scPanel: A tool for automatic identification of sparse gene panels for generalizable patient classification using scRNA-seq datasets -
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+Single-cell RNA sequencing (scRNA-seq) technologies can generate transcriptomic profiles at a single-cell resolution in large patient cohorts, facilitating discovery of gene and cellular biomarkers for disease. Yet, when the number of biomarker genes is large the translation to clinical applications is challenging due to prohibitive sequencing costs. Here we introduce scPanel, a computational framework designed to bridge the gap between biomarker discovery and clinical application by identifying a sparse gene panel for patient classification from the cell population(s) most responsive to perturbations (e.g., diseases/drugs). scPanel incorporates a data-driven way to automatically determine the minimal number of selected genes. Patient-level classification is achieved by aggregating the prediction probabilities of cells associated with a patient using the area under the curve score. Application of scPanel on scleroderma and COVID-19 datasets resulted in high patient classification accuracy using a small number (<20) of genes automatically selected from the entire transcriptome. We demonstrate 100% cross-dataset accuracy to predict COVID-19 disease state on an external dataset, illustrating the generalizability of the predicted genes. scPanel outperforms other state-of-the-art gene selection methods for patient classification and can be used to identify small sets of reliable biomarker candidates for clinical translation.
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Microgliosis, astrogliosis and loss of aquaporin-4 polarity in frontal cortex of COVID-19 patients -
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+The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), causing human coronavirus disease 2019 (COVID-19), not only affects the respiratory tract, but also impacts other organs including the brain. A considerable number of COVID-19 patients develop neuropsychiatric symptoms that may linger for weeks and months and contribute to "long-COVID". While the neurological symptoms of COVID-19 are well described, the cellular mechanisms of neurologic disorders attributed to the infection are still enigmatic. Here, we studied the effect of an infection with SARS-CoV-2 on the structure and expression of marker proteins of astrocytes and microglial cells in the frontal cortex of patients who died from COVID-19 in comparison to non-COVID-19 controls. Most of COVID-19 patients had microglial cells with retracted processes and rounded and enlarged cell bodies in both gray and white matter, as visualized by anti-Iba1 staining and confocal fluorescence microscopy. In addition, gray matter astrocytes in COVID-19 patients were frequently labeled by intense anti-GFAP staining, whereas in non-COVID-19 controls, most gray matter astrocytes expressed little GFAP. The most striking difference between astrocytes in COVID-19 patients and controls was found by anti-aquaporin-4 (AQP4) staining. In COVID-19 patients, a large number of gray matter astrocytes showed an increase in AQP4. In addition, AQP4 polarity was lost and AQP4 covered the entire cell, including the cell body and all cell processes, while in controls, AQP4 immunostaining was mainly detected in endfeet around blood vessels and did not visualize the cell body. In summary, our data suggest neuroinflammation upon SARS-CoV-2 infection including microgliosis and astrogliosis, including loss of AQP4 polarity.
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Coatomer complex I is required for the transport of SARS-CoV-2 progeny virions from the endoplasmic reticulum-Golgi intermediate compartment -
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+SARS-CoV-2 undergoes budding within the lumen of the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and delivers progeny virions to the cell surface by employing vesicular transport. However, the molecular mechanisms remain poorly understood. Using three-dimensional electron microscopic analysis, such as array tomography and electron tomography, we found that virion-transporting vesicles possessed a coated protein on their membrane and demonstrated that the coated protein was coatomer complex I (COPI). During the later stages of SARS-CoV-2 infection, we observed a notable alteration in the distribution of COPI and ERGIC throughout the cytoplasm. Depletion of COPB2, a key component of COPI, led to the confinement of SARS-CoV-2 structural proteins in the perinuclear region, where progeny virions were accumulated within the ERGIC. While the expression levels of viral proteins within cells were comparable, this depletion significantly reduced the efficiency of virion release, leading to the significant inhibition of viral replication. Hence, our findings suggest COPI as a critical player in facilitating the transport of SARS-CoV-2 progeny virions from the ERGIC. Thus, COPI could be a promising target for the development of antivirals against SARS-CoV-2.
