GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern -
+
+Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
+
High throughput screening identifies broad-spectrum Coronavirus entry inhibitors -
+
+The Covid-19 pandemic highlighted the pressing need for antiviral therapeutics capable of mitigating infection and spread of emerging coronaviruses (CoVs). A promising therapeutic strategy lies in inhibiting viral entry mediated by the Spike (S) glycoprotein. To identify small molecule inhibitors that block entry downstream of receptor binding, we established a high-throughput screening (HTS) platform based on pseudoviruses. We employed a three-step process to screen nearly 200,000 small molecules. First, we identified potential inhibitors by assessing their ability to inhibit pseudoviruses bearing the SARS-CoV-2 S glycoprotein. Subsequent counter-screening against pseudoviruses with the Vesicular Stomatitis Virus spike glycoprotein (VSV-G), yielding sixty-five SARS-CoV-2 S-specific inhibitors. These were further tested against pseudoviruses bearing the MERS-CoV S glycoprotein, which uses a different receptor. Out of these, five compounds including the known broad-spectrum inhibitor Nafamostat, were subjected to further validation and tested them against pseudoviruses bearing the S glycoprotein of the alpha, delta, and omicron variants as well as against bona fide SARS-CoV-2 in vitro. This rigorous approach revealed a novel inhibitor and its derivative as a potential broad-spectrum antiviral. These results validate the HTS platform and set the stage for lead optimization and future pre-clinical, in vivo studies.
+
Identification and Analysis of SARS-CoV-2 Mutation and Subtype using 2x tiled Primer Set with Oxford Nanopore Technologies Sequencing for Enhanced Variant Detection and Surveillance in Seoul, Korea -
+
+Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that contains RNA as its genetic material and has caused a global pandemic since its outbreak in 2020. This virus has many mutations, some of which can reduce the effectiveness of existing vaccines. Therefore, next-generation sequencing (NGS) is necessary to accurately identify new mutations. Current NGS analysis of SARS-CoV-2 uses the amplicon analysis method through a multiplex polymerase chain reaction. This study collected and validated RNA samples from patients who tested positive for SARS-CoV-2 from April to July 2022, and selected 613 samples for sequencing. The findings demonstrate the importance of long-read-based NGS analysis and 2x tiled primer set for identifying full SARS-CoV-2 genome sequence with new mutations and understanding the correlation between viral genotypes and patient characteristics for the effective management of SARS-CoV-2.
+
Multi-variate statistical and machine learning reveals the interplay between sex and age in antibody responses to de novo SARS-CoV-2 infection and vaccination -
+
+Prevention of negative COVID19 infection outcomes and infection/vaccine-acquired immunity is associated with the quality of antibody responses, whose variance by age and sex are poorly understood. Integrated, network approaches, identified sex and age effects in antibody responses and neutralization potential of de novo infection and vaccination throughout the Covid-19 pandemic. Cluster analysis found neutralization values followed SARS-CoV-2 specific receptor binding RIgG, spike SIgG and S and RIgA levels based on COVID19 status. Stochastic behavior tests and other analytical methods revealed sex differences only in persons <40y.o. Serum IgA antibody titers correlated with neutralization only in females 40-60y.o. Network analysis found males could improve IgA responses after vaccination dose 2, unlike >60 y.o. females. Complex correlation analyses found vaccination induced less antibody isotype switching and neutralization in older persons, especially in females. Sex dependent antibody & neutralization behavior decayed fastest in older males and with vaccination. Such sex and age characterization by machine learning can direct studies integrating cell mediated responses to define yet elusive correlates of protection and inform age and sex precision-focused vaccine design.
+
Identification of key residues in MERS-CoV and SARS-CoV-2 main proteases for resistance against clinically applied inhibitors nirmatrelvir and ensitrelvir -
+
+The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an epidemic, zoonotically emerging pathogen initially reported in Saudi Arabia in 2012. MERS-CoV has the potential to mutate or recombine with other coronaviruses, thus acquiring the ability to efficiently spread among humans and become pandemic. Its high mortality rate of up to 35 % and the absence of effective targeted therapies call for the development of antiviral drugs for this pathogen. Since the beginning of the SARS-CoV-2 pandemic, extensive research has focused on identifying protease inhibitors for the treatment of SARS-CoV-2. Our intention was therefore to assess whether these protease inhibitors are viable options for combating MERS-CoV. To that end, we used previously established protease assays to quantify inhibition of the SARS-CoV-2 and MERS-CoV main proteases. Furthermore, we selected MERS-CoV-Mpro mutants resistant against nirmatrelvir, the most effective inhibitor of this protease, with a safe, surrogate virus-based system, and suggest putative resistance mechanisms. Notably, nirmatrelvir demonstrated effectiveness against various viral proteases, illustrating its potential as a broad-spectrum coronavirus inhibitor. To adress the inherent resistance of MERS-CoV-Mpro to ensitrelvir, we applied directed mutagenesis to a key ensitrelvir-interacting residue and provided structural models.
+
Sex-Specific Systemic Inflammatory Responses in Mice Infected with a SARS-CoV-2-like Virus and Femur Fracture -
+
+This study investigates the systemic inflammatory response in mice infected with a murine coronavirus (MHV), which shares a common genus with SARS-CoV-2, and sustaining a fracture. The study reveals that the combined inflammatory incidents of MHV infection and fracture disrupt the systemic immune response in both female and male mice, likely leading to immune dysregulation, altered cell recruitment, and disruption of the typical inflammatory cascade. Notably, the study uncovers sex-specific responses that modulate circulating immune factors. Females exhibit elevated levels of inflammatory factors, whereas males demonstrate a diminished response. This divergence is mirrored in cell populations, suggesting that the quantity of immune factors released may contribute to these discrepancies. The findings suggest that an overproduction of proinflammatory cytokines may induce a dysregulated immune response, contributing to the observed poorer prognosis in comorbid cases. These insights could pave the way for therapeutic advancements and treatment strategies aimed at reducing mortality rates in COVID-19 patients with fractures.
+
In field use of water samples for genomic surveillance of ISKNV infecting tilapia fish in Lake Volta, Ghana -
+
+Viral outbreaks are a constant threat to aquaculture, limiting production for better global food security. A lack of diagnostic testing and monitoring in resource-limited areas hinders the capacity to respond rapidly to disease outbreaks and to prevent viral pathogens becoming endemic in fisheries productive waters. Recent developments in diagnostic testing for emerging viruses, however, offers a solution for rapid in situ monitoring of viral outbreaks. Genomic epidemiology has furthermore proven highly effective in detecting viral mutations involved in pathogenesis and assisting in resolving chains of transmission. Here, we demonstrate the application of an in-field epidemiological tool kit to track viral outbreaks in aquaculture on farms with reduced access to diagnostic labs, and with non-destructive sampling. Inspired by the "lab in a suitcase" approach used for genomic surveillance of human viral pathogens and wastewater monitoring of COVID19, we evaluated the feasibility of real-time genome sequencing surveillance of the fish pathogen, Infectious spleen and kidney necrosis virus (ISKNV) in Lake Volta. Viral fractions from water samples collected from cages holding Nile tilapia (Oreochromis niloticus) with suspected ongoing ISKNV infections were concentrated and used as a template for whole genome sequencing, using a previously developed tiled PCR method for ISKNV. Mutations in ISKNV in samples collected from the water surrounding the cages matched those collected from infected caged fish, illustrating that water samples can be used for detecting predominant ISKNV variants in an ongoing outbreak. This approach allows for the detection of ISKNV and tracking of the dynamics of variant frequencies, and may thus assist in guiding control measures for the rapid isolation and quarantine of infected farms and facilities.
