Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients -
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+The full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course of COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover in severe and asymptomatic COVID-19 patients, in relation to clinical outcome. Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues. The immune response to infection was reflected by elevated B cell and monocyte/macrophage cfDNA levels, and by evidence of an interferon response in cells prior to cfDNA release. Strikingly, monocyte/macrophage cfDNA levels (but not monocyte counts), as well as lung epithelium cfDNA and vascular endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated levels of immune-derived cfDNA but did not show evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated levels of vascular endothelial cell and erythroblast cfDNA, suggesting that sub-clinical vascular and erythrocyte turnover are universal features of COVID-19, independent of disease severity. Epigenetic liquid biopsies provide non-invasive means of monitoring COVID-19 patients, and reveal sub-clinical vascular damage and red blood cell turnover.
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Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning -
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+SARS-CoV-2 has continued to evolve throughout the COVID-19 pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2 and BA.2.75. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.
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Recombinant Rotavirus Expressing the Glycosylated S1 Protein of SARS-CoV-2 -
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+Reverse genetic systems have been used to introduce heterologous sequences into the rotavirus segmented double-stranded (ds)RNA genome, enabling the generation of recombinant viruses that express foreign proteins and possibly serve as vaccine vectors. Notably, insertion of SARS-CoV-2 sequences into the segment 7 (NSP3) RNA of simian SA11 rotavirus was previously shown to result in the production of recombinant viruses that efficiently expressed the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the S1 region of the SARS-CoV-2 spike protein. However, efforts to generate a similar recombinant (r) SA11 virus that efficiently expressed full-length S1 were less successful. In this study, we describe modifications to the S1-coding cassette inserted in the segment 7 RNA that allowed recovery of second-generation rSA11 viruses that efficiently expressed the ~120-kDa S1 protein. The ~120-kDa S1 products were shown to be glycosylated, based on treatment with endoglycosidase H, which reduced the protein to a size of ~80 kDa. Co-pulldown assays demonstrated that the ~120-kDa S1 proteins had affinity for the human ACE2 receptor. Although all the second-generation rSA11 viruses expressed glycosylated S1 with affinity for the ACE receptor, only the S1 product of one virus (rSA11/S1f) was appropriately recognized by anti-S1 antibody, suggesting the rSA11/S1f virus expressed an authentic form of S1. Possibly due to the presence of FLAG tags immediately upstream of their S1 signal peptides, the S1 products of the other viruses (rSA11/3fS1 and rSA11/3fS1-His) may have undergone defective glycosylation, impeding antibody binding. In summary, these results indicate that recombinant rotaviruses can serve as expression vectors of foreign glycosylated proteins, raising the possibility of generating rotavirus-based vaccines that can induce protective immune responses against enteric and mucosal viruses with glycosylated capsid components, including SARS-CoV-2.
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Klebsiella pneumoniae Co-infection Leads to Fatal Pneumonia in SARS-CoV-2-infected Mice -
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+SARS-CoV-2 patients have been reported to have high rates of secondary Klebsiella pneumoniae infections. Klebsiella pneumoniae is a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person's immune system is compromised. Despite a high number of K. pneumoniae cases reported in SARS-CoV-2 patients, a co-infection animal model evaluating the pathogenesis is not available. We describe a mouse model to study disease pathogenesis of SARS-CoV-2 and K. pneumoniae co-infection. BALB/cJ mice were inoculated with mouse-adapted SARS-CoV-2 followed by a challenge with K. pneumoniae. Mice were monitored for body weight change, clinical signs, and survival during infection. The bacterial load, viral titers, immune cell accumulation and phenotype, and histopathology were evaluated in the lungs. The co-infected mice showed severe clinical disease and a higher mortality rate within 48 h of K. pneumoniae infection. The co-infected mice had significantly elevated bacterial load in the lungs, however, viral loads were similar between co-infected and single-infected mice. Histopathology of co-infected mice showed severe bronchointerstitial pneumonia with copious intralesional bacteria. Flow cytometry analysis showed significantly higher numbers of neutrophils and macrophages in the lungs. Collectively, our results demonstrated that co-infection of SARS-CoV-2 with K. pneumoniae causes severe disease with increased mortality in mice.
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Asymmetry in the peak in Covid-19 daily cases and the pandemic R-parameter -
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+Within the context of the standard SIR model of pandemics, we show that the asymmetry in the peak in recorded daily cases during a pandemic can be used to infer the pandemic R-parameter. Using only daily data for symptomatic, confirmed cases, we derive a universal scaling curve that yields: (i) reff , the pandemic R-parameter; (ii) Leff, the effective latency, the average number of days an infected individual is able to infect others and (iii) α, the probability of infection per contact between infected and susceptible individuals. We validate our method using an example and then apply it to estimate these parameters for the first phase of the SARS-Cov-2/Covid-19 pandemic for several countries where there was a well separated peak in identified infected daily cases. The extension of the SIR model developed in this paper differentiates itself from earlier studies in that it provides a simple method to make an a-posteriori estimate of several useful epidemiological parameters, using only data on confirmed, identified cases. Our results are general and can be applied to any pandemic.
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Analyzing the Impact of the Covid-19 Pandemic on Stock Market Investments -
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+The Covid-19 pandemic has had a notable impact on financial markets, prompting individuals to reevaluate their risk and return objectives and modify their investment portfolios. This study aims to examine the pandemic’s influence on the portfolio allocation decisions of individual investors. It investigates investors’ perceptions and preferences concerning different investment strategies both before and during the period of heightened anxiety caused by the Covid-19 pandemic. The data for the study was collected from individual investors residing in Delhi and Mumbai. The Analytical Hierarchy Process (AHP) was utilized to rank the investment choices of the participants. The findings indicate that, owing to the current economic uncertainty associated with the pandemic, investors have started realigning their portfolios. As the predictability of returns on risky assets has decreased, investors are shifting towards more conservative portfolios. Nevertheless, the extent of the transition from high-risk to low-risk assets varies among individual investors.
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COVID-19 in person’s social network: Unravelling the Impact on Youth Motivations and Protective Behaviours during the Initial Stages of the COVID-19 Pandemic -
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+The study explores what motivated youth to comply with recommended protective behaviour while being less vulnerable to COVID-19 comparing to other age groups. Additionally, we looked at the relationships between awareness of COVID-19 cases in participants’ social networks and perceptions of risk, motivation, and behaviour in reaction to the pandemic. We applied structural equation modelling on self-reported data from 1,265 undergraduate university students to investigate the role of different motivation types in predicting adherence to a wide range of protective behaviours. The prosocial motivation was equally as strong as the self-interested motivation in explaining young people’s behaviour, while controlled motivation revealed no association. The presence of known COVID-19 cases in people’s social networks affects both perceived risks of disease and motivation to comply. However, while awareness about severe consequences positively affects them, awareness about the mild cases, in contrast, decreases the perceived disease severity.
