The COVID-19 pandemic era impact on the incidence of the custodial death, due to illness in 36 states and union territories of India-A comparison study (2017–2022) -
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+Abstract: Mahatma Gandhi said that “crime is due to diseased mind and jail should have an environment like hospitals for prisoner’s treatment and care”. A lot of research is carried out globally during COVID-19, on the well being of peoples staying outside the prisons, but very few large scale researches are available to know about the well being of the prisoners during COVID-19 era. The data is provided by the Prison Section of all the 36 States/UTs in prearranged Performa of the NCRB, through an application made by NCRB. A total of 11,289 custodial death occurred among the prisoners residing in various prisons of India, during the study period, out of which 9,406 (83.32 percent, Total-9406 (Obs-216, Mean-43.55, Std. Dev.- 68.87, Min-0, Max-401, Std. Err.- 4.69, 95% Conf. Interval of mean-34.31 -52.78) mortalities were attributed due to illness. Compared to year 2020, our study revealed that the COVID-19 year 2021 has attributed to largest (16.47 percent increased illness custodial death and 12.14 percent increased total mortalities) number of custodial death due to illness. The study revealed that during the study period, majority of the mortalities were due to heart diseases in prisoners (27.28 percent, Total-2566 (Obs-216, Mean-11.88, Std. Dev.- 19.30, Min-0, Max-123, Std. Err.- 1.31, 95% Conf. Interval of mean-9.29 -14.47). Cholera / Diarrhoea attributed to the least number of mortalities during the study period (0.21 percent, Total-20 (Obs-216, Mean-0.09, Std. Dev. - 0.40, Min-0, Max-4, Std. Err. - 0.03, 95% Conf. Interval of mean-.04 -.15). This six years of study revealed that most of the custodial death (42%), due to illness in prisoners of India was due to CVDs and pulmonary diseases. This study also revealed that 27% of custodial deaths due to illness were not clearly categorized. Honourable Justice Lokur, of Supreme Court of India, said in a landmark judgment, in 2013, that “The distinction made by the NCRB [National Crime Records Bureau] between natural and unnatural custodial deaths is not clear. For example, if a prisoner dies due to a lack of proper medical attention or timely medical attention, would that be classified as a natural custodial death or an unnatural custodial death?” The policymakers and decision-makers must think on the necessity of developing Prisoners care policies following the COVID-19 pandemic, in light of the findings of this research study.
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Who has the flu? Early winter 2023-24 spread of flu and COVID-19 -
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+Winter 2023-24 has seen an unusual confluence of a variety of respiratory illnesses, ranging from flu to RSV (Respiratory Syncytial Virus) and COVID-19. Between December 21, 2023 and January 29, 2024, we surveyed 30,460 individuals aged 18 and older across all 50 states plus the District of Columbia. We asked them if they had experienced an Influenza-like Illness (ILI) defined as experiencing a fever and cough, or a fever and sore throat, and/or if they had been diagnosed with COVID-19, over the previous month. Amongst those who responded yes to such questions, we asked them whether or not they had sought medical attention. In this report, we summarize our findings across a variety of demographic subgroups, including age, race, education, income, gender, and geography.
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Thymidine Phosphorylase Mediates SARS-CoV-2 Spike Protein Enhanced Thrombosis in K18-hACE2TG Mice -
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+COVID-19, caused by SARS-CoV-2, is associated with arterial and venous thrombosis, thereby increasing mortality. SARS-CoV-2 spike protein (SP), a viral envelope structural protein, is implicated in COVID-19-associated thrombosis. However, the underlying mechanisms remain unknown. Thymidine phosphorylase (TYMP), a newly identified prothrombotic protein, is upregulated in the plasma, platelets, and lungs of patients with COVID-19 but its role in COVID-19-associated thrombosis is not defined. In this study, we found that wild-type SARS-CoV-2 SP significantly promoted arterial thrombosis in K18-hACE2TG mice. SP-accelerated thrombosis was attenuated by inhibition or genetic ablation of TYMP. SP increased the expression of TYMP, resulting in the activation of signal transducer and activator of transcription 3 (STAT3) in BEAS-2B cells, a human bronchial epithelial cell line. A siRNA-mediated knockdown of TYMP inhibited SP-enhanced activation of STAT3. Platelets derived from SP-treated K18-hACE2TG mice also showed increased STAT3 activation, which was reduced by TYMP deficiency. Activated STAT3 is known to potentiate glycoprotein VI signaling in platelets. While SP did not influence ADP- or collagen-induced platelet aggregation, it significantly shortened activated partial thromboplastin time and this change was reversed by TYMP knockout. Additionally, platelet factor 4 (PF4) interacts with SP, which also complexes with TYMP. TYMP enhanced the formation of the SP/PF4 complex, which may potentially augment the prothrombotic and procoagulant effects of PF4. We conclude that SP upregulates TYMP expression, and TYMP inhibition or knockout mitigates SP-enhanced thrombosis. These findings indicate that inhibition of TYMP may be a novel therapeutic strategy for COVID-19-associated thrombosis.
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A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding -
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+The nucleoprotein (N) of SARS-CoV-2 encapsidates the viral genome and is essential for viral function. The central disordered domain comprises a serine-arginine-rich domain (SR) that is hyperphosphorylated in infected cells. This modification is thought to regulate function of N, although mechanistic details remain unknown. We use time-resolved NMR to follow local and long-range structural changes occurring during hyperphosphorylation by the kinases SRPK1/GSK-3/CK1, thereby identifying a conformational switch that abolishes interaction with RNA. When 8 approximately uniformly-distributed sites are phosphorylated, the SR domain competitively binds the same interface as single-stranded RNA, resulting in RNA binding inhibition. Phosphorylation by PKA does not prevent RNA binding, indicating that the pattern resulting from the physiologically-relevant kinases is specific for inhibition. Long-range contacts between the RNA-binding, linker and dimerization domains are also abrogated, phenomena possibly related to genome packaging and unpackaging. This study provides insight into recruitment of specific host kinases to regulate viral function.
