber.org/papers/w31247">study</a> found that many borrowers used the payment pause to “increase borrowing on credit cards, mortgages, and auto loans.” If those debts are ongoing, borrowers may struggle to find room in their monthly budgets to make loan payments once again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bgCsDh">
For the Biden administration, Plan B creates a potent issue for the 2024 election. For advocates, it provides another year or two to be part of a righteous cause. But the price of all that will be paid by debtors in the form of ballooning balances, ruined credit, and more.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i0Ycez">
Meanwhile, the agency within the Department of Education tasked with managing the federal government’s massive $1.6 trillion student loan portfolio has been rocked by an acute <a href="https://www.washingtonpost.com/education/2023/05/09/student-loans-education-department-delays-cuts/">budget crisis</a>. At odds over the Biden administration’s approach to loan forgiveness, Democrats and Republicans in Congress have been unable to agree on increasing the agency’s funding, hamstringing its ability to tackle the largest and most complex logistical challenge in the history of student loans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZYzYy3">
The Biden administration should be relentlessly focused on helping 40 million student borrowers successfully resume payments and avoid the delinquency trap that has befallen past borrowers. It has a powerful tool at its disposal: a <a href="https://studentaid.gov/announcements-events/save-plan">new, very generous program</a> for reducing monthly loan bills and accelerating loan forgiveness, called SAVE. This plan is — confusingly! — entirely separate from the plan the Supreme Court just jettisoned. It is also built on much firmer legal ground and has not been challenged in court.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zIIx26">
To ease the transition back to making loan payments, the Department of Education has announced an “on-ramp” policy, which functions much like the standard grace period that borrowers get after leaving college. For a year, starting in October, people can<em> </em>start making payments, but if they don’t, nonpayment won’t trigger reports to credit agencies or the ticking clock of delinquency and eventual default.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OsmX96">
The on-ramp makes a lot of sense — if it’s accompanied by an all-out effort to get student debtors back on track to repay their loans. Instead, the Department of Education has simultaneously kicked off a complex, multi-step regulatory process to implement Plan B, requiring a morass of meetings, public notices, and comment periods. The inevitable lawsuit blocking the plan can’t be filed until after that process is complete.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XUbdhZ">
That puts debt forgiveness opponents, including Biden’s rival in the presidential election, in the position of having to very publicly block tens of millions of people from getting their loans forgiven, again<em>, </em>just as the 2024 campaign reaches fever pitch. The inevitable defeat in court won’t come until 2025, after Biden has been reelected, or not.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="72g3hq">
The political calculus is obvious. But there are 20 million people out there who were told they would never have to make another student loan payment. Now they’re being told they don’t really have to start paying their loans back for another year, after which the we-promise-it-will-work-this-time Plan B will take effect. If they take President Biden’s word at face value, why would they start making payments in October?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RQY8Ne">
Meanwhile, the same student loan advocates that the White House looks to for policy and political advice are actively discouraging their many followers from enrolling in repayment plans that reduce monthly payments and provide an accelerated, legally defensible path to loan forgiveness. The Debt Collective <a href="https://twitter.com/StrikeDebt/status/1675477522253856768">says</a>, “Anyone who tries to sell you on IDR” (another acronym for the SAVE program) “is not your friend. The program does not work.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JOLEYX">
For anyone who takes this advice or is just confounded by the Biden administration’s confusing and contradictory student loan messaging, interest charges will pile up. To its credit, the Department of Education has <a href="https://studentaid.gov/understand-aid/types/loans/interest-rates#capitalization">largely ended</a> “interest capitalization,” which means most borrowers won’t pay interest on their interest. But interest will still accumulate<em>, </em>and loan balances will grow<em>. </em>And every month without a payment delays when people can have their loans forgiven under SAVE, which the department has the legal authority to implement.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PjhbxP">
Speaking on background, an education department spokesperson said, “The Department has already been directly in touch with borrowers and made clear that anyone who can make payments should do so when the payment pause ends later this year. The Department plans to do additional direct outreach with enhanced communications for borrowers who become delinquent after payments resume.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pZMpMf">
The White House still has the option of not obstructing its own education department’s efforts to restart the student loan collection system. Legal expert Herrine believes a new forgiveness plan might survive Supreme Court scrutiny if it’s narrowly focused on certain distressed borrowers — “a more targeted form of cancellation might make it through,” he says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eaMn8l">
That could also clear space and focus political energy on other initiatives to prevent students from being saddled with unrepayable debt, like long-gestating rules for reining in abusive for-profit colleges. And it would make it easier to strike a congressional budget deal to properly fund the education department professionals charged with the gargantuan task of turning on a loan system that wasn’t designed to be turned off.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cYWVqB">
Everyone could then turn to the challenge of redesigning the higher education financing system from the ground up so we don’t have so many loans that need forgiving. Debt scholars have proposed ideas like a <a href="https://www.nytimes.com/interactive/2023/07/13/opinion/politics/student-loan-payments-resume.html">new federal university system</a>, affordable and open to all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WgBbVU">
For now, though, President Biden has the unenviable responsibility of telling 40 million people they have to write him a monthly check starting in October. But that’s his job, and doing it successfully will require copious amounts of coordination, discipline, and expertise. Instead, he’s sabotaging his own education department for political purposes — and sowing doubt and chaos along the way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PiOH9S">
<em>Kevin Carey writes about education and other issues. He is a vice president at New America, a think tank in Washington, DC. </em>
</p></li>
<li><strong>ChatGPT could make bioterrorism horrifyingly easy</strong> -
<figure>
<img alt="People wearing gas masks and anti-chemical gloves." src="https://cdn.vox-cdn.com/thumbor/cHqY8u2rsgFibJTIvz_-siKSCDs=/286x0:4862x3432/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72520371/GettyImages_454282814.0.jpg"/>
<figcaption>
