Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes -
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+A substantial proportion of acute SARSCoV2 infection cases exhibit gastrointestinal symptoms, yet the genetic determinants of these extrapulmonary manifestations are poorly understood. Using survey data from 239,866 individuals who tested positively for SARSCoV2, we conducted a multi-ancestry GWAS of 80,289 cases of diarrhea occurring during acute COVID19 infection (33.5%). Six loci (CYP7A1, LZFTl1/CCR9, TEME182, NALCN, LFNG, GCKR) met genomewide significance in a trans-ancestral analysis. The top significant GWAS hit mapped to the CYP7A1 locus, which plays an etiologic role in bile acid metabolism and is in high LD (r2= 0.93) with the SDCBP gene, which was previously implicated in antigen processing and presentation in the COVID-19 context. Another association was observed with variants in the LZTFL1/CCR9 region, which is a known locus for COVID19 susceptibility and severity. PheWAS showed a shared association across three of the six SNPs with irritable bowel syndrome (IBS) and its subtypes. Mendelian randomization showed that genetic liability to IBS-diarrhea increased (OR=1.40,95%,CI[1.33,1.47]), and liability to IBS-constipation decreased (OR=0.86, 95%CI[0.79,0.94]) the relative odds of experiencing COVID19+ diarrhea. Our genetic findings provide etiological insights into the extrapulmonary manifestations of acute SARSCoV2 infection.
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Ready-To-Use Investigational Stem Cells, MiSaver, in Patients with Recent Acute Myocardial Infarction, 1 year follow up from a Phase 1 Safety Study -
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+Abstract: Objectives: This study aimed to assess the safety and preliminary efficacy of MiSaver stem cells in enhancing left ventricular ejection function and functional activity among patients with acute myocardial infarction (AMI). Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with heart attacks and strokes accounting for a significant portion of deaths. Recovery of left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is crucial for prognosis, as patients with poor LVEF recovery face increased risks of sudden cardiac arrest events and mortality. Stem cell therapy offers regenerative potential for cardiovascular diseases, yet accessibility remains limited. This study investigates the safety and efficacy of MiSaver, a prefabricated stem cell investigational product, in recent AMI patients, aiming to enhance accessibility and patient outcomes. Methods: Patients admitted for AMI with reduced LVEF (≤45%) were eligible. MiSaver stem cells, matched for blood group, were administered to participants in cohorts of five, with escalating dosages (0.5x10^7, 1.6x10^7, and 5.0x10^7 cells/kg) 2-5 days post-AMI onset. Echocardiographic assessments were conducted upon admission, at 6 months, and at 12 months post-treatment. Results: Out of the initially planned 15 participants, eleven were enrolled in the study. The trial was halted prematurely due to challenges associated with the COVID-19 pandemic and impractical transportation logistics. During the 12-month follow-up period, no study-related adverse events or signs of graft-versus-host disease were reported. At 12 months post-treatment, both the low and middle dose groups, as well as participant 11, showed improved left ventricular ejection fraction (LVEF), accompanied by enhanced Canadian Cardiovascular Society (CCS) class grades compared to baseline. Conclusion: Intravenous infusion of MiSaver stem cells in AMI patients demonstrated safety and tolerability for low and middle dosage groups, suggesting potential for improving left ventricular function following AMI. However, further research with larger cohorts and controlled placebos is necessary to confirm these findings and address trial limitations encountered.
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Disease diagnostics using machine learning of immune receptors -
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+Clinical diagnosis typically incorporates physical examination, patient history, and various laboratory tests and imaging studies, but makes limited use of the human system’s own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis (Mal-ID), an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences. Human-interpretable features of the model recapitulate known immune responses to SARS-CoV-2, Influenza, and HIV, highlight antigen-specific receptors, and reveal distinct characteristics of Systemic Lupus Erythematosus and Type-1 Diabetes autoreactivity. This analysis framework has broad potential for scientific and clinical interpretation of human immune responses.
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How Long is the Worst Part of the COVID-19 Mortality Surge? -
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+Objectives: Define and quantify the critical surge period of existing on-line COVID-19 mortality data; this could be instrumental to decision makers to determine how long health controls should be in place, and how long to expect the public health system to be in great stress. Create and share on-line, open-source software to continuously monitor critical surge periods in various communities as the data set grows. Test the critical surge period computational method on hierarchical data sets of various communities: a) globally; b) countrywide (states in the US); and c) statewide (counties/towns in the US states). Study Design: This was an open-source, on-line, COVID-19 data analytics development with support for web-browsers on any current mobile device. Methods: On-line, timely data for COVID-19 mortality was automatically retrieved by a developed application using the programming Python language and Jupyter electronic notebooks. An on-line, version-controlled code repository was created for the application and also used for providing an open execution environment for the research community. The data was fitted to a modified sigmoid function via an automated non- linear least-squares method. Three optimal parameters were computed and the critical times for the maximum and minimum curvatures of the function were used to obtain the critical surge period. The goodness of the fit was measured by a standard coefficient of determination, and alternatively, by direct pointwise relative error. Results: The software developed (a Python package) is called covid-surge (repository URL: htttps://github.com/dpploy/covid-surge) and available for download from PyPI on-line (URL: https://pypi.org/project/covid-surge/). Using covid-surge, the critical surge period was computed for the communities with the most evolved COVID-19 outbreak. At the time of this writing, the critical surge period was calculated for all countries with fully evolved mortality (12 out of 188) and found to be in average 23 days with 3 days of standard deviation. Similarly, for all states/districts in the US (20 out of 56), the computed average was 25 days with 3 days of standard deviation. Likewise, for the same states in the US, counties/towns that had fully evolved mortality surge (91 total out of 981 that had death cases) had the overall average of the surge period equal to 23 days with a standard deviation of 3 days. The accuracy of these results can be reproduced on-line using the software provided. In addition, forward results using newer data can also be generated by the research community using covid-surge. Conclusions: The surge period for hierarchical data including 12 countries, 20 US states, and 91 US counties/towns is remarkably similar: a 24-day period with 3-day standard deviation for all communities across many countries and the US. All of these communities were under similar COVID-19 controls, including social distancing, improved hygiene, and isolation which helps explain the constancy of the surge period. That is, these communities experienced nearly the same amount of time during the most stressful period of the mortality surge. Although the extent to which epidemic controls are applied can vary from community to community, this study shows that the variability of the surge period is small. As the COVID-19 sweeps over the continents, additional data will be available for fully-evolved communities and a later comparison can be made with covid-surge on-line. This study suggests that communities not yet fully affected by the COVID-19 mortality may expect a period of high stress on their public health system of about 30 days (lower bound). That is, health care organizations should plan to operate at full capacity for a minimum of 30 days.