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A narrow ratio of nucleic acid to SARS-CoV-2 N-protein enables phase separation -
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+SARS-CoV-2 Nucleocapsid protein (N) is a viral structural protein that packages the 30kb genomic RNA inside virions and forms condensates within infected cells through liquid-liquid phase separation (LLPS). N, in both soluble and condensed forms, has accessory roles in the viral life cycle including genome replication and immunosuppression. The ability to perform these tasks depends on phase separation and its reversibility. The conditions that stabilize and destabilize N condensates and the role of N-N interactions are poorly understood. We have investigated LLPS formation and dissolution in a minimalist system comprised of N protein and an ssDNA oligomer just long enough to support assembly. The short oligo allows us to focus on the role of N-N interaction. We have developed a sensitive FRET assay to interrogate LLPS assembly reactions from the perspective of the oligonucleotide. We find that N alone can form oligomers but that oligonucleotide enables their assembly into a three-dimensional phase. At a ~1:1 ratio of N to oligonucleotide LLPS formation is maximal. We find that a modest excess of N or of nucleic acid causes the LLPS to break down catastrophically. Under the conditions examined here assembly has a critical concentration of about 1 micromolar. The responsiveness of N condensates to their environment may have biological consequences. A better understanding of how nucleic acid modulates N-N association will shed light on condensate activity and could inform antiviral strategies targeting LLPS.
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Reduced selection during sweeps lead to adaptive momentum on rugged landscapes -
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+Evolutionary theory seeks to explain the remarkable diversity and adaptability of life on Earth. Current theory offers substantial explanatory power, but it overlooks important transient dynamics that are prominent only when populations are outside equilibrium, such as during selective sweeps. We identify a dynamic that we call "adaptive momentum" whereby lineages with a selective advantage can temporarily sustain more deleterious mutations. This reduction in the strength of purifying selection allows populations to explore fitness valleys that are usually too costly to enter, potentially leading to the discovery of otherwise inaccessible fitness peaks. Using mathematical and agent-based simulations, we demonstrate adaptive momentum and show how periods of disequilibrium become windows of enhanced adaptation. Genetic exploration can occur during these windows without requiring mechanisms such as changing environments or complex landscapes. Adaptive momentum provides a simple potential explanation for bursts of rapid evolution observed in nature, including in pathogens such as SARS-CoV-2 and cancers.
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Deep Learning in Drug Repurposing: A Review of the CoV-DrugX Module within the CoV-DrugX Pipeline -
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+A comprehensive overview of the integration of deep learning techniques in drug repurposing, particularly focusing on the CoV-DrugX module within the CoV-DrugX Pipeline. The paper highlights the significance of drug repurposing in accelerating treatment discovery, especially in the context of the COVID-19 pandemic. It discusses the emergence of deep learning methods, such as recurrent neural networks (RNNs), graph convolutional networks (GCNs), and long short-term memory (LSTM) networks, in predicting drug-target interactions and identifying repurposable drugs. The review emphasizes the role of deep learning in extracting informative features, improving drug discovery, enhancing drug repositioning, and handling large-scale data effectively. Additionally, it explores the applications and advantages of deep learning in drug repurposing, showcasing its potential to revolutionize the field by learning complex relationships from extensive datasets. The abstract sets the stage for a detailed examination of the DrugX moduleās capabilities within the CoV-DrugX Pipeline, shedding light on its contributions to drug discovery and repurposing efforts, particularly in the fight against COVID-19.