Riot police don gas masks and anti-chemical gloves on March 24, 1995, before raiding a commune of the religious cult the “Aum Supreme Truth” in Kamikuishiki village west of Tokyo. | Yoshikazu Tsuno/AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The biggest risk from advanced artificial intelligence is biological.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A13oGW">
In the summer of 1990, three trucks <a href="https://www.files.ethz.ch/isn/156879/CNAS_AumShinrikyo_SecondEdition_English.pdf">sprayed</a> a yellow liquid at different sites in and around Tokyo, including two US Naval bases, Narita Airport, and the imperial palace. The attackers belonged to a group called Aum Shinrikyo, a Japanese cult that aimed to cause the collapse of civilization, making space for the rise of a new society ordered according to their religious ideals. Five years later, Aum would gain notoriety by <a href="https://www.nytimes.com/2018/07/05/world/asia/japan-cult-execute-sarin.html">carrying out</a> sarin gas attacks on the Tokyo subway, killing 13 and injuring thousands.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bKazl1">
Aum intended for the yellow liquid dispersed in the summer of 1990 to contain botulinum toxin, one of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856357/">most poisonous biological substances</a> known to human beings. However, no one was killed in the attacks that summer. One <a href="https://academic.oup.com/cornell-scholarship-online/book/16600/chapter/173667626?login=true">possible factor</a> in their failure is that Aum lacked a crucial bit of knowledge: the difference between disseminating the bacterium Clostridium botulinum<em> </em>and disseminating the highly deadly botulinum toxin it produces. It is unclear whether Aum even managed to acquire a toxin-producing form of the bacterium, and there are also other causes for why Aum’s attack failed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7VgKrf">
But if it had access to contemporary artificial intelligence tools, Aum Shinrikyo, or a similarly malign group, might not have made this and other mistakes. <a href="https://chat.openai.com/">ChatGPT</a> is very good at answering questions and providing knowledge, including on the production of botulinum toxin. If Aum had had access to ChatGPT, would the attacks of the summer of 1990 be remembered as possibly the worst bioterrorism event in history?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2PObk5">
Advances in artificial intelligence have tremendous potential to have positive impacts on science and health. Tools like ChatGPT are revolutionizing how society works and learns, and artificial intelligence applied to biology has led to solving the decade-old <a href="https://www.vox.com/future-perfect/22045713/ai-artificial-intelligence-deepmind-protein-folding">protein folding problem</a> and is transforming <a href="https://www.vox.com/2020/1/31/21117102/artificial-intelligence-drug-discovery-exscientia">drug discovery</a>. However, as artificial intelligence raises the ceiling of biological engineering and helps distribute these powers to a tremendous number of individuals, there is a serious risk that it will enable ill-intentioned actors like Aum Shinrikyo, to potentially devastating effect. As I have discussed in a recent <a href="https://arxiv.org/abs/2306.13952">preprint</a> paper, large language models (LLMs) like ChatGPT, as well as novel AI-powered biological design tools, may significantly increase the risks from biological weapons and bioterrorism.
</p>
<h3 id="0lie8D">
How AI language models are a threat multiplier for bioweapons
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hdHIbh">
Large language models — which are very good at answering questions and teaching about dual-use knowledge — may in particular increase the accessibility of biological weapons. In a recent <a href="https://arxiv.org/abs/2306.03809">exercise</a> at MIT, it took just one hour for ChatGPT to instruct non-scientist students about four potential pandemic pathogens, including options for how they could be acquired by anyone lacking the skills to create them in the lab, and how to avoid detection by obtaining genetic material from providers who do not screen orders.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Bovra1">
At the same time, the story of Aum Shinrikyo’s lack of knowledge about the difference between Clostridium botulinum and botulinum toxin is not an isolated example. Past biological weapons programs have frequently been bottlenecked by not having the right staff, with the required knowledge and expertise, to create an effective bioweapon. Al-Qaeda’s exploration of bioterrorism was led by Rauf Ahmed, who had originally studied microbes related to food production, and thus tried to <a href="https://www.washingtonpost.com/archive/politics/2006/10/31/suspect-and-a-setback-in-al-qaeda-anthrax-case-span-classbankheadscientist-with-ties-to-group-goes-freespan/eeb4e5a1-9d08-4dfa-bccc-5c18e311502a/">quickly learn</a> about anthrax and other pathogens. Over the course of 2001, Rauf used his scientific credentials to <a href="https://www.belfercenter.org/sites/default/files/legacy/files/al-qaeda-wmd-threat.pdf">make headway</a> toward acquiring anthrax. It is not publicly known how far he got; <a href="https://www.belfercenter.org/sites/default/files/legacy/files/al-qaeda-wmd-threat.pdf">he was arrested</a> that December.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nNRisd">
Despite having access to the relevant equipment, Saddam Hussein’s Iraq <a href="http://www.cnn.com/2003/WORLD/meast/04/28/sprj.irq.germ.warfare/index.html">never turned</a> its anthrax weapon from a less potent liquid form into a more dangerous powder form, which can be stored and released at much higher and more predictable concentration. That’s likely because its scientists lacked the knowledge of the relevant process for drying and milling anthrax. As chatbots become more sophisticated, however, they may inadvertently help individuals with malicious intent to upskill on topics that empower them to do harm.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Awy8GH">
But how much can you learn from an AI-powered lab assistant alone? After all, to make a pathogen or a bioweapon, you don’t just need instructional knowledge of the sort that can be dished out by an LLM, you need hands-on, tacit knowledge. <a href="https://en.wikipedia.org/wiki/Tacit_knowledge">Tacit knowledge</a> describes all knowledge that cannot be verbalized and can only be acquired through direct experience. Think of how to ride a bike, or for that matter, how to <a href="https://academic.oup.com/spp/article/41/5/597/1636559">perform molecular biology</a> procedures, which might require knowing how to hold a pipette, shake a flask, or treat your cells. It is difficult to define the extent of this tacit knowledge barrier and how much impact LLMs like ChatGPT may have on lowering it. However, one fact seems clear: If chatbots and AI-powered lab assistants make the creation and modification of biological agents seem more accessible, then it is likely that more individuals will try their hand. And the more who try, the more who will eventually succeed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oNHp5i">
Additionally, ChatGPT is just the beginning of language models and related forms of artificial intelligence. Already now, language models <a href="https://erikaaldendeb.substack.com/p/language-is-not-enough?utm_campaign=post">are revolutionizing</a> the way scientists can instruct lab robots on what work to perform. Soon, artificial intelligence systems will be able to perform ideation and design of experimental strategies. Thus, artificial intelligence will enable and accelerate the increasing automation of science, reducing the number of scientists required to advance large-scale projects. This will make it easier to develop biological weapons covertly.
