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<title>05 April, 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>Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses</strong> -
<div>
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We measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants with COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided subacute/convalescent sera (6-76 weeks post-admission). Compared to 60 controls, brain injury biomarkers (Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in patients with altered consciousness. Tau and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness, and correlated with brain injury biomarker levels. Inflammatory mediators were lower than acute levels in convalescent sera, but levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with Tau levels even at this late time point. When compared to acute COVID-19 patients with a normal GCS, network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase and persists late after COVID-19, and may be driven by a para-infectious process involving a dysregulated host response.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287902v1" target="_blank">Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses</a>
</div></li>
<li><strong>A second update on mapping the human genetic architecture of COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release. The increased number of candidate genes at the identified loci helped to map three major biological pathways involved in susceptibility and severity: viral entry, airway defense in mucus, and type I interferon.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.24.22283874v2" target="_blank">A second update on mapping the human genetic architecture of COVID-19</a>
</div></li>
<li><strong>SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Reports suggest that the potential long-lasting health consequences of SARS-CoV-2 infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. In a nationwide cohort of 2,430,694 50+-year-olds, we compared the rates of non-Covid-19 infectious disease inpatient hospitalizations (of ≥5 hours) following the acute phase of SARS-CoV-2 infection in 930,071 individuals with rates among SARS-CoV-2 uninfected from 1 January 2021 to 10 December 2022. The post-acute phase of SARS-CoV-2 infection was associated with an incidence rate ratio of 0.90 (95% confidence interval 0.88-0.92) for any infectious disease hospitalization. Findings were similar for upper- (1.08, 0.97-1.20), lower respiratory tract (0.90, 0.87-0.93), influenza (1.04, 0.94-1.15), gastrointestinal (1.28, 0.78-2.09), skin (0.98, 0.93-1.03), urinary tract (1.01, 0.96-1.08), certain invasive bacterial (0.96, 0.91-0.1.01), and other (0.96, 0.92-1.00) infectious disease hospitalizations and in subgroups. Our study does not support an increased susceptibility to non-Covid-19 infectious disease hospitalization following SARS-CoV-2 infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23288102v1" target="_blank">SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years</a>
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<li><strong>Spatial Variation in Excess Mortality Across Europe: A Cross-sectional Study of 561 Regions in 21 Countries</strong> -
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Objective: To measure the burden of the COVID-19 pandemic in 2020 at the subnational level by estimating excess mortality, defined as the increase in all-cause mortality relative to an expected baseline mortality level. Design: Statistical and demographic analyses of regional all-cause mortality data. Setting: The vital statistics systems of 21 European countries. Participants: The entire population of 561 spatial units in 21 European countries. Main Outcome Measures: Losses of life expectancy at ages 0 and 60 for males and females. Results: Evidence was found of a loss in life expectancy in 391 regions, while only three regions exhibit notable gains in life expectancy in 2020. For 12 regions, losses of life expectancy amounted to more than 2 years, and three regions showed losses greater than 3 years. Geographic clusters of high mortality were found in Northern Italia, Spain and Poland, while clusters of low mortality were found in Western France, Germany/Denmark and Norway/Sweden. Conclusions: Regional differences of loss of life expectancy are impressive, ranging from a loss of more than 4 years to a gain of 8 months. These findings provide a strong rationale for regional analysis, as national estimates hide significant regional disparities.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.04.23284990v1" target="_blank">Spatial Variation in Excess Mortality Across Europe: A Cross-sectional Study of 561 Regions in 21 Countries</a>
</div></li>
<li><strong>Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.</strong> -
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Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. &gt;4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287498v1" target="_blank">Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.</a>
</div></li>
<li><strong>Early Treatment with Hydroxychloroquine and Azithromycin: A Real-Life Monocentric Retrospective Cohort Study of 30,423 COVID-19 Patients</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objective To estimate the comparative effectiveness of combination therapy with hydroxychloroquine (HCQ) and azithromycin for coronavirus disease 2019 (COVID-19)-related death based on a large monocentric cohort independent of investigators putative biases in a real-world setting. Design Retrospective monocentric cohort study, with comprehensive data collection authenticated by an external bailiff and death reports from a national database (French National Death Registry). Setting Institut Hospitalo-Universitaire Mediterranee Infection Center in Marseille, France. Participants All adults older than 18 years with PCR-proven COVID-19 who were treated directly in our centre between 2 March 2020 and 31 December 2021 and did not refuse the use of their data. Interventions HCQ and azithromycin (HCQ-AZ) as a reference treatment were compared to other regimens containing HCQ, ivermectin and azithromycin alone, combined, or none of these three drugs. The effect of vaccination was also evaluated. Main outcome measures 6-week all-cause mortality. Multivariable logistic regression estimated treatment effectiveness with adjustments for age, sex, comorbidities, vaccination, period of infection or virus variant, and outpatient or inpatient care. Results Total 30,423 COVID-19 patients were analysed (86 refused the analysis of their data) including 30,202 with available treatment data, and 535 died (1.77%). All-cause mortality was very low among patients &lt; 50 years (8/15,925 (0.05%)) and among outpatients treated with HCQ-AZ (21 deaths out of 21,135 (0.1%), never exceeding 0.2% regardless of epidemic period). HCQ-AZ treatment was associated with a significantly lower mortality rate than no HCQ-AZ after adjustment for sex, age, period and patient care setting (adjusted OR (aOR) 95% confidence interval (CI) 0.55, 0.45-0.68). The effect was greater among outpatients (71% death protection rate) than among inpatients (45%). In a subset of 16,063 patients with available comorbidities and vaccinations status, obesity (2.01, 1.23-3.29), chronic respiratory disease (2.93, 1.29-6.64), and immunodeficiency (4.01, 1.69-9.50), on the one hand, and vaccination (0.29, 0.12-0.67) and HCQ-AZ treatment (0.47, 0.29-0.76), on the other hand, were independent factors associated with mortality. HCQ, alone or in any association, was associated with significant protection from death among outpatients (0.41, 0.21-0.79) and inpatients (0.59, 0.47-0.73). Conclusions HCQ prescribed early or late protects in part from COVID-19-related death. During pandemic health crises, financial stakes are enormous. Authentication of the data by an independent external judicial officer should be required. Public sharing of anonymized databases, ensuring their verifiability, should be mandatory in this context to avoid fake publications.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287649v1" target="_blank">Early Treatment with Hydroxychloroquine and Azithromycin: A Real-Life Monocentric Retrospective Cohort Study of 30,423 COVID-19 Patients</a>
</div></li>
<li><strong>Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning</strong> -
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An objective method to identify imminent or current Multi-inflammatory Syndrome in Children (MIS-C) infected with SARS-CoV-2 is highly desirable. The aims were to define an algorithmically interpreted novel cytokine/chemokine assay panel providing such an objective classification. This study was conducted on 4 groups of patients seen at multiple sites of Texas Childrens Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 66 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January-May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August-October 2021 infected with alpha and/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021- January 2022 infected with delta and/or omicron variants. Group 1 was used to train a L1-regularized logistic regression model which was validated using 5-fold cross validation, and then separately validated against the remaining naive groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the algorithmically interpreted cytokine/chemokine assay panel. Standard laboratory markers predict MIS-C with a 5-fold cross-validated AUROC of 0.86 ± 0.05 and an F1 score of 0.78±0.07, while the cytokine/chemokine panel predicted MIS-C with a 5-fold cross-validated AUROC of 0.95 ± 0.02 and an F1 score of 0.91 ± 0.04, with only sixteen of the forty-five cytokines/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine/chemokine panel yielded AUROC =0.98, F1=0.93, on Group 3 it yielded AUROC=0.89 , F1 = 0.89, and on Group 4 AUROC= 0.99, F1= 0.97. Adding standard laboratory markers to the cytokine/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieved equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine/chemokine panel as well as the top ten subset provide a sensitive, specific method to identify MIS-C in patients infected with SARS-CoV-2 in all the major variants identified to date.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.04.23288117v1" target="_blank">Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning</a>
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<li><strong>Beyond dry eye: the greater extent of Sjögren’s systemic disease symptoms, impact of COVID-19 and perceptions towards Telemedicine identified through a patient co-designed study</strong> -
<div>
Background: Sjögren’s (“SHOW-grins”) is a chronic debilitating autoimmune disease characterised by dry eyes and dry mouth, secondary to reduced exocrine function of both the lacrimal and salivary glands. The persistent, severe and serious systemic complications of Sjögren’s are poorly understood and often unappreciated, resulting in significant morbidity and treatment burden. This study aimed to explore experiences of those living with Sjögren’s, specifically access to healthcare and attitude towards telemedicine. Additionally, we sought to collect information regarding the impact of the pandemic on their quality of life (QoL). Methods: Attendees (n=194) of an Irish Sjögren’s Webinar were invited to participate in two online surveys. The first survey gathered information related to demographics, disease, and experiences during the COVID-19 pandemic. A combination of bespoke items and validated questionnaires (EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), COV19-QoL) was used. The second survey consisted of a shortened Telehealth Usability Questionnaire. Both were prepared in collaboration with a patient advocate. Results: Survey 1: n=76; response rate=39.2%. Thirty-one respondents (41.4%) to Survey 1 reported a delay of ≥5 years between the onset of symptoms and diagnosis. Dry mouth was the most common symptom experienced (76.8% n=63), followed by dry eye (74.4% n=61), fatigue (57.3%, n=47) and joint pain (53.7% n=44), but a range of other symptoms were also reported. COV19-QoL results indicated that the pandemic had a detrimental effect on participants’ overall QoL (4.0 ± 1.0) and physical health (4.0 ± 0.8) in particular. COV19-QoL and ESSPRI scores were moderately correlated (0.36, p=0.002). Over 70% of respondents had a medical appointment cancelled, delayed or rescheduled (n=60). Survey 2: n=57; response rate=29.4%. Those that had interacted with telemedicine reported largely positive experiences with the virtual model. Conclusion: Clinicians should be aware of the range of symptoms experienced by patients with Sjögren’s beyond those of sicca and fatigue. COVID-19 has negatively influenced the self-reported health and well-being of those with Sjögren’s, particularly those with higher symptom scores. It is vital that optimised telemedicine models are implemented to ensure continuity in the provision of healthcare for those with chronic illness such as Sjögren’s and in preparation for possible future pandemics. Patient or Public Contribution: A group of people living with Sjögren’s co-designed the structure and content of the webinar where the survey was shared. A PPI contributor also collaborated in the selection of questionnaires used in the study ensuring that the questions asked would best reflect the priorities of patients. They contributed to the writing of this manuscript as co-authors. Additionally, the research team and Sjögren’s patients who contributed to this work have gone on to establish Sjögren’s Research Ireland, a collaboration between patient advocates, researchers, and PPI facilitators.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/6r8nd/" target="_blank">Beyond dry eye: the greater extent of Sjögren’s systemic disease symptoms, impact of COVID-19 and perceptions towards Telemedicine identified through a patient co-designed study</a>
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<li><strong>Head-to head comparison of anterior nares and nasopharyngeal swabs for SARS-CoV-2 antigen detection in a community drive-through test centre in the UK</strong> -