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Published in Early Childhood Education Journal, https://link.springer.com/article/10.1007/s10643-023-01536-1: Interaction quality among children, staff and parents in German ECEC centres in the COVID-19 pandemic - Results from a longitudinal study -
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+Early Education and Care (ECEC) centres had implemented a variety of protective and hygiene measures during the COVID-19 pandemic. Some of these measures temporarily restricted the behaviour of pedagogical staff, children and parents, for example keeping distance from each other or wearing face masks. This may have made it difficult for staff to offer high quality interactions with a positive, sensitive attitude towards children and parents, as would be important for good pedagogical work. Long-term effects of these distance measures on the quality of daily interactions in ECEC centres are largely unexplored. Based on a panel survey among German ECEC centre leaders over a period of one and a half years, we provide a long-term assessment of the impact of specific protective measures on different levels of interactions within ECEC centres, namely on staff-child interactions, interactions of children with each other and the cooperation between staff and parents. We found child-child interaction largely unaffected by the measures, while staff-parent interaction suffered the most. Communication with parents and regular implementation of pedagogical practices have a stabilizing effect, while keeping distance from children, face masks and (pandemic-related) staff shortages worsen staff-child interactions.
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The Usage of Mindsponge Theory for Explaining the Usefulness of Checklist Confirmation Scheme for Identifying Unreliable COVID-19-related Information -
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+The public nowadays can access health information from the internet easily. However, they have difficulty identifying reliable health information from various sources in an infodemic (information and epidemic). Tanemura & Chiba [1] investigated the usefulness of a checklist approach-based confirmation scheme for identifying unreliable COVID-19-related information in 700 Japanese by using test health information related to the efficacy of green tea in preventing COVID-19. Investigated variables were: 1) the usefulness of the developed confirmation scheme for identifying unreliable COVID-19-related health information and 2) the factors that hindered the confirmation scheme’s usefulness. The findings from this study are important for making decisions concerning health in an epidemic. Tanemura & Chiba [1] used the mindsponge theory as the conceptual framework for their study [2]. This theory focuses on the human mind’s information-processing mechanism. Mindsponge comes from the metaphor of sponge, in which the human mind is analogized to a sponge that squeezes out unsuitable values (or information) and absorbs new ones compatible with its core value. The mindsponge mechanism explains how and why an individual observes and ejects values-information conditional on the external setting [3]. According to the mindsponge mechanism, the presence or absence of trust affects information absorption after moving to the multi-filtering system stage [4]. While accessing health information online, the public judge its value with a trust-based subjective evaluation [2]. This determines the perceived benefit of the information and affects individual behavior accordingly. If this developed confirmation scheme for identifying unreliable COVID-19-related health information increased public awareness that health information is unreliable, it may have suppressed the false perception that green tea is effective for preventing COVID-19. However, the explanations with this confirmation scheme in individual-level information filtering systems proved to be insufficient for consumers. Therefore, the most effective strategies involve filtering information at the organizational level rather than the individual level, which should help consumers correctly identify misinformation concerning food and health and promote accurate decision-making [1].
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Targeted Amplification and Genetic Sequencing of the Severe Acute Respiratory Syndrome Coronavirus 2 Surface Glycoprotein -
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+The SARS-CoV-2 spike protein is a highly immunogenic and mutable protein that is the target of vaccine prevention and antibody therapeutics. This makes the encoding S-gene an important sequencing target. The SARS-CoV-2 sequencing community overwhelmingly adopted tiling amplicon-based strategies for sequencing the entire genome. As the virus evolved, primer mismatches inevitably led to amplicon drop-out. Given the exposure of the spike protein to host antibodies, mutation occurred here most rapidly, leading to amplicon failure over the most insightful region of the genome. To mitigate this, we developed SpikeSeq, a targeted method to amplify and sequence the S-gene. We evaluated 20 distinct primer designs through iterative in silico and in vitro testing to select the optimal primer pairs and run conditions. Once selected, periodic in silico analysis monitor primer conservation as SARS-CoV-2 evolves. Despite being designed during the Beta wave, the selected primers remain > 99% conserved through Omicron as of 2023-04-14. To validate the final design, we compared SpikeSeq data and National SARS-CoV-2 Strain Surveillance whole-genome data for 321 matching samples. Consensus sequences for the two methods were highly identical (99.998%) across the S-gene. SpikeSeq can serve as a complement to whole-genome surveillance or be leveraged where only S-gene sequencing is of interest. While SpikeSeq is adaptable to other sequencing platforms, the Nanopore platform validated here is compatible with low to moderate throughputs, and its simplicity better enables users to achieve accurate results, even in low resource settings.
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Improvement of Neisseria gonorrhoeae culture media to enable growth without atmospheric CO2. -
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+Bacterial culture is the crucial step in diagnosing Neisseria gonorrhoeae infections and is the gold standard for determining their antimicrobial resistance profile. However, culture of Neisseria spp. can be challenging in resource poor areas, relying on specialist incubators supplying an atmosphere with 5% CO2 for growth of the bacteria. Even when such incubators are available, the CO2 to run them may be scarce; there were CO2 shortages during the COVID-19 pandemic, for example. Although culture jars with gas packs or candles can be used, these are inefficient in terms of use of incubator space and researcher time. To achieve simplicity in culturing of N. gonorrhoeae, the standard Oxoid GC base medium, made with the Kelloggs glucose and iron supplements was improved with the addition of 0.75 g/L sodium bicarbonate (NaHCO3), which is inexpensive and really available. This improved media was able to sustain gonococcal growth as well as standard GC media in 5% CO2. Chocolate agar and Thayer-Martin agar with sodium bicarbonate was also developed, with all showing good growth of N. gonorrhoeae without the need for atmospheric CO2.
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Diversity of Short Linear Interaction Motifs in SARS-CoV-2 Nucleocapsid Protein -
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+Molecular mimicry of short linear interaction motifs has emerged as a key mechanism for viral proteins binding host domains and hijacking host cell processes. Here, we examine the role of RNA-virus sequence diversity in the dynamics of the virus-host interface, by analyzing the uniquely vast sequence record of viable SARS-CoV-2 species with focus on the multi-functional nucleocapsid protein. We observe the abundant presentation of motifs encoding several essential host protein interactions, alongside a majority of possibly non-functional and randomly occurring motif sequences absent in subsets of viable virus species. A large number of motifs emerge ex nihilo through transient mutations relative to the ancestral consensus sequence. The observed mutational landscape implies an accessible motif space that spans at least 25% of known eukaryotic motifs. This reveals motif mimicry as a highly dynamic process with the capacity to broadly explore host motifs, allowing the virus to rapidly evolve the virus-host interface.
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Associations between SARS-CoV-2 infection and subsequent economic inactivity and employment status: pooled analyses of five linked longitudinal surveys -
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+Background Following the acute phase of the COVID-19 pandemic, record numbers of people became economically inactive (i.e., neither working nor looking for work, e.g., retired), or non-employed (including unemployed job seekers and economically inactive people). A possible explanation is people leaving the workforce after contracting COVID-19. We aim to investigate whether testing positive for SARS-CoV-2 is related to subsequent economic inactivity and non-employment, among people who were in employment prior to the pandemic. Methods The primary source of data are UK longitudinal population studies linked to English NHS digital data, held by the UK Longitudinal Linkage Collaboration (UK LLC). We pooled data from five studies (1970 British Cohort Study, English Longitudinal Study of Ageing, 1958 National Child Development Study, Next Steps, and Understanding Society), established long before the pandemic with between two and eight follow up surveys during the pandemic. The study population comprised people aged 25-65 years during the study period (March 2020 to March 2021) who were employed pre-pandemic. Outcomes were economic inactivity and non-employment status measured at the time of the last follow-up survey (November 2020 to March 2021, depending on study). For participants who could be linked to NHS England data (n=8,174), COVID-19 infection was indicated by a positive SARS-CoV-2 test. For sensitivity analyses, we used a self-reported measure of COVID-19 infection from participants (n=13,881) in the public use files of the five studies. Potential confounders included sociodemographic variables, pre-pandemic self-rated health and occupational class. Logistic regression models estimated odds ratios (ORs) with 95% confidence intervals (95%CIs). Results In adjusted analyses, testing positive for SARS-CoV-2 was very weakly associated with economic inactivity (OR 1.08 95%CI 0.68-1.73) and non-employment status (OR 1.09. 95%CI 0.77-1.55). In sensitivity analyses, self-reported test-confirmed COVID-19 was not associated with either economic inactivity (OR 1.01: 95%CI 0.70 to 1.44) or non-employment status (OR1.03 95%CI 0.79-1.35). Conclusions Among people employed pre-pandemic, testing positive for SARS-CoV-2 was either weakly or not associated with increased economic inactivity or exiting employment. Wide confidence intervals limit the ability to make definitive conclusions, but it appears unlikely that COVID-19 disease explains the increase in economic inactivity among working-age people.
