Pathway Circuit Mapping for Drug Repurposing: CoV-DrugX Tool Sheds Light on Therapeutic Opportunities -
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+The fight against new diseases like COVID-19 demands creative ways to find and reuse existing drugs. This article examines how scientists are rethinking drug use by focusing on cellular pathways as a guide to finding new treatments. A key part of this effort is the CoV-DrugX Pathway Circuit Tool, a new online program developed by Kamal Rawal’s team. This tool uses pathway information and links between genes and drugs to predict how drugs might interact with these pathways, helping researchers quickly find existing drugs that could be repurposed to treat COVID-19. By combining data from various sources, the CoV-DrugX Tool offers a systematic and affordable way to identify drugs that target important pathways involved in COVID-19. However, there are still challenges, such as limited data and the possibility of inaccurate predictions. Despite these limitations, the CoV-DrugX Pathway Circuit Tool is a major step forward in drug discovery. It gives researchers a powerful tool to speed up finding potential treatments during health crises. In the future, this tool could be adapted for other infectious diseases, using its focus on pathways to address urgent medical needs beyond COVID-19.
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Cheating in the wake of COVID-19: How dangerous is ad-hoc online testing for academic integrity? -
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+Worldwide, higher education institutions made quick and often unprepared shifts from on-site to online examination in 2020 due to the COVID-19 health crisis. This development sparked an ongoing debate on whether this development made it easier for students to cheat. We investigated whether students indeed cheated more often in online than in on-site exams and whether the use of online exams was also associated with higher rates of other behaviors deemed as academic dishonesty. To answer our research questions, we questioned 1,608 German students from a wide variety of higher education institutions about their behavior during the summer semester of 2020. The participating students reported that they cheated more frequently in online than in on-site exams. Effects on other measures of academic dishonesty were more negligible. These results speak for the notion that the swift application of ad-hoc online testing during 2020 has led to negative consequences for academic integrity.
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Post-16 students’ experience of practical science during the COVID-19 pandemic and the impact on students’ self-efficacy in practical work -
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+This paper presents the findings from a detailed study investigating UK undergraduate students’ experience of practical science in their post-16 studies during the COVID-19 pandemic. It also examines the perceived confidence and preparedness of the students in relation to areas of practical science skills at the start of their degree courses. The study employed an exploratory sequential mixed methods design, with the findings from focus groups with students at the end of their post-16 studies used to support the development of a comprehensive skills audit and quantitative survey for incoming undergraduate students. Survey data were collected in September and October 2021 from 275 students commencing Biosciences, Chemistry, Physics and Natural Science degrees at two universities in England. The research is important because although almost all students had the opportunity to undertake practical work as part of their post-16 studies during the COVID-19 pandemic, there was considerable variation in students’ experiences. The data indicate that students’ self-efficacy in relation to practical science was impacted by the closures of post-16 education establishments, ongoing social distancing and the removal of the assessment criteria for students to have ‘routinely and consistently’ undertaken each of the practical assessment requirements. The research presents important considerations which are relevant for educators supporting students’ transition from post-16 to Higher Education.
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Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain -
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+Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg relative to a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.
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Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology -
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+The use of metagenomic next-generation sequencing technology to obtain complete viral genome sequences directly from clinical samples with low viral load remains challenging–especially in the case of respiratory viruses–due to the low copy number of viral versus host genomes. To overcome this limitation, target capture sequencing for the enrichment of specific genomes has been developed and applied for direct genome sequencing of viruses. However, as the efficiency of enrichment varies depending on the probes, the type of clinical sample, etc., validation is essential before target capture sequencing can be applied to clinical diagnostics. Here we evaluated the utility of target capture sequencing with a comprehensive viral probe panel for clinical respiratory specimens collected from patients diagnosed with SARS-CoV-2 or influenza type A. We focused on clinical specimens containing low copy numbers of viral genomes. Target capture sequencing yielded approximately 180- and 2000-fold higher read counts of SARS-CoV-2 and influenza A virus, respectively, than metagenomic sequencing when the RNA extracted from specimens contained 59.3 copies/L of SARS-CoV-2 or 544 copies/L of influenza A virus, respectively. In addition, the target capture sequencing identified sequence reads in all SARS-CoV-2- or influenza type A-positive specimens with <26 RNA copies/L, some of which also yielded >70% of the full-length genomes of SARS-CoV-2 or influenza A virus. Furthermore, the target capture sequencing using comprehensive probes identified co-infections with viruses other than SARS-CoV-2, suggesting that this approach will not only detect a wide range of viruses, but also contribute to epidemiological studies.
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Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor-antigen recognition -
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+Understanding the mechanisms of T-cell antigen recognition that underpin adaptive immune responses is critical for the development of vaccines, immunotherapies, and treatments against autoimmune diseases. Despite extensive research efforts, the accurate identification of T cell receptor (TCR)-antigen binding pairs remains a significant challenge due to the vast diversity and cross-reactivity of TCRs. Here, we propose a deep-learning framework termed Epitope-anchored Contrastive Transfer Learning (EPACT) tailored to paired human CD8+ TCRs from single-cell sequencing data. Harnessing the pre-trained representations and the contrastive co-embedding space, EPACT demonstrates state-of-the-art model generalizability in predicting TCR binding specificity for unseen epitopes and distinct TCR repertoires, offering potential values for practical outcomes in real-world scenarios. The contrastive learning paradigm achieves highly precise predictions for immunodominant epitopes and facilitates interpretable analysis of epitope-specific T cells. The TCR binding strength predicted by EPACT aligns well with the surge in spike-specific immune responses targeting SARS-CoV-2 epitopes after vaccination. We further fine-tune EPACT on TCR-epitope structural data to decipher the residue-level interactions involved in T-cell antigen recognition. EPACT not only exhibits superior capabilities in quantifying inter-chain distance matrices and identifying contact residue pairs but also corroborates the presence of molecular mimicry across multiple tumor-associated antigens. Together, EPACT can serve as a useful AI approach with significant potential in practical applications and contribute toward the development of TCR-based diagnostics and immunotherapies.