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Objective: To conduct a head-to-head diagnostic accuracy evaluation of professionally taken anterior nares (AN) and nasopharyngeal (NP) swabs for SARS-CoV-2 antigen detection using rapid diagnostic tests (Ag-RDT). Methods: NP swabs for SARS-CoV-2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) testing and paired AN and NP swabs for the antigen detection were collected from symptomatic participants enrolled at a community drive-through COVID-19 test centre in Liverpool. Two Ag-RDT brands were evaluated: Sure-Status (PMC, India) and Biocredit (RapiGEN, South Korea). The visual read out of the Ag-RDT test band was quantitative scored and the 50% and 95% limit of detection (LoD) of both Ag-RDT brands using AN and NP swabs was calculated using a probabilistic logistic regression model. Results: A total of 604 participants were recruited of which 241 (40.3%) were SARS-CoV-2 positive by RT-qPCR. Sensitivity and specificity of AN swabs was equivalent to the obtained with NP swabs: 83.2% (75.2-89.4%) and 98.8% (96.5-99.6%) utilising NP swabs and 84.0% (76.2-90.1%) and 99.2% (97.0-99.8%) with AN swabs for Sure-Status and; 81.2% (73.1-87.7%) and 99.0% (94.7-86.5%) with NP swabs and 79.5% (71.3-86.3%) and 100% (96.5-100%) with AN swabs for Biocredit. The agreement of the AN and NP swabs was high for both brands with an inter-rater relatability (K) of 0.918 and 0.833 for Sure-Status and Biocredit, respectively. The overall 50% LoD and 95% LoD was 0.9-2.4 x 104 and 3.0-3.2 x 108 RNA copies/mL for NP swabs and 0.3- 1.1 x 105 and 0.7-7.9 x 107 RNA copies/mL and for AN swabs with no significant difference on LoD for any of the swabs types or test brands. Quantitative read-out of test line intensity was more often higher when using NP swabs with significantly higher scores for both Ag-RDT brands. Conclusions: the diagnostic accuracy of the two SARS-CoV-2 Ag-RDTs brands evaluated in this study was equivalent using AN swabs than NP swabs. However, test line intensity was lower when using AN swabs which could influence negatively the interpretation of the Ag-RDT results for lay users. Studies on Ag-RDT self-interpretation using AN and NP swabs are needed to ensure accurate test use in the wider community.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.06.22279637v2" target="_blank">Head-to head comparison of anterior nares and nasopharyngeal swabs for SARS-CoV-2 antigen detection in a community drive-through test centre in the UK</a>
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<li><strong>The re-emergence of influenza following the COVID-19 pandemic in Victoria, Australia</strong> -
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Background: COVID-19 pandemic mitigation measures, including travel restrictions, effectively limited global circulation of influenza viruses. In Australia, travel bans for non-residents and quarantine requirements for returned travellers were eased in November 2021, providing pathways for influenza viruses to be re-introduced. Methods: From 1 November 2021 to 30 April 2022 we conducted an epidemiological study to investigate the re-establishment of influenza in Victoria, Australia. We analyzed case notification data from the Victorian Department of Health to describe case demographics, interviewed the first 200 cases to establish probable routes of virus reintroduction, and examined phylogenetic and antigenic data to understand virus diversity and susceptibility to current vaccines. Results: Overall, 1598 notifications and 1064 positive specimens were analyzed. The majority of cases occurred in the 15-34 year age group. Case interviews revealed a higher incidence of international travel exposure during the first month of case detections and high levels of transmission in university residential colleges associated with the return to campus. Influenza A(H3N2) was the dominant subtype, with a single lineage predominating despite multiple importations. Conclusions: Enhanced testing for respiratory viruses during the COVID-19 pandemic provided a more complete picture of influenza virus transmission compared to previous seasons. Returned international travellers were important drivers of the re-emergence of influenza, as were young adults, a group whose role has previously been under-recognised in the establishment of seasonal influenza epidemics. Targeting interventions, including vaccination, to these groups could reduce influenza transmission in the future.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.02.23288053v1" target="_blank">The re-emergence of influenza following the COVID-19 pandemic in Victoria, Australia</a>
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<li><strong>Risk of Adverse Maternal and Fetal Outcomes Associated with COVID-19 Variants of Concern: A Sequential Prospective Meta-Analysis</strong> -
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Introduction The main objective of this study is to conduct an individual patient data meta-analysis with collaborators from various countries to identify SARS-CoV-2 variants of concern associated with adverse maternal and neonatal outcomes. Methods Eligible studies included registries and single- or multi-site cohort studies that recruited pregnant and recently postpartum women with confirmed COVID-19. Studies must have enrolled at least 25 women within a defined catchment area. Studies also had to have data that overlapped more than a single COVID-19 variant time period. We invited principal investigators already participating in an ongoing sequential, prospective meta-analysis of perinatal COVID-19. Investigators shared individual patient data (IPD) with the technical team for review and analysis. We examined 31 outcomes related to: i) COVID-19 severity (n=5); ii) maternal morbidities including adverse birth outcomes (n=14); iii) fetal and neonatal morbidity and mortality (n=5) and iv) adverse birth outcomes (n=8). SARS-CoV-2 strains that have been identified as variants of concern (VOC) by the WHO were analyzed using the publicly available strain frequency data by Nextstrain.org and strains were classified as dominant when they were more than half of sequences in a given geographic area. We applied a 2-stage IPD meta-analytic framework to generate pooled relative risks, with 95% CI for each dominant variant and outcome pair when there were one or more studies with available data. Results Our data show that the Delta wave, compared to Omicron, was associated with a higher risk of all adverse COVID-19 severity outcomes in pregnancy including risk of hospitalization [RR 4.02 (95% CI 1.10, 14.69), n=1 study], risk of ICU admissions [RR 2.59 (95% CI 1.26, 5.30, n=3 studies], risk of critical care admission [RR 2.52 (95% CI 1.25, 5.08, n=3 studies], risk of needing ventilation [RR 3.96 (95% CI 1.47, 10.71), n=3 studies] and risk of pneumonia [RR 6.73 (95% CI 2.17, 20.90), n=3 studies]. The majority of maternal morbidity and mortality indicators were not at increased risk during any of the COVID-19 variant waves except hemorrhage, any Cesarean section, intrapartum Cesarean section and maternal composite outcome, although data was limited. Risk of fetal and neonatal morbidity and mortality did not show significant increases in risks during any of the COVID-19 waves except stillbirth and perinatal death during the Delta wave ([RR 4.84 (95% CI 1.37, 17.05, n=3 studies], [RR 6.03 (95%CI 1.63, 22.34), n=3 studies], respectively) when compared to the Pre-alpha wave. Adverse birth outcomes including very low birthweight and very preterm birth also showed increased risks during the Delta wave compared to the Pre-alpha wave. Discussion During periods of Delta strain predominance, all COVID-19 severity outcomes were more severe among pregnant women, compared to periods when other COVID-19 strains predominated. In addition, there are limited data comparing the impact of different variants on pregnancy outcomes. This highlights the importance of ongoing genomic surveillance among special populations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23287260v1" target="_blank">Risk of Adverse Maternal and Fetal Outcomes Associated with COVID-19 Variants of Concern: A Sequential Prospective Meta-Analysis</a>
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<li><strong>GILEA: GAN Inversion-enabled latent eigenvalue analysis for phenome profiling and editing</strong> -
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Modeling heterogeneous disease states by data-driven methods has great potential to advance biomedical research. However, a comprehensive analysis of phenotypic heterogeneity is often challenged by the complex nature of biomedical datasets and emerging imaging methodologies. Here, we propose a novel GAN Inversion-enabled Latent Eigenvalue Analysis (GILEA) framework and apply it to phenome profiling and editing. As key use cases for fluorescence and natural imaging, we demonstrate the power of GILEA using publicly available SARS-CoV-2 datasets stained with the multiplexed fluorescence cell-painting protocol as well as real-world medical images of common skin lesions captured by dermoscopy. The quantitative results of GILEA can be biologically supported by editing latent representations and simulating dynamic phenotype transitions between physiological and pathological states. In conclusion, GILEA represents a new and broadly applicable approach to the quantitative and interpretable analysis of biomedical image data.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528026v3" target="_blank">GILEA: GAN Inversion-enabled latent eigenvalue analysis for phenome profiling and editing</a>
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<li><strong>Using macromolecular electron densities to improve the enrichment of active compounds in virtual screening</strong> -
<div>
The quest for more effective virtual screening algorithms is hindered by the scarcity of training data, calling for innovative approaches. This study presents the first use of experimental electron density (ED) data for improving active compound enrichment in virtual screening, supported by ED’s ability to reflect the time-averaged behavior of ligands and solvents in the binding pocket. Experimental ED-based grid matching score (ExptGMS) was developed to score compounds by measuring the degree of matching between their binding conformations and a series of multi-resolution experimental ED grids. The efficiency of ExptGMS was validated using both in-silico tests with the Directory of Useful Decoys-Enhanced dataset and wet-lab tests on Covid-19 3CLpro-inhibitors. ExptGMS improved the active compound enrichment in top-ranked molecules by approximately 20%. Furthermore, ExptGMS helped identify four new and active inhibitors of 3CLpro, with the top showing an IC50 value of 1.9 uM. To facilitate the use of ExptGMS, we developed an online database containing experimental ED grids for over 17,000 proteins.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.04.535535v1" target="_blank">Using macromolecular electron densities to improve the enrichment of active compounds in virtual screening</a>
</div></li>
<li><strong>The Functional RNA Identification (FRID) Pipeline: Identification of Potential Pseudoknot-Containing RNA Elements as Therapeutic Targets for SARS-CoV-2</strong> -
<div>
The COVID-19 pandemic persists despite the development of effective vaccines. As such, it remains crucial to identify new targets for antiviral therapies. The causative virus of COVID-19, SARS-CoV-2, is a positive-sense RNA virus with RNA structures that could serve as therapeutic targets. One such RNA with established function is the frameshift stimulatory element (FSE), which promotes programmed ribosomal frameshifting. To accelerate identification of additional functional RNA elements, we introduce a novel computational approach termed the Functional RNA Identification (FRID) pipeline. The guiding principle of our pipeline, which uses established component programs as well as customized component programs, is that functional RNA elements have conserved secondary and pseudoknot structures that facilitate function. To assess the presence and conservation of putative functional RNA elements in SARS-CoV-2, we compared over 6,000 SARS-CoV-2 genomic isolates. We identified 22 functional RNA elements from the SARS-CoV-2 genome, 14 of which have conserved pseudoknots and serve as potential targets for small molecule or antisense oligonucleotide therapeutics. The FRID pipeline is general and can be applied to identify pseudoknotted RNAs for targeted therapeutics in genomes or transcriptomes from any virus or organism.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535424v1" target="_blank">The Functional RNA Identification (FRID) Pipeline: Identification of Potential Pseudoknot-Containing RNA Elements as Therapeutic Targets for SARS-CoV-2</a>
</div></li>
<li><strong>Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</strong> -
<div>