</p>
<h3 id="dpUYMf">
Biological design tools could simplify bioweapons
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7g9Eh5">
While large language models may eventually push the ceiling of biological design capabilities, more specialized AI tools are already doing this now. Such biological design tools (BDTs) include protein folding models like <a href="https://www.nature.com/articles/s41586-021-03819-2">AlphaFold2</a> and protein design tools like <a href="https://www.bakerlab.org/2023/03/30/rf-diffusion-now-free-and-open-source/">RFdiffusion</a>. These artificial intelligence tools are usually trained on biological data, such as genetic sequences. They are developed by many different companies and academics to help with important biological design challenges, such as developing <a href="https://www.nature.com/articles/d41586-023-01516-w">therapeutic antibodies</a>. As biological design tools become more powerful, they will enable many beneficial advances like the creation of new medications based on novel proteins or designer viruses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="j2qs9N">
But such powerful design capabilities may also exacerbate biological risks. At the extreme, biological design tools could allow the design of biological agents with unprecedented properties. It has been hypothesized that natural pathogens feature a trade-off between how transmissible and how deadly they are; designed pathogens might not feature such evolutionary constraints. A group like Aum Shinrikyo could potentially create a pandemic virus much worse than anything nature could produce and thus, biological design tools could turn pandemics from the catastrophic risks they are now into true existential threats. Biological design tools could also enable the creation of biological agents targeted at specific geographies or populations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R9X5yU">
In the short term, new design capabilities may challenge existing measures to control access to dangerous toxins and pathogens. Existing security measures tend to focus on proscribed lists of dangerous organisms or screening for known threatening genetic sequences. But design tools may simply generate other agents with similar dangerous properties that such measures wouldn’t catch.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MRm7hF">
The good news is that — at least initially — new cutting-edge possibilities enabled by biological design tools will likely remain only accessible to a manageable number of existing experts who will use these facilities for legitimate and beneficial purposes. However, this access barrier will fall as biological design tools become so proficient that their outputs require little additional laboratory testing; in particular, as AI language models learn to interface effectively with the tools. Language models are already being <a href="https://arxiv.org/abs/2304.05376">linked up</a> to specialized science tools to help with specific tasks and then automatically apply the right tool for the task at hand. Thus, the heights of biological design could quickly become accessible to a very large number of individuals, including ill-intentioned actors.
</p>
<h3 id="Epmv0v">
Why we need mandatory gene synthesis rules
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XNM70j">
What can be done to mitigate risks emerging from the intersection of AI and biology? There are two important angles: strengthening general biosecurity measures and advancing risk mitigation approaches specific to new artificial intelligence systems.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="avGSBw">
In the face of increasingly powerful and accessible biological design capabilities, one crucial biosecurity measure is universal gene synthesis screening. The production of the genetic building blocks for a protein or organism is the crucial step in turning digital designs into physical agents. A range of companies specializes in producing such DNA or RNA building blocks. Since 2010, the US government <a href="https://aspr.hhs.gov/legal/syndna/Pages/default.aspx">has recommended</a> that such gene synthesis companies screen orders and customers to ensure only legitimate researchers are accessing genetic material for controlled agents. Many cutting-edge gene synthesis companies perform such screening voluntarily and have formed the <a href="https://genesynthesisconsortium.org/">International Gene Synthesis Consortium</a> to coordinate these activities. However, a significant number of gene synthesis providers still do not screen. Indeed, as the MIT exercise demonstrates, ChatGPT is very adept at pointing out this fact and giving instructions on how to exploit such weaknesses in supply chain security.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z6MUfY">
What is needed is a mandatory baseline for screening synthetic DNA products. Requiring such baseline screening does not go against the interests of companies: Industry leaders across the US and UK have been screening orders voluntarily and <a href="https://www.nti.org/events/benchtop-dna-synthesis-devices-capabilities-biosecurity-implications-and-governance/">are actively calling</a> for a regulatory baseline to prevent competitors from skimping on safety. Measures to make gene synthesis screening mandatory should capture increasingly common benchtop gene synthesis devices and need to be future-proof to include screening for functional equivalents of concerning agents. Similar customer screening baselines are also needed for other crucial service providers at the boundary of the digital-to-physical, such as contract research organizations providing services to synthesize organisms.