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A pan-tissue, pan-disease compendium of human orphan genes -
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+Species-specific genes are ubiquitous in evolution, with functions ranging from prey paralysis to survival in subzero temperatures. Because they are typically expressed under limited conditions and lack canonical features, such genes may be vastly under-identified, even in humans. Here, we leverage terabytes of human RNA-Seq data to identify thousands of highly-expressed transcripts that do not correspond to any Gencode-annotated gene. Many may be novel ncRNAs although 80% of them contain ORFs that have the potential of encoding proteins unique to Homo sapiens (orphan genes). We validate our findings with independent strand-specific and single-cell RNA-seq datasets. Hundreds of these novel transcripts overlap with deleterious genomic variants; thousands show significant association with disease-specific patient survival. Most are dynamically regulated and accumulate selectively in particular tissues, cell-types, developmental stages, tumors, COVID-19, sex, and ancestries. As such, these transcripts hold potential as diagnostic biomarkers or therapeutic targets. To empower future discovery, we provide a compendium of these huge RNA-Seq expression data, and RiboSeq data, with associated metadata. Further, we supply the gene models for the novel genes as UCSC Genome Browser tracks.
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Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike -
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+The trimeric spike protein plays an essential role in the SARS-CoV-2 virus lifecycle, facilitating virus entry through binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediating viral and host membrane fusion. The SARS-CoV-2 spike contains an allosteric fatty acid (FA) binding site at the interface between two neighbouring receptor-binding domains. This site, also found in some other coronaviruses, binds free fatty acids such as linoleic and oleic acid, and other small molecules. Understanding allostery and how this site modulates the behaviour of different regions in this protein could potentiate the development of promising alternative strategies for new coronavirus therapies. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to investigate allosteric effects and identify the communication pathways in the fully glycosylated spike in the original SARS-CoV-2 ancestral variant. The results reveal the allosteric networks that connect the FA site to important functional regions of the protein, including some more than 40 Angstroms away. These regions include the receptor binding motif, an antigenic supersite in the N-terminal domain, the furin cleavage site, the regions surrounding the fusion peptide and a second allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected connection between different allosteric sites. Notably, 65% of amino acid substitutions, deletions and insertions in the Alpha, Beta, Delta, Gamma and Omicron variants map onto or close to the identified allosteric pathways.
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The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm -
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+The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-{gamma} induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF- & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NF{kappa}B using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF- and IFN-{gamma}, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 M, 95% CI= 7.4 to 10.4 M) was comparable to that of paracetamol (IC50 = 7.73 M, 95% CI = 6.14 to 9.73 M). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NF{kappa}B. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.
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Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies -
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+SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) {beta} sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as “sustainers”), but not in “decliners”. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.
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Integrating population-level and cell-based signatures for drug repositioning -
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+Genetics-informed drug repositioning presents a streamlined and cost-efficient way to broaden therapeutic options. However, leveraging the full spectrum of molecular signatures remains underexplored. We introduce TReD (Transcriptome-informed Reversal Distance), integrating population-level disease signatures robust to reverse causality and cell-based drug-induced response profiles. TReD embeds the disease signature and drug profile in a high-dimensional normed space, quantifying the reversal potential of candidate drugs in a disease-related cell screen assay. For illustration, we apply TReD to COVID-19 and type 2 diabetes (T2D). We identify 37 potential drugs against COVID-19, over 70% (27/37) with prior associations, and eight supported by clinical trials. For T2D, we observe reversal signals for 86 compounds on multiple disease signatures, with more than 40% supported by published literature. In summary, we propose a comprehensive genetics-anchored framework integrating population-level signatures and cell-based screens that can accelerate the search for new therapeutic strategies.
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Changes in risk perception during the COVID-19 pandemic in Southeast Alaska: Self-identified determinants of risk and protective behaviors -
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+Social and cultural context shapes how communities perceive health, well-being, and risk. Risk perception can change over time as a product of new information and improved understanding. We investigate risk perception and protective behaviors in Southeast Alaska during the first year of the COVID-19 pandemic. Surveys were circulated at two time points: (1) April-June 2020, before COVID-19 reached epidemic levels in the region, and (2) November 2020-February 2021. Ordinary least squares (OLS) regression models were used to analyze how demographic characteristics of the respondent population influenced risk perception. OLS models were again used to predict how individuals engaged in protective behaviors while controlling for risk perceptions. Controlling for demographic characteristics, risk perception increased as age increased for perceived risk of getting sick and dying from COVID-19, males perceived lower risk in general for all tested variables, and Alaska Native respondents perceived higher risk than non-Alaska Native respondents. Controlling for risk perception, results for protective behaviors were mixed; however, the strongest association identified was that knowing someone with a positive COVID-19 diagnosis increased protective behaviors. Between the two time points, risk perceptions increased significantly for variables related to oneself, others, and community members becoming infected with COVID-19. Protective behaviors like traveling less than normal, buying more cleaning products, and engaging in more subsistence gathering significantly increased. Identifying patterns of risk perception and protective behaviors, and especially how they change over time, are critical to developing place-specific public health recommendations, action, and preparedness plans against future infectious threats.
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Physical distancing and the perception of interpersonal distance in the COVID-19 crisis -
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+In the wake of the COVID-19 pandemic, it has been mandated to keep enlarged distances from others. We interviewed 136 German subjects over five weeks from the end of March to the end of April 2020 during the first wave of infections about their preferred interpersonal distance (IPD) before, during, and after the COVID-19 pandemic. In response to the pandemic, subjects adapted to distance requirements and preferred a larger IPD. This enlarged IPD was judged to persist after the crisis partially. People anticipated keeping more IPD to others even if there was no longer any risk of a SARS-CoV-2 infection. We also sampled two follow-up measurements, one in August, after the first wave had been flattened, and one in October 2020, at the beginning of the second wave. We discuss our findings in light of proxemic theory and an indicator for socio-cultural adaptation beyond the course of the pandemic.
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Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome -
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+Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or "normal density" polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a "left shift" in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that immature neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.