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Adaptive and Maladaptive Pathways of COVID-19 Worry on Well-Being: A Cross-National Study -
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+Objective: In a preregistered study, we examined whether worries about COVID-19 are simultaneously linked with enhanced well-being through social interaction and reduced well-being through depression symptoms. Method: In August 2020, census-matched participants from high and low prevalence regions in the United States and Italy (N = 857) completed assessments of COVID-19 worry, social interaction, depression symptoms, and well-being. Results: Worries about COVID-19 predicted both more social interaction and more depression (ps < .001). In multiple mediational analyses, an adaptive pathway of COVID-19 worry through social interaction was associated with higher well-being, whereas a maladaptive pathway through depression symptoms was associated with lower well-being. Further, a comparison of high and low COVID-19 prevalence regions replicated the mediational findings for social interaction, providing evidence against reverse causation and common method variance. Conclusion: Findings suggest that normative worries about acute stressors may both benefit and undermine well-being, depending on their impact on social behavior or depression symptoms.
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Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11 -
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+Appropriate cellular recognition of viruses is essential for the generation of effective innate and adaptive antiviral immunity. Viral sensors and their signalling components thus provide a crucial first line of host defence. Many exhibit subcellular relocalisation upon activation, triggering expression of interferon and antiviral genes. To identify novel signalling factors we analysed protein relocalisation on a global scale during viral infection. CREB Regulated Transcription Coactivators-2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon a diversity of viral stimuli, in diverse cell types. This movement was depended on Mitochondrial Antiviral Signalling Protein (MAVS), cyclo-oxygenase proteins and protein kinase A. We identify a key effect of transcription stimulated by CRTC2/3 translocation as production of the pro-fibrogenic cytokine interleukin-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2.
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Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera -
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+Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.
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Care-full Collectives and their Care Practices -
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+In my dissertation, I examine different collectives and their practices through different applied theories of care and theorize on new organizational structures and rituals. This is a study of how people came together during the first wave of Covid-19, myself included. It studies these coming-togethers through different “do-ings” and “be–ings” and juxtaposes them with different theories of care. Theories that include Annemarie Mol’s “Logic of Care”, Ella Myers’ “Worldly things”, Jenna Grant’s “Repair as Care”, Sara Ahmed’s “Fragile Connections” and Lucy Suchman’s “Relocating Innovation”. These different theories come from places like medical anthropology, STS, queer theory, and more. I give an honest account of my journey through these collectives and these theories. I also start to propose an alternate way of organizing institutions for mutual aid through two tools - archetypes and axioms.
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Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals. -
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+Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.
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The Constructive and Destructive Power of Social Norms in the Presence of Authoritative Influence -
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+A randomized survey experiment (N=2,868) was conducted at the onset of the COVID-19 pandemic to examine the effects of information provision on individuals’ cooperation with social distancing measures. Employing a 2 × 2 factorial design, the study examined the influence of social comparison and a powerful messenger. Using an online sample of approximately 3,000 Japanese respondents, it was found that participants demonstrated greater cooperation with social distancing measures when they perceived that they had spent a relatively long time outside the home compared with prevailing social norms in the previous week. Conversely, individuals who spent a relatively short time outside the home, exhibited the opposite effect. However, these results were observed solely in conjunction with the influence of a powerful messenger. The study also explored heterogeneous responses based on personality traits. In conclusion, the results highlight the challenges of changing behavior through informational interventions, emphasizing the role of both the characteristics of the sender and recipient of the information.
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Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19 -
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+The variable etiology of persistent breathlessness after COVID-19 have confounded efforts to decipher the immunopathology of lung sequelae. Here, we analyzed hundreds of cellular and molecular features in the context of discrete pulmonary phenotypes to define the systemic immune landscape of post-COVID lung disease. Cluster analysis of lung physiology measures highlighted two phenotypes of restrictive lung disease that differed by their impaired diffusion and severity of fibrosis. Machine learning revealed marked CCR5+CD95+ CD8+ T-cell perturbations in mild-to-moderate lung disease, but attenuated T-cell responses hallmarked by elevated CXCL13 in more severe disease. Distinct sets of cells, mediators, and autoantibodies distinguished each restrictive phenotype, and differed from those of patients without significant lung involvement. These differences were reflected in divergent T-cell-based type 1 networks according to severity of lung disease. Our findings, which provide an immunological basis for active lung injury versus advanced disease after COVID-19, might offer new targets for treatment.
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Within-host genetic diversity of SARS-CoV-2 across animal species -
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+Infectious disease transmission to different host species makes eradication very challenging and expands the diversity of evolutionary trajectories taken by the pathogen. Since the beginning of the ongoing COVID-19 pandemic, SARS-CoV-2 has been transmitted from humans to many different animal species, and viral variants of concern could potentially evolve in a non-human animal. Previously, using available whole genome consensus sequences of SARS-CoV-2 from four commonly sampled animals (mink, deer, cat, and dog) we inferred similar numbers of transmission events from humans to each animal species but a relatively high number of transmission events from mink back to humans (Naderi et al., 2023). Using a genome-wide association study (GWAS), we identified 26 single nucleotide variants (SNVs) that tend to occur in deer – more than any other animal – suggesting a high rate of viral adaptation to deer. Here we quantify intra-host SARS-CoV-2 across animal species and show that deer harbor more intra-host SNVs (iSNVs) than other animals, providing a larger pool of genetic diversity for natural selection to act upon. Within-host diversity is particularly high in deer lymph nodes compared to nasopharyngeal samples, suggesting tissue-specific differences in viral population sizes or selective pressures. Neither mixed infections involving more than one viral lineage nor large changes in the strength of selection are likely to explain the higher intra-host diversity within deer. Rather, deer are more likely to contain larger viral population sizes, to be infected for longer periods of time, or to be systematically sampled at later stages of infections. Combined with extensive deer-to-deer transmission, the high levels of within-deer viral diversity help explain the apparent rapid adaptation of SARS-CoV-2 to deer.
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Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology -
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+Background: Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to people's health, which is a high-risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. Methods: We used a bioinformatics and systems biology approach to investigate the relationship between GC and COVID-19. The gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. Results: A total of 209 shared DEGs were identified to explore the linkages between COVID-19 and GC. Functional analyses showed that Immune-related pathway collectively participated in the development and progression of COVID-19 and GC. In addition, there are selected 10 hub genes including CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, and IFIT2. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. This study also provides insight into the diseases most associated with mutual DEGs, which may provide new ideas for research on the treatment of COVID-19. Conclusions: This research has the possibility to be contributed to effective therapeutic in COVID-19 and GC.