+
+The outbreak of COVID-19 exposed the inadequacy of our technical tools for home health surveillance, and recent studies have shown the potential of smartphones as a universal optical microscopic imaging platform for such applications. However, most of them use laboratory-grade optomechanical components and transmitted illuminations to ensure focus tuning capability and imaging quality, which keeps the cost of the equipment high. Here we propose an ultra-low-cost solution for smartphone microscopy. To realize focus tunability, we designed a seesaw-like structure capable of converting large displacements on one side into small displacements on the other (reduced to [~]9.1%), which leverages the intrinsic flexibility of 3D printing materials. We achieved a focus-tuning accuracy of [~] 5 m, which is 40 times higher than the machining accuracy of the 3D-printed lens holder itself. For microscopic imaging, we use an off-the-shelf smartphone camera lens as the objective and the built-in flashlight as the illumination. To compensate for the resulting image quality degradation, we developed a learning-based image enhancement method. We use the CycleGAN architecture to establish the mapping from smartphone microscope images to benchtop microscope images without pairing. We verified the imaging performance on different biomedical samples. Except for the smartphone, we kept the full costs of the device under 4 USD. We think these efforts to lower the costs of smartphone microscopes will benefit their applications in various scenarios, such as point-of-care testing, on-site diagnosis, and home health surveillance.
+
Social isolation, mental health, and use of digital interventions in youth during the COVID-19 pandemic: a nationally representative survey -
+
+Summary Background: Public health measures to curb SARS-CoV-2 transmission rates may have negative psychosocial consequences in youth. Digital interventions may help to mitigate these effects. We investigated the associations between social isolation, cognitive preoccupation, worries, and anxiety, objective social risk indicators, psychological distress as well as use of, and attitude towards, mobile health (mHealth) interventions in youth during the COVID-19 pandemic. Methods: Data were collected as part of the âMental Health And Innovation During COVID-19 Surveyâ âa cross-sectional panel study including a representative sample of individuals aged 16 to 25 years (N=666; Mage 21·3) (assessment period: 07.05.-16.05.2020). Outcomes: Overall, 38% of youth met criteria for moderate psychological distress and 30% felt âoftenâ or âvery oftenâ socially isolated, even after most restrictive infection control measures had been lifted. Social isolation, COVID-19-related worries and anxiety, and objective risk indicators were associated with psychological distress, with evidence of dose-response relationships for some of these associations. For instance, psychological distress was progressively more likely to occur as levels of social isolation increased (reporting âneverâ as reference group: âoccasionallyâ: adjusted odds ratio [aOR] 9·1, 95% confidence interval [CI] 4·3 â 19·1, p<0·001; âoftenâ: aOR 22·2, CI 9·8 â 50·2, p<0·001;âvery oftenâ: aOR 42·3, CI 14·1 â 126·8, p<0·001). There was evidence that psychological distress, worries, and anxiety were associated with a positive attitude towards using digital interventions, whereas high levels of psychological distress, worries, and anxiety were associated with actual use. Interpretation: Public health measures during pandemics may be associated with poor mental health in youth. Digital interventions may help mitigate the negative psychosocial impact given there is an objective need and subjective demand.
+
Zheln.com: A protocol for a universal living overview of health-related systematic reviews -
+
+BACKGROUND Objectives. 1. Identify and monitor most of published systematic reviews. 2. Tag the identified systematic records with medical specialties. 3. Select or crowdfund reviews for further appraisal. 4. Critically appraise and replicate the selected systematic reviews. 5. Disseminate practice implications of positively appraised reviews to both the public and evidence-based practitioners in health care and other fields associated with intervention into a human life, such as education, business, policy, or ecology. METHODS Eligibility criteria. Record eligibility is assessed by checking the record title and, if the title failed, abstract against the âtrue positive criteriaâ for systematic reviews taken from the publication by Shojania & Bero, 2001 (PMID 11525102). The record/study flow is as follows: All eligible records are amenable for tagging, selection, and crowdfunding process; Only those eligible records that have been selected or crowdfunded are subject to critical appraisal; For all records that have been selected, all relevant reports are collected; Reports are grouped into studies; Only for the studies appraised positively, practical implications are summarized and disseminated. COVID-19 publications are not selected. Crowdfunding an appraisal of any eligible record is possible for any individual or organization. Information sources. MEDLINE via PubMed. Adding other search sources, such as Scopus, OSF, and medRxiv, is planned in the future when more appraisers become available. The Replicated Version of the PubMed Systematic Review Subset Query Zheln Edition (DOI 10.17605/OSF.IO/Z3JU7) will be used. The searches are run daily. Risk of bias. Critical appraisal will feature: Duplication assessment; Replication; Assessment against the MECIR conduct standards; ROB-ME assessment; GRADE assessment. Synthesis of results. No across-studies synthesis is planned. Within-studies, I will formulate explicit practice-relevant statements based on the extracted health outcomes and quality-of-conduct assessment. Also, the process of each critical appraisal is video-recorded and published on YouTube daily. OTHER Funding. The review is crowdfunded; the details are available from the Zheln website (https://zheln.com). Crowd funders had no role in the design of the protocol. They will be able to request critical appraisal and additional critical appraisal (with new data provided) of any eligible record but will not influence the review process otherwise. Registration. The project is hosted on GitHub. Also, there is an umbrella Open Science Framework project that links repositories and preprints (DOI 10.17605/OSF.IO/EJKFC). The protocol for this overview of systematic reviews has been submitted for registration in PROSPERO.
+
Failure to protect: COVID infection control policy privileges poor-quality evidence -
+
+The failure to immediately recognize the urgent need to control airborne spread of COVID-19, including use of adequate personal protective equipment for an airborne pathogen, represents a major medical error that cost âan enormous number of livesâ. Made in the face of significant scientific evidence and a clear requirement to adhere to a precautionary approach, it has still not been fully remedied. To understand the substantial, ongoing gap between science and policy, we carried out an in-depth investigation of an illustrative publication authored by prominent authorities in the fields of Public Health and Infection Prevention and Control, describing a trial of medical masks and N95 respirators for the prevention of COVID-19. Although it was portrayed as among the highest quality evidence available within the Evidence-Based Medicine decision-making paradigm, we found this work to be deeply flawed to the extent that it does not meet basic standards of scientific rigour. Extensive prior work in the respiratory protection field â sufficiently well-established to be incorporated into both national standards and specific recommendations made to address infection control failures in SARS â was ignored. Randomization was compromised, with a statistically significant correlation between female sex and allocation to the higher-risk arm of the trial. Significant conflicts of interest in favour of the reported finding that medical masks are noninferior to N95 respirators in preventing COVID-19 transmission were not disclosed. Prespecified analyses were omitted, and the finding of noninferiority is entirely a product of inappropriate alterations to the trial that were not prospectively registered. Despite numerous flaws biasing the outcome towards a finding of noninferiority, re-analysis using the prespecified approach and noninferiority criterion unambiguously reverses the reported outcome of the trial.