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Confirmation of Covid Infection Status and Reporting of Long Covid Symptoms in a Population-Based Birth Cohort: No Evidence of a Nocebo Effect -
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+Some patients with COVID-19 develop symptoms after the acute infection, known as ‘Long COVID’. We examined whether or not confirmation of COVID-19 infection status could act as a nocebo, using data from questionnaires distributed to the Avon Longitudinal Study of Parents and Children cohort. We examined associations between confirmation of COVID-19 infection status (confirmed by a positive test versus unconfirmed) and reporting of Long COVID symptoms. We explored the roles of sex and anxiety as potential moderators. There was no clear evidence of a strong association between confirmation of COVID-19 infection status and the Long COVID composite score, physical or psychological symptoms, or duration of symptoms. There was no clear evidence of moderation by sex or anxiety. We therefore found no evidence of a nocebo effect. Our data suggest that this psychological mechanism does not play a role in the medical symptomatology experienced by patients with Long COVID.
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Affordable private rental supply and demand: short-term disruption (2016–2021) and longer-term structural change (1996–2021) -
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+This research analyses the ABS Census to reveal changes in the supply of private rental housing affordable and available to lower-income households (Q1 and Q2 households) over both the short term (2016–21) and the longer term (1996–2021). It also provides analysis of how COVID-19 policy and population responses temporarily altered the long-run structural trajectory of the private rental sector (PRS) in Australia. In 2021, the Australian PRS housed more than 2.363 million households, a 17 per cent increase of nearly 340,000 households since the 2016 Census. This growth has been greater than total household growth in each intercensal period since 1996. Between 2016 and 2021 PRS growth was concentrated at mid-market levels; in dwellings renting from around $300–$530 per week ($2021). This continues a major change trend first established in 2011, reinforcing the structural shift to a market concentration of dwellings renting at mid-to-higher levels. The long-term shift in the national distribution of PRS household incomes reveals the growth of households with incomes at mid to high levels ($1,246 a week and above). In 1996, these ‘wealthier’ households comprised 40 per cent of all PRS households (or 489,000 households); in 2021, they comprised 64 per cent (or 1,519,000 households), a 211 per cent increase. In comparison, the total number of PRS households increased by 91 per cent between 1996 and 2021 (from 1,234,000 households to 2,362,000). Over the same time frame, there has been a relatively constant total number of lower income renters in the PRS; 508,000 households in1996 and 488,000 in 2024. Nevertheless, there was a shortage of 348,000 affordable and available private rental homes for very-low income (Q1) households in 2021 and that, as a result, 82 per cent of Q1 PRS households paid unaffordable rents.
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COVID-19 and Changes in Young Adults’ Weight Concerns -
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+The COVID-19 pandemic introduced fundamental challenges to nearly all aspects of college students’ lives, yet changes in key domains of their health, including weight concerns, remain untested. The current study utilized a longitudinal project comprised of 355 young-adult college students (Mage=19.5, 66.8% female, 33.2% male) oversampled for recent substance use behavior. Participants completed multiple assessments (mode=5) from September 2017 to September 2021. Piecewise growth-curve models tested whether COVID-19 onset was associated with changes in the trajectories of young adults’ weight concerns. Analyses also examined participants’ sex as a moderator of these trajectories. On average, participants reported a significant increase in weight concern levels around the start of COVID-19, although weight concern slopes were not significantly different before and after COVID-19. Additionally, moderation analyses showed that females (but not males) had a significant increase in weight concern levels after COVID-19 onset.
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GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects - Conditions: COVID-19 Interventions: Drug: GS-441524; Drug: Placebo Sponsors: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc Not yet recruiting
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UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects - Conditions: COVID-19 Pandemic; COVID-19 Vaccines Interventions: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia Active, not recruiting
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The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19 - Conditions: COVID-19 Pneumonia; COVID-19 Interventions: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) Sponsors: Selda Sarıkaya; Zonguldak Bulent Ecevit University Completed
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World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt - Conditions: Mucormycosis; Rhinocerebral (Etiology); COVID-19 Interventions: Procedure: debridment Sponsors: Nasser Institute For Research and Treatment Completed
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Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial - Conditions: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 Interventions: Drug: Hyperbaric oxygen Sponsors: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk Not yet recruiting
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Mindfulness-based Mobile Applications Program - Conditions: COVID-19; Cell Phone Use; Nurse; Mental Health Interventions: Device: mindfulness-based mobile applications program Sponsors: Yu-Chien Huang Completed
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Attention Training for COVID-19 Related Distress - Conditions: Anxiety Interventions: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training Sponsors: Palo Alto University Not yet recruiting
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Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood. - Conditions: Covid-19 Interventions: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) Sponsors: Vachira Phuket Hospital Recruiting
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UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study) - Conditions: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease Interventions: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg Sponsors: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH Recruiting
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Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers. - Conditions: COVID-19 Interventions: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) Sponsors: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France Not yet recruiting
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High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk - Conditions: Cardiovascular Diseases; Long Covid19 Interventions: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa Sponsors: Federal University of Paraíba; City University of New York Recruiting
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SGB for COVID-induced Parosmia - Conditions: COVID-19-Induced Parosmia Interventions: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection Sponsors: Washington University School of Medicine Recruiting
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From PubMed
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Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2β1 - Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and…
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Sulfated Glycans Inhibit the Interaction of MERS-CoV Receptor Binding Domain with Heparin - Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising…
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The Potential of Usnic-Acid-Based Thiazolo-Thiophenes as Inhibitors of the Main Protease of SARS-CoV-2 Viruses - Although the COVID-19 pandemic caused by SARS-CoV-2 viruses is officially over, the search for new effective agents with activity against a wide range of coronaviruses is still an important task for medical chemists and virologists. We synthesized a series of thiazolo-thiophenes based on (+)- and (-)-usnic acid and studied their ability to inhibit the main protease of SARS-CoV-2. Substances containing unsubstituted thiophene groups or methyl- or bromo-substituted thiophene moieties showed…
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Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells - Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is the inhibition of the integrated stress response-the mechanism through which infected cells arrest translation through the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α). We have recently shown that the human common cold betacoronavirus OC43 actively inhibits eIF2α phosphorylation in response to sodium arsenite, a potent inducer of oxidative…
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Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID - CONCLUSION: Nanoformulations containing EC16 showed properties compatible with nasal application to rapidly inactivate SARS-CoV-2 residing in the olfactory mucosa and to reduce inflammation in the CNS, pending additional formulation and safety studies.