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A Study of the Efficacy of Troxerutin in Preventing Thrombotic Events in COVID-19 Patients - Conditions: COVID 19 Associated Coagulopathy Interventions: Drug: Troxerutin; Drug: Placebo; Drug: placebo + low molecular weight heparin; Drug: troxerutin + low molecular weight heparin Sponsors: Westlake University; Shaoxing Central Hospital Recruiting
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A Study of an Investigational mRNA-1273.815 COVID-19 Vaccine in Previously Vaccinated Adults - Conditions: SARS-CoV-2 Interventions: Biological: Investigational mRNA-1273.815; Biological: Licensed Spikevax Vaccine Sponsors: ModernaTX, Inc. Not yet recruiting
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The Use of Isatidis Root and Forsythia Oral Liquid for the Treatment of Mild Cases of COVID-19: A Trial Clinical Study - Conditions: Treatment of Mild Cases of COVID-19 Interventions: Drug: Langenlianqiao; Drug: LianhuaQingWen; Other: placebo control group Sponsors: Central South University Completed
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Covid-19 and Influenza Oral Vaccine Study - Conditions: covid19 Infection; Influenza, Human Interventions: Biological: Covid-19 vaccine; Biological: Influenza vaccine Sponsors: Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute Ltd Not yet recruiting
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Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID - Conditions: Long COVID; Brain Fog; Cognitive Change Interventions: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose Sponsors: Taipei Veterans General Hospital, Taiwan Not yet recruiting
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Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation - Conditions: COVID-19 Interventions: Other: Guidebook; Other: Guidebook and Myofascial Reorganization® (RMF). Sponsors: University of the State of Santa Catarina; Larissa Sinhorim Recruiting
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Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure - Conditions: Acute Respiratory Failure Interventions: Behavioral: Standard of Care; Behavioral: Rehabilitation Sponsors: Hospital Israelita Albert Einstein Not yet recruiting
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Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD) - Conditions: Post-Acute Sequelae of COVID-19 Interventions: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program Sponsors: University of Minnesota Recruiting
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From PubMed
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Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics - CONCLUSION: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.
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Evaluating mAbs binding abilities to Omicron subvariant RBDs: implications for selecting effective mAb therapies - The ongoing evolution of the Omicron lineage of SARS-CoV-2 has led to the emergence of subvariants that pose challenges to antibody neutralization. Understanding the binding dynamics between the receptor-binding domains (RBD) of these subvariants spike and monoclonal antibodies (mAbs) is pivotal for elucidating the mechanisms of immune escape and for advancing the development of therapeutic antibodies. This study focused on the RBD regions of Omicron subvariants BA.2, BA.5, BF.7, and XBB.1.5,…
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Discovery of components in honeysuckle for treating COVID-19 and diabetes based on molecular docking, network analysis and experimental validation - Molecular docking screening identified ochnaflavone, madreselvin B and hydnocarpin as key components for treating COVID-19 with diabetes in honeysuckle using 3 C-like protease (Mpro), angiotensin-converting enzyme 2 (ACE2), and dipeptidyl peptidase 4 (DPP4) as molecular docking targets, ACE2, DPP4, IL2, NFKB1, PLG, TBK1, TLR4 and TNF were the core targets, and multiple antiviral and anti-inflammatory signalling pathways were involved. Further, the levels of IL-1β and DPP4 in cell supernatant…
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Swine acute diarrhea syndrome coronavirus Nsp1 suppresses IFN-lambda1 production by degrading IRF1 via ubiquitin-proteasome pathway - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an…
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Swine acute diarrhea syndrome coronavirus nucleocapsid protein antagonizes the IFN response through inhibiting TRIM25 oligomerization and functional activation of RIG-I/TRIM25 - Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging Alpha-coronavirus, brings huge economic loss in swine industry. Interferons (IFNs) participate in a frontline antiviral defense mechanism triggering the activation of numerous downstream antiviral genes. Here, we demonstrated that TRIM25 overexpression significantly inhibited SADS-CoV replication, whereas TRIM25 deficiency markedly increased viral yield. We found that SADS-CoV N protein suppressed interferon-beta (IFN-β)…
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Inhibition of influenza A virus and SARS-CoV-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor - Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into…
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Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron - BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic…
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Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health - The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called “gut-lung axis”. Perturbations in gut microbiota composition, termed dysbiosis, can have…
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SARS-CoV-2 causes dysfunction in human iPSC-derived brain microvascular endothelial cells potentially by modulating the Wnt signaling pathway - CONCLUSION: These findings suggest that SARS-CoV-2 infection causes BBB dysfunction via Wnt signaling. Thus, iPSC-BMELCs are a useful in vitro model for elucidating COVID-19 neuropathology and drug development.
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Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer? - Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines’ rapidly waning immunity. Mounting…
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Inhibition of PCSK9 with evolocumab modulates lipoproteins and monocyte activation in high-risk ASCVD subjects - CONCLUSIONS: This trial is the first to demonstrate that PCSK9 mAB with evolocumab can modulate circulating immune cell properties and highlights the importance of “stress” profiling of circulating immune cells that more clearly define immune contributions to ASCVD.
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Discovery and development of novel 10,12-disubstituted aloperine derivatives against HCoV-OC43 by targeting allosteric site of host TMPRSS2 - By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC(50) values of 4.7 and 4.1 μM. A mechanism study revealed that it inhibited the protease activity…
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Protocol to identify flavonoid antagonists of the SARS-CoV-2 main protease - Flavonoids are naturally occurring metabolites of plants that can inhibit the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), which is required for viral replication. Here, we present a protocol to identify flavonoid antagonists of the SARS-CoV-2 Mpro. We describe steps for the expression and purification of Mpro and a kinetic enzymatic assay for Mpro activity using a dequenching fluorescence resonance energy transfer peptide substrate. We then detail…
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DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients - Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and…
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Immunoglobulin G4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant - CONCLUSION: Heterozygosity for gain-of-function IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunological data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.
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From Patent Search
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Will Historic Job Growth Bring an End to the “Vibecession”? - The Labor Department’s March employment report shows the U.S. economy continuing to power ahead. Yet many voters’ perceptions remain stubbornly negative. - link
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Jessica Tisch, the Ex-N.Y.P.D. Official Trying to Tame New York’s Trash - The city has lived in filth for decades. Can Jessica Tisch, a scion of one of the country’s richest families, finally clean up the streets? - link
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Maggie Rogers’s Journey from Viral Fame to Religious Studies - The singer-songwriter’s sudden celebrity made her a kind of minister without training. So she went and got some. - link
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Battling Under a Canopy of Russian and Ukrainian Drones - The commander of one of Ukraine’s most skilled units sent his men on a dangerous mission that required them to elude a swarm of aerial threats. - link
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Park Chan-wook Gets the Picture He Wants - With “The Sympathizer,” the director of “Oldboy” and “The Handmaiden” comes to American television. - link
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From Vox
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Does it matter if Carrie Bradshaw is the worst? -
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+Kim Cattrall, Kristin Davis, Sarah Jessica Parker, and Cynthia Nixon attend a screening of the season three premiere of Sex and the City on June 1, 2000, at the DGA Theatre in Los Angeles. | Ron Galella/Ron Galella Collection via Getty Images
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+Carrie Bradshaw is a menace. That’s the point.