+
The Last Confirmed Case is Not the Last Infection and Catastrophic Outbreaks do Not Require Transmission -
+
+Efforts to prevent transmission of the infectious agent that causes an infectious disease in its capacity as a pathogen are praised and victory is declared after the last case of the expected outcomes of the event in which this disease occurs is confirmed. After all, it is assumed that such expected outcomes of the event in which the pathogen causes the infectious disease are manifestations of this disease and therefore that the last confirmed case in which such outcomes are observed is the last case of infection. But the results obtained while forging the path to immunological concepts which have eluded us since the birth of the repeatedly proven germ theory with the method by which Einstein approximated astronomical reality conceptually while developing General Relativity reveal that outcomes of the event in which the pathogen causes the infectious disease are not manifestations of this disease but rather consequences of the comanifestation of different diseases in the spectrum of the infectious disease. These results enable us to account for the differences between such outcomes which, for instance, in patients with COVID-19 that the current theory of infectious disease pathogenesis expects to produce outcomes that affect the upper respiratory disease, include unexpected conditions such as the chronic ones seen in Long COVID patients and in patients with mpox, which this theory logically deduced to be a skin-affecting disease, include deadly conditions like encephalitis with the consequence that outcomes with such deadly conditions are attributed to underlying conditions even after Spainâs health ministry reported deaths from such outcomes in healthy individuals. And the consequence of the same results is that the last cases of expected outcomes such as those that affect the skin of individuals who are infected with the mpox virus are not the last cases of infection but rather the last cases in which such outcomes appear as the sterile causes of the non-infectious diseases that co-manifest with the infectious disease for the emergence of such outcomes disappear from the population in which undetected spread of the infectious agent occurred long before the widespread appearance of such expected outcomes that called attention to this pathogen or an earlier form of the pathogen, such as the smallpox virus, which is assumed to have been eradicated. It follows in the reality which was visualized to obtain these results that even as the disappearance of such outcomes is being celebrated, the sterile causes of non-infectious diseases which co-manifest with the infectious disease for the emergence of unexpected deadly outcomes, such as those with encephalitis and toxic shock, may be appearing in the population which is already harboring the pathogen silently. And without exciting cause or warning, such deadly outcomes will become widespread in our populations and will decimate them if the only treatments available at the time are still those that reduce viral replication which are unable to bring about the remission of such outcomes. Instead of celebrating the disappearance of cases when the sterile causes of the non-infectious diseases that co-manifest with mpox for the emergence of those expected skin-affecting outcomes disappear, we ought to quickly elucidate the conditions that permit the immunological mechanisms of infection and vaccination to bring about uneventful exposure to such sterile causes even after deadly outcomes of such events have already appeared as achieved, in some cases, by the vaccines of William Coley and Julius Wagner-Jauregg even at a time when nothing was known about the nature of such immunological mechanisms and the remission that followed therapeutic infection in such cases was attributed to fever.
+
Genome-wide Bioinformatics Analysis of Human Protease Capacity for Proteolytic Cleavage of the SARS-CoV-2 Spike Glycoprotein -
+
+The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily enters the cell by binding the virusâs spike (S) glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface, followed by proteolytic cleavage by host proteases. Studies have identified furin and TMPRSS2 proteases in priming and triggering cleavages of the S glycoprotein, converting it into a fusion-competent form and initiating membrane fusion, respectively. Alternatively, SARS-CoV-2 can enter the cell through the endocytic pathway, where activation is triggered by lysosomal cathepsin L. However, other proteases are also suspected to be involved in both entry routes. In this study, we conducted a genome-wide bioinformatics analysis to explore the capacity of human proteases in hydrolyzing peptide bonds of the S glycoprotein. Predictive models of sequence specificity for 169 human proteases were constructed and applied to the S glycoprotein together with the method for predicting structural susceptibility to proteolysis of protein regions. After validating our approach on extensively studied S2â and S1/S2 cleavage sites, we applied our method to each peptide bond of the S glycoprotein across all 169 proteases. Our results indicate that various members of the PCSK, TTSP, and kallikrein families, as well as specific coagulation factors, are capable of cleaving S2â or S1/S2 sites. We have also identified a potential cleavage site of cathepsin L at the K790 position within the S2â loop. Structural analysis suggests that cleavage of this site induces conformational changes similar to the cleavage at the R815 (S2â) position, leading to the exposure of the fusion peptide and subsequent fusion with the membrane. Other potential cleavage sites and the influence of mutations in common SARS-CoV-2 variants on proteolytic efficiency are discussed.
+
Murine Alveolar Macrophages Rapidly Accumulate Intranasally Administered SARS-CoV-2 Spike Protein leading to Neutrophil Recruitment and Damage -
+
+The trimeric SARS-CoV-2 Spike protein mediates viral attachment facilitating cell entry. Most COVID-19 vaccines direct mammalian cells to express the Spike protein or deliver it directly via inoculation to engender a protective immune response. The trafficking and cellular tropism of the Spike protein in vivo and its impact on immune cells remains incompletely elucidated. In this study we inoculated mice intranasally, intravenously, and subcutaneously with fluorescently labeled recombinant SARS-CoV-2 Spike protein. Using flow cytometry and imaging techniques we analyzed its localization, immune cell tropism, and acute functional impact. Intranasal administration led to rapid lung alveolar macrophage uptake, pulmonary vascular leakage, and neutrophil recruitment and damage. When injected near the inguinal lymph node medullary, but not subcapsular macrophages, captured the protein, while scrotal injection recruited and fragmented neutrophils. Wide-spread endothelial and liver Kupffer cell uptake followed intravenous administration. Human peripheral blood cells B cells, neutrophils, monocytes, and myeloid dendritic cells all efficiently bound Spike protein. Exposure to the Spike protein enhanced neutrophil NETosis and augmented human macrophage TNF- and IL-6 production. Human and murine immune cells employed C-type lectin receptors and Siglecs to help capture the Spike protein. This study highlights the potential toxicity of the SARS-CoV-2 Spike protein for mammalian cells and illustrates the central role for alveolar macrophage in pathogenic protein uptake.
+
Gut microbiome remains stable following COVID-19 vaccination in healthy and immuno-compromised individuals -
+
+The bidirectional interaction between the immune system and the gut microbiota is a key contributor to various host physiological functions. Immune-associated diseases such as cancer and autoimmunity, as well as the efficacy of immunomodulatory therapies, have been linked to microbiome variation. While COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunomodulating therapies. We find that the gut microbiome remained remarkably stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results indicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings encourage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.