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Solid-liquid partitioning of Dengue, West Nile, Zika, Hepatitis A, Influenza A, and SARS-CoV-2 viruses in wastewater from across the United States -
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+Limited information is available on the fate of respiratory and arthropod-borne viruses in wastewater. Enteric viruses have been extensively studied in wastewater treatment plants, however partition coefficients have not been well documented. This information is essential for interpreting wastewater-based surveillance (WBS) data and optimizing sample collection and processing methods. In this study, we examined the solid-liquid partitioning behavior of Dengue, West Nile, Zika, Hepatitis A, Influenza A, and SARS-CoV-2 viruses in wastewater. Samples were collected from the primary sludge line of eleven wastewater treatment plants across the United States and spiked with varying concentrations of each virus. Solid and liquid fractions were separated via centrifugation. Viral nucleic acids were extracted and quantified using reverse-transcription digital droplet PCR (RT-ddPCR). Partition coefficients (KF), determined using the Freundlich adsorption model, ranged from 4.0✕10^2 mL/g to 3.9✕10^6 mL/g (median = 1.1✕10^4 mL/g). KF values were not significantly different between viruses. However, significant differences were observed between KF for Zika and West Nile Virus between wastewater treatment plants. Further research is needed to understand how wastewater characteristics might impact the partition of viral markers. The results from this experiment underscore the importance of considering wastewater solids for the early detection and monitoring of viral infectious diseases, particularly in regions with low prevalence of infections.
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COVerAGE-JP: COVID-19 Deaths by Age and Sex in Japan -
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+This database (https://github.com/fumiyau/COVerAGE-JP) collects COVID-19 deaths by age, sex, date, and region in Japan. As with other causes of deaths, deaths related to COVID-19 are reported by local public health center (Hokenjo), which is located in every prefecture and major metropolitan/large cities. 47 prefectures and some metropolitan cities then collect the information about COVID-19 cases and deaths to report the Ministry of Health, Labour, and Welfare (MHLW). Although MHLW provides a summary statistics about the COVID-19 cases and deaths on their webpage, the distribution broken down by age and sex is not available, that leads many volunteering organizations to collect COVID-19 information based on prefectural/municipality reports. However, even these databases do not provide COVID-19 deaths by age and sex. This database thus aims to fill in the gap by collecting COVID-19 related deaths reported by various sources as I discuss below, including prefectures’ press releases or media sources. This document explains the collection of data sources and potential uses of the data.
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Mutational pressure drives enhanced release of proteasome-generated public CD8+ T cell epitopes from SARS-CoV-2 RBD of Omicron and its current lineages -
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+The COVID-19 pandemic was the most dramatic in the newest history with nearly 7 million deaths and global impact on mankind. Here we report binding index of 305 HLA class I molecules from 18,771 unique haplotypes of 28,104 individuals to 821 peptides experimentally observed from spike protein RBD of 5 main SARS-CoV-2 strains hydrolyzed by human proteasomes with constitutive and immune catalytic phenotypes. Our data read that 4 point mutations in the hACE2-binding region RBD496-513 of Omicron B1.1.529 strain results in a dramatic increase of proteasome-mediated release of two public HLA class I epitopes. Global population analysis of HLA class I haplotypes, specific to these peptides, demonstrated decreased mortality of human populations enriched in these haplotypes from COVID-19 after but not before December, 2021, when Omicron became dominant SARS-CoV-2 strain. Noteworthy, currently circulating BA.2.86 and JN.1 lineages contain no amino acid substitutions in RBD496-513 thus preserving identified core epitopes.
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Machine learning-driven COVID-19 early triage and large-scale testing strategies based on the 2021 Costa Rican Actualidades survey -
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+The COVID-19 pandemic underscored the importance of mass testing in mitigating the spread of the virus. This study presents mass testing strategies developed through machine learning models, which predict the risk of COVID-19 contagion based on health determinants. Using the data from the 2021 “Actualidades” survey in Costa Rica, we trained models to classify individuals by contagion risk. After theorize four possible strategies, we evaluated these using Monte Carlo simulations, analyzing the distribution functions for the number of tests, positive cases detected, tests per person, and total costs. Additionally, we introduced the metrics, efficiency and stock capacity, to assess the performance of different strategies. Our classifier achieved an AUC-ROC of 0.80 and an AUC-PR of 0.59, considering a disease prevalence of 0.26. The fourth strategy, which integrates RT-qPCR, antigen, and RT-LAMP tests, emerged as a cost-effective approach for mass testing, offering insights into scalable and adaptable testing mechanisms for pandemic response.
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Molecular epidemiology of invasive Group A Streptococcal infections before and after the COVID-19 pandemic in Switzerland -
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+Group A Streptococcus (GAS, aka Streptococcus pyogenes) poses a significant public health concern, causing a diverse spectrum of infections with high mortality rates. Following the COVID-19 pandemic, a resurgence of invasive GAS (iGAS) infections has been documented, necessitating efficient outbreak detection methods. Whole genome sequencing (WGS) serves as the gold standard for GAS molecular typing, albeit constrained by time and costs. This study aimed to characterize the postpandemic increased prevalence of iGAS on the molecular epidemiological level in order to assess whether new, more virulent variants have emerged, as well as to assess the performance of the rapid and cost-effective Fourier-transform infrared (FTIR) spectroscopy as an alternative to WGS for detecting and characterizing GAS transmission routes. A total of 66 iGAS strains isolated from nine Swiss hospitals during the COVID-19 post-pandemic increased GAS prevalence were evaluated and compared to 15 strains collected before and 12 during the COVID-19 pandemic. FT-IR measurements and WGS were conducted for network analysis. Demographic, clinical, and epidemiological data were collected. Skin and soft tissue infection was the most common diagnosis, followed by primary bacteremia and pneumonia. Viral co-infections were found in 25% of cases and were significantly associated with more severe disease requiring intensive care unit admission. WGS analysis did not reveal emerging GAS genetic distinct variants after the COVID-19 pandemic, indicating the absence of a pandemic-induced shift. FT-IR spectroscopy exhibited limitations in differentiating genetically distant GAS strains, yielding poor overlap with WGS-derived clusters. The emm1/ST28 gebotype was predominant in our cohort and was associated with five of the seven deaths recorded, in accordance with the molecular epidemiological data before the pandemic. Additionally, no notable shift in antibiotic susceptibility patterns was observed. Our data suggest that mainly non-pathogen related factors contributed to the recent increased prevalence of iGAS.