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+In another major licensing grab for Netflix, HBO’s juggernaut Sex and the City officially landed on the platform this week. Older fans of the show are already anticipating the possibility of Gen-Z’s horrified reaction to the raunchy and, in some ways, culturally outdated show. Can today’s youth stomach Carrie’s confusion over bisexuality or the women’s obsession with thinness? Will “puriteens” be scandalized watching Samantha Jones hook up with a random delivery guy?
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+Lest we forget, Sex and the City has been available to stream for years. So the idea that teenagers and early 20-somethings have never engaged with the series before is a little presumptuous. (They’ve surely encountered some fashion inspo TikToks.) Rather, it seems like this move to Netflix has given everyonea chance to reignite the now-decades-long discourse about the show’s storylines and characters.
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+It’s only natural then that social media users are already firing off takes about Carrie Bradshaw. To be fair, fans are nevernot discussing the show’s polarizing protagonist. In the years during and after the show aired in 1998, Carrie was largely celebrated as a feministtriumph — the rare single, childless (and messy) woman in her 30s portrayed in a (somewhat) aspirational light.
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+However, the 2010s saw a wave of essays and criticism reevaluating her character — mostly by emphasizing her more annoying qualities — which the show occasionally downplayed. Was Carrie ever the ideal image of female independence, or just a self-absorbed, self-destructive nightmare?
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+In 2024, the latter opinion has become more of a default perspective, and the primary lens through which many fans seem to enjoy the show. How did this anti-Carrie sentiment come to consume so much of the discourse surrounding SATC — a lighthearted but textually rich show with an abundance of interesting talking points, a slew of actual villains, and three other complex main characters?
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+Is Carrie Bradshaw really thatbad?
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+On one hand, the nonstop Carrie criticisms feel a bit reflexive, more like a meme than an actual analysis of merit. On the other hand, she’s given audiences a lot to be frustrated with over six seasons, from her surprising prudishness to her pathetic longing for her main love interest, Mr. Big.
+
+
+Critics tend to highlight her self-centered tendencies, including cheating on her boyfriend Aidan and having an affair with Big while he was engaged to another woman. Vox’s Alex Abad-Santos writes that Carrie’s essentially the blueprint for what the internet has labeled “main character syndrome,” citing a season four episode — one I consider useless plot filler — where she expected her friend Charlotte to sell her engagement ring to loan her thousands of dollars.
+
+
+More recent TikToks and tweets have used Carrie as an informal case study in insufferable and even “toxic” behavior. In one TikTok, songwriter and content creator Kady Brown (@KadyzRoxz), who makes videos about relationships and mental health, argues that Carrie surpasses the threshold of a “complicated character.” Rather, she considers her a “master manipulator” and “narcissist.”
+
+Brown, 30, tells Vox that she first watched SATC when she was 22. However, in revisiting the show in her late 20s with a “fully developed frontal lobe,” she was met with “an undeniable ick of Carrie.”
+
+
+“I love the series,” she says. “I love most of the women. But, as a proper adult who believes she’s done her healing work, nothing could divorce me from the idea that Carrie has to be stopped!”
+
+
+Brown says, in her rewatch, she was mainly struck by the way Carrie argues with her friends, and she sees the character as an “externalizer.”
+
+
+“Carrie’s weaponized Miranda’s trust issues to avoid accountability in conversations about Big,” she said, referencing a season three episode. “And when Charlotte told Carrie it was a mistake to have dinner with her ex-boyfriend while married to Big, Carrie brought up Charlotte’s fear of being cheated on.”
+
+
+Other fans, like 30-year-old Katherine D. Morgan, an author and SATC watcher since her teens, argue that Carrie’s bad qualities are overstated within the fandom, especially compared to other faulty characters like Charlotte and Samantha — the latter of whom she says is also an “asshole.” Additionally, she says the term “narcissist” is “thrown around way too freely.”
+
+
+“Carrie’s the main character, so, of course, she talks about herself a lot,” Morgan says.
+
+
+“She’s a flawed human being,” she says. “Some people are bad at handling money. Some people date people who aren’t the best for them. Sometimes, those people are your best friends. So if you’re saying this person is terrible, you could also say the people you associate with are terrible.”
+
+
+ Brian Ach/WireImage
+
+Davis, Parker, Nixon, and Cattrall in Sex and the City: The Movie on September 21, 2007.
+
+
+
+The harsh reactions to Carrie’s antics are particularly interesting to see today. In 2024, the “unlikable” protagonist whose life is in shambles is a common leading archetype in many female-driven television comedies, like Sam in the Bridget Everett vehicle Somebody Somewhere or Brooke Dubek in the recently concluded The Other Two. In 2022, the New York Times noticed an increasing appetite for female protagonists “who undermine their own growth” and are “more likely to be mired in failure than striving toward wedding rings and corner offices” — much like Carrie throughout SATC. Love her or hate her, it’s Carrie Bradshaw and her no-good decisions who is responsible for some of our favorite irresponsible women on TV.
+
+
+Subsequent HBO shows like2013’s Girls and2016’s Insecure — as well the Emmy-winning Prime Video show Fleabag, which also premiered in 2016 — relied on this archetype and gained popularity for their honest, sometimes brutal depictions of youngish womanhood. This expectation has taken over reality TV, too. People tune into Bravo’s Real Housewives franchise primarily to watch women make bad decisions and behave in transgressive ways.
+
+
+Morgan notes that the way viewers are trained to watch SATC, compared to other shows, could also have to do with this strong repulsion toward Carrie. The famous question of “Are you a Carrie, Samantha, Miranda, or Charlotte?” can make consuming the show a more self-reflective experience, like filling out a personality questionnaire.
+
+
+“People think that if they can identify with Carrie that suddenly means they’re a godawful person,” Morgan says.
+
+
+Viewers who initially approach the show this way may misunderstand Carrie — and the rest of the women — as characters who are solely meant to be aspirational, relatable avatars as opposed to categorical “antiheroines.” The “antihero” title is often more readily thrown at male protagonists who are violent and/or less morally ambiguous, such as Tony Soprano, Walter White, Dexter Morgan, and Don Draper — even though Carrie, as Keishin Armstrong says, came before all of them.