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Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases -
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+ABSTRACT Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki Disease (KD) or severe bacterial and viral infections is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. Methods: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA-Sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n=22), KD (n=23), definite bacterial (DB; n=28) and viral (DV, n=27) disease, and healthy controls (n=8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C, and association with severity of illness. Results: Plasma levels of CD163, CXCL9, and PCSK9 were significantly elevated in MIS-C with a combined AUC of 86% (95% CI: 76.8%-95.1%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring oxygen, inotropes or with shock. Conclusion: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.
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The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records. -
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+Background The COVID-19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity to ensure safety and appropriateness of ongoing prescribing and a disruption could have significant negative implications for patient care. Aim Using routinely collected data, our aim was to i) describe the SNOMED CT codes used to report medication review activity ii) report the impact of COVID-19 on the volume and variation of medication reviews. Design and setting With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in-situ using the OpenSAFELY platform. Method For each month between April 2019 - March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months. These measures were broken down by regional, clinical and demographic subgroups and amongst those prescribed high risk medications. Results In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID-19 lockdown, monthly activity substantially decreased (-21.1% April 2020), but the rate of patients with a medication review coded in the previous 12 months was not substantially impacted according to our classification (-10.5% March 2021). There was regional and ethnic variation (March 2022 - London 21.9% vs North West 33.6%; Chinese 16.8% vs British 33.0%). Following the introduction of “structured medication reviews”, the rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high risk groups (March 2022 - care home residents 34.1%, 90+ years 13.1%, high risk medications 10.2%). The most used SNOMED CT medication review code across the study period was Medication review done - 314530002 (59.5%). Conclusion We have reported a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period.
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Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition: COVID-19 Intervention: Dietary Supplement: Freeze-dried Mare Milk (Saumal) Sponsor: Asfendiyarov Kazakh National Medical University Not yet recruiting
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Effects of Exercise Training on Patients With Long COVID-19 - Condition: Long COVID-19 Intervention: Behavioral: Exercise training Sponsor: Guangdong Provincial People’s Hospital Recruiting
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Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine. - Condition: COVID-19 Intervention: Procedure: Lymph node aspiration / Blood sampling Sponsor: Assistance Publique - Hôpitaux de Paris Recruiting
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A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition: COVID-19 Interventions: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo Sponsor: GlaxoSmithKline Not yet recruiting
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A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines - Condition: COVID-19 Interventions: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg) Sponsor: Novavax Not yet recruiting
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Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome - Conditions: Fatigue; Post-Acute COVID-19 Syndrome Intervention: Procedure: Immunoadsorption vs. sham immunoadsorption Sponsor: Hannover Medical School Not yet recruiting
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Non-ventilated Prone Positioning in the COVID-19 Population - Conditions: COVID-19; Proning; Oxygenation; Length of Stay Interventions: Other: Proning group; Other: Control group Sponsor: Baylor St. Luke’s Medical Center Completed
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HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19 - Conditions: COVID-19; Delirium; Critical Illness Interventions: Combination Product: Active HD-tDCS; Combination Product: Sham HD-tDCS Sponsors: Suellen Andrade; City University of New York Completed
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RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms - Conditions: Long COVID-19; Long COVID Interventions: Drug: Paxlovid 25 day dosing; Drug: Paxlovid 15 day dosing; Drug: Control Sponsor: Kanecia Obie Zimmerman Not yet recruiting
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A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults - Condition: SARS-CoV-2 Interventions: Biological: CV0701 Bivalent High dose; Biological: CV0701 Bivalent Medium dose; Biological: CV0701 Bivalent Low dose; Biological: CV0601 Monovalent High dose; Biological: Control vaccine Sponsors: GlaxoSmithKline; CureVac Not yet recruiting
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RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms - Conditions: Long COVID; Long Covid19; Long Covid-19 Interventions: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham Sponsor: Duke University Not yet recruiting
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Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition: Post Acute Sequelae Covid-19 Hyposmia Interventions: Drug: Beclomethasone; Other: Placebo; Device: Microsponge Sponsor: Duke University Not yet recruiting
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PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Condition: SARS-CoV-2 Interventions: Drug: Upamostat; Drug: Placebo (PO) Sponsors: Henry M. Jackson Foundation for the Advancement of Military Medicine; Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies; FHI Clinical, Inc.; RedHill Biopharma Limited Not yet recruiting
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RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms - Conditions: Long COVID; Long Covid19; Long Covid-19 Interventions: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham Sponsor: Duke University Not yet recruiting
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Impact of COVID-19 on Sinus Augmentation Surgery - Condition: Bone Loss Interventions: Procedure: Sinus lift in patients with positive COVID-19 history; Procedure: Sinus lift with negative COVID-19 history Sponsor: Cairo University Completed
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From PubMed
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Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…
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Structural basis of anti-SARS-CoV-2 activity of HCQ: specific binding to N protein to disrupt its interaction with nucleic acids and LLPS - SARS-CoV-2 nucleocapsid (N) protein plays the essential roles in key steps of the viral life cycle, thus representing a top drug target. Functionality of N protein including liquid-liquid phase separation (LLPS) depends on its interaction with nucleic acids. Only the variants with N proteins functional in binding nucleic acids might survive and spread in evolution and indeed, the residues critical for binding nucleic acids are highly conserved. Hydroxychloroquine (HCQ) was shown to prevent the…
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Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis - CONCLUSIONS: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.
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SARS-CoV-2 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones - The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds,…
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Identification of a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection - We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)’s binding proteins and found that GAPDH participates in cADPR-mediated Ca^(2+) release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR-GAPDH complex structure, we performed the structure-based drug screening, identified several small chemicals with high docking scores to cADPR’s binding pocket…
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Discovery and evaluation of active compounds from Xuanfei Baidu formula against COVID-19 via SARS-CoV-2 Mpro - CONCLUSION: Acteoside is regarded as a representative active natural compound in XFBD to inhibit replication of SARS-CoV-2, which provides the antiviral evidence and some insights into the identification of SARS-CoV-2 M^(pro) natural inhibitors.
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Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2 - CONCLUSION: Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.