+
Community Care Intervention to Decrease COVID-19 Vaccination Inequities - Conditions: COVID-19 Vaccination Interventions: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) Sponsors: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) Recruiting
+
PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED - Conditions: COVID-19 Interventions: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question Sponsors: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University Not yet recruiting
+
Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos - Conditions: Vaccine Hesitancy Interventions: Behavioral: Multilevel Intervention Sponsors: San Diego State University Not yet recruiting
+
Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID Syndrome: A Randomized Controlled Trial - Conditions: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment Interventions: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care Sponsors: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH) Not yet recruiting
+
Stem Cell Study for Long COVID-19 Neurological Symptoms - Conditions: Post-Acute COVID-19 Syndrome Interventions: Biological: Stem Cell Sponsors: Charles Cox; CBR Systems, Inc. Not yet recruiting
+
Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial - Conditions: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue Interventions: Other: COVIDEx Sponsors: Lawson Health Research Institute; Western University Not yet recruiting
+
Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents - Conditions: Long COVID Interventions: Drug: Metformin; Other: Placebo Sponsors: Trust for Vaccines and Immunization, Pakistan Not yet recruiting
+
A Randomized Trial Evaluating a mRNA VLP Vaccineâs Immunogenicity and Safety for COVID-19 - Conditions: COVID-19; SARS-CoV-2 Infection Interventions: Biological: AZD9838; Biological: Licensed mRNA vaccine Sponsors: AstraZeneca Not yet recruiting
+
âThe Effect of Aerobic Exercise and Strength Training on Physical Activity Level, Quality of Life and Anxiety-Stress Disorder in Young Adults With and Without Covid-19â - Conditions: COVID-19 Interventions: Behavioral: Aerobic Exercise and Strength Training Sponsors: Pamukkale University Active, not recruiting
+
Vale+TĂș Salud: Corner-Based Randomized Trial to Test a Latino Day Laborer Program Adapted to Prevent COVID-19 - Conditions: COVID-19 Interventions: Behavioral: COVID-19 Group Problem Solving; Behavioral: Standard of Care; Behavioral: Booster session Sponsors: The University of Texas Health Science Center, Houston; National Institute on Minority Health and Health Disparities (NIMHD) Recruiting
+
Safety Study of SLV213 for the Treatment of COVID-19. - Conditions: COVID-19 Interventions: Other: Placebo for SLV213; Drug: SLV213 Sponsors: National Institute of Allergy and Infectious Diseases (NIAID) Not yet recruiting
+
Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine - Conditions: SARS CoV 2 Infection Interventions: Diagnostic Test: RIPH2 Sponsors: CerbaXpert Not yet recruiting
+
+
From PubMed
+
+
Phase IIÂ study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19 - CONCLUSION: Our results suggest a potential role for bemnifosbuvir in blunting COVID-19 progression.
+
Molecular mechanisms of dexamethasone actions in COVID-19: Ion channels and airway surface liquid dynamics - The COVID-19 pandemic has been a global health crisis of unprecedented magnitude. In the battle against the SARS-CoV-2 coronavirus, dexamethasone, a widely used corticosteroid with potent anti-inflammatory properties, has emerged as a promising therapy in the fight against severe COVID-19. Dexamethasone is a synthetic glucocorticoid that exerts its therapeutic effects by suppressing the immune system and reducing inflammation. In the context of COVID-19, the severe form of the disease is oftenâŠ
+
Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma - CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.
+
Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection - The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus disease (COVID-19) is ongoing. Therefore, effective prevention of virus infection is required. Pyrroloquinoline quinone (PQQ), a natural compound found in various foods and human breast milk, plays a role in various physiological processes and is associated with health benefits. In this study, we aimed to determine the effects of PQQ on preventing coronavirus infections using a proxy Feline InfectiousâŠ
+
Dobrava hantavirus and coinciding SARS-CoV-2 infection mimicking thrombotic microangiopathy and responding to a single dose of eculizumab - The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has refocused scientific interest on gaining insight into the pathophysiology of systemic viral diseases. Complement activation has been characterized as a driver of endothelial injury and microvascular thrombosis in acute respiratory distress syndrome as well as hantavirus hemorrhagic fever with renal syndrome. On this occasion, we wish to report a case of severe hantavirus disease with coinciding SARS-CoV-2âŠ
+
Cardiovascular safety pharmacology of ivermectin assessed using the isoflurane-anesthetized beagle dogs: ICH S7B follow-up study - Antiparasitic ivermectin has been reported to induce cardiovascular adverse events, including orthostatic hypotension, tachycardia and cardiopulmonary arrest, of which the underlying pathophysiology remains unknown. Since its drug repurposing as an antiviral agent is underway at higher doses than those for antiparasitic, we evaluated the cardiovascular safety pharmacology of ivermectin using isoflurane-anesthetized beagle dogs (n=4). Ivermectin in doses of 0.1 followed by 1 mg/kg wasâŠ
+
Ligand concentration determines antiviral efficacy of silica multivalent nanoparticles - We have learned from the recent COVID-19 pandemic that the emergence of a new virus can quickly become a global health burden and kill millions of lives. Antiviral drugs are essential in our fight against viral diseases, but most of them are virus-specific and are prone to viral mutations. We have developed broad-spectrum antivirals based on multivalent nanoparticles grafted with ligands that mimic the target of viral attachment ligands (VALs). We have shown that when the ligand has aâŠ
+
Broad-spectrum antiviral activity of two structurally analogous CYP3A inhibitors against pathogenic human coronaviruses in vitro - Coronaviruses pose a permanent risk of outbreaks, with three highly pathogenic species and strains (SARS-CoV, MERS-CoV, SARS-CoV-2) having emerged in the last twenty years. Limited antiviral therapies are currently available and their efficacy in randomized clinical trials enrolling SARS-CoV-2 patients has not been consistent, highlighting the need for more potent treatments. We previously showed that cobicistat, a clinically approved inhibitor of Cytochrome P450-3A (CYP3A), has direct antiviralâŠ
+
Protection effects of mice liver and lung injury induced by coronavirus infection of Qingfei Paidu decoction involve inhibition of the NLRP3 signaling pathway - CONCLUSIONS: To sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.
+
A broadly reactive antibody targeting the N-terminal domain of SARS-CoV-2 spike confers Fc-mediated protection - Most neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells. One neutralizing NTD mAb, SARS2-57, protects K18-hACE2 mice against SARS-CoV-2 infection in an Fc-dependent manner. Structural analysisâŠ
+
Chemical Composition of Thyme (Thymus vulgaris) Extracts, Potential Inhibition of SARS-CoV-2 Spike Protein-ACE2 Binding and ACE2 Activity, and Radical Scavenging Capacity - Water and ethanol extracts of dried thyme (Thymus vulgaris) were analyzed for chemical composition, inhibition of the SARS-CoV-2 spike protein-ACE2 interaction, inhibition of ACE2 activity, and free radical scavenging capacity. Thirty-two compounds were identified in water extract (WE) and 27 were identified in ethanol extract (EE) of thyme through HPLC-MS. The WE (33.3 mg/mL) and EE (3.3 mg/mL) of thyme inhibited the spike protein-ACE2 interaction by 82.6 and 86.4%, respectively. The thyme WEâŠ
+
Pre-pandemic Executive Function Protects Against Pandemic Anxiety in Children with and Without Autism Spectrum Disorder - The COVID-19 pandemic may have exacerbated depression, anxiety, and executive function (EF) difficulties in children with autism spectrum disorder (ASD). EF skills have been positively associated with mental health outcomes. Here, we probed the psychosocial impacts of pandemic responses in children with and without ASD by relating pre-pandemic EF assessments with anxiety and depression symptoms several months into the pandemic. We found that pre-pandemic inhibition and shifting difficulties,âŠ
+
Implementing PCR testing in general practice-a qualitative study using normalization process theory - CONCLUSION: In its current form, the added diagnostic value of using POC PCR testing in general practice was not sufficient for the professionals to justify the increased work connected to the usage of the diagnostic procedure in daily practice.