One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) in their genomes. These conserved RNA structures are often essential for viral replication, transcription, or translation. In this report, we discovered and optimized a new coumarin derivative C30 that binds to a four-way RNA helix called SL5 in the 5’ UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a novel sequencing-based method namely cgSHAPE-seq, in which the acylating chemical probe was directed to crosslink with the 2’-OH groups of ribose at the ligand binding site. This crosslinked RNA could then create read-through mutations during reverse transcription (i.e., primer extension) at single-nucleotide resolution to uncover the acylation locations. cgSHAPE-seq unambiguously determined that a bulged G in SL5 was the primary binding site of C30 in the SARS-CoV-2 5’ UTR, which was validated through mutagenesis and in vitro binding experiments. C30 was further used as a warhead in RNA-degrading chimeras (RIBOTACs) to reduce viral RNA expression levels. We demonstrated that replacing the acylating moiety in the cgSHAPE probe with ribonuclease L recruiter (RLR) moieties yielded RNA degraders active in the in vitro RNase L degradation assay and SARS-CoV-2 5’ UTR expressing cells. We further explored another RLR conjugation site on the E ring of C30 and discovered potent activity in vitro and in cells. The optimized RIBOTAC C64 inhibited live virus replication in lung epithelial carcinoma cells.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.03.535453v1" target="_blank">Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5’ untranslated region</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Safety &amp; Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MIR 19 ®;   Combination Product: Standard therapy<br/><b>Sponsor</b>:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™;   Drug: Placebo<br/><b>Sponsors</b>:   Jose David Suarez, MD;   Sesderma S.L.;   Westchester General Hospital Inc. DBA Keralty Hospital Miami;   MGM Technology Corp<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: MP0420;   Drug: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Molecular Partners AG;   University of Minnesota<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AZD7442;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   AstraZeneca;   University of Minnesota<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: PF-07304814;   Drug: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Pfizer;   University of Minnesota<br/><b>Suspended</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: VIR-7831;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Vir Biotechnology, Inc.;   GlaxoSmithKline;   University of Minnesota<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BRII-196;   Biological: BRII-198;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Brii Biosciences Limited;   University of Minnesota<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: LY3819253;   Biological: Placebo;   Biological: Remdesivir<br/><b>Sponsors</b>:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Eli Lilly and Company;   University of Minnesota<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Nasal Treatment for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Optate;   Drug: Placebo<br/><b>Sponsor</b>:   Indiana University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: usual care and follow-up by a nurse;   Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>:   Centre Hospitalier Universitaire de Saint Etienne<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Chinese Herb;   Diagnostic Test: Placebo<br/><b>Sponsor</b>:   Chinese University of Hong Kong<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 to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>:   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Drug: PF-07817883;   Drug: Placebo<br/><b>Sponsor</b>:   Pfizer<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>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Other: conventional western medicine treatment;   Drug: Dexamethasone oral tablet;   Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>:   China-Japan Friendship 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>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Intervention</b>:   Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsor</b>:   First Affiliated Hospital of Wenzhou Medical University<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>Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: NP-101;   Other: Placebo<br/><b>Sponsor</b>:   Novatek Pharmaceuticals<br/><b>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>Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants</strong> - The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the epitopes and genotypes of these antibodies. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their…</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>Phosphatidylglycerol-specific phospholipase C from Amycolatopsis sp. NT115 strain: purification, characterization, and gene cloning</strong> - Recently, phosphatidylglycerol (PG) focused on its important role in chloroplast photosynthesis, mitochondrial function of the sperm, an inhibitory effect on SARS-CoV-2 ability to infect naïve cells and reducing lung inflammation caused by COVID-19. To develop an enzymatic PG determination method as the high-throughput analysis of PG, a PG-specific phospholipase C (PG-PLC) was found in the culture supernatant of Amycolatopsis sp. NT115. PG-PLC (54 kDa by SDS-PAGE) achieved the maximal activity…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral Activity of Cell Membrane-Bound Amphiphilic Polymers</strong> - We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to…</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 Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers</strong> - CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.</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>Cyanometabolites: molecules with immense antiviral potential</strong> - Cyanometabolites are active compounds derived from cyanobacteria that include small low molecular weight peptides, oligosaccharides, lectins, phenols, fatty acids, and alkaloids. Some of these compounds may pose a threat to human and environment. However, majority of them are known to have various health benefits with antiviral properties against pathogenic viruses including Human immunodeficiency virus (HIV), Ebola virus (EBOV), Herpes simplex virus (HSV), Influenza A virus (IAV) etc….</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>Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis</strong> - Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90β on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b 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>CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury</strong> - In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers…</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 synergistic effect of Cu-MOF nanoparticles and immunomodulatory agent on SARS-CoV-2 inhibition</strong> - In this work, HKUST-1 and Cu-BDC nanoparticles were used as delivery systems for the early anti-COVID-19 drug, hydroxychloroquine. The antiviral MOF/drug combinations significantly reduced the infectivity of SARS-CoV-2, which can be attributed to the nanometric size of the carriers, the presence of copper in the MOF nodes, and the semi-controlled release of the drug.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico and <em>in vitro</em> evaluation of antiviral activity of wogonin against main protease of porcine epidemic diarrhea virus</strong> - The high mortality rate of weaned piglets infected with porcine epidemic diarrhea virus (PEDV) poses a serious threat to the pig industry worldwide, demanding urgent research efforts related to developing effective antiviral drugs to prevent and treat PEDV infection. Small molecules can possibly prevent the spread of infection by targeting specific vital components of the pathogen’s genome. Main protease (Mpro, also named 3CL protease) plays essential roles in PEDV replication and has emerged as…</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>G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters</strong> - The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across &gt;5 million SARS-CoV-2 genomes. The G4…</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>Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice</strong> - The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW)…</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>Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites</strong> - SARS-CoV-2 has been responsible for the major worldwide pandemic of COVID-19. Despite the enormous success of vaccination campaigns, virus infections are still prevalent and effective antiviral therapies are urgently needed. Viroporins are essential for virus replication and release, and are thus promising therapeutic targets. Here, we studied the expression and function of recombinant ORF3a viroporin of SARS-CoV-2 using a combination of cell viability assays and patch-clamp electrophysiology….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Famotidine on COVID-19: Killing Virus or Opposing ARDS?</strong> - Since the first detection of SARS-CoV-2 in China, COVID-19 (Corona Virus Disease 2019) has taken the lives of more than six million people. Although some antivirals seem proper for treatment, the investigation of finding the best therapeutic approach for COVID-19 is still continuing. Some observational research showed that famotidine has promising effects in addition to its acid-suppressing characteristics in the treatment of COVID-19. The definite viricidal effect of famotidine is not…</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 inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins</strong> - Ritonavir, originally developed as HIV protease inhibitor, is widely used as a booster in several HIV pharmacotherapy regimens and more recently in Covid-19 treatment (e.g., Paxlovid). Its boosting capacity is due to the highly potent irreversible inhibition of the cytochrome P450 (CYP) 3 A enzyme, thereby enhancing the plasma exposure to coadministered drugs metabolized by CYP3A. Typically used booster doses of ritonavir are 100-200 mg once or twice daily. This review aims to address several…</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>Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022</strong> - CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and…</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 Return of the Non-stop Trump News Cycle</strong> - The former President’s indictment in Manhattan means the reprieve from his dominance of American media is officially over. Will it be any better this time? - <a href="https://www.newyorker.com/news/annals-of-communications/the-return-of-the-non-stop-trump-news-cycle">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Architect’s Dream of Rebuilding a Battered City in Ukraine</strong> - Max Rozenfeld has spent much of the war imagining how the destruction of Kharkiv presents opportunities for reinventing its future. - <a href="https://www.newyorker.com/news/dispatch/an-architects-dream-of-rebuilding-a-battered-city-in-ukraine">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What Israel’s Crisis Reveals About Its Democratic Compromises</strong> - Amid widespread protests, the Prime Minister has halted a package of illiberal reforms. What are the roots of his effort—and of its rejection? - <a href="https://www.newyorker.com/news/q-and-a/what-israels-crisis-reveals-about-its-democratic-compromises">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The People Versus Donald J. Trump</strong> - Manhattan District Attorney Alvin Bragg is effectively accusing the former President of defrauding voters in 2016. - <a href="https://www.newyorker.com/news/our-columnists/the-people-versus-donald-j-trump">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Courtroom Made Donald Trump Look Small</strong> - At his arraignment, all the former President could do was sit and listen. - <a href="https://www.newyorker.com/news/our-local-correspondents/a-courtroom-made-donald-trump-look-small">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The old new idea at the heart of Biden’s economic policy</strong> -
<figure>
<img alt="Biden, wearing sunglasses and a suit and tie, walks in front of a large piece of construction equipment." src="https://cdn.vox-cdn.com/thumbor/Wx18j9h3xUx-WfyL0uVFI6Ywiu4=/190x0:3217x2270/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72149544/1243076542.0.jpg"/>
<figcaption>
President Joe Biden visits the groundbreaking of a new Intel semiconductor plant in Johnstown, Ohio, on September 9, 2022. Intel is moving some manufacturing back to the United States — a key goal of Biden’s industrial policy. | Andrew Spear/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Industrial policy is back — if it ever left.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O1AG6e">
Across the political spectrum, a consensus has emerged that President Joe Biden is making a <a href="https://fortune.com/2023/02/08/biden-state-of-the-union-industrial-policy/">sharp turn</a>, embarking on a <a href="https://www.nytimes.com/2023/02/12/opinion/economy-ira-infrastructure-clean-energy.html">bold experiment</a>, and turning to a <a href="https://www.wsj.com/articles/past-u-s-industrial-policy-offers-lessons-risks-for-chips-program-df48c4d1">governing framework outside the economic mainstream</a>: He is embracing industrial policy, where the government takes an active hand encouraging investment in emerging industries, new factories, equipment, and research, across the public and private sectors.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GRjsDa">
With a suite of legislation and executive branch initiatives, the Biden administration has only too happily highlighted its willingness to roll up its sleeves and take charge of investment decisions in the real economy: port and freight expansion programs, <a href="https://www.vox.com/policy-and-politics/2022/7/28/23281757/whats-in-climate-bill-inflation-reduction-act">clean energy tax credits</a> and loans, boosts to manufacturing in regions that had been left behind, and massive subsidies to re-establish an entire <a href="https://www.vox.com/recode/2022/7/27/23277664/chips-act-solve-chip-shortage-biden-manufacturing">domestic microchip ecosystem</a>, to name a few.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Oqqpzh">
His cheerleaders, who’ve embraced labels like <a href="https://www.nytimes.com/2021/09/19/opinion/supply-side-progressivism.html">supply-side progressivism</a>, argue the Biden agenda is a bold new vision that corrects a congenital American failure to dictate a clear national economic strategy. <a href="https://www.wsj.com/articles/industrial-policy-chips-act-semiconductors-biden-special-interest-fa2e21e6">Detractors argue</a> that governments don’t know how to invest better than the market, and that picking winners and losers based on often ideological or strategic considerations, rather than purely economic ones, risks massive inefficiency.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8ZWi4f">
But just how novel is this “experiment”?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3i7D3v">
There’s good reason to question the idea that America ever really gave up on industrial policy, or that Biden has embarked on an exception to the laissez-faire rules governing American capitalism.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BqxTwU">
Industrial policy is arguably <em>the</em> American contribution to economic thinking. The idea that the government could use its hand to direct the free market’s course — as opposed to letting the market run unfettered, or, on the other end of the spectrum, bringing it under total state control — reached its heyday alongside the so-called “golden era” of capitalism following World War II.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mp7ljR">
Even as neoliberal free-market thinking rose to dominance from the 1970s through 2020, industrial policy proved a powerful tool many presidents were reluctant to abandon — even if they avoided calling it by its name.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eYv9tG">
It has persisted as central to American political economy not despite the fact that industrial policy is often an effective means of reshaping society through economic development, but because of it.