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Deuteration for Metabolic Stabilization of SARS-CoV-2 Inhibitors GC373 and Nirmatrelvir - Nirmatrelvir and GC373 inhibit the SARS-CoV-2 3CL protease and hinder viral replication in COVID-19. As nirmatrelvir in Paxlovid is oxidized by cytochrome P450 3A4, ritonavir is coadministered to block this. However, ritonavir undesirably alters the metabolism of other drugs. Hydrogens can be replaced with deuterium in nirmatrelvir and GC373 to slow oxidation. Results show that deuterium slows oxidation of nirmatrelvir adjacent to nitrogen by ∼40% and that the type of warhead can switch the site…
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Structures of SARS-CoV-2 N7-methyltransferase with DOT1L and PRMT7 inhibitors provide a platform for new antivirals - The RNA N7-methyltransferase (MTase) activity of SARS-CoV-2’s nsp14 protein is essential for viral replication and is a target for the development of new antivirals. Nsp14 uses S-adenosyl methionine (SAM) as the methyl donor to cap the 5’ end of the SARS-CoV-2 mRNA and generates S-adenosyl homocysteine (SAH) as the reaction byproduct. Due to the central role of histone MTases in cancer, many SAM/SAH analogs with properties of cell permeability have recently been developed for the inhibition of…
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Mega-scale desalination efficacy (Reverse Osmosis, Electrodialysis, Membrane Distillation, MED, MSF) during COVID-19: Evidence from salinity, pretreatment methods, temperature of operation - The unprecedented situation of the COVID-19 pandemic heavily polluted water bodies whereas the presence of SARS-CoV-2, even in treated wastewater in every corner of the world is reported. The main aim of the present study is to show the effectiveness and feasibility of some well-known desalination technologies which are reverse osmosis (RO), Electrodialysis (ED), Membrane Distillation (MD), multi effect distillation (MED), and multi stage flashing (MSF) during the COVID-19 pandemic. Systems’…
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An RBD bispecific antibody effectively neutralizes a SARS-CoV-2 Omicron variant - Potent neutralizing antibodies (nAbs) against SARS-CoV-2 are a promising therapeutic against the ongoing COVID-19 pandemic. However, the continuous emergence of neutralizing antibody escape variants makes it challenging for antibody therapeutics based on monospecific nAbs. Here, we generated an IgG-like bispecific antibody (bsAb), Bi-Nab, based on a pair of human neutralizing antibodies targeting multiple and invariant sites of the spike receptor binding domain (RBD): 35B5 and 32C7. We…
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Effects of official information and rumor on resource-epidemic coevolution dynamics - Epidemic-related information and resources have proven to have a significant impact on the spread of the epidemic during the Corona Virus Disease 2019 (COVID-19) pandemic. The various orientation role of information has different effects on the epidemic spreading process, which will affect the individual’ awareness of resources allocation and epidemic spreading scale. Based on this, a three-layer network is established to describe the dynamic coevolution process among information dissemination,…
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Deciphering and targeting host factors to counteract SARS-CoV-2 and coronavirus infections: insights from CRISPR approaches - Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses depend on host factors for the process of viral infection and replication. A better understanding of the dynamic interplay between viral pathogens and host cells, as well as identifying of virus-host dependencies, offers valuable insights into disease mechanisms and informs the development of effective therapeutic strategies against viral infections. This review delves into the key host factors that facilitate or…
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Antibody response to inactivated COVID-19 vaccine in patients with type 2 diabetes mellitus after the booster immunization - CONCLUSIONS: Patients with T2DM showed impaired antibody responses after booster vaccination for more than 6 months. Decreased anti-BA.4/5 responses give rise to the possibility of breakthrough infections for both patients with T2DM and HCs.
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Azithromycin exposure during pregnancy disturbs the fetal development and its characteristic of multi-organ toxicity - AIMS: Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an “emerging pollutant”, is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE.
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From Patent Search
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+Daily-Dose
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Biden’s Moral Calculus in Brokering a Saudi-Israeli Peace Deal - The U.S. is trying to land a tripartite agreement that could dramatically alter its involvement in the Middle East. - link
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Public Opinion About Trump’s Criminality Is Shifting—a Bit - As prosecutors release details of the charges and evidence against him, minds are slowly changing among less partisan voters—and maybe even among Republicans. - link
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Georgia’s Broad Racketeering Law May Now Ensnare Donald Trump - Fani Willis, the Fulton County district attorney, often relies on Georgia’s capacious RICO statute—though critics say that she has stretched it past the law’s intent. - link
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The New Trump Indictment and the Reckoning Ahead - With the former President still far ahead of the rest of the Republican field, the American electorate is likely headed for a crucial test. - link
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Regina Spektor on “Home, Before and After,” and a Trip to the Boundary Waters - The singer talks to the music critic Amanda Petrusich about her most recent album, and the writer Alex Kotlowitz makes an annual pilgrimage to the northern woods of Minnesota. - link
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From Vox
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We’re in a really odd hurricane season -
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+Despite unusually hot waters, forecasters expect a “near normal” hurricane season in 2023. | Michael Laughlin/Sun Sentinel/Tribune News Service via Getty Images
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+Oceans are at record high temperatures, but El Niño is keeping a lid on tropical storms in the Atlantic.
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+Hot water is the fuel for tropical cyclones like hurricanes and typhoons, and the weather this year has boosted the octane rating of the world’s oceans.
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+As of Tuesday, the National Hurricane Center was tracking one weather system that could possibly lead to a tropical storm. Even if they don’t lead to named storms, these systems could still bring heavy rain and high waves to US shores.
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+Ordinarily, all this hot water would portend a season of intense tropical storms in the Atlantic, but there’s another unusual force tamping down on severe weather: An already-strong El Niño this year is roiling the Pacific Ocean. El Niño cycles on and off at intervals anywhere from two to seven years. Its knock-on effects reshape weather around the world, and over the Atlantic Ocean, El Niño tends to disrupt hurricane formation.
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+Back in May, the National Oceanic and Atmospheric Administration (NOAA) predicted that the combination of hot water and unstable air from El Niño would lead to a “near normal” hurricane season in the Atlantic, with 12 to 17 named storms and one to four major hurricanes. So far, that forecast is holding.
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+However, because air and water temperatures around the world are reaching record highs, forecasters are trying to expect the unexpected. There’s already been some unprecedented activity: Tropical storms Bret and Cindy around the Caribbean marked the first time two tropical storms formed in the month of June since record-keeping began in 1851. It’s a sign that the ocean was charged up with a lot of heat early in the season.
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+This year, NOAA scientists are also testing out a new system that could better predict one of the most dangerous aspects of hurricanes. While hurricane forecasting has seen huge improvements in recent years, the global climate is shifting into uncharted territory, so researchers have to continue to adapt in order to anticipate these storms and save lives.
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+What makes this year’s hurricane season so strange
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+A tropical cyclone — those giant spinning storms you can see from space — requires water temperatures to be at least 80 degrees Fahrenheit down to a depth of 150 feet. It begins as a tropical depression. When sustained winds top 39 miles per hour, it’s called a tropical storm, and when wind speeds reach 74 mph, it’s called a typhoon or hurricane. (In the Atlantic and the eastern Pacific oceans, these storms are called hurricanes; in the western Pacific, they’re called typhoons.)
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+While hot water is the key ingredient needed to brew a tropical storm, this year has introduced some other strong flavors.
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+“There is a relationship between sea surface temperature warming and potential intensity of tropical cyclones, but also there’s a number of other factors at play,” said Jane Baldwin, an assistant professor of earth system science at the University of California Irvine. “It doesn’t really work to just say, ‘Because temperatures are increasing, we’re going to see more storms or stronger storms.’”
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+The waters surrounding Florida are scorching hot. Experts are deploying numerous measures to protect, relocate, and “bank” live fragments of coral to help Florida’s Coral Reef survive a heat crisis that may last for months.https://t.co/1EGEKkLkvTpic.twitter.com/eIPtE60RFX
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+A big factor to consider is not just the sea surface temperature but the temperature gradient between different parts of the ocean. And then we have to consider the air above the water.