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AI-Driven Drug Repurposing for COVID-19: Revolutionizing Therapeutic Discovery and Treatment Strategies -
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+In March of 2020, a deadly disaster caused a global pandemic all across the globe. This paper elucidates the concept of drug repurposing, a strategy that harnesses existing drugs for new therapeutic purposes. Leveraging drugs already approved for other indications offers a promising avenue for rapid deployment against COVID-19, circumventing the lengthy and costly process of drug development from scratch. Central to the drug repurposing approach is the utilization of sophisticated computational tools one such development is in the form of CoV-DrugX DL-200 which helps integrate over 200 chemoinformatics properties to analyze drug structures and characteristics and whether or not the drug can be repurposed or not. By accepting input in the form of SMILE structure, canonical SMILE structure, drug name, or DrugBankID, the database employs advanced algorithms to predict the potential candidates. This data-driven approach enables researchers and clinicians to expedite the identification of candidate drugs for clinical trials, accelerating the search for effective therapeutics for the pandemic that was caused and for any other catastrophe that we might face.
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The Challenges of Engaging African American Communities During a Public Health Crisis: The Role of Government Information, COVID-19 Discourse, and Emotional Content on Social Media -
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+[Forthcoming in International Journal of Strategic Communication] During a public health crisis, social media platforms play a pivotal role in circulating information and influencing public reactions. This research investigates the dynamics of public engagement with COVID-19-related content and government information sources within African American online communities, a population that has experienced significant health risks and inequities. Using advanced computational research methods, we analyzed 199,542 posts from 1,152 communities created between January 2020 and December 2022. The present research focused on the presence of COVID-19-related content, government information sources, the emotions of anger and fear in these posts, and their associations with user engagement metrics. The results indicated that posts discussing COVID-19 and those incorporating government information sources tend to receive lower levels of engagement. On the other hand, posts with higher levels of anger generated more shares and comments. The findings suggest a ātriple disadvantageā in user engagement for social media messages that reference government sources and discuss public health risks without delivering strong negative emotions. These patterns are crucial not only for understanding the challenges faced by the at-risk population but also for aiding researchers and practitioners in developing more effective communication strategies during public health crises.
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A cultural-historical study of affordances for agency when children play in the city environments in Rome -
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+Children in the Antique Rome showed their agency when playing in the city environment, in other words, the environment afforded them to play and develop their agency. Today, the city is still the same, but childhood is different. We investigated how children play and perform their agency in the city environment today, after the restrictions of Covid19. 60 play episodes were observed by naturalistic observation and analyzed qualitatively. The results show that affordances for agency realized by three distinctive ways, and it also was not performed. The results are useful for childhood and play researchers, educators and playground designers.
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Unravelling the Brexit-COVID-19 Nexus: Assessing the Decline of EU Student Applications into UK Universities -
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+Whilst the numbers of international students attending UK universities has been increasing in recent years, the 2021/22 and 2022/23 academic years saw a decline in applications from EU domiciled students. This decline is hypothesised to represent a direct result of the end of free movement due to the UKās withdrawal from the European Union (EU), with varying impacts across institutions and study subjects. However, the extent of this decline remains to be estimated and disentangled from the impacts of the COVID-19. Using difference-in-differences in a hierarchical regression framework and Universities and Colleges Admissions Service (UCAS) data, we aim to quantify the decline in the number of student applications post-Brexit. We find evidence of an overall decline of 65 per cent in the 2021 academic year in successful applications from EU students. We note that this decline is more severe for non-Russell Group institutions, and for Health and Life Sciences and Arts and Languages. Further, we explore the spatial heterogeneity of the impact of Brexit across EU countries of origin; seeing the greatest effects for Poland and Germany but that this varies depending on institution type and subject. We are also able to show that higher rates of COVID-19 stringency in the country of origin led to greater applications for UK HE. Our results hold importance for government and institutional policymakers seeking to understand where losses are occurring and how international students respond to external shocks and policy changes. By quantifying the distinct impacts of Brexit and COVID-19, our study offers valuable insights to guide strategic interventions aimed at sustaining the UKās attractiveness as a destination for international students.