+
+
+“She was one of TV’s first, if not the first, true TV antiheroine,” Keishin Armstrong says. “She smoked. She drank. She was absolutely excruciating to watch as she chased after Big.”
+
+
+“I was longing for more flawed female characters at the time, which was still very much the era of sunny chick lit and rom-com heroines,” she says. “Their worst flaws were that they were clumsy or shopped too much.” (In Carrie’s case, being an occasional klutz and a shopping addict were the least of her problems.)
+
+
+Carrie sucks. So what?
+
+
+That said, it’s hard not to attribute at least some of the compulsive nitpicking of Carrie to sexist attitudes. Compared to the male mobsters on The Sopranos or Don Draper — who are babygirlified online and met with lighthearted takes about their sex appeal — there seems to be an expectation that Carrie should have a strong moral character. (When weighed against murderers and serial misogynists, she does.) She even somehow gets a worse rap than the terrible men on SATC, like Big, a middle-aged fuckboy, or Aidan, who took her back after she cheated on him just to emotionally torment her.
+
+
+Overall, these repeated declarations of Carrie’s “awfulness” seem to misunderstand her flaws as a bug and not a feature of a show about a group of rich, solipsistic white women. There’s a valid argument that it’s pleasant to watch characters grow and reflect on their mistakes. For example, Carrie’s continually misguided antics in Sex and the City 2 and the Max reboot And Just Like That… feel like legitimate failures in the progression of her arc. However, watching the original series solely through anti-Carrie goggles is missing the point and half the humor of the partly surreal and ridiculous show.
+
+
+Likewise, would a more refined, less “delulu” version of Carrie result in an equally compelling and outrageous series? Morgan argues no, claiming that “nothing would’ve happened” if it weren’t for Carrie acting out on her insecurities and constantly ignoring red flags. At the very least, Carrie gave viewers something to talk about and debate together.
+
+
+There’s also a fine line between a character being unlikable and unwatchable. Based on the sheer amount of people who love and repeatedly watch SATC, Carrie seemingly doesn’t fit into the latter category. That also rings true for content creator Brown, who says that Carrie doesn’t entirely spoil the show for her. Maybe this is because Carrie’s less pleasant attributes largely result in self-sabotage — which she miraculously tends to bounce back from — rather than causing harm to her friends. While she’s occasionally gotten into tiffs with the other women, as they all have, she remains a well-qualified lead character in a love story about the ups and downs of female friendship.
+
+
+Similarly, Morgan believes that Carrie is mostly a “good friend,” recalling how she supported Samantha during her breast cancer diagnosis and Charlotte after her miscarriage. “Everyone reaches out to her.”
+
+
+On a more basic note, Keishin Armstrong says that Carrie just seems like an amusing person to have in your friend circle.
+
+
+“I think of Carrie as that friend whose choices you always roll your eyes at, but you’re friends with anyway,” she says. “She gets you into good parties and clubs and always has some entertaining story about how much her life sucks, even if it’s probably her fault.”
+
+
The Michigan school shooter’s parents face precedent-setting sentences -
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+
+
+Students, parents, teachers, and community members gather for a vigil at the Lake Point Community Church following a shooting at Oxford High School on November 30, 2021, in Oxford, Michigan. | Matthew Hatcher/Getty Images
+
+
+
+The Michigan school shooter begged for help. His parents laughed it off.
+
+
+Today, the parents of the 2021 Michigan school shooter will cross a grim legal threshold: They will be the first parents in American history to be sentenced for their own criminal responsibility in relation to a mass shooting committed by their child.
+
+
+In separate trials held earlier this year, Jennifer and James Crumbley were each found guilty of four counts of involuntary manslaughter after their son opened fire in the hallways of his school, Oxford High School, in Michigan on November 30, 2021 — just hours after school administrators had summoned the Crumbleys to campus to alert them that their son seemed to be having violent fantasies.
+
+
+The Crumbleys face up to 15 years in prison for their roles in the crime. Their son, who was 15 years old at the time of the shooting, was sentenced in December to life in prison without parole. Prosecutors have asked the judge in the trials to sentence both Crumbleys to at least 10 years.
+
+
+Although the case is precedent-setting, gun rights advocates haven’t really embraced it as a cause, likely due to the troubling circumstances that led up to the shooting.
+
+
+Prosecutors had argued that James and Jennifer Crumbley, both strident gun enthusiasts, enabled their son to commit the shooting in three key ways: by continually ignoring what should have been warning signs regarding his mental health, by purchasing a firearm they intended for him to illegally own, and by failing to secure the gun away from him — even after school officials alerted them to the problem.
+
+
+In other words, the very facts that made prosecutors charge the Crumbleys and handed them their precedent-setting convictions might also limit that precedent’s reach.
+
+
+The Michigan shooter’s parents ignored an alarming series of warning signs — and arguably enabled their son’s violence
+
+
+According to an independent report released by the school district in October, multiple people failed at multiple points to prevent the 2021 shooting.
+
+
+For months prior, the Crumbleys’ son, Ethan Crumbley, repeatedly asked his parents for help handling his mental health and showed signs of depression and mental illness. In texts sent to them, for example, he exhibited growing paranoia and complained multiple times of seeing ghosts or demons in their home when he was alone. But the Crumbleys ignored or dismissed his concerns.
+
+
+“I actually asked my dad to take [me] to the Doctor yesterday but he just gave me some pills and told me to ‘Suck it up,’” Ethan texted a friend in April 2021.
+
+
+“My mom laughed when I told her.”
+
+
+ Courtesy Detroit Police
+
+James and Jennifer Crumbley at the time of arrest.
+
+
+
+Four days before the shooting, James Crumbley took his son with him to buy a gun, a Sig Sauer 9mm that prosecutors argued they intended for their son’s personal use, despite him being well under 18, the legal age for gun ownership in Michigan.
+
+
+One day before the shooting, Ethan was caught at school looking up bullets to use with the gun and was disciplined. Instead of expressing concern, his mother joked over text, “lol I’m.not mad. you have to learn not.to.get caught.”
+
+
+The morning the shooting occurred, Ethan accessed the gun and took it to school in his backpack. Later, a schoolteacher alerted authorities after he drew a collection of disturbing images on a math worksheet, including a gun very similar to the Sig Sauer his father had just bought. Next to the gun, he sketched a person who appeared to be riddled with bullet wounds. Below it, he wrote, “The thoughts won’t stop — help me,” along with other messages like “blood everywhere” and “my life is useless.”