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+One of the effects of El Niño is that it introduces more wind shear above the Atlantic. Between 5,000 feet and 35,000 feet above the ocean, the wind can drastically change direction and speed. These sudden wind shifts can rip up nascent tropical storms or extinguish them before they even form in the first place.
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+El Niño tends to have the opposite effect over the Pacific. The water in this ocean is also much warmer than normal, but the air is more stable than over the Atlantic. In El Niño years, the central and eastern Pacific tend to see more active hurricanes. Earlier this month, Tropical Storm Calvin passed just south of Hawaii.
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+Scientists have a new way to stay ahead of one of the most dangerous aspects of hurricanes
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+Last September, Hurricane Ian hit Florida’s Gulf Coast at Category 4 strength, with 155 mph sustained winds, driving a storm surge as high as 18 feet. Deaths from disasters in general have been declining around the world for nearly a century, but Ian defied that trend and killed at least 149 people. It was the deadliest storm to hit the mainland US since Katrina in 2005 and the deadliest in Florida since 1935.
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+A big part of why Hurricane Ian was so dangerous was that it was so hard to predict. These days, forecasters can map an accurate path of a hurricane 72 hours ahead or more, buying valuable time to evacuate, compared to 20 years ago, when such predictions could only come out 24 hours ahead of the storm. But Ian followed a less-traveled route for hurricanes that was harder to model, and small deflections in its path led to bigger swings in where it would make landfall. Local officials waited too long to order evacuations because they thought that early forecasts showed that their counties were outside the most dangerous region of the storm.
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+Another force behind Hurricane Ian’s destruction was that it underwent rapid intensification. That’s when a hurricane gains more than 35 mph in wind speed over 24 hours. The sudden speedup can turn a threatening storm into a monster, leaving little time for people to get out of the way. Ian actually rapidly intensified twice during its rampage.
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+“You can go from a tropical storm at night to a hurricane in the morning,” said Sundararaman Gopalakrishnan, who leads NOAA’s hurricane modeling team.
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+As average temperatures rise, some scientists expect that the conditions for rapid intensification will become more common.
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+ Giorgio Vera/AFP via Getty Images
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+Hurricane Ian was the deadliest hurricane to strike the US mainland since Hurricane Katrina.
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+Forecasters are starting to get their hands around this phenomenon. This year, NOAA is trying out the Hurricane Analysis and Forecast System, which could anticipate hurricane tracks as far as seven days out and provide more useful predictions about rapid intensification. Gopalakrishnan said this model was a huge feat. NOAA has been working on this for decades, teaming up across its various offices and with outside partners to gradually improve their predictions.
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+The tricky thing is that it’s really hard to see inside a major storm like a typhoon. Satellite images only zoom in so far, so scientists often look into the storms themselves. That can require flying manned aircraft into hurricanes, but as of late, NOAA has been using more autonomous vehicles that can fly and float. That has given scientists a better read of the mechanism that leads hurricanes to spool up quickly.
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+“We’ve reached a point where we are starting to understand how storms undergo rapid intensification,” Gopalakrishnan said. The HAFS model creates what he described as a “telescoping nest” that lets scientists zoom into particular parts of the storm to see its boundaries and how its intensity is changing. The goal though is to make sure the forecasts are useful for people so they can plan to protect themselves and their property, and that means first figuring out where cyclones will land. And while HAFS also improves storm track forecasts, it’s not perfect, and making these projections better is still a high priority. “It’s location, location, location,” Gopalakrishnan said.
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+All the while, the planet’s climate is continuing to change, amplifying many of the destructive elements of storms like rainfall and storm surge. Even as predictions get better, researchers warn there may be more surprises in store.
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The Chosen, the Christian megahit about Jesus, explained -
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+Jesus and his disciples, depicted in the hit Christian series The Chosen. | Angel / Vertical Films
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+The Chosen’s Christian nepo baby roots — and other ways the hit drama might surprise you.
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+In this age of endless streaming cancellations, it’s a rare thing for a show — even one with a cult following — to last multiple seasons, let alone thrive while doing so. Yet The Chosen, the popular Christian TV series about the life and times of Jesus and his disciples, has carved out an exception for itself on multiple fronts.
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+The show, from Utah-based Angel Studios, lately of Sound of Freedom fame, has gained somegrudging praise from reviewers and enormous loyalty from legions of fans who stream the show on the Angel website and other platforms. In November 2022, when the first two episodes of The Chosen’s third season were shown by Fathom Events, which distributes special releases to movie theaters, it became Fathom’s highest-grossing event of all time. Its massive success led the CW to pick it up, elevating the show from a word-of-mouth streaming hit to a proper network television gamble.
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+When the show debuted on linear TV on July 16, it did so to 500,000 viewers — a shave off the reported 100 million global viewers who’ve streamed the series, but not a bad start for the CW. Later in July, as the dual WGA/SAG strike got underway, The Chosenmade headlines when SAG granted it an exemption as an independent production to wrap up filming its fourth season in Midlothian, Texas. The CW plans to air the entire series over the next six months, with the season three finale scheduled to air on Christmas Eve. After that, the network will be primed to premiere season four to an even bigger audience. With the SAG exemption, it may in fact be one of the few scripted shows to air in 2024.
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+The crowdfunded show is interesting from a business standpoint, and also a cultural one. Is it possible to faithfully represent the story of Christ — a figure whose personal politics would probably alienate most modern-day Christians — in a way that’s honest enough to feel truthful, yet anodyne enough to avoid driving away the show’s enormous, right-leaning fan base? The Chosen is trying. Thanks to an emphasis on humanizing its many characters and directly engaging its fans, it has flourished — and with the show’s producers planning on seven seasons, its cultural imprint has only begun to be felt.
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+What, exactly, is The Chosen? And is it any good?
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+The Chosen is a show about Jesus Christ, adapted from the four books of the Bible known as the Gospels, which each tell the story of his birth, life, and death through the varying viewpoints of their writers. All three seasons are available to stream on Angel’s website, as well as Peacock; the first season can be found on Netflix, too.
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+Creator Dallas Jenkins has steadfastly reiterated in interviews that his primary goal with the show is to “accurately represent the character and intentions of Jesus and the Gospels” without “think[ing] too much about who it appeals to.” Jenkins brought his project to Angel Studios, where he was able to raise over $10 million for season one and a combined $30 million for seasons two and three. During this time, Angel Studios has seen annual revenue of over $120 million; crowdfunding contributors received a stake in The Chosen LLC and are supposed to earn back their investment plus 20 percent, though it’s unclear whether anyone has actually received profits.
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+The show itself makes clear, via a disclaimer in the first episode, that “all Biblical and historical context and any artistic imagination are designed to support the truth and intention of the Scriptures.” If this all sounds like a very serious undertaking, then consider that to much of its audience, fictionalizing the Bible is one of the most serious tasks there is.
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+The Chosen devotes a fair amount of screen time to world-building, helping its audience understand the sociopolitical context in which Christ was born. The Roman Empire, straining under its own weight, faced increased resistance and rebellion from an overtaxed population in the Middle East. Persecution of Jews grew more intense during this period, while competing Jewish factions created dissent and division among the group.