+
Inhibition of bradykinin in SARS-CoV-2 infection: a randomised, double-blind trial of icatibant compared with placebo (ICASARS) - SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently by a lymphocytic pneumonitis. Coagulopathy, thrombosis and hypotension occur. Worse disease occurs with age, obesity, ischaemic heart disease, hypertension and diabetes.These features may be due to abnormal activation of the contact system. This triggers coagulation and the kallikrein-kininâŠ
+
Antiviral peptides inhibiting the main protease of SARS-CoV-2 investigated by computational screening and in vitro protease assay - The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in viral replication and transcription and received great attention as a vital target for drug/peptide development. Therapeutic agents such as small-molecule drugs or peptides that interact with the Cys-His present in the catalytic site of Mpro are an efficient way to inhibit the protease. Although several emergency-approved vaccines showed good efficacy and drastically dropped theâŠ
+
+
From Patent Search
+
+
+
\ No newline at end of file
diff --git a/archive-daily-dose/06 December, 2023.html b/archive-daily-dose/06 December, 2023.html
new file mode 100644
index 0000000..1f775f0
--- /dev/null
+++ b/archive-daily-dose/06 December, 2023.html
@@ -0,0 +1,408 @@
+
+
+
+
+
+ 06 December, 2023
+
+Daily-Dose
+
+
The Lessons of Pandemic Inflation - As the inflation rate continues to fall, a new White House study emphasizes the central role that supply-chain disruptions have played in the economy. - link
+
Donald Trumpâs Latino Campaign Begins - Democrats fear that Univision has turned to the right, but the network may be the least of their problems. - link
+
The Difference That Sandra Day OâConnor Made - The late Supreme Court Justice had a keen feeling for the real-world impact of the Courtâs decisions. - link
+
Why Ron DeSantis Doesnât Have a Prayer in Iowa - The Florida governor has won the backing of the stateâs political establishmentâand the electorate has always been skeptical of Trump. So what went wrong? - link
+
Columbia Suspended Pro-Palestine Student Groups. The Faculty Revolted - Like other universities, the school has cracked down on activism among students, citing fears of antisemitism. Some professors think itâs gone too far. - link
+
+
From Vox
+
+
The Israel-Hamas war is tearing American cultural institutions apart -
+
+
+
+In October, 92NY, one of New Yorkâs best-known arts and culture spaces, drew fire after trying to postpone a visit from author Viet Thanh Nguyen. Nguyen had signed an open letter criticizing Israelâs actions in Gaza. | Noam Galai/Getty Images
+
+
+
+Artists are protesting Israelâs offensive. The art and literary worlds are struggling to respond.
+
+The war between Israel and Hamas is roiling the arts and literary worlds. The death toll in Gaza, which has surpassed 15,500 people, according to the Gaza Health Ministry, has compelled thousands of artists and writers to speak out against Israelâs military actions and the institutions they think are failing to meet the moment. Many are accusing organizations of trying to suppress the speech of people critical of Israel and are demanding that institutions issue public statements about where they stand. The artists and writers, in turn, are facing backlash from organizations, donors, and other artists, who see a failure to appropriately acknowledge the victims of Hamasâs terrorist attack on October 7 and the rise in global antisemitism since the conflict began.
+
+
+The conflict is forcing leaders to navigate larger existential questions about the power and limits of arts institutions at this moment, including whether museums should try to stay neutral or whether they should take an active role in responding to political and social issues. These questions arenât entirely new, but theyâve taken on a new sense of urgency amid current politics and deepening polarization since 2016, experts say.
+
+
+âGalleries, museums, curators, and the people who are in charge of art programs have become much more invested in the idea that institutions and artworks have a political or a social function,â says JJ Charlesworth, an art critic and editor at ArtReviewmagazine. âThe idea of the art gallery as some kind of special or isolated separate space is, I think, very out of fashion. Itâs causing friction now because, particularly in America, the interests that support cultural institutions donât always share the same politicsâ as the artists.
+
+
+How museums are navigating broader cultural changes
+
+Museums are, in some ways, responding to larger societal shifts, including the expectation that they more accurately reflect the diversity of the communities they are a part of. They also have to consider how to stay relevant in a world where thereâs more media and culture competing for their visitorsâ attention.
+
+
+Balancing the need to be current, especially in the midst of major political moments, is tricky, says Mary Elizabeth Williams, a former museum professional whoâs written about how museums should approach political activism and protest art. âAs people become more divided in the United States, thereâs voices calling for action, but museums need to balance that and find a way to engage in their communities but not alienate certain members of the population.â Cultural organizations risk losing funders and even their nonprofit status if they make the wrong move, she says.
+
+
+Decisions about whether and when to show controversial work can also be difficult. The wrong move can reflect poorly on an institution, both in the moment and for decades to come. The Corcoran Gallery in Washington, DC, faced public backlash for decades over canceling a 1989 show by photographer Robert Mapplethorpe, who was gay, due to fear that anti-gay lawmakers would attack it for its themes and depictions of male sexuality. The decision by four major museums to delay a retrospective by the Jewish painter Philip Guston in 2020 because some of his paintings featured cartoonish, unglamorous depictions of white-hooded Klansmen, similarly invited widespread criticism.
+
+
+ Getty Images
+
+Interior Secretary Deb Haaland tours âThe Land Carries Our Ancestors: Contemporary Art by Native Americansâ exhibition at the National Gallery of Art in September. The following month, two artists pulled their work from the long-awaited exhibit, citing US military aid to Israel as the reason.
+
+
+
+Why artists and writers are protesting over the war
+
+
+Amid the Israel-Hamas war, museums are once again getting blowback for canceling events and not displaying artwork they fear will bring unwanted attention. Manhattanâs El Museo del Barrio was denounced by artists in late October for deciding not to show a piece prominently featuring the Palestinian flag. Leadership at the Frick Pittsburgh, an art museum in Pennsylvania, was called out after postponing an upcoming Islamic art exhibition. The museum director initially told the press that they realized the exhibition âfor many people, especially in our community, would be traumatic.â After Muslim and Jewish groups criticized the decision, the Frick said in a separate statement that it postponed the show because it hadnât prepared it with their âcharacteristic engagement with broad community partners, in this case the Pittsburgh Muslim community.â
+
+Laura Raicovich, author of Culture Strike: Arts and Museums in an Age of Protest and former director of the Queens Museum, says that museums have never been purely neutral spaces, but rather are always reflections of a societyâs cultural values, norms, and power structures. Itâs the divergence between the lived experiences of museum workers and artists, and the collectors, dealers, and institutions that support them â and who tend to be wealthier â thatâs becoming more difficult to ignore.