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Discovery of RdRp Thumb-1 as a novel broad-spectrum antiviral family of targets and MDL-001 as a potent broad-spectrum inhibitor thereof - Part I: A Bioinformatics and Deep Learning Approach -
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+Positive sense, single-stranded RNA (+ssRNA) viruses consist of 12+ viral families that contain mild pathogens to pandemic-causing viruses like SARS-CoV-2, yet all share a vital and highly conserved RNA-dependent RNA polymerase (RdRp). While RdRp is the target of several viral inhibitors, the active site has several pitfalls when translating in vitro inhibitors to the clinic. The highly polar residues within the active site often necessitate the use of highly polar or charged compounds, especially when designing nucleoside analog inhibitors, posing significant challenges in optimizing drug-likeness and membrane permeability for clinical efficacy. Here, we investigated the broad-spectrum potential of the allosteric Thumb-1 cryptic site of the RdRp, which to date has only been adequately studied in Hepatitis C Virus (HCV). To explore this potential antiviral target, we used a suite of bioinformatics techniques, including homology modeling and multiple sequence alignments, to reveal the conserved landscape of the Thumb-1 site across +ssRNA viruses. We then used ChemPrint, our Mol-GDL (Molecular-Geometric Deep Learning) machine learning model to predict drug inhibition of the Thumb-1 site in RdRp across +ssRNA viruses. Here, we identify MDL-001 as a promising broad-spectrum antiviral candidate with favorable properties that enable oral and once-a-day dosing. We also show how the cryptic nature of the Thumb-1 site masks itself to conventional virtual screening techniques, like docking, where activity prediction is heavily based on solving or predicting an accurate structure of the open pocket. This study demonstrates the utility of this approach in drug discovery for broad-spectrum antivirals that target the Thumb-1 site.
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Predicting Functional Conformational Ensembles and Binding Mechanisms of Convergent Evolution for SARS-CoV-2 Spike Omicron Variants Using AlphaFold2 Sequence Scanning Adaptations and Molecular Dynamics Simulations -
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+In this study, we combined AlphaFold-based approaches for atomistic modeling of multiple protein states and microsecond molecular simulations to accurately characterize conformational ensembles and binding mechanisms of convergent evolution for the SARS-CoV-2 Spike Omicron variants BA.1, BA.2, BA.2.75, BA.3, BA.4/BA.5 and BQ.1.1. We employed and validated several different adaptations of the AlphaFold methodology for modeling of conformational ensembles including the introduced randomized full sequence scanning for manipulation of sequence variations to systematically explore conformational dynamics of Omicron Spike protein complexes with the ACE2 receptor. Microsecond atomistic molecular dynamic simulations provide a detailed characterization of the conformational landscapes and thermodynamic stability of the Omicron variant complexes. By integrating the predictions of conformational ensembles from different AlphaFold adaptations and applying statistical confidence metrics we can expand characterization of the conformational ensembles and identify functional protein conformations that determine the equilibrium dynamics for the Omicron Spike complexes with the ACE2. Conformational ensembles of the Omicron RBD-ACE2 complexes obtained using AlphaFold-based approaches for modeling protein states and molecular dynamics simulations are employed for accurate comparative prediction of the binding energetics revealing an excellent agreement with the experimental data. In particular, the results demonstrated that AlphaFold-generated extended conformational ensembles can produce accurate binding energies for the Omicron RBD-ACE2 complexes. The results of this study suggested complementarities and potential synergies between AlphaFold predictions of protein conformational ensembles and molecular dynamics simulations showing that integrating information from both methods can potentially yield a more adequate characterization of the conformational landscapes for the Omicron RBD-ACE2 complexes. This study provides insights in the interplay between conformational dynamics and binding, showing that evolution of Omicron variants through acquisition of convergent mutational sites may leverage conformational adaptability and dynamic couplings between key binding energy hotspots to optimize ACE2 binding affinity and enable immune evasion.
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Improving estimates of epidemiological quantities by combining reported cases with wastewater data: a statistical framework with applications to COVID-19 in Aotearoa New Zealand -
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+Background: Timely and informed public health responses to infectious diseases such as COVID-19 necessitate reliable information about infection dynamics. The case ascertainment rate (CAR), the proportion of infections that are reported as cases, is typically much less than one and varies with testing practices and behaviours, making reported cases unreliable as the sole source of data. The concentration of viral RNA in wastewater samples provides an alternate measure of infection prevalence that is not affected by clinical testing, healthcare-seeking behaviour or access to care. Methods: We constructed a state-space model with observed data of levels of SARS-CoV-2 in wastewater and reported case incidence and estimated the hidden states of R and CAR using sequential Monte Carlo methods. Results: Here, we analysed data from 1 January 2022 to 31 March 2023 from Aotearoa New Zealand. Our model estimates that R peaked at 2.76 (95% CrI 2.20, 3.83) around 18 February 2022 and the CAR peaked around 12 March 2022. We calculate that New Zealand9s second Omicron wave in July 2022 was similar in size to the first, despite fewer reported cases. We estimate that the CAR in the BA.5 Omicron wave in July 2022 was approximately 50% lower than in the BA.1/BA.2 Omicron wave in March 2022. Conclusions: Estimating R, CAR, and cumulative number of infections provides useful information for planning public health responses and understanding the state of immunity in the population. This model is a useful disease surveillance tool, improving situational awareness of infectious disease dynamics in real-time.
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Distal Protein-Protein Interactions Contribute to SARS-CoV-2 Main Protease Substrate Binding and Nirmatrelvir Resistance -
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+SARS-CoV-2 main protease, Mpro, is responsible for the processing of the viral polyproteins into individual proteins, including the protease itself. Mpro is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g. E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g. P252L, T21I, L50F), which restore the fitness of viral replication. Although the mechanism of resistance for the active site mutations is apparent, the role of the non-active site mutations in fitness rescue remains elusive. In this study, we use the model system of a Mpro triple mutant (L50F/E166A/L167F) that confers not only nirmatrelvir drug resistance but also a similar fitness of replication compared to the wild-type both in vitro and in vivo. By comparing peptide and full-length Mpro protein as substrates, we demonstrate that the binding of Mpro substrate involves more than residues in the active site. In particular, L50F and other non-active site mutations can enhance the Mpro dimer-dimer interactions and help place the nsp5-6 substrate at the enzyme catalytic center. The structural and enzymatic activity data of Mpro L50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying Mpro and substrate interactions, and offers important insights into Mpro function, resistance development, and inhibitor design.