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+The show’s focal ensemble characters in the first several seasons are not entirely who you might expect. Rather, they include a number of figures who rarely get much, if any, significant attention in mainstream biblical adaptations. There’s religious leader-turned-tax collector Nicodemus (Erick Avari); Matthew (Paras Patel), another tax collector, whom The Chosen presents as being on the autism spectrum; hotheaded Simon, a.k.a. Peter (Shahar Isaac), and his brother, brooding fisherman Andrew (Noah James); and Mary Magdalene (Elizabeth Tabish), a sex worker dealing with alcoholism and addiction even after she meets Christ. The show’s fascination with Mary Magdalene follows innumerable depictions of her as a redeemed “fallen woman” who still continues to possess an erotic mystique, a kind of slutty muse; The Chosen, at least, humanizes her beyond merely traversing the virgin/whore divide and giving her an unrequited crush on Jesus.
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+Issues that plague the modern Christian church get their fair share of attention in the series. Poverty is a constant reality for the disciples and most people they meet. Multiple episodes focus on the racial tension between the Jews and Samaritans, with Jesus roundly castigating his followers for their own prejudices. Throughout the show, as in the Bible, he embraces people who are sick, disabled, and outcast, despite his disciples’ clear discomfort with his actions. At the same time, the disciples grapple with their own issues: perpetual money problems, relationship concerns, and jealousy and competitiveness — we might even say toxic masculinity — among the group.
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+This everyman approach to the story feels novel, especially among the pantheon of biblical adaptations that emphasize Christ’s larger-than-life divinity. That’s not to say that such moments aren’t present — there are entire episodes devoted to Jesus’s miracles, which he performs accompanied by a chorus of swooning vocals. But for the most part, The Chosen circles slowly around its ensemble, letting their relationship to each other, to the world, to religion, and finally to Jesus himself unfold little by little.
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+How much you care about all of this arguably largely hinges on how much you’re already primed to care about these people. As biblical figures, they’re already familiar to much of The Chosen’s audience. As characters, however, the Chosen leads don’t really scream charisma, and the screenwriting from Jenkins and Ryan Swanson can feel plodding and laborious rather than character-driven and narratively inspired.
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+The cast, while diverse, also produces a slightly discordant effect. Few Jewish actors are in the main cast, though the production pays careful attention to Jewish rituals and culture. Characters are played by actors who are ethnically Arab (including Jonathan Roumie, who plays Jesus), Latin, North African, and South and Southeast Asian; Roman centurions speak with British accents, while other characters have American or Indian accents. The credits are a fusion of rock and gospel set over visuals that recall midcentury (Jewish) designer Saul Bass, lest you forget that the team behind this production are all thoroughly American, with a thoroughly American understanding of what it means to love and follow Jesus.
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+That’s because The Chosen’s origins — not its biblical origins, but its capitalist ones — lie in nothing less than a good old-fashioned nepo baby backstory.
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+The Christian nepo baby roots of The Chosen
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+The Chosen was something of a (pardon us) Hail Mary for Angel Studios. The studio began as the streaming filter company VidAngel, which made a splash by allowing Christian audiences to watch sanitized edits of mainstream movies and TV shows. The problem was that all of this was illegal and resulted in VidAngel having to pay $62 million in a copyright lawsuit. After its subsequent bankruptcy, the company rebranded itself as simply Angel, a studio for crowdfunded Christian projects.
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+Enter Dallas Jenkins. Jenkins is the son of Jerry B. Jenkins, who with Tim LaHaye wrote the mega-selling Left Behind franchise that galvanized Christian fiction during the ’90s and ’00s. Those books, with their emphasis on revelation and Christian martyrdom, pushed a narrative of Christ as a powerful figure of vengeance and retribution. That image fully aligned with the evolving version of evangelical Christianity as a reflection of patriarchal values, with a strong authoritarian man heading up every family, made in the image of a macho version of God himself.
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+LaHaye, along with other religious conservatives like Jerry Falwell, was a celebrity Christian leader who helped turn evangelical Christianity toward the political far right. Jerry Jenkins has defended his co-writer LaHaye (who according to Jenkins did none of the writing, but rather served as a “biblical consultant”) against a litany of charges related to fundamentalism and bigotry. But Jenkins, like his Left Behind books, arguably pushes a belief in dispensationalism — the worldview that Christians are currently in the end times, which underlies much of Christian extremism.
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+It’s unclear how much of his father’s beliefs Dallas Jenkins has carried forward, but Jerry Jenkins is directly responsible for his son’s breakthrough success. After graduating from a small Christian college in Minnesota, dad set son up with “our own little production company and staff.” In his early years as a filmmaker, Jenkins made several short film projects for the Chicago-based Harvest Bible Chapel megachurch. When one of them, The Shepherd, became popular with parishioners in 2017, Jenkins’s mission to turn the film into a series ignited interest from Angel.
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+The Chosen, Jenkins’s pet project — and an idea he says he received from God, who he claims told him, “my people deserve good stuff” — was the first crowdfunding initiative that Angel launched following its rebirth. With its first season raising about $11 million from around 16,000 donors, the series has been widely touted as the most successful creative crowdfunding project of all time.
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+Angel’s business model is simple, and a bit novel: The focus is on cultivating loyalty and grassroots financial contributions from fans. The company considers those who contribute to a crowdfund as having “paid it forward” for other viewers to watch; when you stream a show on its platform, you’re encouraged to write a public thank-you note on every episode in response. Viewers can also post commentary in episode sidebars. According to the Wall Street Journal, Chosen extras paid (not were paid) $1,000 just to be present for the filming of the Sermon on the Mount. You can’t buy that sort of mystique, not when it comes hand-wrapped in a divine package.
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+Even with The Chosen striking lucrative deals with Netflix, Peacock, Lionsgate, and the CW, the show remains crowdfunded. When the crowdfunding goal between seasons three and four jumped dramatically from $18 million to $40 million, Angel’s fans helped pay to bring the show to every language on earth — even as the company boasted to investors of raking in more than $100 million in annual revenue. Where all of that extra money is going isn’t precisely clear, but The Chosen does have the gloss of an expensive historical drama.
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+So what’s the theology behind all of this? Good question!
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+It’s worth asking what exactly audiences are getting when they consume The Chosen. Among the most novel aspects of the series is its careful lack of sermonizing. As Catholic World’s Paul Senz put it, “One of the notable achievements of The Chosen is that Jenkins’ theological positions are nearly impossible to discern from the show.” The show’s lack of sermonizing has won praise from audiences for being diverse but not “woke” — for, essentially, not shoving the impact of identity down viewers’ throats.
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+That doesn’t mean theologies haven’t been duly imposed upon it. In May, the show received backlash because some fans spotted a crew member sporting a Pride flag in behind-the-scenes footage. Jenkins was at pains to downplay both the flag itself and political factions on set, explaining in a YouTube video, “Our cast and crew have wildly different beliefs. They run the spectrum. Sometimes they wear T-shirts or hats that go across the spectrum from a Pride flag or a MAGA hat or a ‘Jesus Saves’ shirt. No one on our set has been triggered, and no one on our set minds.”
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+The response from conservative media like the Daily Wire, which had fueled the backlash, was to reluctantly detach from blaming The Chosen itself for the degeneracy of a single crew member in order to support the work of the show overall. Others weren’t so forgiving; one critic castigated the show for suggesting that being gay is acceptable, including by making Jesus (entirely accurately) “a long haired, hippy, effeminate who goes to bars.” The question of how Christ himself might have responded to a Pride flag in his midst rarely came up.