+
+
+âAs the work within the museum has come under pressure to be more reflective of larger society, it gets further away from the lives of many of the people serving on the board, so thereâs a widening of the gap,â Raicovich says. âThe museum director ends up being the translator between the two, oftentimes the protector between one and the other. Theyâre supposed to negotiate the space. That is really impossible. Itâs just too big of a gap.â
+
+
+The literary world is grappling with similar debates. Organizers of the Frankfurt Book Fair in Germany drew sharp rebuke in October for postponing an awards ceremony for the Palestinian writer Adania Shibli. In November, more than 2,000 poets and writers signed an open letter pledging to boycott the Poetry Foundation, a nonprofit that publishes Poetry magazine, after writer Joshua Gutterman Tranen said that a review heâd written had been âshelvedâ because of its anti-Zionist themes.
+
+
+âCultural institutions have long benefitted from the brilliant work of writers and artists who have put their hearts and lives on the line to tell their stories,â Noor Hindi, a Palestinian American poet who co-authored the letter, told Vox in a statement. âWe are serving them, not the other way around ⊠These institutions and publications make a mockery of our work, our names, and our histories when they refuse to take a stand as our governments endorse, arm, and fund the oppression of our people.â
+
+
+A spokesperson for the Poetry Foundation disputed the idea that it tried to silence a writer for political reasons, calling it âmisinformation.â The spokesperson told Vox, âThis led to the current boycott, as well as something that foundation staff were hoping to avoid in the first place: pulling attention away from the people and organizations sharing news and resources about the crisis.â
+
+
+For Jewish cultural institutions that have historically supported Israel, the conflict is making it difficult to continue operating. In October, 92NY, one of New York Cityâs premier art and cultural spaces, tried to postpone an event with Viet Thanh Nguyen, the Pulitzer-Prize winning Vietnamese American author, over his public statements on the crisis, including signing a letter that cited an Israeli historian calling the Israeli governmentâs actions in Gaza âa textbook case of genocide.â âWe are a Jewish institution that has always welcomed people with diverse viewpoints to our stage,â the organization said in a statement. âThe brutal Oct. 7 attack by Hamas on Israel ⊠has absolutely devastated the community. Given the public comments by the invited author on Israel and this moment, we felt the responsible course of action was to postpone the event while we take some time to determine how best to use our platform and support the entire 92NY community.â
+
+
+The event happened anyway, at a nearby bookstore, but the fallout was substantial. Employees of the 92NYâs poetry center resigned in protest, and other writers pulled out of upcoming events. The organization has since announced that its literary series is on hold while it considers its next steps.
+
+
+Open letters of protest are everywhere â not without consequence
+
+
+In addition to the open letter to the Poetry Foundation, and the one signed by Nguyen and Irish novelist Sally Rooney, a group of over 1,800 Jewish writers, including Naomi Klein and Tavi Gevinson, published a letter in early November disavowing the idea that criticism of Israel was inherently antisemitic. Another group, Writers Against The War On Gaza, have issued a statement of solidarity with the Palestinian people and in âopposition to the silencing of dissent and to racist and revisionist media cycles.â They are joined in open-letter writing by authors who have participated in the Palestine Festival of Literature, scholars who have studied Palestine and Israel, and members of the media criticalof Israelâs killing of journalists and the way US-based news outlets have covered the conflict.
+
+
+They go in the other direction, too: In October, a group of Israeli authors and academics penned a letter excoriating the left in the US and around the world for what they say is a failure to appropriately condemn the violence perpetrated against Israeli civilians by Hamas.
+
+
+The letters are proving consequential, as prominent figures resign or are fired because of their association. David Velasco, the editor-in-chief of the magazine Artforum, was fired in late October for publishing an open letter on the magazineâs website signed by hundreds of members of the arts community, which called for an immediate ceasefire and said there was âample evidence that we are witnessing the unfolding of a genocide.â Artforumâspublishers, in an update posted to the site, said that the letter, âwas misinterpreted as being reflective of the magazineâs position [and] understandably led to significant dismay among our readers and community, which we deeply regret. It also put members of our team in the untenable position of being represented by a statement that was not uniformly theirs.â Velasco told the Timeshe had âno regrets,â and at least four staffers resigned in protest.
+
+
+How the art and literary worlds will move forward after these major rifts is an open question. So many artists and writers have made it clear where they stand. Leadership of the cultural institutions theyâre associated with, who have to weigh a different set of concerns, meanwhile, may not be willing, or even capable, of meeting them in this moment.
+
+
+âIt would be great if museums didnât have to think about donors, or funding, or their status,â Williams says. âBut thatâs just the reality that we live in.â
+
+
+
+
+
+
Whatâs inside this crater in Madagascar? -
+
+
+
+
+On satellite imagery, we spotted a village inside a strange crater in Madagascar. We set out to learn how it got there.
+
+
+Right in the center of the island nation of Madagascar thereâs a strange, almost perfectly circular geological structure. It covers a bigger area than the city of Paris â and at first glance, it looks completely empty. But right in the center of that structure, thereâs a single, isolated village: a few dozen houses, some fields of crops, and dirt roads stretching out in every direction.
+
+
+When we first saw this village on Google Earth, its extreme remoteness fascinated us. Was the village full of people? How did they wind up there? And what did life look like in such a place? To find out, we teamed up with a local crew in Madagascar and fell down a rabbit hole of geology and mapping along the way. Itâs a story of how continental shifts and volcanic geology came together to form a place for a group of people to call home.
+
Billionaires had a surprisingly bad day in the Supreme Court today -
+
+
+
+Senator Elizabeth Warren (D-MA) is a leading proponent of taxing very rich peopleâs assets. | Getty Images
+
+
+
+Even this very conservative Court appears reluctant to blow up the federal governmentâs power to tax rich people.
+
+
+The Supreme Court spent much of Tuesday morning beating up Andrew Grossman, a lawyer asking the justices to revive a long-defunct limit on Congressâs ability to levy taxes.
+
+
+The case Grossman was arguing, Moore v. United States, is widely viewed as a preemptive strike on wealth taxes â that is, taxes that target the stockpiled wealth of very rich people and that donât simply tax the income rich people earn off of their wealth.
+
+
+During her 2020 presidential campaign, Sen. Elizabeth Warren (D-MA) proposed a 2 percent wealth tax on Americans worth over $50 million, but neither Warrenâs proposed tax nor anything similar has ever become law, and thereâs no chance that it will become law so long as Republicans control at least one house of Congress.
+
+
+In any event, most of the justices appeared extraordinarily skeptical of Grossmanâs arguments, and of the idea that the Court should revive a long-discredited limit on the federal governmentâs taxing power which the Court briefly embraced during its Lochner Era â an age where the justices regularly signed onto dubious legal arguments that protected capital from taxes and from workplace regulation.
+
+
+Only Justices Samuel Alito and Neil Gorsuch appeared to have any sympathy at all for Grossmanâs attacks on Congressâs power to tax investors. And, while both men threw a barrage of hostile questions at Solicitor General Elizabeth Prelogar, Alito and Gorsuchâs colleagues seemed uninterested in humoring them.