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Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells -
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+The ability of SARS-CoV-2 to evade antiviral immune signaling in the airway contributes to the severity of COVID-19 disease. Additionally, COVID-19 is influenced by age and has more severe presentations in older individuals. This raises questions about innate immune signaling as a function of lung development and age. Therefore, we investigated the transcriptome of different cell populations of the airway epithelium using pediatric and adult lung tissue samples from the LungMAP Human Tissue Core Biorepository. Specifically, lung lobes were digested and cultured into a biomimetic model of the airway epithelium on an air-liquid interface. Cells were then infected with SARS-CoV-2 and subjected to single-cell RNA sequencing. Transcriptional profiling and differential expression analysis were carried out using Seurat. The clustering analysis identified several cell populations: club cells, proliferating epithelial cells, multiciliated precursor cells, ionocytes, and two biologically distinct clusters of ciliated cells (FOXJ1high and FOXJ1low). Interestingly, the two ciliated cell clusters showed different infection rates and enrichment of processes involved in ciliary biogenesis and function; we observed a cell-type-specific suppression of innate immunity in infected cells from the FOXJ1low subset. We also identified a significant number of genes that were differentially expressed in lung cells derived from children as compared to adults, suggesting the differential pathogenesis of SARS-CoV-2 infection in children versus adults. We discuss how this work can be used to identify drug targets to modulate molecular signaling cascades that mediate an innate immune response and begin to understand differences in COVID-19 outcomes for pediatric vs. adult populations.
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Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans -
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+Middle-East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections in endemic regions. Most vaccines and therapeutics in development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts, however, are limited by a poor understanding of antibody responses elicited by infection along with their durability, fine specificity and contribution of distinct S antigenic sites to neutralization. To address this knowledge gap, we analyzed S-directed binding and neutralizing antibody titers in plasma collected from individuals infected with MERS-CoV in 2017-2019 (prior to the COVID-19 pandemic). We observed that binding and neutralizing antibodies peak 1 to 6 weeks after symptom onset/hospitalization, persist for at least 6 months, and broadly neutralize human and camel MERS-CoV strains. We show that the MERS-CoV S1 subunit is immunodominant and that antibodies targeting S1, particularly the RBD, account for most plasma neutralizing activity. Antigenic site mapping revealed that polyclonal plasma antibodies frequently target RBD epitopes, particularly a site exposed irrespective of the S trimer conformation, whereas targeting of S2 subunit epitopes is rare, similar to SARS-CoV-2. Our data reveal in unprecedented details the humoral immune responses elicited by MERS-CoV infection, which will guide vaccine and therapeutic design.
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Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation - Conditions: COVID-19 Interventions: Other: Guidebook; Other: Guidebook and Myofascial Reorganization® (RMF). Sponsors: University of the State of Santa Catarina; Larissa Sinhorim Recruiting
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Effect of Probiotic Strain Lactobacillus Paracasei PS23 on Brain Fog in People With Long COVID - Conditions: Long COVID; Brain Fog; Cognitive Change Interventions: Dietary Supplement: Lactobacillus paracasei PS23; Dietary Supplement: microcrystalline cellulose Sponsors: Taipei Veterans General Hospital, Taiwan Not yet recruiting
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Evaluation of the Impact of Rehabilitation Strategies and Early Discharge After Respiratory Failure - Conditions: Acute Respiratory Failure Interventions: Behavioral: Standard of Care; Behavioral: Rehabilitation Sponsors: Hospital Israelita Albert Einstein Not yet recruiting
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Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD) - Conditions: Post-Acute Sequelae of COVID-19 Interventions: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program Sponsors: University of Minnesota Recruiting
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From PubMed
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TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency - INTRODUCTION: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition.
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Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19 - CONCLUSIONS: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.
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Quercetin inhibition of porcine intestinal alpha coronavirus in vitro and in vivo - CONCLUSIONS: Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.
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Immunogenicity and efficacy of VLA2001 vaccine against SARS-CoV-2 infection in male cynomolgus macaques - CONCLUSIONS: We demonstrate that the VLA2001 adjuvanted vaccine is immunogenic both in mouse and NHP models and prevent cynomolgus macaques from the viruses responsible of COVID-19.
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A rigorous theoretical and numerical analysis of a nonlinear reaction-diffusion epidemic model pertaining dynamics of COVID-19 - The spatial movement of the human population from one region to another and the existence of super-spreaders are the main factors that enhanced the disease incidence. Super-spreaders refer to the individuals having transmitting ability to multiple pathogens. In this article, an epidemic model with spatial and temporal effects is formulated to analyze the impact of some preventing measures of COVID-19. The model is developed using six nonlinear partial differential equations. The infectious…
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A randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV) - CONCLUSION: Viral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.
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SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling - Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since its emergence in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse…
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Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19? - The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and…
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In vitro suppression of porcine epidemic diarrhea virus by Panax notoginseng saponins: assessing antiviral potential - Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity…
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The death domain-associated protein suppresses porcine epidemic diarrhea virus replication by interacting with signal transducer and activator of transcription 1 and inducing downstream ISG15 expression - Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute enteric disease in piglets and severely threatens the pig industry all over the world. Death domain-associated protein (DAXX) is a classical chaperone protein involved in multiple biological processes, such as cell apoptosis, transcriptional regulation, DNA damage repair, and host innate immunity. However, whether DAXX functions in the anti-PEDV innate immune responses remains unclear. In this study, we found that…
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Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots - CONCLUSION: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.
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Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection - CONCLUSION: Both LNP-Trap and LNP-Trim formulations were able to safely and effectively inhibit SARS-CoV-2 pseudoviral infection in airway epithelial cells. These studies provide proof-of-principle for a localized treatment approach for SARS-CoV-2 in the upper airway.
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Transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus - Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been explored extensively, the pathophysiology of the disease is not completely understood. Moreover, genes and potential treatment targets related to auditory hallucinations remain unknown. In this study, we examined transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus in rats by performing RNA…
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Acceptance, safety, and immunogenicity of a booster dose of inactivated SARS-CoV-2 vaccine in patients with primary biliary cholangitis - Inactivated coronavirus disease 2019 (COVID-19) vaccines showed impaired immunogenicity in some autoimmune diseases, but it remains unclear in primary biliary cholangitis (PBC). This study aimed to explore the antibody response to the inactivated COVID-19 vaccine in individuals with PBC, as well as to evaluate coverage, safety, and attitudes toward the COVID-19 vaccine among them. Two cohorts of patients with PBC were enrolled in this study. One cohort was arranged to evaluate the immunogenicity…
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Vgamma9Vdelta2 T-cells are potent inhibitors of SARS-CoV-2 replication and represent effector phenotypes in COVID-19 patients - Vγ9Vδ2 T-cells play a key role in the innate immune response to viral infections through butyrophilin (BTN)-3A. Here, we reported that blood Vγ9Vδ2 T-cells decreased in clinically mild COVID-19 compared to healthy volunteers (HV), and was maintained up to 28-days and in the recovery period. Terminally differentiated Vγ9Vδ2 T-cells tend to be enriched on the day of diagnosis, 28-days after and during the recovery period. These cells showed cytotoxic and inflammatory activities following…
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From Patent Search
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Biden’s Increasingly Contradictory Israel Policy - A former State Department official explains the Administration’s sharpening public critique of Israel’s war and simultaneous refusal to “impose a single cost or consequence.” - link
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How Chinese Students Experience America - COVID, guns, anti-Asian violence, and diplomatic relations have complicated the ambitions of the some three hundred thousand college students who come to the U.S. each year. - link
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The Hottest Restaurant in France Is an All-You-Can-Eat Buffet - Les Grands Buffets features a seven-tiered lobster tower, a chocolate fountain, and only what it considers traditional French food. Gourmands are willing to wait months for a table. - link
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So You Think You’ve Been Gaslit - What happens when a niche clinical concept becomes a ubiquitous cultural diagnosis. - link
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The Brazilian Special-Forces Unit Fighting to Save the Amazon - As miners ravage Yanomami lands, combat-trained environmentalists work to root them out. - link
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From Vox
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“Equivalent to having 50 Super Bowls”: The staggering — and lucrative — scale of eclipse tourism -
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+The upcoming solar eclipse on April 8 should be viewed through eclipse glasses, no matter where you’re watching it from. | Michael M. Santiago/Getty Images
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+More people will travel for this event than for one of the country’s biggest games.