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+Therein lies the true power of The Chosen: Its depiction of Christ is pleasing enough to summon this kind of loyalty from fans. But despite the themes it engages with, its avoidance of politics is so deft that it never does the Christlike work of challenging its audience’s concepts of unconditional love, government oppression, and what it means to truly embrace the marginalized.
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+As The Chosen reminds us, Jesus once said, “He who has ears to hear, let him hear.” The show’s larger message — and Christ’s larger message — seems to be getting lost in all the noise.
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Why everyone is on strike -
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+Welcome to Hot Strike Summer, where everyone, it seems, is on strike. | Hollywood To You/Star Max/GC Images
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+From actors to delivery drivers, why 2023 is a perfect storm for strikes.
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+Everyone, it seems, is on strike or threatening to be. Not only have delivery drivers, teachers, and hotel workers taken to picket lines in recent months, so have the people who play them on TV.
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+Actors in SAG-AFTRA and writers in the Writers Guild of America (WGA) are both on strike — the first time that’s happened in 63 years. In July, United Airlines pilots negotiated a 40 percent raise over the next four years, and soon after American Airlines pilots were able to get a similar deal (both unions had voted to strike if they didn’t get a suitable contract). UPS narrowly missed a strike this summer that could have disrupted much of the US economy, gaining big pay increases for both full- and part-time workers, in addition to things like AC in new trucks and no forced overtime on their days off.
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+This was all after Starbucks workers, upset with their company’s refusal to bargain for a first contract, went on strike at more than 150 locations around the country earlier this summer. Meanwhile, Amazon drivers, hotel staff, and fast food workers have all been on strike at some point this summer. And more big strikes are potentially on the horizon as the contract between the United Auto Workers and the Big Three American auto manufacturers will expire this fall.
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+“All these different struggles, all happening at the same time, in all these different industries, involving all these different groups of workers, all making these connections between their struggles,” Barry Eidlin, an associate professor of sociology at McGill University, said.
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+“You’re seeing that in a way that I have not seen in my lifetime.”
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+Like the year before it, 2023 is shaping up to be a big year for strikes. It’s only halfway through the year and there have been 177 work stoppages, according to data provided by Bloomberg Law. Before last year, when there were a total of 316 strikes, the last time the number of work stoppages was that high was 2007 — and that was for the full year. Of course, this level of labor action is nowhere near what America had in the decades prior to the 1990s, when a much bigger share of the population was unionized. Still, experts say the recent uptick is unique and notable — and potentially part of a resurgent labor movement.
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+But Eidlin says it can be tough to know when you’re in the middle of it. He noted that during the civil rights movement, there was a lot of time between hugely important events, like the Brown v. Board of Education ruling in 1954 and the Montgomery Bus Boycott of 1955, and the iconic Greensboro sit-ins of 1960 and the Freedom Rides of 1961.
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+“If you’re in 1958 or ’59, there’s nothing telling you that this one court decision and this one bus boycott in this one place is going to be what we now see as the beginnings of this big movement that changes the entire society,” Eidlin said. “There are these sort of episodic bursts, and you only connect the dots retroactively.”
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+ Jeff Kowalsky/Bloomberg via Getty Images
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+UPS workers held a practice picket before they agreed to a contract.
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+The current potential labor moment — if it is one — might have started with teacher strikes in Chicago in 2012 and in Arizona, West Virginia, and Oklahoma (the so-called Red State Revolt) in 2018 and 2019, according to Eidlin.
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+But why are so many workers striking now? A constellation of factors is at play.
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+Much of the union activity has to do with structural issues of inequality that were exacerbated by the pandemic, during which the public called many people “essential workers” while their employers treated them like the opposite. For many, working conditions worsened over the past three years, and worker pay hasn’t kept up.
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+“The big deal is something that’s been a problem in the US for centuries: The rich get rich and the poor get poorer,” Art Wheaton, director of labor studies at Cornell University’s ILR School, said. “And right now, the CEOs and executives have been doing really, really well in terms of their compensation over the last five years. And people can’t even keep up with inflation.”
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+He added, “If billionaires have enough money to fly to space and you can’t pay your rent, you have no sympathy for the company.”
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+Rising wages haven’t kept up with inflation, which means that working people don’t have the same spending power they once did, making workers’ situations more tense. At the same time, companies have raked in record profits, which is not sitting well with their employees.
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+Meanwhile, unemployment rates have stayed at or near-record lows, emboldening employees to strike since they have other options. The pandemic also made many realize what was important in life, pushing them to “work to live” rather than “live to work.” Indeed, many of the same factors that fed the Great Resignation are fueling the strikes.
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+“There’s a general tension and discontent,” Wheaton said. “So going out on strike is a release to let people express some of their frustration, trying to say, ‘We deserve better.’”
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+This year also happens to be one in which a number of major union contracts are up for negotiations. And union leaders are taking a much more aggressive approach than they have in years past to try and get bigger wins for their members. The strikes are about getting big pay jumps and much better conditions, rather than defending against concessions.
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+And workers themselves are driving many of the labor actions, in what’s considered a much more grassroots approach to organizing than in recent history. That means workers are more personally invested in their labor actions than if they were simply compelled to do so by their union.
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+Labor activity also feeds off other labor activity. When one group of workers witnesses another group of workers strike — or actually win better conditions and pay, as the Teamsters did with UPS — it inspires others to do so. A win in one union can also give other unions leverage. American Airlines pilots, for example, pointed to the United Airlines contract in their negotiations. And the UPS contract will likely spell higher wages even for non-union FedEx workers in a tight hiring market, lest FedEx lose much-needed employees to its competition.
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+“Once workers see other workers having some success through their unions, it increases their willingness to take the risk that it takes to organize in the first place or strike over a contract,” said Susan Schurman, a professor at Rutgers University’s labor and management school.
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+Schurman herself was on strike earlier this year with the AAUP-AFT union. She credits the strike and the ensuing “extraordinary” contract they got to the willingness of senior, full-time faculty to band together with adjuncts and graduate students. Even though their situations are different, they are intertwined, since universities are increasingly relying on adjuncts, who are paid less and who have less job security, to teach.
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+More and more, it seems workers are showing up not only for their peers and people at the same company or organization, but also for workers completely unrelated to them, in what people in labor relations call “horizontal solidarity.”
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+That means members of the Writers Guild showed up to Teamsters rallies, and the Teamsters have refused to make deliveries to the studios. Starbucks workers can be found supporting Amazon workers and vice versa.
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+ Mario Tama/Getty Images
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+Starbucks workers joined striking SAG-AFTRA and Writers Guild of America (WGA) members on their picket lines this summer.
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+“This is the first time I will tell you — and I’ve been in this field of labor relations for a very long time — of seeing this kind of horizontal solidarity, unions supporting other unions,” Schurman said. “The unions themselves have increasingly understood, ‘Hey, next time it could be us,’” she added. “Part of it is just understanding that the economy is now much more interconnected.”
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+And even when they are worlds apart, workers in different industries are finding similarities. AI could impact a variety of jobs, from using the technology to monitor drivers and track movements in warehouses to writing scripts and broadcasting the likenesses of actors on screen indefinitely.
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+Climate change, too, threatens to make work more miserable for a broad swath of workers, independent of industry. And increasingly, negotiations and strikes are factoring in environmental concerns.
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+“We’ve documented both last summer and this summer multiple strikes by groups like fast food workers where workers are just spontaneously walking out in both Texas and California because of terrible heat,” said Johnnie Kallas, a PhD candidate and director of Cornell’s Labor Action Tracker. “That’s one example of a new type of activity that may grow in prominence.”