</p>
<h3 id="JrybeI">
Advancing governance of artificial intelligence
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bxUDPq">
In addition to general biosecurity measures, we also need artificial intelligence-specific interventions. The first focus should be mitigating risks from large language models because not only are these models likely already lowering barriers to biological misuse, but also because their capabilities may increase quickly and unpredictably. One crucial challenge that applies across the whole range of risks posed by large language models is that new and dangerous capabilities may only become clear after the release of the model.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a2purL">
A particularly crucial role in mitigating risks from LLMs may be played by <a href="https://arxiv.org/pdf/2305.15324.pdf">pre-release evaluations</a> of model capabilities. Such pre-evaluations are necessary to ensure that new models do not contain dangerous capabilities on public release — and if conducted by a third party, they could ensure that companies have taken appropriate steps during training and fine-tuning to reduce the chance that these models could enable biological misuse. Releasing models through <a href="https://www.governance.ai/post/sharing-powerful-ai-models">structured access</a> methods, such as the web ChatGPT interface, can ensure that safeguards can be continuously updated. In contrast, <a href="https://www.vox.com/technology/2023/7/28/23809028/ai-artificial-intelligence-open-closed-meta-mark-zuckerberg-sam-altman-open-ai">open-sourcing a powerful LLM</a> has significant risks because fine-tuning and safeguards may be easily removed, and if new dangerous capabilities are discovered, it would be impossible to retract a model or update its safeguards.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2zXRTj">
Generally, the potential impact of artificial intelligence tools on the risk of biological misuse raises a profound question: Who should be able to access dual-use scientific capabilities? For policymakers trying to answer this question, it will be vital to consider diverse voices from across different disciplines, demographics, and geographies. This will require difficult trade-offs between the openness of scientific areas relating to pathogens, law enforcement and monitoring of data streams for illicit activities, and increasing risk of misuse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Hfb9cs">
One sensible position might be that language models like ChatGPT do not need to provide anyone with detailed step-by-step instructions to create a dangerous strain of pandemic flu. Therefore, it might on balance be preferable if public versions of such models do not give detailed answers to questions on this and other dual-use topics. Notably, Anthropic’s recently released cutting-edge language model <a href="https://claude.ai/login">Claude 2</a> features a notably higher barrier than GPT-4 for handing its users detailed instructions for dangerous experiments.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cRI5sI">
At the same time, it is important that these tools enable scientists with appropriate training and approval to develop new medications and vaccines. Thus, differentiated access methods are needed for AI-powered lab assistants and biological design tools. This might require advancing ways for legitimate scientists to authenticate themselves online. For instance, to access model capabilities for predicting immune evasion variants of influenza virus to inform vaccine design, a scientist might need to authenticate and provide appropriate documentation of biosafety and dual-use review.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hQvj6V">
Beyond exacerbating biosecurity risks, advances in artificial intelligence also present an opportunity. As progress in AI spurs more rigorous gene synthesis screening, this will strengthen biosecurity more broadly. And as biological risks drive AI governance measures like pre-release evaluations of large language models, this will mitigate a wider array of artificial intelligence risks. Swift action by policymakers will not only enhance safety but also pave the way for reaping the many benefits of artificial intelligence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3u1pf5">
<em>Jonas Sandbrink is a biosecurity researcher at the University of Oxford and a biological security adviser at the UK Cabinet Office. This article is based on his recently published </em><a href="https://arxiv.org/abs/2306.13952"><em>preprint</em></a><em> titled “Artificial intelligence and biological misuse: Differentiating risks of language models and biological design tools.” This article reflects only the opinion of the author and not of the organizations with which he is affiliated.</em>
</p></li>
<li><strong>The new crisis of masculinity</strong> -
<figure>
<img alt="Drawing of a man falling in liminal space." src="https://cdn.vox-cdn.com/thumbor/ZBXSoMSCKT2jRGKpVkzW_E8mpxQ=/304x0:5168x3648/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72520318/GettyImages_1321669280.0.jpg"/>
<figcaption>
Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What’s the matter with men — and how do we fix it?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="v8DZ2q">
What’s going on with men?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XMEBv8">
It’s a strange question, but it’s one people are asking more and more, and for good reasons. Whether you look at <a href="https://www.brookings.edu/articles/boys-left-behind-education-gender-gaps-across-the-us/#:~:text=In%201970%2C%20just%2012,now%20going%20the%20other%20way.">education</a> or the <a href="https://www.cbsnews.com/news/men-workforce-work-companies-struggle-fill-jobs-manufacturing/">labor market</a> or <a href="https://nida.nih.gov/news-events/news-releases/2023/06/men-died-of-overdose-at-2-3-times-greater-a-rate-than-women-in-the-us-in-2020-2021">addiction rates</a> or <a href="https://www.washingtonpost.com/politics/2022/09/30/suicides-are-spiking-among-young-men/">suicide attempts</a>, it’s not a pretty picture for men — especially working-class men.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jqek6o">
Normally, more attention on a problem is a precursor to solving it. But in this case, for whatever reason, the added awareness doesn’t seem all that helpful. The “masculinity” conversation feels stuck, rarely moving beyond banal observations or reflexive dismissals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bhCqQs">
A <a href="https://www.washingtonpost.com/opinions/2023/07/10/christine-emba-masculinity-new-model/">recent essay</a> by the Washington Post columnist Christine Emba on this topic was different. It was — apologies for the cliché — one of those pieces that “broke through.” Besides being well done, Emba’s treatment of the topic was uncommonly nuanced, which is increasingly hard to do when tackling “controversial” topics.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eVq6US">
So I invited Emba onto <a href="https://podcasts.apple.com/us/podcast/the-project-of-socratic-love-with-agnes-callard/id1081584611?i=1000611288941"><em>The Gray Area</em></a> to talk about the state of men and what she thinks the way forward might look like. Below is an excerpt of our conversation, edited for length and clarity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n0c49i">
As always, there’s much more in the full podcast, so listen and follow <em>The Gray Area</em> on <a href="https://podcasts.apple.com/gb/podcast/the-gray-area-with-sean-illing/id1081584611">Apple Podcasts</a>, <a href="https://podcasts.google.com/search/vox%20conversations">Google Podcasts</a>, <a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP">Spotify</a>, <a href="https://www.stitcher.com/show/vox-conversations">Stitcher</a>, or wherever you find podcasts. New episodes drop every Monday and Thursday.