+
+Instead, it could well be the upcoming solar eclipse on April 8, which could see as many as 4 million people in the US journeying to view it. This year’s total solar eclipse is particularly special for the US: Although the phenomenon happens globally every 18 months, this one will be visible across a huge swath of the country, making witnessing it more accessible. Plus, the eclipse is expected to last longer than the prior one did in 2017, adding to its allure.
+
+
+When it comes to the scale of travel we can expect, it’s “equivalent to having 50 Super Bowls simultaneously from Texas to Maine,” says Michael Zeiler, who helps run the Great American Eclipse website. Such tourism is set to generate upward of $1 billion in revenue across numerous cities, from Austin, Texas, to Rochester, New York. These cities will all be prime places to see the eclipse, which will be fully visible in parts of the southern US, the Midwest, and New England.
+
+
+
+
+NASA’s interactive map shows best times, places to watch total solar eclipse https://t.co/KMh6vmdvdM
+
+Hotels and campgrounds in places where the full eclipse will be visible have long been sold out, with tens of thousands of visitors expected to flock to these cities. “This is likely going to be the single biggest tourism event we’ve ever had,” Michael Pakko, a University of Arkansas economist, tells the Washington Post, regarding the more than $100 million in revenue the state is expecting. Towns and businesses are also going all out by investing in eclipse music festivals, theme park rides, and viewing parties.
+
+
+Those traveling for this year’s eclipse join a long tradition of eclipse-chasers, who’ve been in awe of these events and who revel in sharing this communal experience. The rarity of such phenomena and the opportunity to enjoy them simultaneously with others bolsters their draw, experts say. The interest in eclipse tourism also comes as people’s willingness to travel has rebounded following the pandemic.
+
+
+“The simple now-or-never of an eclipse is extremely motivating,” Jaime Kurtz, a psychology professor at James Madison University, told Vox. “The collective enthusiasm for the eclipse might also be a driving force. It’s unifying.”
+
+
+There’s something about eclipses
+
+
+Eclipse-chasers, or people who seek out eclipses when they happen, are drawn to this phenomena because of how unique it is, how infrequently it happens, and how much wonder it inspires. Some also have a specific interest in astronomy and space, and see eclipses as a way to explore that.
+
+
+“It lifts you out of your everyday experience, and is such a remarkable feeling to be suddenly enveloped by a wave of darkness for a few minutes; it’s like standing on the surface of an alien planet,” said Zeiler, who has seen 11 eclipses on six continents. Zeiler traces a growing trend of eclipse tourism to the 1970s, when a group of astronomy enthusiasts first organized a cruise off the coast of Nova Scotia to see a solar eclipse. Since then, traveling to see eclipses has only become more popular as fascination with the phenomena has grown.
+
+
+“No matter what I do, no matter how much I describe it, no matter how many videos you watch, they all fall short of being able to witness this for yourself,” Fred Espenak, an astrophysicist and eclipse-chaser, told Vox’s Brian Resnick and Joss Fong.
+
+
+
+
+
+
+
+The event is also rarely visible to this degree in the US. In 2017, the eclipse had a narrower “path of totality,” or a smaller area where it could be seen in full from start to finish. This year, 31.6 million people already live in that larger path, making it easier for people to travel to it. And the next total solar eclipse to be visible in the US isn’t expected until the 2040s, which makes the upcoming one a prized experience.
+
+
+“One of the reasons that we get value from experiences is because we think of them as less interchangeable than other ways that we could spend our money,“ Amit Kumar, a marketing and psychology professor at the University of Texas at Austin, told Vox.
+
+
+Eclipses are also a singular event because so many people across the country — and world — are witnessing the same thing at the same time, fueling a feeling of connectivity and community that can be particularly powerful, Kumar said.
+
+
+The desire to share in that feeling is just one factor that helps explain the high numbers of people willing to travel for this phenomenon, with local economies reaping benefits in the process. “Each eclipse is different. And that’s why we keep going again and again,” says Zeiler.
+
+
+
+
+
+
+
Trump has set up a perfect avenue for potential corruption -
+
+
+
+Truth Social’s big shareholders pose potential conflicts of interest for Trump. | Omar Marques/SOPA Images/LightRocket via Getty Images
+
+
+
+With Truth Social going public, big investors could easily buy influence in a second Trump term.
+
+
+Truth Social, Donald Trump’s social media platform, has not exactly been a resounding business success story, but it recently made the former president a whole lot richer.
+
+
+That’s because Trump Media, the network’s parent company, went public last week and catapulted Trump’s net worth to an estimated $7.5 billion.
+
+
+Now you might be wondering how Trump’s social media company is worth that much money. And the short answer is: It isn’t.
+
+The long answer, however, is that while Trump Media’s valuation is entirely illogical from a financial perspective — as one finance professor told CNN, “The stock is pretty much divorced from fundamentals” — its early success in trading can be boiled down to one simple fact: Donald Trump is running for president, and there’s a decent chance that he’ll be back in the White House this time next year.
+
+
+Truth Social, in other words, is a way for Trump’s supporters to personally offer him financial support at a time when he desperately needs it. That might be why the company’s volatility looks similar to meme stocks for now. As one analyst told my colleague Nicole Narea, people might buy up Trump Media stock so “they can express their beliefs and commitment.”
+
+
+For those with deep pockets, it’s also an opportunity to curry favor with the former president.
+
+
+Why does any of this matter?
+
+
+Before becoming one of the world’s richest 500 people on Bloomberg’s billionaires index for the first time last week, Trump was in financial trouble.
+
+
+He was cash-strapped and on the hook for nearly half a billion dollars because of two civil suit verdicts, and the attorney general of New York was preparing to seize some of his assets. He has since averted that outcome — at least for now — after the court reduced his required bond and he secured an 11th-hour bond agreement.