</p>
<h3 id="taCXi4">
The surprisingly long history of industrial policy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O5F0oK">
The Biden administration has pitched industrial policy as not only a sound economic strategy but also a remedy to a national anxiety about decline.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mf9sYx">
It comes out of a recognition that China has <a href="https://www.atlanticcouncil.org/commentary/transcript/brian-deese-on-bidens-vision-for-a-twenty-first-century-american-industrial-strategy/">outcompeted America</a> in some crucial high-tech sectors, and that many American communities <a href="https://www.whitehouse.gov/briefing-room/speeches-remarks/2022/10/13/remarks-on-executing-a-modern-american-industrial-strategy-by-nec-director-brian-deese/">suffered grievously</a> from deindustrialization. Though the United States is still the richest, most powerful country on the planet, it finds itself playing catch-up to other nations when it comes to maintaining the cutting edge and ensuring broad-based prosperity.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zuItoG">
Squint a little, and America’s situation at its founding looked similar. Though colonists in the 13 colonies enjoyed the <a href="https://www.jstor.org/stable/204406">highest standard of living on earth</a> at the time, the Industrial Revolution roared loudest not here but in Britain, which meant that costly manufactured goods were <a href="https://www.stlouisfed.org/publications/regional-economist/fourth-quarter-2019/industrialization-trade-balance">overwhelmingly imported</a>, creating a major drain on national finances.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W4JPEJ">
Britain’s <a href="https://journals.sagepub.com/doi/full/10.1177/0308518X221102960">economic might was built in tandem with its naval hegemony</a>, which threatened the ability of the newly independent United States to trade with major economies, like France, that were often hostile to Britain. The financing needed for capital investment created a massive market in government debt that put Britain at the center of the world’s most powerful financial system.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="akrN2q">
So in order to trade, not only did America have to make nice with a nation with which it had just fought a bloody war of independence, but it also depended on that country for lending to invest in just about anything.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gMP1FQ">
Many among the Federalist camp of the nation’s founders, particularly <a href="https://founders.archives.gov/documents/Hamilton/01-10-02-0001-0007">Alexander Hamilton</a>, believed the country’s course couldn’t just be left to the free market. Rather, they believed that government had to deliberately spark an American industrial revolution if it wanted to survive as a country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jw6KHa">
So they put their thumbs on the scales and created what was known as the <a href="https://web.archive.org/web/20060106154801/http://www.newamerica.net/index.cfm?pg=article&amp;DocID=1080">American (or National) System</a>. It included high tariffs to promote domestic manufacturing, and debt-financed public spending projects, like building a navy, that not only protected national security but guaranteed revenue for advanced sectors like shipbuilding and Connecticut’s early arms industry.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FwCh4b">
Internal improvements, such as the Erie Canal, reduced transportation and distribution costs for domestic firms while working to knit the separate states into one country. A central bank encouraged long-term fixed investment over short-term speculation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ylT7tF">
The United States elaborated on this basic theme for nearly two centuries. It was also the formula for <a href="https://www.phenomenalworld.org/analysis/developmentalisms/">basically every successful major industrialization</a> that followed the original in Britain: 19th-century Germany, Stalin’s USSR, post-World War II Western Europe and East Asia, and post-Mao China.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ioXa2x">
As economic journalist Joe Studwell wrote in his book <a href="https://delong.typepad.com/files/studwell.pdf"><em>How Asia Works</em></a>, economists often tell a story about the free market as the basis of prosperity. But in the real world, the made-in-America Hamiltonian interventionist approach has proved the only real route to continuous growth and improving standards of living.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V5Hizm">
Industrial policy distinctly fell out of favor during the so-called neoliberal era, from the 1970s to 2008, when economic policymakers in the developed world sought not to spark industrial growth but rather to tame a growth machine so overheated that prices rose at a dizzying pace.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EAkc4u">
So instead of pushing big firms to build more factories and produce more widgets, central bankers, legislators, and regulators in both major parties pursued reforms that increased returns to owners of capital: raising interest rates, lowering top income tax rates, deregulating finance, and privatizing many of the state-owned or sponsored assets that had grown so massive during the midcentury height of public-private industrial cooperation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2w70iO">
The idea was that investors would keep investing if they were sure they could reap handsome rewards. Neoliberal policies arguably crushed the Great Inflation of the 1970s, but they worked only too well at rewarding investors for amassing private stores of wealth: As economist <a href="https://www.theguardian.com/books/2014/apr/28/thomas-piketty-capital-surprise-bestseller">Thomas Piketty demonstrated in his book <em>Capital in the Twenty-First Century</em></a>, neoliberalism encouraged wealth hoarding, not productive investment.
</p>
<h3 id="j6BpCW">
Capitalists can’t be trusted to manage capitalism
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oEoLNa">
At its heart, industrial policy strives to solve a “classic Keynesian political problem,” says economic historian Yakov Feygin, director of the Berggruen Institute’s Future of Capitalism program: The only way to grow the economy is ultimately through productivity-enhancing investment — but there are enormous upfront costs to building new plants or buying new equipment, especially at the technological bleeding edge, while returns are years in the future if they ever come at all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7UY2Gg">
If only capitalists get to decide when to invest, they may — rightfully — decide that the unpredictability of future demand and credit conditions make it difficult to justify expanding capacity in crucial sectors even in the face of soaring prices. They fear the “<a href="https://www.sciencedirect.com/topics/economics-econometrics-and-finance/bullwhip-effect">bullwhip effect</a>,” where investors may put up cash for new plants or equipment to respond to higher prices, only for those prices to fall before new production can actually come online.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jqCCXu">
We saw an example of this dynamic with the rash of “<a href="https://www.spglobal.com/commodityinsights/en/market-insights/latest-news/oil/071421-capital-discipline-is-slowing-growth-in-us-oil-production-but-how-long-will-it-last">capital discipline</a>” that drove gas and oil prices so high through much of 2021 and 2022. Typically we think that producers will respond to price rises with more production, which should eventually bring prices back down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8MRtJo">
But investment in new capacity to produce enough for rising demand takes time, and in an environment disrupted by war and pandemics, investors may not be sure the demand driving prices up today will last long enough to pay off the costs of new equipment or a plant that only starts generating revenue months or years down the line.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CSJeD6">
It’s much safer to rake in the profits that come with unexpectedly high prices, which is what <a href="https://www.fitchratings.com/research/corporate-finance/sustained-high-oil-prices-to-test-us-energys-capital-allocation-production-discipline-14-03-2022">shareholders demanded of energy companies</a> for much of last year. In other words, as Feygin put it, “bottlenecks are incentivized.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zHbaAV">
The government, for better or worse, has the unique ability to stabilize the investment cycle and goad risk-averse private capital into making desperately needed, but enormously costly, long-term investments.
</p>
<h3 id="BvIwJZ">
Industrial policy has always been with us
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WUJPD2">
Though Biden has put a unique focus on rebuilding fraying supply chains, “the US has always done investment strategy,” says Feygin, even in recent years, when that policy impulse had supposedly vanished.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="erPiF6">
Take, for instance, Operation Warp Speed under former President Donald Trump, which guaranteed enormous revenues to the makers of MRNA vaccines for Covid-19: Had this policy not been in place, Pfizer and Moderna may not have been able to justify the immense cost of standing up new factories and distribution networks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lR5FjT">
Before that, the Obama administration’s <a href="https://www.marketplace.org/2018/11/13/what-did-america-buy-auto-bailout-and-was-it-worth-it/">auto bailout</a> saved an entire American industry from the short-term liquidationist impulses of Wall Street. The Bush administration’s <a href="https://www.nytimes.com/2008/12/21/business/worldbusiness/21iht-admin.4.18853088.html">pro-homeownership policies</a> drove new home construction to <a href="https://fred.stlouisfed.org/series/PERMIT">multi-decade highs</a>, and once the policies cratered in the 2008 crash, the <a href="https://www.builderonline.com/builder-100/strategy/the-great-recession-builders-look-back_o">homebuilding industry didn’t recover for more than a decade</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7MQuDj">
President Bill Clinton <a href="https://www.nytimes.com/1992/11/10/science/clinton-to-promote-high-technology-with-gore-in-charge.html">boosted the high-tech sector</a> to smooth the industrial transition from the end of the Cold War’s arms-making boom to a civilian economy.