</p>
<div id="DtkB6b">
</div>
<hr class="p-entry-hr" id="dXybHc"/>
<h4 id="HYlYaf">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZBAKuB">
Worrying about the “state of men,” as you say in your piece, is an old American pastime, so what makes this moment different?
</p>
<h4 id="iWPIMd">
Christine Emba
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tm9AYG">
I think that now we have actual data showing that men do seem to be in a real crisis, and we also have data on how the world has changed. We can all see this in our own lives. Our social structure, our work structure, our economy, has changed really significantly over the past 30 to 40 years. And that necessarily changes how people fit into the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xpdKxA">
A lot of the changes have had a direct effect on men specifically. So we can look at the stats that we have right now about how men are doing, and we see that <a href="https://www.brookings.edu/articles/the-male-college-crisis-is-not-just-in-enrollment-but-completion/#:~:text=Over%201.1%20million%20women%20received,master's%20degree%2C%20relative%20to%20women.">for every 100 bachelor’s degrees awarded to women, only 74 are awarded to men</a>. We know that when you’re looking at deaths of despair, which is a more recent phenomenon, <a href="https://www.cnn.com/videos/us/2022/11/26/smr-reeves-men-in-trouble.cnn#:~:text=Men%20account%20for%20almost%203,the%20labor%20force%20is%20plummeting">3 out of 4 of those deaths are males</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oQ6mll">
And then there are social factors, too. There’s been a change in who the high earners in our society are. In 2020, <a href="https://www.usatoday.com/story/money/2020/03/03/gender-wage-gap-more-women-out-earning-husbands/4933666002/#:~:text=About%20half%20of%20women%20say,to%20the%20Pew%20Research%20Center.">nearly half of women reported in a survey</a> that they out-earn or make the same amount as their husband or romantic partner. And in 1960, that was fewer than 4 percent of women.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LcRlGB">
So we’ve seen the economy change in ways that have moved away from the strength jobs, from traditional union jobs and factory and labor jobs that were mostly seen as male jobs and helped promote this idea of the man as the provider who can take care of a whole family on one income. Now it’s more about soft-skilled credentialism and that favors jobs that tend to skew toward women. Because of the feminist movement and women’s advances — which, to be clear, is a great thing — women have entered schools and the economy in force and they’re doing really well. And I think men are beginning to feel a little bit worried and lost in comparison.
</p>
<h4 id="UKS3eK">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HmYCHN">
Why is this such a difficult problem to talk about, especially for people on the left?
</p>
<h4 id="QsSGTw">
Christine Emba
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hzUXVu">
This was actually one of the major inspirations for writing this piece, because I was trying to get at that question, and I even felt as I was working on this piece my own reluctance to attend to it empathetically. I theorize that there are a couple reasons for this.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OLmQZe">
First of all, justifiably I think, progressives and people on the left want to preserve the gains that have been made for women over the past several decades. The feminist movement and movements for women’s equality are still pretty fragile. We saw during the COVID-19 pandemic that suddenly it was women dropping out of the workforce en masse. It’s really easy, on the left and just in politics generally, to think of things as being zero-sum. So there’s this fear that if we start helping men, then we’ll just have forgotten about women and there won’t be space or time for women anymore. I think that’s a mistake. We should be able to do two things at once. We can recognize that both women and men are members of our society and we should want to help everyone.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z7B9j9">
I think there’s also something really appealing to someone with a progressive mindset about the idea of gender neutrality, or gender neutrality as an ethos that we should aspire to and avoid making distinctions between men and women or masculine and feminine. We’ve moved in liberal society toward a real ideal of individualization; the idea that there could be one form of masculinity or manhood that’s good risks alienating people who don’t necessarily fit into that box. And then ascribing certain traits to men, especially if they’re positive traits, might create worries that we’re subtracting those traits from women. If we say that men are leaders, does that mean that women are always going to be followers? Or if men are strong, are we actually saying that women are weak? I think there’s a fear of doing that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dzN3bD">
Finally, I think there’s a generalized resentment, especially after the Me Too moment — but also after a feminist movement in the 2010s that encouraged a pretty silly and uncritical form of man-hating and misandry where it was cool to be like, <em>Men are trash, men suck. Wouldn’t the world be better without men? What are they even for? </em>It was a feeling that you needed to do this sort of thing to prove your liberal bona fides that you love women enough.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VHterx">
There’s also the fact that because progressives in the mainstream have not really taken up the masculinity question, the people who have taken it up tend to be on the right and often they tend to be problematic figures. You see incels and men’s rights activists and Ben Shapiro burning Barbies, and there’s a fear that if you speak up for men, everyone’s going to be like,<em> You seem too interested in this. Are you one of them?</em> It’s a branding problem.
</p>
<h4 id="drM7m0">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pn34IG">
It’s definitely true that the left, for all of these reasons, has ceded this space to the right and the right has happily filled the vacuum. So what do you see happening with people like <a href="https://www.vox.com/world/2018/3/26/17144166/jordan-peterson-12-rules-for-life">Jordan Peterson</a> and <a href="https://www.vox.com/culture/2023/1/4/23539528/andrew-tate-arrest-jail-rape-human-trafficking">Andrew Tate</a>? These are very different people, I’m not equating them, but they inhabit this space in revealing ways.