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Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning - SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds. Further filtering, performed by applying two machine learning algorithms, identified…
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Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies - The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection’s spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their…
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Silver Nanoparticles In Situ Synthesized and Incorporated in Uniaxial and Core-Shell Electrospun Nanofibers to Inhibit Coronavirus - In the present study, we sought to develop materials applicable to personal and collective protection equipment to mitigate SARS-CoV-2. For this purpose, AgNPs were synthesized and stabilized into electrospinning nanofiber matrices (NMs) consisting of poly(vinyl alcohol) (PVA), chitosan (CHT), and poly-ε-caprolactone (PCL). Uniaxial nanofibers of PVA and PVA/CHT were developed, as well as coaxial nanofibers of PCL[PVA/CHT], in which the PCL works as a shell and the blend as a core. A crucial…
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The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19 - The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing and effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms of action and some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. The most effective small-molecule drug approved to date for the…
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An Antiherpesviral Host-Directed Strategy Based on CDK7 Covalently Binding Drugs: Target-Selective, Picomolar-Dose, Cross-Virus Reactivity - The repertoire of currently available antiviral drugs spans therapeutic applications against a number of important human pathogens distributed worldwide. These include cases of the pandemic severe acute respiratory coronavirus type 2 (SARS-CoV-2 or COVID-19), human immunodeficiency virus type 1 (HIV-1 or AIDS), and the pregnancy- and posttransplant-relevant human cytomegalovirus (HCMV). In almost all cases, approved therapies are based on direct-acting antivirals (DAAs), but their benefit,…
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The Role of Extracellular Vesicles in SARS-CoV-2-Induced Acute Kidney Injury: An Overview - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions worldwide since its outbreak in the winter of 2019. While extensive research has primarily focused on the deleterious respiratory effects of SARS-CoV-2 in recent years, its pan-tropism has become evident. Among the vital organs susceptible to SARS-CoV-2 infection is the kidney. Post SARS-CoV-2 infection, patients have developed coronavirus disease 19 (COVID-19), with reported incidences of COVID-19 patients…
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SARS-CoV-2 Spike Protein Stimulates Macropinocytosis in Murine and Human Macrophages via PKC-NADPH Oxidase Signaling - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While recent studies have demonstrated that SARS-CoV-2 may enter kidney and colon epithelial cells by inducing receptor-independent macropinocytosis, it remains unknown whether this process also occurs in cell types directly relevant to SARS-CoV-2-associated lung pneumonia, such as alveolar epithelial cells and macrophages. The goal of our study was to investigate…
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Correlation of Experimental and Calculated Inhibition Constants of Protease Inhibitor Complexes - Predicting the potency of inhibitors is key to in silico screening of promising synthetic or natural compounds. Here we describe a predictive workflow that provides calculated inhibitory values, which concord well with empirical data. Calculations of the free interaction energy ΔG with the YASARA plugin FoldX were used to derive inhibition constants K(i) from PDB coordinates of protease-inhibitor complexes. At the same time, corresponding K(D) values were obtained from the PRODIGY server. These…
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The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy - Fibrosis is a chronic pathology resulting from excessive deposition of extracellular matrix components that leads to the loss of tissue function. Pulmonary fibrosis can follow a variety of diverse insults including ischemia, respiratory infection, or exposure to ionizing radiation. Consequently, treatments that attenuate the development of debilitating fibrosis are in desperate need across a range of conditions. Sphingolipid metabolism is a critical regulator of cell proliferation, apoptosis,…
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Isolation and Identification of a Tibetan Pig Porcine Epidemic Diarrhoea Virus Strain and Its Biological Effects on IPEC-J2 Cells - Porcine epidemic diarrhoea virus (PEDV) is a coronavirus that can cause severe watery diarrhoea in piglets, with high morbidity and mortality rates, seriously hindering the healthy development of the global swine industry. In this study, we isolated a strain of PEDV from Tibetan pigs and named it CH/GS/2022. Subsequently, we screened the apoptosis signals of PEDV-infected IPEC-J2 cells and studied the correlation between apoptosis signals and cell apoptosis. The results showed that different…
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From Patent Search
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+Daily-Dose
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Inside North Korea’s Forced-Labor Program in China - Workers sent from the country to Chinese factories describe enduring beatings and sexual abuse, having their wages taken by the state, and being told that if they try to escape they will be “killed without a trace.” - link
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Legal Weed in New York Was Going to Be a Revolution. What Happened? - Lawsuits. Unlicensed dispensaries. Corporations pushing to get in. The messy rollout of a law that has tried to deliver social justice with marijuana. - link
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The Snake with the Emoji-Patterned Skin - In the wild, ball pythons are usually brown and tan. In America, breeding them to produce eye-catching offspring has become a lucrative, frenetic, and—for some—troubling enterprise. - link
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Matt Gaetz’s Chaos Agenda - The Florida Republican is among the most brazen and controversial figures in Donald Trump’s G.O.P. He’s also among the most influential. - link
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The Trials of Alejandro Mayorkas - The Secretary of Homeland Security has been forced to respond to an unprecedented flow of migrants to the U.S.-Mexico border. Why are Republicans in Congress impeaching him for it? - link
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From Vox
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Is oat milk unhealthy? That’s the wrong question. -
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+Oatly oat milk at a grocery store in Chicago. | Scott Olson/Getty Images
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+The unhelpful, distracting debate about whether oat milk is bad for you totally misses the point.
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+Is oat milk good or bad for you?
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+That’s the question a bunch of recent news headlines have asked. I really hate that question.