+
+
+
+As I’ve written before, Trump’s financial problems are not just worrisome for him but for the whole country. His enormous debts would be a serious liability for any candidate for public office, let alone the presidency.
+
+
+It’s hard to know how worried to be, however: Trump’s finances are quite opaque.
+
+
+But read another way, that means that not only do his businesses — which he refused to divest from when he was president and which continued to work with other countries during his time in the White House — present potential conflicts of interest, but the public also has few ways of knowing the extent of those conflicts, or what they might even be.
+
+
+On the plus side, that Trump Media is publicly traded makes Trump’s finances slightly more transparent because we can keep track of who the major shareholders might be. But that alone isn’t enough because when Trump Media went public, it became an avenue for exactly the kind of corruption I was writing about.
+
+
+“It puts him in a position where he could be subjected to outside influence by foreign entities and other special interests at the cost, perhaps, of US national security or other interests,” Virginia Canter, the chief ethics counsel at the Citizens for Responsibility and Ethics in Washington, told Vox.
+
+
+ Daniel Steinle/Bloomberg via Getty Images
+
+
+But if buying stocks is legal, how could it lead to corruption?
+
+
+Imagine, for example, you were a wealthy lobbyist looking to influence a second Trump administration.
+
+Or, you could turn to his public company and buy up a bunch of stock to help it stay afloat. Should he become president again, you could have leverage over him because if you decide to dump your shares, you could put a dent in Trump’s overall net worth.
+
+
+Now here’s a more tangible example: As Citizens for Responsibility and Ethics in Washington pointed out on X, the biggest institutional investor in the shell company that merged with Truth Social was GOP megadonor Jeffrey Yass, who also happens to be a major investor in TikTok’s parent company.
+
+
+While there’s no proof that Yass played a direct role in Trump changing his stance on whether or not TikTok should be banned, Trump did only change his tune after building up his business relationship with Yass. It’s unclear how much stock Yass still owns in Trump Media after the merger, but that’s just one example of how messy these potential conflicts of interest can be.
+
+
+That’s not to mention the possibility of foreign businesses, governments, or oligarchs flocking to buy up shares in Trump’s company, putting him in direct violation of the Constitution’s emoluments clause should he win in November. That’s an accusation that plagued his presidency, when foreign governments spent millions of dollars renting out rooms at his hotels or leasing office space in his buildings.
+
+
+“It’s not good for the country if we were to elect a president who, again, is really in business to enrich himself and [Trump Media] provides a direct vehicle for those seeking his favor to do so,” Canter said.
+
+
+And that, in the end, is why Trump’s potential return to the White House is so dangerous: In addition to having plenty of bad and reckless ideas, his presidency could be up for sale.
+
She’s been chasing solar eclipses for three decades. What’s she after? -
+
+
+
+A total solar eclipse in Belitung, Indonesia, on March 9, 2016. | Donal Husni/NurPhoto/NurPhoto via Getty Images
+
+
+
+This scientist has seen nearly 20 solar eclipses. She’s trying to solve a mystery that could help protect Earth.
+
+
+On Monday, April 8, millions of people will get to see the Great North American Eclipse. Most people on the continent will see a partial solar eclipse, the sun gradually getting smaller as the moon passes in front of it.
+
+
+But if you’re in exactly the right place — along the narrow path of totality that runs from Mexico to Indianapolis to Montreal — the moon is going to line up directly in front of the sun and completely block it out.
+
+
+“When it happens, it feels like magic. It feels supernatural,” says Shadia Habbal, a professor of solar physics at the University of Hawaii. “It hits you in every part of your body. You just feel like something is surrounding you. Something is taking you to a place you’ve never been before.”
+
+
+When the moon fully blocks the sun, it’s the only time you can see the sun’s atmosphere, the corona, which is made up of particles constantly shooting away from the sun. “Sometimes they’re streaming away happily,” says Habbal. “But sometimes you have what we call a storm or an explosion at the sun.”
+
+
+ Carlos Avila Gonzalez/The San Francisco Chronicle via Getty Images
+
+The sun’s corona is visible as the moon obscures the sun during the 2017 total solar eclipse.
+
+
+
+Radiation from solar storms often ends up hitting Earth, which can lead to beautiful phenomena like the northern lights. But it can also cause massive problems, like energy grid disruptions, major blackouts, or even taking down satellites.
+
+
+Despite how much damage solar storms can do to our tech on Earth, scientists are still struggling to predict them. And that’s because they don’t understand that much about how the corona works.
+
+
+Even though it extends millions of miles away from the surface of the sun into freezing cold space, the corona is still a million degrees hotter than the surface of the sun. And scientists aren’t sure why. Which is why Habbal became an eclipse chaser.
+
+
+I recently spoke with Habbal for an episode of Unexplainable, Vox’s podcast that explores scientific mysteries, unanswered questions, and all the things we learn by diving into the unknown. This conversation has been lightly edited and adapted for the website.
+
+
+
+
+
+
+Noam Hassenfeld
+
+
+You’ve been chasing solar eclipses for almost 30 years. You even founded a group, Solar Wind Sherpas, whose mission is to chase eclipses. How did you first get interested in studying these phenomena?
+
+
+Shadia Habbal
+
+
+I was doing models of the corona, trying to figure out what processes heat the corona. And I realized that the temperature was a critical piece of information I needed to have. But the data that was available at the time wasn’t giving me the answer I was looking for. So, I knew that eclipses were the key observations to get to that answer.
+
+
+Noam Hassenfeld
+
+
+So the first eclipse you saw was when you were already researching the corona?
+
+
+Shadia Habbal
+
+
+Yes, the first solar eclipse I saw was in 1995 in India, and it was a very, very short eclipse. It was 42 seconds long, but it was probably the most spectacular one I saw. The eclipse happened around 8 in the morning. And when it happened, I saw the corona, these rays upon rays just expanding from the sun, extending all the way to infinity, visually. But we only had 42 seconds, so I couldn’t spend too much time looking around or anything. We had to really pay attention to operating the cameras that we had. I thought, “Okay, one measurement and that’s it.” But we realized that one wasn’t enough. We had to keep trying.
+
+
+Noam Hassenfeld
+
+
+Where have you and your team been since then?
+
+
+Shadia Habbal
+
+
+We’ve been to Mongolia. We’ve been to Antarctica. We’ve been to Libya. We’ve been to Tatakoto in French Polynesia. To Svalbard, you know, northern Norway, beyond the Arctic Circle. We’ve been to Syria, Chile, Argentina, Zambia, and South Africa. And this one will be my 20th.
+
+
+Noam Hassenfeld
+
+
+Why do you need an eclipse to study the corona? Can’t you do this artificially, put something up to block out most of the sun?