</p>
<h4 id="tYSgJV">
Christine Emba
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mUMpVt">
It’s a super interesting question. I do think that it’s important to try and draw distinctions here. There’s sort of a spectrum of what I call in the piece “the manfluencers” — a ridiculous word for a ridiculous phenomenon. But there is a range of people who are maybe slightly more benign. I think Jordan Peterson started out as more benign, although he’s gotten fringier since, to people like Andrew Tate, who I think are just straightforwardly bad people. And you have also people like Josh Hawley and Joe Rogan and Bronze Age Pervert and all of these people in between.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9Y1hwq">
I think it’s just factually accurate that conservatives and the right have always been more invested in — and more clear about — gender roles. So it’s almost natural that they have a clearer vision of what manhood is and what men should do. But I think they realize that there was an opening here. Young men especially are looking for role models and realizing that they feel unsure and uncomfortable of their place in the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qz9Sx0">
There’s a young man who I interviewed for the piece, who was like, <em>I just want someone to tell me how to be.</em> If the progressive left is like, <em>We’re not going to tell you that, just be a good person, you don’t need rules.</em> And then young men are like, <em>No, I’m really asking you. I really want rules, actually</em>, the right is happy to give them those rules.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XstQsk">
If people have an identity as a man or masculine, the right is not going to say it’s toxic and only talk about toxic masculinity. They’re positive about it and they frame it as something that you want to aspire to, that’s actually transgressive and great and historically superior to whatever’s going on today, for better or worse. And being told that your identity is a positive thing, and here’s a road map to how to fulfill it, whether it’s actually good or bad, that something is going to beat out nothing anytime.
</p>
<h4 id="pU37lY">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ObDGgz">
I think there’s something earnest about Peterson’s project, or there certainly was, but the Tate phenomenon is different. To me, this is what happens when masculinity becomes steeped in fear and resentment. With Tate, unlike Peterson, there’s no pretension to anything virtuous. It’s just, <em>Hey, the world hates you. The world wants to make you weak, wants to make you soft, so take what you can get, crush your enemies, abuse women, double down on everything they hate about you.</em> It’s the weak person’s vision of a strong person. It’s the 19-year-old Nietzsche reader who didn’t make it past the preface.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IrJBLP">
But I still don’t think a lot of people quite understand Tate’s reach. Do you see him as a creature of a very particular moment or do you think he represents something bigger and more enduring?
</p>
<h4 id="iN86NX">
Christine Emba
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CqtCXh">
The Tate phenomenon, as you say, isn’t just about Tate. There’s a whole space with very online figures like Bronze Age Pervert, or BAP, who wrote this book, <em>Bronze Age Mindset</em>, that’s become a very conservative phenomenon. I think you’re exactly right. This is a vision of masculinity that’s super basic and sort of tailored to a 15-year-old who doesn’t know any better. It’s all about just shouting and showing off your cars and your women and your money, and that’s what being a man is. It’s very clear: just work out and be mean. It’s simple and it’s superficially appealing because there are a lot of fast cars and pretty girls. And I guess that appeals especially to young men who haven’t thought about it very much.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OkXtvL">
But I do think, in the absence of better road maps, in the absence of other models, people like Tate present a very clear, visible model. He’s everywhere. You see him everywhere if you’re a kid online. I think that’s also part of what has let him be underestimated. His reach is enormous among younger men, like middle school through high school-aged kids. They’ve all heard of Andrew Tate, to the point that, actually, in Britain, where he’s from, there was a campaign last year where teachers in high schools and middle schools were talking amongst themselves about how to combat Tateism in the classroom because these middle schoolers who had watched Andrew Tate videos were getting up in class and telling their female teachers to shut up, because they don’t listen to women, and that’s what Tate taught them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hPpNxG">
His videos spread on TikTok and YouTube and Facebook before <a href="https://www.vox.com/the-goods/23318861/andrew-tate-tiktok-instagram-youtube-banned">he was banned</a> from all of those sites. Fifty-five-year-old dads weren’t necessarily on TikTok, and I think didn’t realize how much reach he had and how much of a hold he had. And the same with all of these online figures who are sort of flying under the radar because they’re online. But I do think it’s important what you point out about their immorality.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Wdc9tY">
Jordan Peterson, and even to some extent the Josh Hawley figures, are saying, <em>Well, it’s good to be a man, but also being a man means being responsible in some way, contributing to society in some way. </em>The Tateist version of masculinity is totally divorced from anything positive. It’s just about defining yourself in opposition to women and taking what you can get. But it’s a clear path and it feels almost transgressive, which I think is part of its appeal because he’s like, <em>Call me toxic. I love being toxic. I am toxic masculinity.</em> To a 15-year-old edgelord, that is aspirational, I guess. But it’s really ugly and it’s not good for society in any way.
</p>
<h4 id="t0fwO9">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nDKrCh">
What do you think a truly healthy masculinity looks like? You identify three traits in the piece — protector, provider, and procreator — and I know a lot of people will hear that and, not without reason, immediately think of the patriarchy of yesterday. Do you think that’s a mistake?