</p>
<h3 id="3HW5z8">
The distortions may be half the point
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8QgHKQ">
Many economic commentators <a href="https://www.wsj.com/articles/chips-act-subsidies-progressives-industrial-policy-gina-raimondo-joe-manchin-7da07403?mod=article_inline">dinged the Biden administration</a> for its recent decision to require semiconductor factories to offer child care if they wanted federal subsidies. Child care requirements on a program intended to protect a vital supply chain seemed like a <a href="https://www.nytimes.com/2023/04/02/opinion/democrats-liberalism.html">classic example</a> of an industrial policy perverted by political concerns, an unrelated sop to Democratic interest groups, or even social engineering in disguise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gdpdxp">
But industrial policy is attractive to policymakers precisely because it can provide the means for enacting a particular vision of society. As historian <a href="https://twitter.com/_timbarker?lang=en">Tim Barker</a> has written in a <a href="https://dash.harvard.edu/handle/1/37372276">recent dissertation</a>, the post-World War II “golden age of capitalism” and the American lifestyle of mass prosperity and suburban consumption owe far more to a particular form of industrial policy — the military Keynesianism of the Cold War arms buildup and the space race — than the common story of an explosion of pent-up consumer demand fueling growth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Tp8jm8">
By the peak of the midcentury boom in the late 1950s through the 1960s, the biggest manufacturing employer was not the civilian-focused auto industry, but the almost entirely government-subsidized aerospace industry, which did 80 percent of its business with the Department of Defense.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GnkFeb">
Looking at macroeconomic data, Barker found that the 1950s and ’60s did not show a transition from an investment-heavy World War II era to a flowering of private consumption, as <a href="https://www.pbs.org/wgbh/americanexperience/features/tupperware-consumer/">popular narratives</a> about that time suggest. Instead, the consumption share of the economy stagnated, while booms and busts corresponded almost exactly with boosts in defense spending.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VMvJhZ">
The American dream, Barker’s work suggests, rested on a foundation of a thoroughly militarized economy. While economists typically talk about <a href="https://en.wikipedia.org/wiki/Guns_versus_butter_model">social welfare and defense spending as competing macroeconomic priorities</a> — guns versus butter — the 1950s and 1960s were an era when jobs making guns provided much of the butter. Think of the quintessential postwar Californian suburban nuclear family: chances are, dad was an aerospace or defense engineer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4nqcWi">
This could lead politicians to make some cynical choices. When capitalism dipped into crisis in the early 1970s, Nixon <a href="https://www.fordlibrarymuseum.gov/library/document/0314/1552646.pdf">told members of his Cabinet</a>, “To goose the economy, the private sector is the best place. In government the best place is the military,” and urged military planners to look for forms of war spending that could provide an economic boost back home.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kuasmk">
War spending helped Nixon reward and grow his “silent majority” political base who lived in the suburbs and the Sunbelt where the defense and aerospace industries had exploded. Of course, Nixon was aware of the politically explosive nature of increasing spending on an unpopular Vietnam War to sustain domestic prosperity, and said, “Don’t discuss jobs outside this room … Don’t write any memos on this.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3Im36A">
Biden, meanwhile, can afford to be “more explicit” about using investment spending to accomplish social goals, according to Feygin of the Berggruen Institute. “The US has a very weak welfare state, but that doesn’t mean it has a small state,” Feygin says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6E2un0">
By driving investment into leading industries, the government creates the kind of jobs that provide benefits — like child care — seen in welfare states. The hope is that employers in other sectors will feel the need to offer similar benefits to compete for labor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6Tnyef">
Industrial spending can also have massive regional impacts, as Cold War defense spending did in places like <a href="https://www.jstor.org/stable/445307">California</a> or<a href="https://www.longislandhistoryproject.org/cold-war-long-island/"> Long Island</a>, and as Biden seeks to do with <a href="https://www.brookings.edu/blog/the-avenue/2023/03/06/bidens-big-bet-on-place-based-industrial-policy/">“place-based” programs</a> for a “battery belt” in areas previously devastated by deindustrialization.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a3Pxg8">
Biden’s industrial policy only constitutes a sharp deviation when viewed narrowly next to the neoliberal era — an era that, to be sure, also saw its own government interventions in the economy. Another way to see it is as a return to the roots of the early American economy, and the mid-20th-century economy that those policies eventually nurtured.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vKoyDm">
Biden’s economic team is betting on something Hamilton knew: Long-term investment in the real economy is essential, but private investors might not provide it. That’s where government can — and should — step in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fM57aW">
</p></li>
<li><strong>10 new documentaries to watch for, from Thomas Kinkade to Y2K</strong> -
<figure>
<img alt="An apple being measured." src="https://cdn.vox-cdn.com/thumbor/6qfGSU6-sJatsXuYDTcVnDmV00w=/0x0:1920x1440/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72149482/acommonsequence.0.jpg"/>
<figcaption>
A scene from <em>A Common Sequence.</em> | Sundance Institute
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The best nonfiction of the spring festival circuit is on the way.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x8hHgJ">
Summer is for blockbusters, fall is for prestige movies, but late winter and early spring — whether or not you realize it — is when many of the year’s smaller, more daring, more provocative films start showing up. Festivals in places as far-flung as Berlin and Austin, New York City and Columbia, Missouri, show some of the most exciting and challenging films from around the world.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Xj5N4W">
And often the best of these are nonfiction movies, films that invert and defy what we’ve come to believe a documentary has to be. From dozens of documentaries I saw in this year’s early spring season, I’ve selected 10 to keep an eye on. You won’t want to miss them, whether they show up in a regional festival near you now or in a theater or streaming platform later.
</p>
<h3 id="2pMpme">
<em>Art for Everybody</em>
</h3>
<figure class="e-image">
<img alt="A man in a suit sits next to a painting of a lighthouse." src="https://cdn.vox-cdn.com/thumbor/1n5WDGQd1h-YXqIspYyqnFe1pxk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560356/artforeverybody.jpg"/> <cite>Art for Everybody</cite>
<figcaption>
Thomas Kinkade in <em>Art for Everybody.</em>
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZsAyu1">
When news broke in 2012 that the artist Thomas Kinkade had died of a drug and alcohol overdose, public response was somewhere between disbelief and schadenfreude. The self-dubbed “Painter of Light,” with his cozy landscapes and cottages, had become synonymous with either peace or kitsch, depending on who you talked to; his mass-market paintings and enormously popular branding were widely derided in the art world, and he courted the disdain as a way of bolstering his family-friendly, conservative-focused, faith-forward brand. But the real man was much more complicated, and with the help of Kinkade’s family, admirers, detractors, and skeptics, Miranda Yousef’s excellent documentary explores the real man behind the brand. Even if you think you know Kinkade’s whole deal, this film is remarkable, probing how the cultivation of a public image in conservative Christian America, and the maintenance of that public image, has shifted and exploded since the 1990s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FyRbSE">
<strong>How to watch it: </strong><em>Art for Everybody</em> premiered at SXSW; watch <a href="https://www.facebook.com/artforeverybodyfilm/">the film’s Facebook page</a> for updates.
</p>
<h3 id="dP0VbI">
<em>Art Talent Show</em>
</h3>
<figure class="e-image">
<img alt="A man sits, watching younger artists draw on canvases. " src="https://cdn.vox-cdn.com/thumbor/FD3mz3U541TqcQOyzW_4v0i6b1k=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560361/arttalentshow.jpg"/> <cite>Art Talent Show</cite>
<figcaption>
A scene from <em>Art Talent Show</em>.
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It’s a weird time to be in the art world. Like many art schools around the world, Prague’s Academy of Fine Arts employs a rigorous admissions process for young artists who hope to study with its renowned teachers. <em>Art Talent Show</em>, directed by Adéla Komrzý and Tomáš Bojar, is a fly-on-the-wall, wickedly funny peek into that process, focused on the teachers who must evaluate students’ portfolios and interview them for admission and, sometimes, argue with them quite fiercely. <em>Art Talent Show</em> showcases the friction between generations, particularly in their view of what’s important for a career in art. Is it originality? Having provocative ideas? Technical skill? The artist’s identity markers? And who really gets to say?
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lx2A2j">
<strong>How to watch it: </strong><em>Art Talent Show</em> made its US premiere at the True/False Film Festival; watch <a href="https://www.filmmovement.com/art-talent-show">the film’s website</a> for updates.
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<em>A Common Sequence</em>
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You watch <em>A Common Sequence</em> for a while before you realize what it’s about, but when it hits, it hits hard. Experimental filmmakers Mary Helena Clark and Mike Gibisser start with the achoque, an endangered species of salamander, and the culture of fishing and mysticism around it, then glide gracefully into observing apples on trees in Washington state, then ways in which Indigenous people have been sought after and exploited by modern medical research for their DNA. Eventually, it becomes clear that this is a story about the building blocks of life — our DNA and the DNA of flora and fauna across the globe — and the struggle to keep its sequencing public rather than allowing private interests and corporations to take it for themselves. It’s an engrossing film, one that demands full attention but also, brilliantly, rewards it.
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<strong>How to watch it: </strong><em>A Common Sequence</em> made its US premiere at Sundance and is currently playing at festivals.
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<h3 id="vQWSNK">
<em>Confessions of a Good Samaritan</em>
</h3>
<figure class="e-image">
<img alt="An X-ray type image of a human skull and brain, with a blurry image of Penny Lane in the background, looking contemplative." src="https://cdn.vox-cdn.com/thumbor/dEnm8gL4Aq2yIeUiWmNkuFQwkVk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560367/goodsamaritan.jpg"/> <cite>Sandbox Films</cite>
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A scene from <em>Confessions of a Good Samaritan.</em>
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Filmmaker Penny Lane is best known as a director of films like <em>Hail, Satan! </em>and <em>Listening to Kenny G</em>, but for <em>Confessions of a Good Samaritan,</em> she puts herself in the frame, too. Lane decides to become an altruistic kidney donor — in other words, to donate her kidney to a stranger — and to document the process while also examining the idea of altruism more broadly. What prompts people to help someone they don’t know? And what does it mean to take that risk? <em>Confessions of a Good Samaritan</em> is a winsome, provocative, and thoughtful exploration of the ethics of selflessness, the twistiness of human nature, and a culture that grapples with both.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JAaVIa">
<strong>How to watch it: </strong><em>Confessions of a Good Samaritan</em> premiered at SXSW and is currently playing at festivals.