+
+
+At one point, Justice Brett Kavanaugh, a Republican, interrupted Alito to ask Prelogar a softball question â a clear sign that Kavanaugh was unpersuaded by Alitoâs arguments. At another point, Justice Amy Coney Barrett, another Republican appointee, cut off a similar line of questions by Gorsuch.
+
+
+All of this said, the Court did spend a considerable amount of time while Prelogar was arguing the governmentâs case hunting around for a way to decide the Moore case narrowly. It is possible that the Court upholds the specific tax at issue in the Moore case on such narrow grounds that the justices could leave the door open to striking down a Warren-style wealth tax at some future date.
+
+
+But fiscal policy wonks who feared that Moore could blow a massive hole in the federal governmentâs finances can probably heave a sigh of relief. At the end of the day, Grossmanâs arguments appeared to be too weak, and too rooted in discredited legal theories that the Court abandoned nearly a century ago, to persuade even this very conservative Supreme Court.
+
+
+What is the specific issue before the Court in Moore?
+
+
+The full array of legal issues in Moore is dizzyingly complex. To completely understand the case, someone must have a working knowledge of how tax accounting typically works, how it works for certain investors who are taxed differently than others, how the Court once read a provision of the Constitution enacted to preserve a Union between free states and slaveholders to protect investors from taxes, and why the United States amended its Constitution to restore the federal governmentâs ability to tax investment income. (I explain all of these details here.)
+
+
+But the shortest explanation of whatâs at issue in Moore is that it asks whether the Constitution prohibits Congress from taxing investment income before that income is ârealizedâ â meaning that the investor has sold an asset for a profit or otherwise disposed of that asset.
+
+
+Ordinarily, investors are not taxed right away when their assets gain value. If an investor buys $5,000 worth of stock, for example, and holds onto it for 10 years until its value grows to $25,000, they will pay no taxes at all on that stock during that 10-year period. If they then sell the stock for its $25,000 market value, they will pay taxes on the $20,000 in profit they made.
+
+
+As the Supreme Court explained in Helvering v. Horst (1940), this ordinary rule â the rule that investments are not taxed until they are sold or otherwise realized â is âfounded on administrative convenience.â It is often difficult to determine how much an asset is worth before it is sold, so delaying taxation until realization prevents a situation where no one can be sure how much a particular taxpayer owes the government.
+
+
+The specific tax at issue in Moore is a one-time tax, enacted as part of the Tax Cuts and Jobs Act of 2017, in order to partially offset the cost of a large tax break that law gave to corporations.
+
+
+Before this 2017 bill became law, the United States attempted to tax US corporationsâ overseas income. Under the old regime, however, corporations could defer taxation of their foreign profits indefinitely by creating a foreign subsidiary. Income earned by these foreign subsidiaries would not be taxed until it was repatriated into the United States, giving companies a strong incentive to hoard money overseas and away from US tax collectors.
+
+
+The 2017 law largely gave up on trying to tax this overseas corporate income. But it also imposed a one-time tax on US investors in foreign corporations in order to offset some of the lost revenue resulting from the new tax regime. Under this offset, certain investors in foreign corporations must pay a percentage of the money that the corporation has kept overseas, even though the investor has not sold their stock or received any of that money as a dividend.
+
+The plaintiffs in Moore are US investors in a company that provides supplies to farmers in India. In 2017, they paid an additional $14,729 in taxes due to the one-time provision. They then sued to get this money back, claiming that the Constitution forbids the federal government from taxing unrealized income.
+
+
+So how is the case likely to be decided?
+
+
+Grossmanâs core argument is that the Supreme Courtâs decision in Eisner v. Macomber(1920), which held that âenrichment through increase in value of capital investment is not income in any proper meaning of the term,â outright forbids Congress from taxing unrealized income. And, if Grossman had made this argument a century ago, heâd have a really strong case.
+
+
+But we are no longer living in the 1920s, and the Supreme Court has repudiated Macomber so many times that, near the end of the argument, Justice Ketanji Brown Jackson suggested that maybe the best thing the Court could do is to explicitly overrule that decision.
+
+
+Among other things, the Supreme Court said in Commissioner v. Glenshaw Glass (1955), that Macomberâs narrow definition of âincomeâ was ânot meant to provide a touchstone to all future gross income questions.â And Glenshaw Glass was only one of the Courtâs decisions casting doubt on Macomber. In 1954, one year before Glenshaw Glass was decided, a federal appeals court said that Macomber âhas been limited to its specific facts.â
+
+
+Moreover, as both Justices Sonia Sotomayor and Barrett pointed out to Grossman, the current tax code is absolutely riddled with provisions that tax unrealized income, in violation of the rule that the Court briefly embraced in Macomber. These include provisions taxing partners on a partnershipâs income, even if that money hasnât yet been distributed to the individual partners, as well as taxes governing entities such as âSubpart Fâ and âSubpart Sâ corporations whose investors are taxed similarly.
+
+
+As Barrett told Grossman, itâs unclear how these longstanding taxes can be distinguished from the tax at issue in Moore, except for the fact that the tax before the Court is a âone shot.â
+
+
+Similarly, as Justice Elena Kagan pointed out, it is âquite well-settledâ that the United States may tax individual shareholders on unrealized income from a foreign corporation because these sorts of taxes prevent Americans from stashing their money in a foreign company where it cannot be taxed.
+
+
+Meanwhile, Alito and Gorsuch, the only two justices who seemed to have much of an appetite for reviving Macomber, often descended into baroque historical arguments that are unlikely to persuade any of their colleagues.
+
+
+Alito, for example, spent a surprising amount of time jousting with Prelogar about why lawyers in an 1895 tax case did not cite a different, 1871 tax case that Prelogar discusses in her brief. Gorsuch, similarly, claimed that the Justice Department agreed with Macomberâs definition of income in a brief it filed in 1918.
+
+
+These are, to say the least, very unusual arguments. Courts do not typically interpret the Constitution based on what a lawyer said during the Woodrow Wilson administration.
+
+
+That said, while there are almost certainly five votes â and possibly as many as seven votes â to uphold the 2017 tax provision at issue in Moore, many of the justices spent Prelogarâs time at the podium looking for a way to decide this case narrowly. Justice Clarence Thomas, for example, repeatedly suggested that unrealized income from corporate stock could be taxed because the corporation has realized that income even if it hasnât distributed it to its investors. A similar tax on unrealized income from real estate, however, would not be allowed.
+
+
+Similarly, Justice Brett Kavanaugh suggested that the Court could avoid entirely the question of whether Congress may tax unrealized income because income earned by a corporation should count as realized income once the corporation earns it.
+
+
+Likewise, in an exchange with Alito, Prelogar told the Court that, if Congress were to enact a particularly aggressive tax, such as a tax on all unrealized investments in every Americanâs retirement fund, the Court might strike that tax down on the grounds that Congress has not historically claimed the power to enact such a sweeping tax.
+
+
+But Alitoâs fear of such a ridiculous tax appeared limited to Alito. As Kavanaugh said in response, âMembers of Congress want to get reelected,â and a lawmakerâs desire to remain in the good graces of their voters should be enough to ward off absurd tax proposals.