+
+
+Despite these indicators, neither James nor Jennifer alerted the school to the fact they had just purchased a gun similar to the one shown in the drawing. They left him at the school and went back to their jobs, without returning home to make sure the gun was still secured. School administrators neglected to search Ethan’s backpack, where the gun was still hidden.
+
+
+A few hours after this meeting, the Crumbleys received reports of the school shooting and immediately began frantically messaging him. “He must be the shooter,” Crumbley texted her boss.
+
+
+By then, however, it was too late to intervene.
+
+
+The Crumbleys are the first parents to be held criminally responsible for their role in a child’s mass shooting
+
+
+Again, this is a precedent-setting case.
+
+
+Michigan prosecutor Karen McDonald told CBS News after James Crumbley’s trial in March that she hadn’t initially been thinking about what precedents did or didn’t exist, but that the facts of the case led her to the decision to prosecute. “The very first question I asked was, ‘Where did he get that gun, and how did he get it?’ And that question led to some really disturbing facts,” she said. “I think it’s a rare set of facts, but I also think that we don’t ask the question enough.”
+
+
+
+The Crumbleys’ lawyers fought the case’s legality from the start — arguing there was no justification for bringing charges against parents for the actions of their son, and that the decision to press charges could lead to overzealous prosecution of gun owners in the future. But a state appellate court ruled that the trials could move forward, pointing out that Ethan Crumbley’s actions were “reasonably foreseeable.”
+
+
+Even as it did so, however, the court acknowledged it was an unusual case.
+
+
+Prosecutors argued that both parents failed to exercise “reasonable care” of their son, and went even further in failing to restrict his access to the gun. The Crumbleys have never admitted to buying the Sig Sauer for their son’s use, but in any case, they seemed to make only a token effort to secure the gun away from him.
+
+
+Gun safety experts recommend that considerable care be taken when storing a gun away from family members — in particular, making sure the gun and the bullets are kept locked and separate from each other.
+
+
+“Securing the gun is the whole thing,” James Crumbley’s anonymous jury foreman told the Detroit Free Press after his verdict in March.
+
+
+While the extraordinary circumstances of this case make it unlikely that every parent of a school shooter could face prosecution, the Michigan shooter shares plenty of common red flags with other school shooters that parents should be alert to. The Crumbleys have claimed ignorance, but they’ve also reportedly shown a lack of remorse, with James Crumbley claiming to be a “martyr” for the cause of gun rights.
+
+
+Jurors clearly disagreed. “It’s not gonna fix nothing,” James Crumbley’s jury foreman said after his verdict. “It’s just a start … it’s a start of things.”
+
The Supreme Court will decide if states can ban lifesaving abortions -
+
+
+
+Demonstrators participate in an abortion rights rally outside the Supreme Court as the Court hears oral arguments in Food and Drug Administration v. Alliance for Hippocratic Medicine on March 26, 2024. | Anna Moneymaker/Getty Images
+
+
+
+A federal law requires hospitals to provide abortions when necessary to prevent serious health consequences. The justices could neutralize that law.
+
+A federal law, the Emergency Medical Treatment and Labor Act (EMTALA), requires nearly all hospitals to provide “such treatment as may be required to stabilize the medical condition” of “any individual” who arrives at the hospital’s ER with an “emergency medical condition.” Though the law does not specifically mention abortions, EMTALA is written in capacious terms — requiring covered hospitals to perform an emergency abortion when that is the appropriate treatment to resolve a patient’s medical emergency.
+
+
+And yet, last January, the Supreme Courteffectively nullified EMTALA, at least for patients who require abortion. Moyle, which the Court will hear the last full week of April, asks whether this nullification should be made permanent.
+
+
+The case involves a conflict between the federal law and Idaho’s unusually restrictive anti-abortion statute, which permits physicians to perform an abortion when “necessary to prevent the death of the pregnant woman,” but not when a patient’s pregnancy only threatens to disable or seriously harm them.
+
+
+EMTALA, meanwhile, requires most hospitals to provide whatever care is necessary to stabilize a patient who is at risk of “serious impairment to bodily functions,” “serious dysfunction of any bodily organ or part,” or other nonfatal consequences that are defined as medical emergencies by EMTALA. So, for example, if a patient’s uterus could be destroyed, but she is likely to survive if untreated, EMTALA requires hospitals to perform an abortion if terminating the pregnancy would stabilize the patient’s medical condition.
+
+So, again, Moyle should be an easy case, and a federal district court ruled in 2022 that Idaho’s abortion ban must give way to EMTALA when a pregnant patient has a medical emergency that must be treated with an abortion.
+
+
+Last January, however, the Supreme Court temporarily blocked this district court’s order, reinstating Idaho’s sweeping abortion ban while the justices ponder the Moyle case. That’s a strong sign that, despite EMTALA’s clear text, the justices could permanently neutralize the federal law’s protections for people who must have an abortion to avoid catastrophic medical consequences. (No justice publicly dissented from this temporary order, but justices sometimes disagree with the Court’s orders but do not note their dissent.)
+
+
+Moyle is a test of whether these justices will follow the text of a clearly drafted law
+
+
+EMTALA is a reasonably straightforward statute. It only applies to hospitals with emergency rooms, and only to those hospitals that accept Medicare funds. That’s most hospitals because Medicare provides health coverage to Americans over the age of 65.
+
+
+The primary purpose of this law is to ensure that hospitals provide emergency medical care to patients who may not be able to pay for it. But the law is also written in expansive terms. It states that “if any individual … comes to a hospital and the hospital determines that the individual has an emergency medical condition,” the hospital typically must “stabilize the medical condition.” (In limited circumstances, the hospital may transfer the patient to another facility.)
+
+
+EMTALA also defines the term “emergency medical condition” to include not just life-threatening medical conditions, but also conditions that place a patient’s health in “serious jeopardy” or that threatens serious harm to a patient’s “bodily functions” or “any bodily organ or part.”
+
+
+Faced with this fairly explicit text, Idaho’s lawyers (and a separate team of lawyers representing the state’s GOP legislature) offer several arguments to justify leaving its broad abortion ban in place.
+
+Both the state’s brief and the state legislature’s brief also lean heavily into a provision of federal Medicare law which provides that EMTALA should not be read “to authorize any Federal officer or employee to exercise any supervision or control over the practice of medicine or the manner in which medical services are provided.” They claim that this provision prevents EMTALA from being read to alter which medical procedures can legally be performed in Idaho.