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An Outbreak of Selective Attribution: Partisanship and Blame in the COVID-19 Pandemic -
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+Crises and disasters give voters an opportunity to observe the incumbentās response and reward or punish them for successes and failures. Yet even when voters perceive events similarly, they tend to attribute responsibility selectively, disproportionately crediting their party for positive developments and blaming opponents for negative developments. We examine selective attribution during the COVID-19 pandemic in the United States, reporting three key findings. First, selective attribution rapidly emerged during the first weeks of the pandemic, a time in which Democrats and Republicans were otherwise updating their perceptions and behavior in parallel. Second, selective attribution is caused by individual-level changes in perceptions of the pandemic. Third, existing research has been too quick to explain selective attribution in terms of partisan-motivated reasoning. We find stronger evidence for an explanation rooted in beliefs about presidential competence. This recasts selective attributionās implications for democratic accountability.
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Public Engagement with COVID-19 Preprints: Bridging the Gap Between Scientists and Society -
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+The surge in preprint server use, especially during the Covid-19 pandemic, necessitates a reex-amination of their significance in the realm of science communication. This study rigorously investigates discussions surrounding preprints, framing them within the contexts of systems theory and boundary objects in scholarly communication. An analysis of a curated selection of COVID-19-related preprints from bioRxiv and medRxiv was conducted, emphasizing those that transitioned to journal publications, alongside the associated commentary and Twitter activity. The dataset was bifurcated into comments by biomedical experts versus those by non-experts, encompassing both academic and general public perspectives. Findings revealed that while peers dominated nearly half the preprint discussions, their presence in Twitter dia-logues was markedly diminished. Yet, intriguingly, the themes explored by these two groups diverged considerably. Preprints emerged as potent boundary objects, reinforcing, rather than obscuring, the delineation between scientific and non-scientific discourse. They serve as cru-cial conduits for knowledge dissemination and foster inter-disciplinary engagements. None-theless, the interplay between scientists and the wider public remains nuanced, necessitating strategies to incorporate these diverse discussions into the peer review continuum without compromising academic integrity and to cultivate sustained engagement from both experts and the broader community.
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Psychological distance to science as a predictor of science skepticism across domains -
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+The current paper presents and tests psychological distance to science (PSYDISC) as a domain-general predictor of science skepticism. Drawing on the concept of psychological distance, PSYDISC reflects the extent to which individuals perceive science as a tangible undertaking conducted by people similar to oneself (social), with effects in the here (spatial) and now (temporal), and as useful and applicable in the real world (hypothetical distance). In six studies (2 preregistered; total N = 1,630) and two countries, we developed and established the factor structure and validity of a scale measuring PSYDISC. Crucially, higher PSYDISC predicted skepticism beyond established predictors, across science domains. A final study showed that PSYDISC shapes real-world behavior (COVID-19 vaccination uptake). The current work thus provides a novel tool to predict science skepticism, as well as a construct that can help to further develop a unifying framework to understand science skepticism across domains.
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GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern -
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+Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
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Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy -
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+Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy. The combination of laminar flow and multiple dyes enable the detection of correlated fluorescence signals, providing information on nanoparticle volumes and specific chemical composition properties, such as viral envelope proteins. We evaluated and validated the assay using fluorescent beads and viruses, including SARS-CoV-2. Additionally, we demonstrate how hydrodynamic focusing enhances the assay sensitivity for detecting clinically-relevant virus loads. Based on our results, we envision the use of this technology for clinically relevant bio-nanoparticles, supported by the implementation of the assay in a portable and user-friendly setup.