+
+
+So the Moore decision may wind up being a nothingburger that upholds the 2017 tax provision on narrow grounds without saying much at all about the constitutionality of a Warren-style wealth tax. Still, most of the justices seemed to agree with Kavanaugh that Congress, and not the Court, should typically decide who is taxed and how they are taxed.
+
+
+
From The Hindu: Sports
+
+
Pujara, the pitch-whisperer with a better strike rate than Compton -
+
Watch | How is a cricket bat made? - A visit to the BDM factory in Meerut, Uttar Pradesh, where artisans show the various stages in the crafting of a cricket bat
+
Prime Volleyball League 2023 | Kochi Blue Spikers retains Erin, George, Jibin and Abhinav ahead of player auctions - The auction for PVLâs third edition will be held in Bengaluru on Dec. 7
+
Abhay Singh goes down to Baptiste Masotti - Tauranga
+
ICC rankings | Ravi Bishnoi becomes worldâs No.1 T20I bowler - 23-year-old Ravi Bishnoi was Indiaâs go-to bowler in the just-concluded series against Australia, taking nine wickets from five games
+
+
From The Hindu: National News
+
+
4 tourists from Kerala who died in J&K remembered as hardworking youth by their village in Palakkad - The fourâSudesh, Anil, Rahul and Vigneshâwere part of a 13-member tourist group from the Nedungode area in Chittur here. The car they were in lost control at a turn near the Zojila Pass, on the Srinagar-Leh National Highway, and fell into a ravine.
+
Techie dies of injuries after crashing cycle into parked goods canter -
+
NHRC urged for withdrawal of cases against Sompeta thermal plant agitators - The agitators are unable to get passports, government jobs and other benefits owing to the cases registered against them 13 years ago, says A.P. BC Association
+
Here are the big stories from Karnataka today - Welcome to the Karnataka Today newsletter, your guide from The Hindu on the major news stories to follow today. Curated and written by Nalme Nachiyar.
+
Online money gaming, gambling: Kerala Government proposes Ordinance for amending State GST Act - Kerala Cabinet decision aimed at bringing in more clarity to taxation provisions related to online money gaming and gambling
+
+
From BBC: Europe
+
+
UAE extradites British trader Sanjay Shah to Denmark - The money Danish authorities are seeking to recoup over fraud charges amounts to nearly 0.5% of the countryâs entire GDP.
+
Bosnian Serb leader Dodik on trial for defying international envoy Schmidt - Milorad Dodik is accused of refusing to recognise rulings by the man overseeing peace in Bosnia.
+
German cabinet tries to solve âno-debtâ crisis after court outlaws budget - The coalition meets for the last time this year on Wednesday after the budget is declared illegal.
+
Olive oil price skyrockets as Spanish drought bites - Spain is the biggest olive oil producer. Two years of drought there are affecting prices worldwide.
+
Zelensky abruptly cancels US Senate briefing amid funding row - The Ukrainian president pulled out of a briefing with senators debating more funds for Ukraine.
+
+
From Ars Technica
+
+
The Morgan XP-1 is an extremely eccentric English electric vehicle - The three-wheel convertible EV weighs little so should actually be quite efficient. - link
+
NASA says SpaceXâs next Starship flight could test refueling tech - SpaceX appears on track for at least a preliminary propellant transfer test next year. - link
+
Man dies on way home from Panera after having three âchargedâ lemonades - A large lemonade contains up to 390 mg of caffeine, nearly the FDAâs daily safe limit. - link
+
The Fallout TV series trailer is here, and itâs loaded with homages to the games - The show looks faithfulâmaybe to a fault. Letâs look at what the trailer reveals. - link
+
New report illuminates why OpenAI board said Altman âwas not consistently candidâ - Insider report details clash over one board memberâs criticism in an academic paper. - link
+
+
From Jokes Subreddit
+
+
Hospital Wit -
+
+
+This actually happened a few hours ago. So I had to take my mother to the hospital today for a procedure. The receptionist called us up and she was the only one there as her coworker had gone on break. As Iâm wheeling my mother to the desk to do the paperwork, a nice old man approaches the desk.
+
+
+He says to the receptionist âIâm here to pick up my wifeâ
+
+
+I perk up at this and say âI didnât even know they offered that service hereâ
+
+
+Well everyone turns to look at me and without missing a beat I continue âIâll take a wife alsoâ
+
+
+Then everyone cracked up.
+
+
+Currently in the waiting room fretting about my mother so hopefully telling a funny story out in to the world will get me some (non reddit) karma
+
+The Finnish President was planning a visit to a border town in the USSR. The local Kommissar, hoping to impress the Finns, decided to visit a local school. In preparation, he had all the children learn new songs, march in formation, wear their best uniforms, etc. Propaganda at its finest.
+
+
+The big day arrived and the Kommissar stood before the students and loudly asked âWho has the best schools in the world?â To which the student replied âThe Soviet Union!â He asked again âWho has the best playgrounds and candies in the world?â Again the students shouted âThe Soviet Union!â This went on for a about half an hour when the Finnish President heard a little boy crying.
+
+
+âWhatâs the matter, child? Why are you crying?â
+
+
+âBecause I want to go to the Soviet Union!â
+
+
+(My father was born in USSR and he always loved this joke.)
+
There was once a man who was obsessed with tractors⊠-
+
+
+He owned multiple tractors and tractor-themed merchandise. Toy tractors, tractor calendars, posters, everything.
+
+
+One day he and his wife were riding one of his tractors around a field, when his wife fell out and was ran over. She died of her injuries and the man was distraught. He vowed to never enjoy tractors again and sold all of his tractors and merchandise.
+
+
+A few years later he decides to start dating and lands a date with a beautiful woman. He takes her to a fancy cocktail bar for their date.
+
+
+During the date one of the bartenders messes up a cocktail and the room fills with smoke. Everyone is coughing and panicking but the man simply stands up, inhales all the smoke, walks to the door and blows it all outside.
+
+
+His date is amazed and asks, âHow did you do that?â
+
+A priest and a nun were lost in a blizzard. After a while, they came upon a small cabin.
+
+
+Being exhausted, they prepared to go to sleep. There was a stack of blankets and a sleeping bag on the floor â but only one bed. Being a gentleman, the priest said, âSister, you sleep on the bed. Iâll sleep on the floor in the sleeping bag.â
+
+
+Just as he got zipped up in the bag and was beginning to fall asleep, the nun said âFather, Iâm cold.â
+
+
+He unzipped the sleeping bag, got up, got a blanket and put it on her.
+
+
+Once again, he got into the sleeping bag, zipped it up and started to drift off to sleep when the nun once again said, âFather, Iâm still very cold.â
+
+
+He unzipped the bag, got up again, put another blanket on her and got into the sleeping bag once again. Just as his eyes closed, she said, âFather, Iâm sooooo cold.â
+
+
+This time, he remained there, giving the woman a wink and a smile, then said, âSister, I have an idea. Weâre out here in the wilderness where no one will ever know what happened. Letâs pretend weâre married.â
+
+
+The nun purred, âSounds good to me.â
+
+
+To which the priest yelled out, âOkay then â get up and get your own stupid blanket!â
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25134873/GettyImages_1695120669.jpg)
Getty Images
+
+
+