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+Obviously, how the food we eat affects our health is very important. But most foods — including nondairy milks — are not universally good or bad for everyone. Whether or not oat milk is bad for your health depends on a lot of things: your current body condition, the context in which you’re consuming it, and how much of it you’re drinking, to name a few.
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+“Simple ‘good or bad’ stories about traditional milk or nondairy milks, such as oat milk, often overlook the complexity of nutrition,” Hassan Vatanparast, a professor of nutrition at the University of Saskatchewan who has studied non-dairy milks, told me over email.
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+This healthy/unhealthy dichotomy also obscures a much more complicated set of factors that determine what we eat. For many of us, health is high on that list. But so is taste, cost, presence of allergens, and environmental impact. We live in a time that begs us to think beyond ourselves, beyond our bodies, and to recognize that what we eat affects the world around us — often in very serious ways.
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+So, what should we drink? That question has been gnawing at me, and so I read some things and talked to some experts to try to figure it out.
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+If you’re a healthy person, a daily oat milk latte is not a problem
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+Many recent stories about oat milk raise concerns about the drink’s effect on blood sugar — more specifically, that it causes a spike in blood sugar following consumption. So let’s start there.
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+Repeated spikes in blood sugar (i.e., a fast build-up of glucose in your blood) are famously not good. It’s linked to cardiovascular disease and insulin resistance, a precursor to diabetes. What does oat milk have to do with it? It’s higher in starch (a carb) than some other nondairy milks, and starch is converted into simple sugars when you digest it. That raises your blood sugar. (This conversion of starch to more simple sugars also happens when oats are processed into oat milk, which is why oat milk often tastes somewhat sweet, even if sugar isn’t listed as an ingredient.)
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+But it’s normal for food to raise your blood sugar, especially if that food is a processed grain. For most people, that won’t be a problem. If you’re healthy and not loading your diet with starchy carbs, you should have no problem regulating your blood sugar after a cup of oat milk and bringing glucose levels back down after a spike. To be clear, oat milk is not a sugary drink like, say, soda.
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+Going a bit deeper: Nutritionists use a rating system called the glycemic index to measure how quickly different foods raise our blood sugar (which is different from just the total amount of sugar in something because different kinds of sugar have different effects on blood sugar — it’s confusing). In general, oat milk has only a “moderate” glycemic index, Vatanparast told me. That means it’s not particularly bad for blood sugar or particularly good.
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+I asked the oat milk company Oatly about this, too. The company’s nutrition specialist, Kate Twine, said that its popular Barista Edition, which is slightly fattier than regular Oatly, has a medium glycemic index. If you factor in the serving size (e.g., one cup), using a related measure called glycemic load, the blood sugar profile is even better — the glycemic load is “low,” she said.
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+One somewhat obvious takeaway is that the amount of milk (and thus carbs) you’re drinking matters. What you’re consuming with it matters, too. Foods high in fiber, protein, and fat can blunt the impact on blood sugar because they slow down the absorption of glucose. (Cow’s milk has a lower glycemic index than oat milk and other nondairy milks, but a more comparable glycemic load. Rice milk, meanwhile, has a very high glycemic index and load. The bottom line: A cup of oat milk is probably not going to be a problem for blood sugar.)
+
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+But there’s an important caveat: For people with diabetes or insulin resistance, glucose — and the presence of starchy carbs — obviously matters a lot more. “If you have diabetes, oat milk may not be the best option since it’s one of the higher carbohydrate-containing milk substitutes,” Marion Groetch, a registered dietitian and director of nutrition services at Jaffe Food Allergy Institute, a division of the Icahn School of Medicine at Mount Sinai, told me. But if you’re not diabetic and otherwise eat well, Groetch said, there’s not much of a concern with having an oat milk latte every day.
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+These milks are typically higher in fiber and lower in fat than dairy and some other nondairy milks, such as coconut (assuming you avoid full-fat options or those with added sugar).
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+Additives like rapeseed oil and emulsifiers (which essentially prevent the ingredients from separating), common among nondairy milks including oat milk, are generally recognized as safe by national and international health authorities, Vatanparast said.
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+That said, there’s some research linking emulsifiers — and especially synthetic emulsifiers like carboxymethylcellulose and polysorbate 80 — to potentially harmful changes in the gut microbiome. The real-world implications are not clear or well-tested. The studies I read suggest that there aren’t serious safety concerns with the emulsifiers used by popular oat milk brands (I reviewed several), such as gellan gum, though more research is needed.
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+
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+So, where does that leave us? Drinking oat milk is probably fine for your body unless you’re drinking large quantities of it, already loading your diet with carbs, and/or diabetic. If most of your day’s liquid is coming from any milk, plant-based or not, that’s probably not great. Moderation is key.
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+The other reason why you might consider a milk “good” or “bad”
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+Now is a good time to mention: I’m not vegan, I occasionally eat dairy, and I don’t really love any of the nondairy milks. They’re all kind of eh. But I typically choose to consume oat and soy milks because they taste good enough in coffee and cereal, I can afford them, and, importantly, it’s an easy way to support the welfare of cows and reduce my carbon footprint.
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+That’s another reason why I find the “is it good vs. bad for you” debate over oat milk kind of icky: It distracts from these other important considerations, catering instead to the public’s desire for simple, comfortable answers. I want choosing something as basic as milk to be simple, but it’s not.
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+My personal perspective is that I like cows, and the treatment they receive at a typical dairy seems, at best, unkind. Farmers repeatedly impregnate cows and take away their calves right after they’re born. If those babies are male, they are usually turned into veal or raised for beef. If they’re female, the calves are typically dehorned and docked, and also eventually slaughtered (when their milk production wanes). I’m having trouble imagining that this is a happy existence.
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+I’m also aware that, globally, a liter of dairy milk produces around three times as much carbon emissions as the same amount ofplant-based milk. Cows release methane, a potent greenhouse gas, through their burps and manure. The chart below, drawing on a 2018 study from the journal Science, is especially revealing. It shows that nondairy milks — and especially oat milk — not only release fewer emissions but also require less land and water. They tend to pollute less, too. (Growing feed for cows requires a lot of land, fertilizers, and pesticides.)