</p>
<h3 id="Ilb91k">
<em>Forms of Forgetting</em>
</h3>
<figure class="e-image">
<img alt="A hand reaches out to an elephant trunk." src="https://cdn.vox-cdn.com/thumbor/IIaQleLcl3lrEHRFmxlypmBd_3c=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560377/formsofforgetting.jpg"/> <cite>Forms of Forgetting</cite>
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An image from <em>Forms of Forgetting.</em>
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<em>Forms of Forgetting</em>, from director Burak Çevik, keeps shape-shifting beneath the audience. First it’s a film about … ice fishing, maybe? But then we’re listening in as Nesrin and Erdem, who broke up 14 years earlier, watch and comment upon footage of themselves discussing why they broke up, which in turn was filmed a few years earlier. Then the film spools off in other directions, investigating how our memories, for better or worse, are invested in our bodies, the structures we inhabit, the worlds and narratives we carry around with us. It’s esoteric, sure, but personal and even painful, extending what you can do with a movie and letting time expand and collapse into itself.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n87qRQ">
<strong>How to watch it: </strong><em>Forms of Forgetting</em> premiered at Berlinale; watch <a href="https://burakcevik.com/formsofforgetting">Çevik’s website</a> for upcoming screenings.
</p>
<h3 id="Mlw5KM">
<em>Hummingbirds</em>
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<figure class="e-image">
<img alt="Two young people wearing novelty glasses sip sodas." src="https://cdn.vox-cdn.com/thumbor/YfXvrWuD7wAT_J5wSinOM6LVHAU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560382/hummingbirds.jpg"/> <cite>Extra Terrestrial Films</cite>
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A scene from <em>Hummingbirds</em>.
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Silvia Del Carmen Castaños and Estefanía “Beba” Contreras, best friends living in Laredo, Texas, are both stars and directors in <em>Hummingbirds</em>, shot during the summer of 2019. Shot in collaboration with a set of more experienced filmmakers, the film follows the pair as they whirl through a series of adventures: protesting for reproductive rights, playing music and bingo, spending the hot nights exploring the streets of their city. They have serious conversations about their families, their families’ immigration status, and the future — and they sparkle the whole time. It’s often funny and heartbreaking at once, capturing the excitement and anticipation of a moment that flashes by and disappears before you realize how fleeting it is.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dp9NCQ">
<strong>How to watch it: </strong><em>Hummingbirds</em> premiered at Berlinale; watch <a href="http://extra-terrestrial-films.com/hummingbirds">the film’s website</a> for updates.
</p>
<h3 id="rUzksx">
<em>Natalia</em>
</h3>
<figure class="e-image">
<img alt="A black and white image of a woman in a nun’s garb, wearing headphones and staring out the window." src="https://cdn.vox-cdn.com/thumbor/NWjCGQx-kGw3jG9HHmgdinsFxo8=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560385/natalia.jpg"/> <cite>Natalia</cite>
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A scene from <em>Natalia</em>.
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Elizabeth Mirzaei’s <em>Natalia</em>, shot in black and white, centers on a young woman who is preparing to take her vows as a nun in the Byzantine Catholic tradition. Its subject, who has taken the name Natalia, earned a degree and dated men seriously before entering the order as a novice. Now, she’s sorting through her complex feelings about committing to a life of celibacy and devotion to God; is this really the life God wants for her? And if so, why does she feel pain? <em>Natalia</em> is careful and beautiful, a portrait of spiritual struggle, fear, and the meaning of real peace.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IhZOIT">
<strong>How to watch it: </strong><em>Natalia</em> premiered at the True/False Film Festival and is currently playing at festivals.
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<h3 id="F2gIkA">
<em>Ramona</em>
</h3>
<figure class="e-image">
<img alt="A young woman with a pregnant-looking belly stands in a room, a boom mic above her head." src="https://cdn.vox-cdn.com/thumbor/h-T3tHLnwFbx50P6zdlALWiFxow=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560394/ramona.jpg"/> <cite>Ramona</cite>
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An image f<em>ro</em>m<em> Ramona.</em>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Me4oQ6">
Victoria Linares Villegas was intending to make a movie about a pregnant teenager in the Dominican Republic, where teenage pregnancy is common. She’d cast Camilla Santana in the role. But when the pandemic thwarted her plans, the project pivoted and became <em>Ramona</em>, a documentary in which Santana interviews other pregnant girls and young women, both to research her role and to understand better their lives. From there, Santana starts to inhabit the role, trying to fully embody her character; we watch an artist learning what it means to really empathize, or if that’s even possible. Fiction and nonfiction blur in <em>Ramona</em>, which doesn’t shrink from the harsh reality that these girls and women, living in a culture in which abortion is unthinkable, often lack support and stability in their new roles. The cycle perpetuates itself, and the stories they tell explore what it means to be a woman.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7RX3tU">
<strong>How to watch it: </strong><em>Ramona</em> premiered at the True/False Film Festival and is currently playing at festivals.
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<h3 id="RTqQT3">
<em>Three Women</em>
</h3>
<figure class="e-image">
<img alt="An older woman in a kerchief stands near a field, holding a bunch of balloons." src="https://cdn.vox-cdn.com/thumbor/UvRxPxw90rHi2fGKem_mp4ZEgvQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560403/threewomen.jpg"/> <cite>Three Women</cite>
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A scene from <em>Three Women</em>.
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It is 2019 in the remote Ukrainian village of Stuzhytsya, and the young people are leaving. There’s no opportunity here, and that’s the backdrop against which three older women — a post office clerk, a biologist, and a farmer — are living their lives. Director Maksym Melynk started filming the women, asking them questions about their work and the future, and slowly becomes drawn into their world. What transpires is a darkly funny documentary about a world struggling for survival, a country on the brink, and women making the best of a dying village.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EB4Ajm">
<strong>How to watch it: </strong><em>Three Women</em> made its US premiere at the True/False Film Festival and is currently playing at festivals.
</p>
<h3 id="JLuZ39">
<em>Time Bomb Y2K</em>
</h3>
<figure class="e-image">
<img alt="A man with a hat that says 01/01/Oh, Oh! sits in an office crowded with papers." src="https://cdn.vox-cdn.com/thumbor/RiUjHRY3zosMv3Tp8GKIFyGFCaY=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24560409/timebomb.jpg"/> <cite>HBO</cite>
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A scene from <em>Time Bomb Y2K.</em>
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From where we sit now, the panic around the “Y2K bug” — a code glitch that could have caused mass chaos when the calendar ticked over from 1999 to 2000 — feels like a distant memory, almost quaint. It ended up being a nothingburger, but that was, in part, because people started sounding the alarm years earlier. <em>Time Bomb Y2K</em> uses archival footage from the late 1990s to reconstruct what happened and why, and the results are often comical. But what it establishes, subtly, is something much darker: that while we were all focused on a bug, the seeds of all kinds of today’s plagues were taking root, from radical nationalism and gun fervor to mass inattention to the climate crisis to the undermining of expertise and authority. The movie ends on a positive note, one that looks toward the future, but it’s bittersweet all these years later.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="atMHUF">
<strong>How to watch it: </strong><em>Time Bomb Y2K</em> premiered at the True/False Film Festival and will be distributed by HBO.
</p></li>
<li><strong>The viral story of a girl and her goat explains how the meat industry indoctrinates children</strong> -
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<img alt="A girl sits on the ground looking at her goat, who is held by a leash and looking back at her." src="https://cdn.vox-cdn.com/thumbor/MGPwGcp6Nks5-K1Ne2OJA5Q5OLo=/0x0:480x360/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72149394/IMG_4505.0.jpeg"/>
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Jessica Long’s daughter and her goat, Cedar. | Advancing Law for Animals
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The slaughter of Cedar the goat shines a light on the ideology of 4-H.
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The <a href="https://www.sacbee.com/news/local/article273127820.html">story</a> of a California girl and her goat named Cedar, which captured <a href="https://www.latimes.com/california/story/2023-03-30/goat-slaughter-shasta-county-fair">national</a> and <a href="https://metro.co.uk/2023/03/31/california-girl-sues-fair-after-pet-goat-is-auctioned-and-barbecued-18539054/">international</a> <a href="https://www.insider.com/lawsuit-police-seized-girls-pet-goat-cedar-after-auction-dispute-2023-3">headlines</a> this past week, almost reads like it could have been penned by a Hollywood screenwriter. The tale of a child battling cruel adults for the life of a beloved animal companion has been the plot of everything from a classic children’s story (<a href="https://en.wikipedia.org/wiki/Charlotte%27s_Web"><em>Charlotte’s Web</em></a>), sci-fi film (2017’s <a href="https://www.vox.com/culture/2017/5/19/15662370/okja-review-cannes-netflix-controversy-boos"><em>Okja</em></a>), and even an episode of <em>The Simpsons</em> (“<a href="https://www.imdb.com/title/tt1215758/">Apocalypse Cow</a>”).
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The tale begins in the experience of <a href="https://4-h.org/about/">millions of children</a> who enroll annually in their local 4-H clubs — a more than century-old national youth organization run by the US Department of Agriculture that teaches personal development skills through agricultural and home economics projects. Last year, the 9-year-old daughter of Jessica Long, a resident of Shasta County in northern California, acquired a baby goat for a 4-H “livestock project.” The idea was that she would raise the goat until he was ready to be auctioned for slaughter at the local county fair, a common activity for 4-H members.
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But raising Cedar led Long’s daughter to care deeply for him and, on the eve of the auction last June, she pleaded for the goat to be spared. The fair organizers refused. Then, Republican state Sen. Brian Dahle, a farmer and unsuccessful 2022 California gubernatorial candidate, submitted a winning bid of $902 for Cedar’s meat, of which $63.14 was to go to the fair. Later that night, in a last-ditch effort to save Cedar the goat from slaughter, Long and her daughter took him from the fair.
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But that’s when the plot took a dark turn no Hollywood studio would greenlight. The Shasta District Fair claimed Long had stolen Cedar, demanded she surrender the goat for butchering, and threatened to involve the police if she did not. Long refused. That’s when the Shasta County Sheriff’s Office got involved. Armed with a search warrant, officers drove more than 500 miles across northern California, seized Cedar from the Sonoma County property where he had been taken, and returned him to Shasta County, where he was slaughtered. Long is now suing county officials for violating her daughter’s civil rights.