+
+
+But this argument also conflicts with the text of federal law. Even if the Court agrees that requiring doctors to perform medically necessary abortions constitutes “supervision or control over the practice of medicine,” the statutory provision Idaho points to only prohibits “any Federal officer or employee” from exercising such supervision.
+
+
+No federal officer or employee — meaning, a member of the federal executive branch — has decreed that Idaho hospitals must provide emergency abortions. Rather, the Biden administration argues that Congress made this determination when it enacted EMTALA.
+
+
+The anti-abortion briefs also point to several provisions of the EMTALA statute which require hospitals to offer stabilizing care to a pregnant patient’s “unborn child” if a medical emergency endangers the fetus’s life. They claim that reading the federal law to require emergency abortions would “put it at war with” its provisions protecting fetal life.
+
+
+But this argument is also at odds with EMTALA’s text. The federal statute provides that a hospital meets its obligations under EMTALA if it “offers” a patient medically stabilizing treatment and “informs the individual (or a person acting on the individual’s behalf) of the risks and benefits” of that treatment.
+
+
+Thus, when a pregnant patient faces a medical emergency that endangers both the patient and their fetus,the hospital’s obligation is to offer treatment that will stabilize both patients. And, in the tragic case where a patient is forced to choose between an abortion, which would stabilize their own condition, or a treatment which would save the fetus but leave the mother at risk, EMTALA requires the hospital to offer both treatments, and inform the patient of the terrible choice they must make.
+
+
+And then the hospital must honor the patient’s choice, even if the state does not approve of it.
+
+
+Idaho also wants the Supreme Court to fundamentally alter the balance of power between Congress and the states
+
+
+Idaho’s two legal teams also make a pair of arguments that seek to weaken Congress in fundamental ways and to place novel new limits on the federal government’s ability to preempt state laws.
+
+The major questions doctrine claims that Congress must “speak clearly” if it wishes to give a federal agency the power to decide a question of “vast ‘economic and political significance.’” This doctrine is not mentioned in the Constitution or in any federal law, and appears to have been made up entirely by Republican appointees to the Supreme Court.
+
+
+Even if you accept this made-up doctrine as legitimate, however, it is not at all clear why it is relevant to the Moyle case. By its own terms, the major questions doctrine only applies when a federal agency claims the authority to decide an important policy question. But no federal agency — meaning, an agency within the Executive Branch — has made any policymaking decision of any kind in Moyle. Rather, the question is whether a law enacted by Congress requires Idaho hospitals to perform emergency abortions.
+
+
+Idaho, in other words, is arguing that a made-up legal doctrine, which appears in no legal text and that was fabricated entirely by judges, should be read to limit Congress’s ability to decide important policy questions. If the Court agrees, that would be an extraordinary transfer of power from an elected Congress to an unelected judiciary.
+
+
+The state’s strongest legal argument, meanwhile, turns on the fact that EMTALA’s obligations only apply to hospitals that accept federal Medicare funds.
+
+
+The Supreme Court has long held that, when Congress spends money, it may impose conditions on the recipients of that money — including on state governments. So, for example, the Court held in South Dakota v. Dole (1987) that Congress may require states that accept federal highway funds to raise their drinking age to 21 (Congress thought that the roads would be safer if there were less underage drinking and driving).
+
+
+In Moyle, however, the question is whether private hospitals that accept Medicare funds must perform emergency abortions. Idaho claims that, because it has not weighed in on whether to accept that funding, it has not consented to having its own state law overridden by EMTALA. And it argues that such consent is necessary for a federal spending program to override a state law.
+
+
+Idaho actually does have some legal support for this argument. In Pennhurst State School & Hospital v. Halderman (1981), the Supreme Court said that a state’s decision to accept federal funds is “much in the nature of a contract: in return for federal funds, the States agree to comply with federally imposed conditions.” So that does suggest that a state need not comply with “federally imposed conditions” if it did not “agree to comply” with them.
+
+
+But the Justice Department also cites many Supreme Court cases holding that Congress preempted a state law when it enacted a federal spending program that does not provide grants to states. Thus, in Coventry Health Care v. Nevils(2017), the Court held that the federal government’s decision to offer its own employees health plans that violate Missouri law preempts that state law. And in Bennett v. Arkansas (1988), the Court held that federal Social Security law overrides an Arkansas law that allowed the state to seize an incarcerated person’s Social Security benefits.
+
+
+Indeed, as recently as last year, the Court held in Health and Hospital Corporation v. Talevski (2023) that private plaintiffs may sue to enforce provisions of federal Medicaid law that impose obligations on institutions that accept Medicaid funds. Talevski rested on the proposition that conditions attached to federal grant programs are “laws” just like any other federal law, and thus can be enforced using the same mechanism individuals would use to enforce a different law.
+
+
+So, while Pennhurst offers some legal support for Idaho’s claim that EMTALA cannot modify a state law without the state’s consent, there are myriad cases supporting the opposing proposition. A justice who is determined to deny emergency abortions to patients who need them could rely on Pennhurst to achieve that result, but such a decision risks undermining countless other acts of Congress that override state laws.
+
+
+The Court’s decision in Moyle is likely to determine whether some women live or die
+
+
+Theoretically, Idaho’s law permits abortions when necessary to save a patient’s life. Many other states with abortion bans have broader exemptions on the books, which theoretically permit an abortion when a patient faces serious health consequences that may not be life-threatening.
+
+This happened, moreover, despite the fact that Texas law permits abortions when a patient “has a life-threatening physical condition” or faces a “serious risk of substantial impairment of a major bodily function” that relates to their pregnancy.
+
+
+Incidents like this are common because many state legal provisions permitting emergency abortions have never been interpreted by any court, or have been interpreted largely by Republican judges who are hostile to abortion. So hospital lawyers often cannot know in advance when their state’s courts will allow doctors to perform an abortion, and doctors who guess wrong risk very serious criminal charges.
+
+
+If the Supreme Court reads EMTALA to say what it actually says in Moyle, that would relieve some of this uncertainty. It would mean that doctors or patients who cannot obtain a state court order permitting an emergency abortion could also seek such an order from federal court. It would also mean that, over time, a body of case law would develop establishing when federal law entitles someone experiencing a medical emergency to an abortion.
+
+
+But all of that depends on whether these justices, a majority of whom voted to overrule Roe v. Wade, will set aside their personal opposition to abortion and read EMTALA to do what it actually says.
+
+
+
From The Hindu: Sports
+
+
Hockey | India eyes cohesive effort to keep five-Test hockey series alive against Australia - The Indians were drubbed 1-5 and 2-4 by Australia in the first two matches of the series, which is a part of preparations for this year’s Paris Olympics for both the sides.