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+I don’t mean to imply that avoiding dairy is an easy choice. It requires wrestling with the pain that a declining dairy industry would cause. I’ve met loads of farmers in my career as a journalist (and before that as a researcher), and it’s clear to me that they love their animals. Many of them are also working to reduce their emissions. Farming families also obviously make their living from consumer demand for dairy products (just as other farmers make their living from growing plants). The growing popularity of oat milk is a threat, and one that a powerful dairy lobby is trying hard to eliminate.
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+I don’t live under the delusion that by not drinking dairy I live a cruelty-free life. No such life exists. The coffee I put my milk in likely comes from land that’s been cleared of forests (once home to a more abundant array of wildlife). The cafes I go to use plastic lids. My clothes come from oil (nylon) and industrial fields of cotton. It’s a nightmare!
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+Nonetheless, I’ll probably continue opting for plant-based drinks. Drinking oat milk is not obviously bad or good, but relative to other ways I can help out, it’s easy.I’m increasingly aware — I almost wish I wasn’t — that choosing to buy dairy is choosing to cause harm to farm animals, wildlife, and our planet.
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+
The South Carolina primary was a joke. It tells us something deadly serious. -
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+Trump speaks at a campaign rally. | Nic Antaya/Bloomberg via Getty Images
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+Trump’s inevitable romp to victory in Nikki Haley’s home state reveals how strong his hold on the GOP is — and how dangerous he remains to democracy.
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+Tonight, in the South Carolina Republican presidential primary, Donald Trump defeated rival Nikki Haley in her home state. Ordinarily, this might feel like big news, as the Palmetto State tends to host one of the most important early contests. Joe Biden’s 2020 victory in the state, after dismal finishes in Iowa and New Hampshire, is one of the biggestreasons he’s president today.
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+I and others have been arguingthis for yearsnow. Yet during those same years, many prominent people in politics and the media deluded themselves into thinking he might be dethroned. They have been wrong every time and continued to be wrong long after the strength of Trump’s grip on the GOP could not be denied.
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+There’s a lesson to be learned from this track record of failure, one deeper than just “Republicans really like Donald Trump.” Trump’s persistence tells us something critical about the nature of the current Republican party — and why it’s become such a danger to American democracy.
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+
+How Trump keeps wiggling his way out of jams
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+Ever since the early stages of the 2016 GOP primary, the same pattern has repeated itself over and over again: Some new development that looked politically dangerous for Trump ends up not mattering at all. This happened so many times in the 2016 election cycle alone that it became a running joke during the campaign.
+
+
+@BronzeHammer
+
+
+The pattern continued through Trump’s presidency, and most strikingly after January 6 — when Trump managed to maintain majority support in the Republican party after inciting an honest-to-god insurrection. At that point, you’d think it would be obvious that Trump was going to cruise to renomination in 2024. Yet somehow, the delusions of a Trump collapse persisted.
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+During the January 6 Committee meetings in summer 2022, there was widespread speculation that the dramatic public hearings had weakened Trump’s hold on the GOP. Republican primary voters proceeded to disprove this theory by booting the House members who voted for his impeachment and nominating full-MAGA election deniers, like Arizona’s Kari Lake, to contest key swing races around the country.
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+Then she lost by double-digits in her supposed stronghold of New Hampshire, and the writing was on the wall in great big bold letters.
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+None of this speculation tracked Trump’s poll numbers. The former president consistently led in the polling averages, generally by wide margins. So why did so many get this so wrong?
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+Sometimes, the explanation is mundane wishcasting: centrist or anti-Trump Republicans desperately wishing to avoid a choice between a threat to democracy and a Democrat. But in some cases, there’s a more interesting explanation — that even some of the GOP’s critics didn’t fully appreciate what it had become.
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+New York magazine’s Jonathan Chait, one of the more perceptive of these critics, was an early booster of DeSantis’s chances. In August of last year, he admitted that he had gotten it wrong — and wrote an interesting column trying to explain why he erred. Chait’s basic argument is that Trump’s cult of personality was far more powerful than he had appreciated.
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+“Defeating Trump in a contest determining who can most effectively advance ideological or party goals is difficult but attainable. It is obviously impossible to defeat Trump in a contest of who is most loyal to Trump,” Chait concluded.
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+This is surely a key part of the story. But it also raises a more fundamental question that Chait doesn’t attempt to answer: Why does the Republican base have such unwavering faith in the man?
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+Trump’s celebrity charisma alone isn’t enough of an explanation. Otherwise, former California Gov. Arnold Schwarzenegger would bestride the GOP like a colossus. Nor is Trump’s fawning coverage in the conservative media. Fox News has repeatedly tried to turn the Republican base away from Trump and toward figures like DeSantis, only to have to kiss the ring when the voters didn’t follow their lead.
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+The answer, at least as far as I can tell, is that Trump’s cult is the product of his unique ability to channel the cultural grievances at the heart of the current Republican party.
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+Again and again, social scientists found that the best predictor of Trump support among Republican voters is the degree to which they feel discomfort with the changing nature of American demographics and social norms. Trump has sold himself as the only person capable of fighting back against the alleged elite conspiracy behind these changes, saying things like “I alone can fix it” and “I am your retribution.” From these building blocks, he has created a full-scale political movement dedicated to reconquering America.
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+ Scott Olson/Getty Images
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+The crowd as former President Donald Trump arrives at a rally on February 17, 2024, in Waterford, Michigan.
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+Trump’s appeal isn’t premised on delivering concrete policy goals, nor even “owning the libs” with high-profile stunts. It is about assuaging the sense of fear and resentment at their America being replaced: about achieving victories that assuage the sense of psychological assault created by things like mass immigration, a Black president, shifting gender roles, and a beloved beer brand cutting an ad with a transinfluencer. Donald Trump, as a figure, represents the America they know and love. His victories are their victories, his defeats their defeats.