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+All of these issues are also factoring into broad public support for unions, which is at its highest level since 1965, according to Gallup. Current labor actions at companies and organizations that are household names — and the media coverage they generate — only stand to make workers’ plights and union efforts more widely known.
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+“People who never heard of unions now know about unions,” Rutgers’ Schurman said. “Everybody knows when Brad Pitt’s on strike.”
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From The Hindu: Sports
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Racehorse trainer D. Netto suspended for doping offence -
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Successor, Rasputin and Flaming Lamborgini excel -
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Giving youngsters exposure: said Hardik Pandya on Rohit, Kohli being rested - Skipper Rohit and former captain Kohli were rested in the second and the third ODIs of the series, which India won 2-1
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Yamuna recedes below warning mark in Delhi - Delhi has grappled with unprecedented waterlogging and floods this month
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We don’t ask for luxury, Hardik Pandya slams West Indies board - Led by Hardik in the absence of Rohit Sharma, India thrashed the West Indies by 200 runs to clinch the three-match ODI series 2-1
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From The Hindu: National News
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Vandana Das awarded MBBS degree posthumously -
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CUET-UG not based on CBSE syllabus, examines students of different boards on equal footing: Education Ministry - The test examines students of different boards on equal footing, Union Minister of State for Education Subhas Sarkar said in a written reply in the Rajya Sabha
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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 by The Hindu Bureau.
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Congress’ choice of new Maharashtra LoP forefronts factionalism in party’s State unit - OBC leader Vijay Wadettiwar’s appointment has disgruntled Congress loyalists from western Maharashtra, who view it as a move to appease NCP chief Sharad Pawar
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Data | In India, women do seven hours of housework, men under three hours - This trend is consistent for women across income levels and caste groups
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From BBC: Europe
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Ukraine war: Drones target Odesa grain stores near Romania border - A grain silo has been damaged and fires have broken out in Ukraine’s Danube port of Izmail.
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Niger coup: Evacuated European nationals arrive in Paris and Rome - It comes amid growing anti-French sentiment, with France’s embassy recently coming under attack.
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‘It’s like playing with death’ - Ukraine’s female front line soldiers - Women in the Ukrainian military describe their battles against Russia and sexism within their ranks.
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Watch moment police dog sniffs out €1m hidden cash - The Italian canine named ‘Elio’ foiled a cash smuggling attempt at a bus station near the city of Florence.
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Best friends killed in crash on way to school dance - Kiea McCann, 17, and her friend Dlava Mohamed, 16, died on Monday near the Irish town of Clones.
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From Ars Technica
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Canon warns printer users to manually wipe Wi-Fi settings before discarding - If you thought a factory reset wipes Wi-Fi passwords, you’d be wrong. - link
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Western Digital HDD capacity hits 28TB as Seagate looks to 30TB and beyond - WD believes it can wring a bit more capacity out of existing PMR and SMR tech. - link
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The Atlantic is frying, but so far hurricanes are dying. What’s going on? - Can wind shear and sinking air hold historically high sea temperatures at bay? - link
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Meta loses battle in EU, will ask for consent to show personalized ads - Changes will impact Facebook, Instagram users in Europe as early as this fall. - link
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The Google Assistant is getting a big reboot around generative AI - “Supercharging” the Assistant means some layoffs and a lot of leadership changes. - link
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From Jokes Subreddit
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Free Sex w every fill up. -
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+There was this gas station in Anderson, SC trying to increase its sales, so the owner put up a sign saying “Free Sex with Fill-up.”
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+Soon Bubba pulled in, filled his tank, and then asked for his free sex. The owner told him to pick a number from 1 to 10, and if he guessed correctly, he would get his free sex. Bubba guessed 8 and the proprietor said, “No, you were close. The number was 7. Sorry, no free sex this time but maybe next time”.
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+Some time thereafter, Bubba, along with his buddy Cletus, pulled in again for a fill-up, and again he asked for his free sex. The proprietor again gave him the same story and asked him to guess the correct number. Bubba guessed 2 this time, and the proprietor said, “Sorry, it was 3. You were close but no free sex this time”.
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+As they were driving away, Bubba said to Cletus, “I think this is a scam…. that game is rigged and he doesn’t give away free sex”. Cletus replied, “No, it’s not rigged – my wife went there twice last week and won both times.”
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A beautiful, voluptuous woman went to a gynecologist. The doctor took one look at this woman and all his professionalism went out the window. He immediately told her to undress. After she had disrobed the doctor began to stroke her thigh. -
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+He asked her, “Do you know what I’m doing?” “Yes,” she replied, “you’re checking for any abrasions or dermatological abnormalities.” “That is right,” said the doctor. He then began to fondle her breasts. “Do you know what I’m doing now?” he asked. “Yes,” the woman said, “you’re checking for any lumps or breast cancer.” “Correct,” replied the shady doctor. Finally, he mounts his patient and started having sexual intercourse with her. He asked, “Do you know what I’m doing now?” “Yes,” she said. “You’re getting herpes; which is why I came here in the first place!”
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+A sexy Irish blonde at a Casino, seemed a little intoxicated She bet 20,000 Euro on a single Roll of dice. She said - “I hope you don’t mind, but I feel Luckier when I’m nude.” With that, she removed her clothes, rolled the dice and yelled-“Come on baby, Mama needs new clothes!” As the Dice came to a stop, she jumped and yelled - “Yes, Yes,I Won.. I Won..” She hugged each dealer and picked up her winnings and clothes and left. The dealers gazed at each other, dumb founded. Finally, one of them asked-“What number rolled on the dice?” The other - “I don’t know, I thought you were watching.”
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A small man goes to prison and gets sent to his cell. -
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+When he meets his new cellmate, he finds out it’s this enormous Michael Clark Duncan looking black guy. The cellmate tells him “Hey boy, you and me? We’re married now!!! So do you want to be the husband, or you want to be the wife?” The little man replies back “Oh god….. I really don’t want to do this, but if I have to…. I guess I’d rather be the husband.” The enormous cellmate replies back “Okay, honey, that sounds good to me. Now get over here, and suck your wife’s dick!!!”
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+Officer: You were speeding, sir. License and registration
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+John: Dude, I got no license
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+Officer: You’re driving without a license?
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+John: hell yeah!
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+Officer: And registration?
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+John: I jacked this car!
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+Officer: Are you serious?
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+John: Dude, I killed the driver! I popped a cap in him with this gun I’ve got in the glove box. His body’s in the trunk now!!
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+Officer: Stay right there!!! returns to his vehicle and connects to dispatch I need backup NOW!!!
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+within the next couple of minutes, there were several cops at the scene including the chief of police who walks over to John
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+Chief: Sir, can you open your trunk
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+John: Sure
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+John popped open his trunk and it was empty
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+Chief: alright, now let me take a look inside of your glove box
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+John opened his glove box and the chief couldn’t find any weapons
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+Chief: you wouldn’t happen to have your license and registration, would you?
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+John: of course I do
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+John present his license and registration. He was eligible to drive and the car belonged to him
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+Chief: Alright, I’m confused. The officer who called me said that you had a dead body in your trunk, a firearm in your glove box and that you were driving without a license in a stolen car.
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+John: Yeah, I bet that lying son of a bitch also told you that I was speeding
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Giorgio Vera/AFP via Getty Images
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Jeff Kowalsky/Bloomberg via Getty Images
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Mario Tama/Getty Images
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