</p>
<h4 id="oqIwab">
Christine Emba
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9SRL5G">
Another great question. Even when I was writing the piece, I was wrestling with my reluctance to try and define masculinity or cheer on masculinity too much and my belief that we actually need to do just that. One of the things about the piece that seemed to strike a lot of people was the fact that I admitted that I like men. I want them to be happy. And I also do think that there is something distinctive that one could call manhood or masculinity that is a different thing than womanhood or femininity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rklabM">
So you pulled out the concepts of protector, provider, procreator, and I got those from the anthropologist, David Gilmore, <a href="https://yalebooks.yale.edu/book/9780300050769/manhood-in-the-making/">who did this cross-country study</a> a couple decades ago looking at what it meant to be a man in all of these different groups across several continents. He found out that almost every society did have a concept of masculinity that was distinctive from just being male. It was something that you earned and was also distinctive from being female. It had to do with being someone who protected the people around you in your community, who provided in some way for your family. That often looked like not just providing, but creating surplus in some ways and sharing that with others. And then there was the idea that procreating, having a family, was what being a successful male looked like.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jLtSYk">
In our modern moment, I think that can look like a lot of different things. In my essay, there’s a callout where I ask people to write in and tell me about their ideal of masculinity. When I think about masculinity myself, there are a couple of attributes that seem to come up a lot, and it’s stuff like strength used well and responsibility, performing your duties, looking out for people who are weaker than you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GCEbpy">
The pushback that I get very often when I talk about this is what I was saying earlier, people are like, <em>Why do you have to say that’s being a good man? Why is leadership or ambition or adventurousness a male trait? Aren’t women leaders? </em>And of course, yes, but I do think that being a good person is not a clear enough road map. It’s not a strong enough, clear enough norm, and that’s what younger people especially are looking for.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TyJLJP">
I think what it means to be a good person is in some ways tied to your embodiment, to your human form as a male person or a female person. For instance, [younger] men tend to be — though not always — much stronger than the average woman or old person. So being a good person, if that is your embodiment, necessarily means thinking about what that says about your responsibilities. What do you do with that strength?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PsLCvt">
Richard Reeves, who wrote the book <em>Of Boys and Men</em>, talks about how masculinity and femininity, or male and female, overlap a lot. But on the far ends of the spectrum, there are very big differences, and that tends to be where our definitions of male and female come from.
</p>
<h4 id="l6BYym">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f7VwXx">
It’s true that you can’t talk about masculinity and femininity without acknowledging some differences between the sexes. And yet, that acknowledgment is utterly compatible with the reality that much of what we call gender is a performance, is a cultural construct. And I don’t know why we seem unable to avoid this zero-sum trap. You see this in lots of other cultures where there’s a respect for the masculine and feminine ideal. There’s no zero-sum relationship. These are poles at opposite ends of the continuum, and possessing virtues at both ends of the spectrum is seen as wise and healthy. I don’t know why we can’t do that.
</p>
<h4 id="qLh8C5">
Christine Emba
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TMZy5D">
America really likes extremes. I think we like things that are very clear-cut and we’re used to seeing things that way and seeing them used to marginalize people or somehow denigrate people who don’t fit the exact norms. I think people who think of themselves as good progressives and liberals really don’t want to do that, and so shy away from espousing norms because they might leave someone out. And I understand that. But for the people who are asking for a road map, who want to be told who to be, just saying B<em>e whoever you want to be, but be a good one</em> is just not helpful.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KXTth0">
There’s also an age factor here and I noticed this in the responses to the piece. There were older men who would write in and say, <em>What’s the problem? I’m a man, I feel great about it. I don’t see the issue.</em> That’s great for you, but for young people, who don’t have that much life experience, who are trying to figure out who to be, having some kind of norm or ideal, even if it’s loose, can be helpful. And then as you grow older and you get life experience and you figure out how you fit in the world, you make the norm up for yourself. But they’re looking for a starting point.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sw9tbi">
<em>To hear the rest of the conversation, </em><a href="https://open.spotify.com/episode/5A0IlKC5zLFhc1iF8nj7US?si=jNJlEL7QSa-Ut9JMAsb41g"><em>click here</em></a><em>, and be sure to follow </em><a href="https://www.vox.com/thegrayarea">The Gray Area</a><em> on </em><a href="https://podcasts.apple.com/gb/podcast/the-gray-area-with-sean-illing/id1081584611"><em>Apple Podcasts</em></a><em>, </em><a href="https://podcasts.google.com/search/vox%20conversations"><em>Google Podcasts</em></a><em>, </em><a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP"><em>Spotify</em></a><em>, </em><a href="https://www.stitcher.com/show/vox-conversations"><em>Stitcher</em></a><em>, or wherever you listen to podcasts.</em>
</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>V.S. Sampath named Electoral Officer for HCA polls</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>It’s Anita vs Sanjay for WFI chief’s post</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>Indian wrestlers claim 11 medals</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>It won’t stay bad forever: India hockey coach Fulton on poor PC conversion rate</strong> - India vice-captain and midfielder Hardik Singh said patience is what paid off for the team against Malaysia, besides noting that controlling the tempo helps in creating goal-scoring chances</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>India’s top-order under pressure in must-win game, spinners need to stop Pooran juggernaut</strong> - The slow pitches on offer have not been the best for batting but as skipper Hardik Pandya pointed out after the loss on August 7, India should have a found way to score additional 10-20 runs</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>HC directs SPC to avert law and order problem over dispute over student concession</strong> - Justice P.V. Kunhikrishnan observes that “it seems that the student concession rate had not been enhanced in decades”. HC urges govt. and student organisations to have a relook at the price</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>Not planning to withdraw NLC expansion: Union Minister Pralhad Joshi</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>Kannur University to provide higher education to students affected by communal riots in Manipur</strong> - Separate seats to be allotted. Varsity has taken such a decision considering applications received from student organisations of Manipur, says Vice-Chancellor</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>Bilkis Bano case convicts driven by “blood thirsty” approach to hunt and kill Muslims, Supreme Court told</strong> - The Gujarat government had raised preliminary objections with regard to the petitions filed in the matter other than the one by Bilkis Bano</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 Karnataka today</strong> - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated by Nalme Nachiyar.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Russia hits blood transfusion centre, says Zelensky</strong> - President Volodymyr Zelensky described the attack as a “war crime” and perpetrators as “beasts”.</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>Belarus isolates political prisoners to break their spirit</strong> - Families of Belarusian political prisoners say loved ones are being denied any outside contact.</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 Irish Light: Woman abused by paper which falsely said vaccine killed her son</strong> - Promoting a Covid conspiracy theory, the Irish Light’s editor accuses the mum of “massive fraud”.</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>German police investigate death of Mexican student</strong> - The body of María Fernanda Sánchez was found in a canal in Berlin two weeks after she disappeared.