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+This frame helps us understand why Trump can’t be beaten inside Republican politics. It also clarifies why Trump has been able to steer the Republican party so harshly against democracy.
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+By making his very person into a stand-in for the existential struggle for America’s soul, he has created a world where any loss represents an intolerable blow against everything good about the country. Such a setback can only come from a place of deep corruption — from the Swamp and “Democrat-controlled cities.” And if American democracy has truly been subverted this thoroughly, the logical conclusion is clear: We have to “fight like hell” to save it.
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+The South Carolina primary’s irrelevance points to this deeper and darker story. It is one we must wrestle with in order to truly appreciate the stakes in the coming general election.
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+Update, February 24, 7:30 pm: This article was first published on February 24, 2024, and has been updated with the results of the South Carolina primary.
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What kids lose without snow days -
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+What ever happened to a good old-fashioned snow day? | Getty Images/fStop
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+Virtual learning means missing out on a different kind of education.
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+We had many superstitions when I was a kid. Wear your pajamas inside out. Or wear your underwear on the outside of your PJs. Gargle a bit of saltwater right before bed. When you put your shoes away, make sure they’re backward; left shoe on the right-hand side, right on the left.
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+Our teachers would remind us of these tricks during the school day before a potential snowfall. That night, we would all do our part, hoping and praying that we’d awaken to a sheet of fresh snow, deep enough to render our schools closed for the day.
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+On those mornings, we’d wake up earlier than usual to stare at the local news channel, filled with anticipation as the names of all the local school districts drifted across the screen, anxious to see our own listed among the lucky ones.
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+If a snow day was announced, it was pure elation as we rushed to get our winter bibs and boots on to go out and play in the fresh snow, joining our friends and neighbors for sledding or snowballing or snowman building. We’d return home after a few hours for hot chocolate and soup before putting on dry clothes and heading back out again.
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+Growing up on the Jersey Shore, we rarely had to endure very snowy winters. But each year, we could count on at least one or two snow days minimum. Sometimes, like the great blizzard of ’96 — which, at one point, rendered the whole of the New Jersey Turnpike closed — we’d get entire stretches of days off to play in our sudden winter wonderland.
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+Of course, back then we didn’t have access to the internet like we do now. We couldn’t be in class from the comfort of home.
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+With the proliferation of virtual learning, do kids even get to enjoy the magic of an unexpected snow day anymore? Are true snow days an endangered species?
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+Earlier this month, nearly 1 million students in New York City’s public school system learned that their schools would remain open, despite the threat of a predicted half-foot of snowfall (in the end, estimates ended up being a bit high, with John F. Kennedy International Airport reporting just over 4 inches of accumulation). Classes would be held virtually, they were told — even though there was a network outage that prevented smooth proceedings. There was plenty of pushback, even including some reports of teachers telling parents to ignore the edict from Mayor Eric Adams.
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+But the point remained: Access to virtual learning was robbing kids of one of the premier highlights of youth (at least in those geographical sweet spots like New Jersey, where snow falls sometimes in the winter).
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+Because there’s nothing wrong with a day or two spent sitting at home, making snowmen. At least not according to Melanie Killen, a professor of human development and quantitative methodology at the University of Maryland.
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+“Snow days need to be sledding days,” she said. Snow days offer “a different kind of learning … an important kind of learning.”
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+I spoke with Killen a few days after those inches of snow blanketed New York City, wondering what effect the growing loss of snow days has on school-aged children. I suggested snow days offer students something of a brain break from the regular grind of school-based learning. Killen was quick to correct me.
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+“I wouldn’t necessarily call it a ‘brain break,’” Killen said. “Kids are out there using their brains in different ways on snow days. It’s a break from the traditional teacher-children dissemination, which kids need.”
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+Killen likened the typical snow day of the past to something like an extended recess, highlighting how during that less structured playtime, kids continue to learn. She added that almost everything about playing in the snow offers some sort of quantifiable lesson about the world.
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+Killen described how throwing snowballs was like a lesson in physics, how sledding involved implicit mathematics, and how even the very snow itself provided children with a sense of material understanding. After all, anyone who’s ever played in the stuff knows exactly what kind of snow makes the best snowballs.
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+These more free-form social settings also allow children to learn how to interact with other people in the world, how to infer intentions and expectations, and how to learn about fairness, morality, and justice. This is known as social cognition, which, according to the American Psychological Association, is the way “people perceive, think about, interpret, categorize, and judge their own social behaviors and those of others.”
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+According to Killen, free-form interactions, like those on a snow day, are prime real estate for the development of social cognition in children.
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+Going virtual on snowy days “undermines the power of peer interactions, which are fundamental for contributing to change and development,” Killen said.
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+To contest Adams’s point: When children are making snowmen, they are absolutely learning.
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+Where I live now in Chapel Hill, North Carolina, Andy Jenks is the name people anticipate hearing on a snowy weekday morning. As the chief communications officer for Chapel Hill/Carrboro City Schools,Jenks is the guy on the prerecorded voice message telling us whether or not our schools are closed for the day when snow falls or ice accumulates. Jenks has become such a legend among the local high school kids that homemade signs sporting Jenks’s face were held high above the student section at the recent Chapel Hill/East Chapel Hill rivalry basketball game.
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+But while Jenks may get all the praise (or disdain, depending on the nature of the voicemail), the decision on whether or not to close schools is not his. Rather, it’s a decision made by the school system’s superintendent after being informed by what Jenks calls the system’s “operations team.” After observing weather reports and taking a look out the window on a snowy morning, that team makes a suggestion to the superintendent, who then has the final call as to whether or not schools will be closed for that day. Some version of this is standard protocol for most school districts in America.
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+“Generally speaking, it comes down to safety,” Jenks said. “If we believe we can safely transport kids to school and if our staff can safely transport themselves to school … then we can have school. But if things call safety into question — an accumulation of snow or ice, wind, or other factors — at that point … [we might] close school altogether.”
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+Jenks also points to local and regional infrastructure as a pivotal factor in the decisions to keep schools open or closed. And while everyone loves to dunk on how the South handles snow, it’s important to remember that places like ours simply aren’t armed with fleets of plows and salt trucks. It can sometimes take days to clear every road in town.