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Cedar’s case might seem like an isolated if viral news story. The lawsuit was filed last August to <a href="https://www.sacbee.com/news/local/article265138311.html">limited</a> media attention, but in the wake of a story first published in the <a href="https://www.sacbee.com/news/local/article273127820.html">Sacramento Bee</a> on March 29 and subsequent <a href="https://twitter.com/JennyENicholson/status/1641582010916569090">viral Twitter posts</a>, it has been covered everywhere from the <a href="https://www.latimes.com/california/story/2023-03-30/goat-slaughter-shasta-county-fair">Los Angeles Times</a> to the <a href="https://www.washingtonpost.com/nation/2023/04/03/goat-slaughter-lawsuit/">Washington Post</a> and <a href="https://www.dropbox.com/s/l298j6ns90pnenu/Vanessa%20Shakib%20-%20CNN-TV%20News%204-3-2023%20%20CNN%20Tonight_2.mp4?dl=0">CNN</a>, among others. But the whole affair reflects a bigger point about how programs like 4-H, the <a href="https://4-h.org/about/history/">largest</a> youth organization in the country, train generations of children to act against their better moral judgments. Implicit in 4-H’s livestock projects is the view that farm animals <a href="https://shop4-h.org/collections/animal-agricultural-science-curriculum/products/beef-curriculum-1-bite-into-beef">are fungible commodities</a> with one correct use — food — a belief that also undergirds the politics of meat in America. Put simply, it takes quite a bit of hard work to convince people to treat animals as nothing but meat, but hundreds of billions of dollars a year depend on it.
</p>
<h3 id="fnv6ci">
One goat versus the multibillion-dollar meat industry
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The police who seized Cedar on behalf of the fair association were working in a political context shaped by agricultural interests. The action reflects a common pattern of law enforcement overreach in service of the meat industry that’s also evident in, for example, the <a href="https://www.nytimes.com/2022/10/08/science/animals-rights-piglets-smithfield.html">FBI’s</a> <a href="https://theintercept.com/2018/06/07/animal-rights-activists-face-multiple-felony-charges-brought-by-prosecutors-with-ties-to-smithfield-foods/">raids</a> on farm sanctuaries in pursuit of animals <a href="https://www.vox.com/future-perfect/23647682/factory-farming-dxe-criminal-trial-rescue">rescued</a> by activists from factory farms.
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In this case, Long’s <a href="https://www.dropbox.com/s/scmay6jsmdd3vwa/16_First%20Amended%20Complaint%20-%20E.L.%20v.%20Shasta%20Sheriffs.pdf?dl=0">lawsuit</a> argues, she was accused of a theft she couldn’t possibly have committed since her daughter was still the legal owner of the animal when she removed him from the fair and, as a minor, she had the right under California law to <a href="https://leginfo.legislature.ca.gov/faces/codes_displaySection.xhtml?sectionNum=6710.&amp;nodeTreePath=13.4.2&amp;lawCode=FAM">disaffirm any contract</a> she’d made to sell him. The suit also claims that the police committed a number of errors in their seizure of Cedar, including the use of a criminal search warrant in a case she argues was civil, and then not following the California requirement to hold onto evidence — which, in this case, would have meant keeping Cedar alive. The defendants named in the case — including the county, three Shasta police officers, the Shasta District Fair and Event Center, the fair’s CEO, and another person affiliated with the fair — denied most of the allegations in a formal <a href="https://www.dropbox.com/work?preview=18_County+Answer.pdf">response</a> to the suit.
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Shasta County, which sprawls along the foothills of California’s Cascade mountains, is a relatively rural, sparsely populated, and poor county by state standards. While <a href="https://www.shastaedc.org/regional-data/workforce/">only 1 percent of its workforce is employed directly in agriculture</a>, it is politically dominated by the Republican Party, which has thick state and national relationships to farming interests and claims farmers and ranchers as an important constituency. California may be better known for Hollywood and Silicon Valley, but the state is also the <a href="https://data.ers.usda.gov/reports.aspx?ID=17844">nation’s top agricultural and dairy producer</a>, and farming has been a major force in its economic development. Especially in the deep red counties of the Central Valley and far north, farm interests still pack an outsized political punch in this otherwise Democratic-dominated state.
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At the same time, California’s <a href="https://www.census.gov/newsroom/press-releases/2022/urban-rural-populations.html">mostly urban and suburban populace</a> has become increasingly critical of agriculture’s impacts, especially around the treatment of animals. In 2018, 62.7 percent of California voters passed <a href="https://www.vox.com/future-perfect/22576044/prop-12-california-eggs-pork-bacon-veal-animal-welfare-law-gestation-crates-battery-cages">a proposition</a> to strengthen the state’s animal welfare standards, a measure that is now being challenged by the pork industry <a href="https://newrepublic.com/article/166932/legal-fight-californias-prop-12-animal-rights">before the US Supreme Court</a>. But in many rural counties, the agricultural lobby and culture are still strong, with local elites boosting programs that bear the imprint of rural identity, such as 4-H and FFA (what used to be called Future Farmers of America).
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What happened to Cedar, which <a href="https://www.reddit.com/r/news/comments/128qsdr/when_a_9yearold_girl_didnt_want_her_goat_to_be/">struck</a> <a href="https://twitter.com/JennyENicholson/status/1641582010916569090">so</a> <a href="https://twitter.com/lwoodhouse/status/1641646596701192192">many</a> readers as absurd and out of proportion, shines a light on the ideology of 4-H. One of us (Gabriel) has written a <a href="https://gendersexualityfeminist.duke.edu/books/4-h-harvest-sexuality-and-state-rural-america">book</a> about the organization’s importance in American history. In its initial years, 4-H aimed to teach rural youth how to be successful farmers and homemakers. Enrolled youth focused on producing an outstanding agricultural or domestic economy product to competitively exhibit at the county fair: an egg-laying chicken, a home-sewn dress, a plump tomato, a jar of preserved berries, or a fattened calf, for example. Livestock projects like the one Long’s daughter took on, in which children care for a farm animal in preparation for auction and slaughter, date back to the organization’s founding, though today 4-H’s curriculum also spans things like computer science and photography, more recent additions intended to broaden the organization’s appeal to urban and suburban youth without farm experience.
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Many Americans might assume 4-H represents an organic expression of rural civic pride, but <a href="https://www.pennpress.org/9780812247534/the-4-h-harvest/">its history</a> is deeply interwoven with the <a href="https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/21587/Youth%20as%20Infrastructure.pdf?sequence=2&amp;isAllowed=y">leviathan of federal power</a>, particularly the US Department of Agriculture’s efforts to cultivate capital-intensive, <a href="https://newrepublic.com/article/164874/abolish-department-agriculture">debt-financed agriculture</a> across large swaths of rural America. Since 4-H’s founding, the USDA has indirectly administered the program through a network of local agents, and it still legally owns the 4-H name and its iconic clover emblem. (A 1939 law makes the misuse of the 4-H name or emblem <a href="https://uscode.house.gov/view.xhtml?req=granuleid:USC-2000-title18-section707&amp;num=0&amp;edition=2000">a federal crime</a>.)
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<img alt="Two boys in cowboy hats lead pigs with what appear to be pig whips around an outdoor fair space. " src="https://cdn.vox-cdn.com/thumbor/F5JXGleRXwe-brDrQzNTPYwI83c=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24562496/GettyImages_1404493264.jpg"/> <cite>Amy Toensing/Getty Images</cite>
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Youth show their 4-H pigs at a county fair in Montana.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LbevqH">
Training rural youth to think about animals as products has been a central part of 4-H livestock projects. County fair associations, the quasi-governmental organizations that run the fair and manage the fairgrounds, frequently function as pass-throughs for the civic investments of <a href="https://muse.jhu.edu/pub/134/article/885668/pdf?casa_token=xhCrwnDi_MIAAAAA:iTrISsC_PvX87EbuRtU1puOd3GjaVEUsPn8G1YXefjZGO3qddcI2peyEDfzI8PJ5RWC1nsfX">large businesses and wealthy farmers</a>. Historically, those players supported fair associations and 4-H clubs, donating livestock and small, interest-free, non-collateralized loans for feed and other supplies — similar to what is now termed “<a href="https://www.google.com/books/edition/Microfinance_Handbook/ciFt3kcRYGIC?hl=en&amp;gbpv=0">microfinance</a>” in international economic development literature. They then purchased back the matured animals at county and state auctions, usually well above market value (Dahle bid $902 for Cedar, compared to an estimated <a href="https://ageconsearch.umn.edu/record/330124">market rate for goats of roughly $300 or less</a>) to stoke enthusiasm about the livestock business among the community’s youth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LmIwvB">
But today, such livestock projects sit in an uneasy relationship to a meat industry defined by <a href="https://www.dukeupress.edu/porkopolis">inhuman scale, speed, and brutality</a>. Sociologists Colter Ellis and Leslie Irvine have <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/tsq.12047?casa_token=XmjwRM-YOG4AAAAA%3ATFcy9LMPJ8sm5R8M4deBTHor7t9GuxnJP1_tBaMxLnJ8OVVdKDdQTICxD462DS9l0yXjaIj8WAyK">argued</a> that 4-H’s livestock projects implicitly teach young people how to manage the emotional dissonance that can result from sending a beloved companion animal to a grisly fate. The program’s cognitive and emotional socialization is consistent with broader strategies deployed in animal agriculture to justify what many workers may experience as the disturbing and even traumatic labor of slaughter, Ellis <a href="https://www.tandfonline.com/doi/abs/10.1111/tsq.12047">contends</a>. Livestock projects systematically undercut and confound the basic moral intuitions youthful participants like Long’s daughter start with, teaching them that it’s natural and right to lovingly care for an animal companion and then slaughter it and sell it as meat for a tidy profit.