+
+
+Shadia Habbal
+
+
+Well, because that doesn’t do as good a job as a natural eclipse.
+
+
+Noam Hassenfeld
+
+
+Why doesn’t it do as good of a job?
+
+
+Shadia Habbal
+
+
+It’s a very small blocker whereas the moon is huge. So it dims the light to the point where the sky is like nighttime.
+
+
+Noam Hassenfeld
+
+
+Ah, okay. Let’s say I go outside and I want to study the corona. If I hold up a quarter in front of the sun and block the sun, I still wouldn’t see the corona, because the coin is so close to my eye. Everything would be filled up with sunlight.
+
+
+Shadia Habbal
+
+
+Yes. With an eclipse, you get the very intricate structures very, very close to the sun, and you get everything that’s streaming away as you look farther away. So, you see this continuous transition from the surface outward that you don’t get with any other instruments at the moment.
+
+
+Noam Hassenfeld
+
+
+What are the instruments you use when you study the eclipse?
+
+
+Shadia Habbal
+
+
+Our optical systems are like very small telescopes. But the key element is something we call a spectrometer, which is like a prism when you let the light go through a prism and it splits the colors, and so we capture these different colors. And each color corresponds to a different temperature in the corona.
+
+
+Noam Hassenfeld
+
+
+Is it fair to say you’re creating a temperature map of the corona?
+
+
+Shadia Habbal
+
+
+Of the corona, yes, exactly.
+
+
+Noam Hassenfeld
+
+
+And that map is going to help make these models of how the corona works more accurate?
+
+
+Shadia Habbal
+
+
+Yes, exactly.
+
+
+Noam Hassenfeld
+
+
+Are we close at all to being able to use some of these models to be like, “Okay, we’ve got to prepare the electrical grid, we’ve got to prepare the satellites for a solar storm?”
+
+
+Shadia Habbal
+
+
+Not yet. We have some clues. We know what’s causing them, but we can’t predict when they will happen. And that’s one of the things we’re trying to gather some more information from our eclipse observations.
+
+
+Noam Hassenfeld
+
+
+Are we any closer than we were 30 years ago?
+
+
+Shadia Habbal
+
+
+Yes, but we still don’t have a full … we don’t have a reliable answer.
+
+
+Noam Hassenfeld
+
+
+I like that you can laugh about that. What would you say is the biggest obstacle in eclipse observations or chasing eclipses?
+
+
+Shadia Habbal
+
+
+The weather.
+
+
+Noam Hassenfeld
+
+
+Ok, now I’m laughing.
+
+
+Shadia Habbal
+
+
+It’s true! We lost 40 percent of our observations to clouds.
+
+
+Noam Hassenfeld
+
+
+Wow, 40 percent?
+
+
+Shadia Habbal
+
+
+Mmhm.
+
+
+Noam Hassenfeld
+
+
+So out of how many eclipses?
+
+
+Shadia Habbal
+
+
+
+
For example, this would be my 20th. We lost 40 percent. We lost eight.
+
+
+Noam Hassenfeld
+
+
+I imagine that’s got to be really disappointing.
+
+
+Shadia Habbal
+
+
+Well, it’s heartbreaking, yes. Because, so, many times what happens during, just a little bit before totality, the temperature drops and you have atmospheric conditions that happen suddenly. Once in South Africa, it was perfectly crystal clear skies and a cloud formed smack in front of the sun just before totality. Here was a cloud, it just decided to be right in front of the sun and then it dispersed the moment the eclipse was over.
+
+
+ Yulii Zozulia/Ukrinform/Future Publishing via Getty Images
+
+The moon partially eclipses the sun as clouds largely obscure the sky in Odesa, Ukraine, on October 25, 2022.
+
+
+
+Noam Hassenfeld
+
+
+So you’re set up, you have your equipment, a cloud shows up, and then you’re just done? You can’t do anything?
+
+
+Shadia Habbal
+
+
+Yeah, you lost everything. You have no data. And another time we were in Kenya, we had a sandstorm just 15 minutes before the eclipse. We were close to a lake and basically the wind pattern shifted. And then all of a sudden we were looking toward the sun and a colleague of mine turned around and he said, “Oh! S… H—” [Habbal begins to spell the word — you know which one — and then stops herself] I said, “What’s the matter?” We looked back and this huge cloud was coming barreling toward us.
+
+
+Noam Hassenfeld
+
+
+What did you do?
+
+
+Shadia Habbal
+
+
+We covered the equipment. We had to. It was very, very fast. And we were totally clouded out.
+
+
+Noam Hassenfeld
+
+
+It just seems like there must be a better way to do this.
+
+
+Shadia Habbal
+
+
+Well, there are ways. Recently we were in Antarctica and unfortunately we were clouded out. It was really heartbreaking because the sky was crystal clear the day before. And crystal clear two hours after totality. One of my colleagues, he just came up with the idea and said, “why don’t we fly a kite?”
+
+
+Noam Hassenfeld
+
+
+Fly a kite?
+
+
+Shadia Habbal
+
+
+Well, it’s not just any type of kite. It’s quite large, it has a wingspan of about 6 and a half meters. We attached a spectrometer to it. The idea is that if it’s cloudy with a kite, you can go up to 4–5,000 meters and you can get above the clouds, and we tried it last year in Australia.
+
+
+Noam Hassenfeld
+
+
+What was it like testing something like this? Were you nervous?
+
+
+Shadia Habbal
+
+
+Yes, we were very nervous, but it was the most exhilarating experience. It was like watching the Sputnik. And the other option we’re trying this year is [working with] NASA’s research aircraft called the WB-57. Now that airplane flies up to 60,000 feet where there are no clouds.
+
+
+Noam Hassenfeld
+
+
+And that airplane, is it flying along the path of totality?
+
+
+Shadia Habbal
+
+
+Exactly. The engineers and the pilots of this NASA project can follow the path of totality.
+
+
+Noam Hassenfeld
+
+
+How close are we to being able to predict the corona? Are all these measurements helping these predictions?
+
+
+Shadia Habbal
+
+
+Yes, but like any scientific research, you discover something and then you discover that there’s a lot more to discover. This is the beauty of scientific research is you’re never done.
+
+
+Noam Hassenfeld
+
+
+So, you’re just gonna keep on chasing eclipses for the rest of your career?
+
+
+Shadia Habbal
+
+
+I’ll keep on chasing eclipses until I can’t chase them anymore, and then somebody else has to do it.
+
+
+
+
From The Hindu: Sports
+
+
Juliette, Santissimo, Celestial and Mojito show out -
+
IPL-17, DC vs KKR | Rishabh Pant fined ₹24 lakh for second over rate offence - Delhi Capitals captain Rishabh Pant fined ₹24 lakh for slow over rate in IPL 2024 match against Kolkata Knight Riders
+
Bayer Leverkusen on the verge of historic double after reaching German Cup final - Xabi Alonso’s team, which also leads the Bundesliga by 13 points, marked its 40th game of the season unbeaten in all competitions.