</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>Mother and baby among six dead after migrant boats sink off Italian coast</strong> - A mother and her one-year-old baby, from the Ivory Coast, are among the dead.</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>Turning my Framework laptop into a tiny desktop was fun. Now it needs a job.</strong> - “Reuse” doesn’t get as much attention as the other two Rs, but it’s important. - <a href="https://arstechnica.com/?p=1951787">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SpaceX conducts a mostly successful test of its Super Heavy booster</strong> - There were positives and negatives to be taken away from the test firing. - <a href="https://arstechnica.com/?p=1959183">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>T cells burn out just a few hours after encountering cancer tumors</strong> - Why do T cells become exhausted within a few hours of bumping into cancer? - <a href="https://arstechnica.com/?p=1959111">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Review: Oppenheimer is pure visual poetry</strong> - Technically it’s a biopic, but it doesn’t play like one. - <a href="https://arstechnica.com/?p=1957638">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What are “drainer smart contracts” and why is the FBI warning of them?</strong> - Scam sites often pose as outlets selling non-fungible tokens. - <a href="https://arstechnica.com/?p=1959148">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A young soldier was sent to the personnel office and assigned the task of registering recruits for life insurance.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Because of the cost, most soldiers didn’t buy the life insurance, but after only 1 month on the job he had sold a record number of policies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His captain noticed but thought it was a fluke. However, the following month, he doubled sales. A month later, when he set the army record for policies sold, the captain got a call from the general. He was so impressed he decided he wanted to meet the young soldier and learn the secret of his sales success.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The general and the captain went to the personnel office and asked the soldier his secret.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I don’t know, I just sell them the insurance,” he shrugged.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well, let’s see you in action,” the general said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They called in a recruit and sat in as the young soldier went through his pitch.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Now, there’s a great life insurance plan,” he began.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Uh, I don’t think so,” the recruit said. “It costs a lot.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I know, but if you buy the insurance and get killed in battle, the army has to pay your survivors $200,000,” he said. “But, if you don’t have insurance, they pay your survivors $6,000.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Yeah? So?” the recruit said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“So,” he said, nodding at the general. “Who do you think this asshole is going to send into battle first?”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/brother_p"> /u/brother_p </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15k2dub/a_young_soldier_was_sent_to_the_personnel_office/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15k2dub/a_young_soldier_was_sent_to_the_personnel_office/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Jewish shop owner in a largely Christian town hears a knock on the door.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">He opens, and sees representatives of the local church.</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Excuse us, Mr. Shainski, - they say. - Our church is in a bad state now, so we decided to build a new one. Seeing as you are known as a very wealthy and generous person, could you spare anything?
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Shainski thinks. On the one hand, the people of the town are his clients; how can he refuse and offend them? It’s bad for business. On the other, he is a Jew; how can he donate for a Christian church?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Listen, - he says. - Before you build the new church, I imagine you’ll need to demolish the old church, right?
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Yes, of course. How else?
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">And I believe it must cost a lot of money, right?
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Yes, we estimate it will cost about… ten thousand dollars.
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Excellent, here is a check for ten thousand dollars!
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
</li></ul></li></ul></li></ul></li></ul></li></ul></li></ul></div>
<!-- SC_ON -->
submitted by <a href="https://www.reddit.com/user/Omeganian"> /u/Omeganian </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15kc1yt/a_jewish_shop_owner_in_a_largely_christian_town/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15kc1yt/a_jewish_shop_owner_in_a_largely_christian_town/">[comments]</a></span></li>
</ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A lawyer sits next to a blonde on a plane, and he really wants her to notice him, but she shows no interest.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lawyer is not used to being rejected, so he says:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Let’s play a game. We go back and forth and ask each other questions, and if you don’t know the answer, you give the person $5.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The blonde isn’t interested, and she declines.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After 20 minutes of silence, the lawyer says:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Ok, let’s play the same game, but if you miss a question, you give me $5. If I miss a question, I give you $300.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The blonde is intrigued by the money, so she agrees.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lawyer smiles and asks her:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What’s the weight of the moon?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The blonde says, “I don’t know,” and gives him the $5
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Then she asks him:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What goes up with two legs and comes down with 3?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lawyer doesn’t know the answer to the question but does not want to admit it, so he spends the rest of the flight trying to figure it out. During this time, the blonde naps in peace. When the plane lands, the lawyer hands the blonde the $300.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As they’re getting off the plane, the lawyer runs up to her and says:
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“Please, what’s the answer to the question?”
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The blonde smiles, hands him $5, and calmly walks away.
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​
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I hope you liked the joke! It’s pretty long, so thanks if you read the whole thing!
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/PonyCraft1"> /u/PonyCraft1 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15k4osn/a_lawyer_sits_next_to_a_blonde_on_a_plane_and_he/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15k4osn/a_lawyer_sits_next_to_a_blonde_on_a_plane_and_he/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My wife said I look like a Greek god.</strong> - <!-- SC_OFF --></p>
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Her actual words were “Put your clothes on, we’re in a museum” but I know what she meant.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/incredibleinkpen"> /u/incredibleinkpen </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15k34ov/my_wife_said_i_look_like_a_greek_god/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15k34ov/my_wife_said_i_look_like_a_greek_god/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s the difference between a northern fairy tale and a southern fairy tale?</strong> - <!-- SC_OFF --></p>
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A northern fairy tale begins, “Once upon a time, …” A southern fairy tale begins, “Y’all ain’t gonna believe this shit…!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/kvilletim"> /u/kvilletim </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/15khchh/whats_the_difference_between_a_northern_fairy/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/15khchh/whats_the_difference_between_a_northern_fairy/">[comments]</a></span></p></li>
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