</p>
<h3 id="XVu5U3">
Livestock production teaches kids mercilessness
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S0pMht">
Learning that lesson is key to participating in commercial livestock farming at any scale, whether on a local or factory farm, since the grinding imperatives of long-term profit and contractual obligation must ultimately trump childish sentimentalism for small and large farmers alike. The cultural code in farm communities dictates that children must behave as though animals are commodities and avoid challenging social norms shaped by agriculture or be prepared to be treated as pariahs. As Long’s lawsuit notes, she and her daughter “feared that deviation from a 4-H program through resisting the slaughter of livestock would upset other 4-H members and community members.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hDWa5x">
This is why the child’s defiance was so threatening to the fair, its agents, and, by extension, the American agricultural system, and why it was met with the full force of the law. By suggesting that animals may deserve mercy and that the people who raise them might not want them killed, the family broke a social contract, a rupture that is apparent in Long’s correspondence with county fair officials. Sending Cedar to slaughter was “to teach our youth responsibility” and was “unfortunately out of my hands,” Shasta Fair Association CEO Melanie Silva told Long in an email. There was no opt-out clause, no room for individual conscience or moral judgment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TIuxH5">
That’s a feature of 4-H’s livestock projects, not a bug. Farm animals are to be treated as abstract and fungible, as indistinguishable from one another as one cellophane-wrapped steak is from the next. If an exception is made to spare one animal’s life, the whole ideology is undermined.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f18hPB">
Philosopher Cora Diamond, in her writing about <a href="https://www.jstor.org/stable/3749876">what could sway humans to treat animals better</a>, has noted that mercy is the quality of recognizing the suffering of one over whom we wield power and choosing to treat them with compassion. To make mercilessness into a virtue, as such programs inherently do, propels violence against the vulnerable, whether animal or human, but it also strips people of what Diamond sees as our human moral capacity. Mercy <a href="https://bearistotle.substack.com/p/andrew-yangs-dog-and-my-dog">emerges</a> not because we are bound by some abstract inhuman rule, but the opposite — because <a href="https://read.dukeupress.edu/books/book/550/chapter-abstract/124532/Injustice-and-Animals?redirectedFrom=fulltext">we are exposed</a> to the particular suffering of a creature in our power and moved by our consciences to spare them, as Long’s daughter was.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uaLimG">
Perhaps the county’s brutal response to a single girl’s act of mercy came in part because she reminded the adults around her that they were not metaphysically bound to cruelty to animals; they could choose mercy, but chose not to. One child’s torch-bright act of conscience illuminated the willingness of adults around her to substitute the brittle formalisms of market logic, economic exchange, and contract for the operation of ethical reflection, a kind of moral torpor without which modern animal agriculture would be impossible.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5yoeiV">
For 4-H, the slaughter of Cedar has created bad publicity that could well spark an identity crisis. In response to <a href="https://carsey.unh.edu/publication-rural-america-lost-population-over-past-decade-for-first-time-in-history">declining rural populations</a>, 4-H has worked hard to renew its relevance through projects aimed at urban and suburban children that appeal to liberal sensibilities about sustainability and food ethics, as journalists Kiera Butler and Sarah McColl <a href="https://www.ucpress.edu/book/9780520275805/raise">have</a> both <a href="https://modernfarmer.com/2017/07/4-h-indoctrination-nation/">observed</a>. Those sensibilities are increasingly difficult to square with the program’s deep ties to animal agriculture, a tension more regularly evident in <a href="https://www.npr.org/sections/thesalt/2017/08/30/545603450/for-4-h-kids-saying-goodbye-to-an-animal-can-be-the-hardest-lesson">teary-eyed children</a> forced to give up their animals for slaughter than in police raids.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WnAKKf">
A girl and her 4-H goat paint a picture of farming and food that is a far cry from the ceaseless brutality of the industrial abattoir. In death, Cedar may well remind parents that as long as 4-H teaches children to treat animals as commodities, the slaughterhouse will always be the final destination. The mercilessness of the meat industry may, at any moment, barge into their pastoral scene, sirens blaring, search warrants in hand, to execute a contract and a beloved animal alike.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hz2ubU">
<em>Gabriel N. Rosenberg is the associate professor of gender, sexuality, and feminist studies and history at Duke University. His first book, </em><a href="https://gendersexualityfeminist.duke.edu/books/4-h-harvest-sexuality-and-state-rural-america">The 4-H Harvest</a><em> (University of Pennsylvania Press, 2016), explores the history of the United States Department of Agriculture’s iconic rural youth organization. </em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iyuLFD">
<em>Jan Dutkiewicz is a visiting fellow at Harvard Law School. He has published widely about the environmental, public health, and legal aspects of food production in academic journals and publications including Vox, the Guardian, Wired, and the New Republic.</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>ICC player rankings | Shubman Gill reaches career-best 4th spot in ODIs; Suryakumar Yadav remains top T20I batter</strong> - Apart from Gill, Virat Kohli (seventh) and Rohit Sharma (eighth) too feature in the top 10 in ICC ODI player rankings</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>IPL 2023, KKR vs RCB | Depleted Kolkata Knight Riders seek home comfort against star-studded Royal Challengers Bangalore</strong> - The excitement will be at an all-time high for both teams, with crowd-puller Virat Kohli in the visitors’ dug out</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>IPL 2023 | PBKS sign Gurnoor Singh Brar as Angad Bawa’s replacement</strong> - Raj Angad Bawa, who played two games for PBKS in IPL 2022, has been ruled out of IPL 2023 due to a left shoulder injury</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>IPL 2023 | Unfair to criticise Prithvi and Sarfaraz: Agarkar</strong> - Both Prithvi Shaw and Sarfaraz Khan have struggled against top quality pace attack so far in IPL 2023</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>Premier League | Chelsea held 0-0 by Liverpool again after Potter’s exit</strong> - Joao Felix and Mateo Kovacic went close in the opening minutes followed by chances that went untaken by Kai Havertz in another toothless display for the Blues, who have scored only 29 times in 29 EPL games.</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>185 ‘outsiders’ bought land in Jammu and Kashmir in last 3 years: Govt</strong> - A total of 1,559 Indian companies, including multinational companies, have made investments in the UT, said Union Minister of State for Home Nityanand Rai</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>80-feet Samavayi Road inaugurated in Tirupati</strong> - Municipal Corporation of Tirupati lays the road at a cost of ₹6.50 crore; MLA Bhumana Karunakar Reddy inaugurates the road on Wednesday</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>Renaming of Aurangabad: Supreme Court junks plea, says issue in realm of govt</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>Search continues for tourists still trapped in Sikkim avalanche</strong> - Some seven people were confirmed killed and at least 13 injured according to police officials</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>Joshimath crisis | Local activists threaten to block traffic on route to Badrinath</strong> - The Joshimath Bachao Sangharsh Samiti’s demands include scrapping the NTPC’s Tapovan-Vishnugad hydel project and the Helang-Marwadi bypass project</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>Macron and von der Leyen: Europe’s good cop and bad cop to meet Xi Jinping</strong> - Macron and von der Leyen will send a message of unity and talk tough on Ukraine - will China listen?</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>Spanish TV star Ana Obregón reveals surrogate baby is her late son’s</strong> - Ana Obregón, 68, reveals a baby born in the US was fathered by her son who died of cancer.</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>Nato’s border with Russia doubles as Finland joins</strong> - Finland hands over the document to become the 31st Nato member, in a setback for Russia’s Vladimir Putin.</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>Darya Trepova: Russia cafe bomb suspect charged with terrorism</strong> - Darya Trepova is remanded in custody until 2 June for the killing of pro-war blogger Vladlen Tatarsky.</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>Grandmother with Alzheimer’s faces deportation from Sweden</strong> - Bedridden Kathleen Poole faces a “disgraceful” attempt to deport her to the UK, her family say.</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>Open garage doors anywhere in the world by exploiting this “smart” device</strong> - A universal password. Unencrypted user data and commands. What could go wrong? - <a href="https://arstechnica.com/?p=1929120">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Competence wins over excitement with the 2023 Mercedes-Benz EQE SUV</strong> - This is Mercedes’ fourth new EV, and the one best-designed for American tastes. - <a href="https://arstechnica.com/?p=1928935">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can you fool a monkey with a magic trick? Only if it has opposable thumbs</strong> - Sharing biomechanical ability may be key to anticipating movements of the same limbs in others. - <a href="https://arstechnica.com/?p=1928725">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New buckling spring keyboards re-create IBM’s iconic Model F for modern computers</strong> - USB, modern OS support and customization options meet vintage IBM inspiration. - <a href="https://arstechnica.com/?p=1929037">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Apple joins Amazon, Google, and Microsoft in tech industry layoffs</strong> - The layoffs are a drop in the bucket compared to cuts at competitors, though. - <a href="https://arstechnica.com/?p=1929040">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>They say Donald Trump was charged with crimes that would have been ignored if someone else had committed them</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I guess orange really is the new black.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/KarmicComic12334"> /u/KarmicComic12334 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12cfvb1/they_say_donald_trump_was_charged_with_crimes/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12cfvb1/they_say_donald_trump_was_charged_with_crimes/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My wife walked in on me while I was watching porn.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In a panic reflex I instantly changed to a random channel, the fishing channel.<br/> As my wife walks out again she says: “you should stay on the porn channel… you know how to fish.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/FourFourtyTwo"> /u/FourFourtyTwo </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12bs6rw/my_wife_walked_in_on_me_while_i_was_watching_porn/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12bs6rw/my_wife_walked_in_on_me_while_i_was_watching_porn/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A policeman pulls a farmer over for speeding and proceeds to write him a ticket…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The farmer notices some flies buzzing around annoying the officer. The policeman is shooing flies more than he’s writing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The farmer says “I see you’re being bothered by those circle flies.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The policeman says, “If that’s what you call them, yes, they are somewhat annoying.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The farmer says, “Yeah, we call them that because we see them circling around the rear ends of horses.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The policeman says, “Hmmm. Did you just call me a horse’s ass?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The farmer says, “Oh, no sir, officer. I have way too much respect for those who serve in law enforcement to ever say such a thing.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The policeman says, “Well, that’s a good thing, then.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The farmer adds, “But it’s hard to fool those circle flies.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/DarthBalls1976"> /u/DarthBalls1976 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12c45c4/a_policeman_pulls_a_farmer_over_for_speeding_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12c45c4/a_policeman_pulls_a_farmer_over_for_speeding_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three women are sick of their boss always leaving work early on a Tuesday One Tuesday, they all agree to wait 20 minutes after the boss has left, then sneak out themselves - their boss would never know.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The brunette left and decided to go shopping.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The redhead decided to hit the gym before meeting some friends for drinks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The blonde decided to go home and surprise her husband, but when she arrive home she heard noises in the bedroom. She slowly walked up, peaked through the door, and saw her husband in bed with her boss. Mortified, she closed the door and crept out of the house.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The next day back at work, the girls met up and discussed if they should all skip out early again next week.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No way” said the blonde, “Yesterday, I almost got caught!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12bshfg/three_women_are_sick_of_their_boss_always_leaving/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12bshfg/three_women_are_sick_of_their_boss_always_leaving/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Old joke I translated, hope it works in English.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A son comes home from school one day and tells his dad he’s confused. “Today we learned about practically and theoretically. I tried all day but I don’t get it!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The dad thinks for a minute and tells him “Go ask your mom if she’d sleep with a stranger for a million dollars” The son comes back and says “She said yes right away!” “Now go ask your sister the same thing” Kid runs off and comes back “She thought about it for a moment but also said yes”.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The dad sits him down “You see son, now theoretically we have two million dollars, but practically we only got two whores”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Althure37"> /u/Althure37 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/12brpwv/old_joke_i_translated_hope_it_works_in_english/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/12brpwv/old_joke_i_translated_hope_it_works_in_english/">[comments]</a></span></p></li>
</ul>
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