+
Candidates Chess: Indians in hunt, but Nepomniachtchi clear favourite on first rest day - With four rounds done out of 14, there are 10 more games still to play. Things have been going well for the Indians but not in the purest way possible.
+
IPL-17: RR vs GT | Jaiswal’s form a concern as Rajasthan Royals look to keep winning juggernaut rolling - Rajasthan Royals captain Sanju Samson has been leading Rajasthan Royals from the front, scoring 178 runs from four games including two fifties.
+
IPL 2024 | Ruturaj Gaikwad says he was told about leading Chennai Super Kings in 2022 - Chennai Super Kings’ Ruturaj Gaikwad, who led from the front in the win against KKR on April 8 night, was stunningly appointed CSK captain a day before the IPL opener on March 22
+
CSK vs KKR | Ravindra Jadeja joins Kohli, Rohit, Raina in IPL’s 100-catches club - Jadeja became just the fifth player to complete 100 catches as a fielder in IPL history
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+
From The Hindu: National News
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+
KWDT-II sets April 29 deadline for A.P. to file statement in water dispute - Telangana alleges that AP is delaying proceedings in tribunal due to its pending SC case
+
‘We are not outsiders’: Manipuris who took refuge outside State yearn to vote in LS polls - Displaced people living in relief camps in the State will be able to vote in the elections. However, there is no such arrangement for those outside the State unable to return home because they feel it’s still not safe
+
Kerala’s Vellamunda Maoist case: NIA court finds four Maoists guilty - Prosecution case was that the Maoists trespassed on the house of a policeman and terrorised him and his family members with guns and threatened them of death on April 24, 2014 at Vellamunda in Wayanad in Kerala
+
Jagga Reddy rules out changes in PCC leadership, says Revanth doing his best as CM and PCC president -
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Jana Vignana Vedika urges public to embrace natural beverages -
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+
From BBC: Europe
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First ever climate change victory in Europe court - “We are not made to sit in a rocking chair and knit,” said one of the older Swiss women who won.
+
Record hot March sparks ‘uncharted territory’ fear - Monthly hot streak continues in March with scientists struggling to explain the scale of recent heating.
+
One dead as bridge falls on railway in Russia - The incident in the western city of Vyazma halts all train traffic, cutting gas supplies to many people.
+
Vatican stands firm on sex change and surrogacy - The Vatican remains opposed to concepts like abortion and euthanasia, describing them as “grave violations”.
+
Why is Russia trying to frame Ukraine for concert massacre? - Parroting the Kremlin line, Russian media is ignoring IS claims of responsibility for the Crocus City attack.
+
+
From Ars Technica
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+
Moments of totality: How Ars experienced the eclipse - The 2024 total eclipse is in the books. Here’s how it looked across the US. - link
+
Teen’s vocal cords act like coin slot in worst-case ingestion accident - Luckily his symptoms were relatively mild, but doctors noted ulceration of his airway. - link
+
MIT License text becomes viral “sad girl” piano ballad generated by AI - “Permission is hereby granted” comes from Suno AI engine that creates new songs on demand. - link
+
AI hardware company from Jony Ive, Sam Altman seeks $1 billion in funding - A venture fund founded by Laurene Powell Jobs could finance the company. - link
+
FCC chair rejects call to impose Universal Service fees on broadband - New fees on broadband could cause “major upheaval,” FCC plan says. - link
+
+
From Jokes Subreddit
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+
Two idiots decided that they weren’t going anywhere in life and thought they should go to college to get ahead. The first goes in to see the counselor, who tells him to take Math, History, and Logic. -
+
+
+“What’s Logic?” the first idiot asks.
+
+
+The professor answers by saying, “Let me give you an example.”
+
+
+“Do you own a weedeater?”
+
+
+“I sure do.”
+
+
+“Then I can assume, using logic, that you have a yard,” replied the professor.
+
+
+“That’s real good!”
+
+
+The professor continues, “Logic will also tell me that since you have a yard, you also own a house.”
+
+
+Impressed, “Amazin!”
+
+
+“And since you own a house, logic dictates that you have a wife.”
+
+
+“That’s Betty Mae! This is incredible!” The idoit is obviously catching on.
+
+
+“Finally, since you have a wife, logically I can assume that you are heterosexual,” said the professor.
+
+
+“You’re absolutely right! Why that’s the most fascinatin’ thing I ever heard! I can’t wait to take that logic class!!”
+
+
+The idiot, proud of the new world opening up to him, walks back into the hallway, where his friend is still waiting.
+
+
+“So what classes are ya takin’?” asks the friend.
+
+
+“Math, History, and Logic!” he replies.
+
+
+“What in tarnation is logic???” asked his friend.
+
+
+“Let me give you an example. Do ya own a weedeater?” he asked.
+
+So I interviewed for another job. The interviewer said he was looking for someone who is responsible.
+
+
+I replied, “Well, I’m exactly who you want. At my previous job, whenever anything went wrong, they said I was responsible!”
+
+
+Somehow, I actually got the job. They said they could pay me $25/hr right now and increase it to $35/hr in 12 months. “So when can you start?” they asked.
+
+It’s up to his knees and he can’t get out. Finally he sees a guy walking his dog and shouts “Hey Mr, I’m stuck in this quick sand. Please help me get out”
+
+
+The dog walker says “I’ll get you out, no problem but first you go to suck my dick!”
+
+
+The guy says “what? Fuck off you dirty bastard”
+
+
+15 minutes later, the quick sand is now passed his hips. He sees a man riding a bike and shouts “Hey Mr, I’m stuck in this quick sand please help me get out”
+
+
+The cyclist says “sure, no problem but first you got to suck my dick”
+
+
+The guy says “wtf is wrong with you man, get the fuck out of here you dirty bastard!”
+
+
+20 minutes later, the quicksand is now up to the guys chin, he’s minutes away from dying. He finally sees a man jogging by and shouts “Mr, Mr…..please get me out of this quick sand. I’ll do anything, I’ll suck your dick, I’ll suck it so fucking good”
+
+
+The jogger says “fuck off your dirty bastard” and stomps his head under the sand.
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+/cdn.vox-cdn.com/uploads/chorus_asset/file/25379898/GettyImages_76955792.jpg)
Brian Ach/WireImage
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+/cdn.vox-cdn.com/uploads/chorus_asset/file/25375410/James_and_Jennifer_Crumbley.jpg)
Courtesy Detroit Police
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