+
Morning Digest | BJP got 75% of ₹582 crore worth electoral bonds bought by loss making firms; Sanjay Nirupam expelled from Congress, and more - Here is a select list of stories to start the day
+
ISL | East Bengal punishes nine-man Kerala Blasters -
+
+
From The Hindu: National News
+
+
Demand for tankers only from west part of Hyderabad: Telangana Govt -
+
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.
+
Development economist Suresh Babu is the new director of MIDS -
+
PM Modi in Cooch Behar, says Opposition spreading rumours about CAA - I am saying remove corruption; the Opposition is saying ‘save the corrupt’, the Prime Minister alleged
+
Sandeshkhali violence | Calcutta High Court reserves judgement on petitions - In High Court, the West Bengal Government questions conviction rate of Central agencies; ED accuses State of non-cooperation
+
+
From BBC: Europe
+
+
Russia’s neighbours urge Nato allies to bring back military service - Following Vladimir Putin’s full-scale invasion of Ukraine, conscription is being rebooted and expanded across Europe.
+
Italian island offers rampant goats up for adoption - A remote Italian island where goats outnumber humans six to one is trying to give them away.
+
Air passengers face extra year of 100ml liquid rule - Major airports will not have new scanners at all security lanes by the summer, the BBC understands.
+
School shooting brings up tough questions for Finland - Finland’s age of criminal responsibility, gun laws and children’s mental health are in the spotlight following the Vantaa shooting.
+
Finnish school shooting motivated by bullying - police - The suspect is accused of killing a boy aged 12 and wounding two girls in Vantaa.
+
+
From Ars Technica
+
+
Pentagon calls for tighter integration between military and commercial space - “I would have never written the requirements for Starship.” - link
+
Google might make users pay for AI features in search results - Plan would represent a first for what has been a completely ad-funded search engine. - link
+
Bird flu flare: Cattle in 5 states now positive as Texas egg farm shuts down - The risk to the general public remains low, federal officials say. - link
+
Spotify’s second price hike in 9 months will target audiobook listeners - Bloomberg report claims price hike coming to Australia, Pakistan, and the UK first. - link
+
How to hack the Jacksonville Jaguars’ jumbotron (and end up in jail for 220 years) - The story that just keeps getting worse. - link
+
+
From Jokes Subreddit
+
+
I finally found the jackass and honeycomb joke from GOT by Tyrion Lannister -
+
+
+I once brought a jackass and a honeycomb into a brothel. The Madame asked, “what can we do for you?” I said, “I need a woman to lay with, for mine has left me.” The Madame asked “You poor thing; whatever for? And why do you have a jackass and a honeycomb?” “Well,” I answered, “my woman stumbled upon a genie in a bottle, and he granted her 3 wishes. The first was to have the nicest ass in the land, so he gave her this jackass. Her second wish was for a ‘house fit for a queen’, so he gave her this beehive.” The Madame asked, “And what of the third wish?” “For her third wish, my woman asked the genie to make my cock hang down past my knee.” “Well, that one’s not so bad!” the Madame exclaimed. “‘Not so bad!?’, I replied,”I used to be 6 feet tall!"
+
+.. when one of them asks the other two how they died.
+
+
+“I came home early from work. When I walked in the door I could smell cigar smoke and my wife was half naked. I knew she was cheating and sure enough when I looked out the window there was the mailman smoking a cigar and smiling! I was so enraged that I grabbed the fridge and threw it out the window. I immediately passed out. I must have had a heart attack!” says the first man.
+
+
+The second replies “Wow, I was having a great day, walking my regular postal route and smoking a cigar like I always do when I heard a window smash and suddenly I was here!”
+
+
+The two men look at each other in realization. Then then look to the third man who asked the question. “So there I was, naked in the fridge…”
+
A young boy says to his father “Dad, our maths teacher is asking to see you.” -
+
+
+“What happened?” The father asks.
+
+
+"Well, she asked me, ‘how much is 7 * 9?’ I answered ‘63’ , then she asked, ‘and 9 * 7?’ So I asked ‘what’s the fucking difference?’
+
+
+“Indeed, what is the difference?” asks the father. ‘’Sure, I’ll go.’’
+
+
+The next day, the boy comes home from school and says, “Dad, have you gone by the school?”
+
+
+“Not yet.”
+
+
+“Well when you do, come and see the gym teacher also.”
+
+
+“Why?” asks the father.
+
+
+“Well we had a gym class today, and he asked me to raise my left arm, I did. Then my right arm, I also raised it. Then he asked me to lift my right leg, so I did. ‘Now,’ he says, ‘lift your left leg,’ so I asked, ‘What, am I suppose to stand on…. my cock??’”
+
+
+“Exactly,” says the father. “Alright, I’ll come.”
+
+
+The next day, the boy asks his father “Did you go to the school?” “No, not yet.”
+
+
+“Don’t bother, I got expelled.”
+
+
+Surprised, the father asks “Why did you get expelled?”
+
+
+“Well, they summoned me to the principal’s office, and sitting there were the math teacher, the gym teacher, and the art teacher.”
+
+
+“The fuck was the art teacher doing there!?” asks the father.
+
To the irritation of the judge, a man was trying to be excused jury service. “Tell me,” rapped the judge, “is there any good reason why you cannot serve as a juror in this trial?” The man replied: “I don’t want to be away from my job that long.” “Can’t they do without you at work?” -
An elderly man in Florida had owned a large farm for several years. -
+
+
+He had a large pond in the back, fixed up nice: picnic tables, horseshoe courts, a volleyball court, and so me apple and peach trees. The pond was properly shaped and fixed up for swimming. One evening the old farmer decided to go down to the pond and look it over, as he hadn’t been there for a while. He grabbed a five gallon bucket to bring back some fruit. As he neared the pond, he heard voices shouting and laughing with glee. As he came closer he saw it was a bunch of young women skinny-dipping in his pond. He made the women aware of his presence and they all went to the deep end. One of the women shouted to him, “We’re not coming out until you leave!” The old man frowned, “I didn’t come down here to watch you ladies swim naked or make you get out of the pond naked.” Holding the bucket up he said, “I’m here to feed the alligator.”
+
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25369843/GettyImages_2128588467.jpg)
Daniel Steinle/Bloomberg via Getty Images
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25369094/1409000218.jpg)
Carlos Avila Gonzalez/The San Francisco Chronicle via Getty Images
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25369098/1244231401.jpg)
Yulii Zozulia/Ukrinform/Future Publishing via Getty Images
+