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+Considering as much, if a small portion of the student body lives on roads that can’t be plowed, the whole of the student body gets a snow day.
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+“No one is going to get left behind on account of the weather,” Jenks said.
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+There’s also the question of what’s become known as the digital divide: the socioeconomic gap between those who have reliable access to computers and the internet and those who don’t. For a relatively wealthy school district like Chapel Hill/Carrboro, where each middle and high school student gets a school-issued laptop, it’s less of an issue. Some studies have estimated that as many as 12 million kids across America lack sufficient access to reliable internet access. Some school districts, like Chapel Hill/Carrboro, have taken to sending some students home with wifi hotspots when extended closures are forecast. One district in Wisconsin has even experimented with using drones to deliver connectivity.
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+In many ways, it’s simply easier for the district to cancel school on a snowy day.
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+Sadly, the students of Chapel Hill/Carrboro City Schools haven’t heard Andy Jenks’s prerecorded voice telling them they have a sudden day off due to snow in some time. It’s been 764days at the time of this writing. It’s a number Jenks hopes will soon reset to zero.
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+“All of us used to be kids and we do appreciate the enjoyment of a good old-fashioned snow day on a fresh winter morning,” he said. “We still believe that kids should have that experience.”
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+
From The Hindu: Sports
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India need 192 runs to win 4th Test against England - Ashwin had taken three wickets in quick succession to help India make a comeback after the hosts conceded a 46-run first-innings lead
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Yathiraj, Pramod, Krishna win gold at Para Badminton World Championships - The world No. 3 Yathiraj, a Paralymic silver medallist, outwitted Indonesia’s Fredy Setiawan 21-18 21-18 in SL4 final (standing/lower limb impairment/minor) for her maiden world title
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ICC suspends Hasaranga for two matches, Gurbaz fined 15% of match fees - Hasaranga was found guilty of breaching the article 2.13 of the ICC Code of Conduct for Players and Player Support Personnel when towards the end of the third and final T20I on February 21 when he approached the on-field umpire Lyndon Hanibal to criticise a decision regarding a full toss delivery not being adjudged a no-ball.
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Australia win rain-hit third T20 against New Zealand by 27 runs - Responding to Australia’s 118-4 from 10.4 overs, New Zealand scored 98-3, falling short of a target adjusted to 126 off 10 overs under the Duckworth-Lewis-Stern method
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Morning digest | Indian ‘helper’ dies in Russian war zone; Centre discloses key consumption expenditure survey data after 11-year gap, and more - Here is a select list of stories to start the day
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From The Hindu: National News
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PM Modi dedicates five AIIMS, inaugurates multiple development projects from Rajkot - Prime Minister also laid the foundation stone and dedicated to the nation more than 200 Health Care Infrastructure Projects worth more than ₹11,500 crore across 23 States /UTs.
How hike in Fair and Remunerative Price for sugarcane will affect farmers and sugar mills | Explained - As Centre hikes of sugarcane FRP amid farmers protest, problems plaguing sugar industry remain unsolved. Here’s a look at what FRP is, how it affects MSP and the ongoing protests
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4 MLAs from Congress, NPP join the BJP in Arunachal Pradesh - Congress and the National People’s Party now have two legislators each in the 60-member House
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Small industries, artisans suffering in country as Chinese goods flooding markets: Rahul Gandhi - Gandhi was addressing a gathering after his ‘Bharat Jodo Nyay Yatra‘ arrived in Aligarh from Moradabad via Sambhal
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From BBC: Europe
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Navalny’s body returned to mother 8 days after death - Alexei Navalny’s mother has been demanding the return of his body since his death in a Russian prison.
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‘I refuse to die’: Couple saved from Valencia fire hail dramatic rescue - Sara Jorge and her boyfriend say they were saved by a mixture of luck and a desire to live.
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Eiffel Tower set to reopen after six-day strike - Workers first walked out on Monday in a dispute over the way the tower was managed.
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Farmers’ anger erupts at trade show in Paris - Clashes erupt between security forces and farmers protesting at the presence of President Macron.
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Two years into Russia’s invasion, exhausted Ukrainians refuse to give up - Ukrainians may be fatigued by the war, but they still see it as a fight for survival.
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From Ars Technica
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How your sensitive data can be sold after a data broker goes bankrupt - Sensitive location data could be sold off to the highest bidder. - link
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Yelp: It’s gotten worse since Google made changes to comply with EU rules - Users are even more likely to stick with Google due to one change, says Yelp. - link
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RTO doesn’t improve company value, but does make employees miserable: Study - Data is consistent with bosses using RTO to reassert control and scapegoat workers. - link
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Vending machine error reveals secret face image database of college students - Facial-recognition data is typically used to prompt more vending machine sales. - link
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Plucky crew of Star Trek: Discovery seeks a strange artifact in S5 trailer - “It has been a hell of a journey. But everything ends someday.” - link
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+
From Jokes Subreddit
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A bus stops and two Italian men get on. -
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+They sit down and engage in an animated conversation. The lady sitting behind them ignores them at first, but her attention is caught when she hears one of the men say the following:
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+“Emma come first. Den I come. Den two asses come together. I come once-a-more. Two asses, they come together again. I come again and pee twice. Then I come one lasta time.”
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+“You foul-mouthed swine. In this country we don’t talk about our sex lives in public!” yelled the shocked lady.
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+“Hey, coola down lady,” said the man. “Who talkin’ abouta sexa? I’m a justa tellin’ my frienda how to spella ‘Mississippi’.”
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a boy was standing in his father’s wheat farm for several hours….. -
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+His father finally asked him “son, why are you wasting your time standing out here?” Son replied “father, I am not wasting my time, I am trying to win a nobel prize!” The father thought he was studying the environment and was impressed, still he asked “how do you plan on doing that?” Son replied “I have heard that people who won Nobel prizes were outstanding in various fields. So I am doing the same.”
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@BronzeHammer
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