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Effects of Unsupervised Inspiratory Muscle Training on Ventilation Variability in Post-covid-19 Patients. - Conditions: COVID-19 Interventions: Device: Experimental Group Sponsors: Universidade Federal do Rio Grande do Norte Recruiting
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A Phase IV Vaccine Study Under the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 (COVID-19) Vaccines. - Conditions: SARS CoV 2 Infection Interventions: Biological: Johnson & Johnson Sponsors: Jens D Lundgren, MD; Ministry of the Interior and Health, Denmark Completed
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Detoxification From the Lipid Tract - Conditions: COVID-19 Vaccine Adverse Reaction Interventions: Device: electroencephalogram biofeedback; Device: electrical brain stimulation; Device: ultra-low frequency transcranial magnetic stimulation; Drug: Sertraline Hydrochloride; Drug: Clonazepam; Drug: Alprazolam; Drug: Metoprolol; Drug: Olanzapine; Drug: Pravastatin Sodium 20 MG; Drug: Sacubitril Valsartan Sodium Hydrate Sponsors: Pachankis, Yang I., M.D.; First Affiliated Hospital of Chongqing Medical University Completed
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Covid-19 and Influenza Oral Vaccine Study - Conditions: covid19 Infection; Influenza, Human Interventions: Biological: Covid-19 vaccine; Biological: Influenza vaccine Sponsors: Vaxine Pty Ltd; Australian Respiratory and Sleep Medicine Institute Ltd Not yet recruiting
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A Study of an Investigational mRNA-1273.815 COVID-19 Vaccine in Previously Vaccinated Adults - Conditions: SARS-CoV-2 Interventions: Biological: Investigational mRNA-1273.815; Biological: Licensed Spikevax Vaccine Sponsors: ModernaTX, Inc. Not yet recruiting
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A Study of the Efficacy of Troxerutin in Preventing Thrombotic Events in COVID-19 Patients - Conditions: COVID 19 Associated Coagulopathy Interventions: Drug: Troxerutin; Drug: Placebo; Drug: placebo + low molecular weight heparin; Drug: troxerutin + low molecular weight heparin Sponsors: Westlake University; Shaoxing Central Hospital Recruiting
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The Use of Isatidis Root and Forsythia Oral Liquid for the Treatment of Mild Cases of COVID-19: A Trial Clinical Study - Conditions: Treatment of Mild Cases of COVID-19 Interventions: Drug: Langenlianqiao; Drug: LianhuaQingWen; Other: placebo control group Sponsors: Central South University Completed
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Fascial Tissue Response To Manual Therapy: Implications In Long Covid Rehabilitation - Conditions: COVID-19 Interventions: Other: Guidebook; Other: Guidebook and Myofascial ReorganizationĀ® (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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From PubMed
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Ivermectin: A Multifaceted Drug With a Potential Beyond Anti-parasitic Therapy - Ivermectin was first discovered in the 1970s by Japanese microbiologist Satoshi Omura and Irish parasitologist William C. Campbell. Ivermectin has become a versatile pharmaceutical over the past 50 years. Ivermectin is a derivative of avermectin originally used to treat parasitic infections. Emerging literature has suggested that its role goes beyond this and may help treat inflammatory conditions, viral infections, and cancers. Ivermectinās anti-parasitic, anti-inflammatory, anti-viral, andā¦
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Interleukin inhibitors and the associated risk of candidiasis - Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individualās susceptibility to Candida infections. Variations in the severity ofā¦
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New meroterpenoids and polyketides from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1 and their anti-inflammatory and SARS-CoV-2 M(pro) inhibitory activities - Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of Ā¹H, ^(13)C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC(50) values of 1.78 Ī¼M and 1.54 Ī¼M, respectively. Moreover, theyā¦
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Development of a fluorescent scaffold by utilizing quercetin template for selective detection of Hg2+: Experimental and theoretical studies along with live cell imaging - Quercetin is an important antioxidant with high bioactivity and it has been used as SARS-CoV-2 inhibitor significantly. Quercetin, one of the most abundant flavonoids in nature, has been in the spot of numerous experimental and theoretical studies in the past decade due to its great biological and medicinal importance. But there have been limited instances of employing quercetin and its derivatives as a fluorescent framework for specific detection of various cations and anions in theā¦
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Storytelling and Deliberative Play in the Oregon Citizensā Assembly Online Pilot on COVID-19 Recovery - This article draws on the deliberative play framework to examine empirical examples of storytelling in an online deliberative forum: The Oregon Citizen Assembly (ORCA) Pilot on COVID-19 Recovery. ORCA engaged 36 citizens in deliberation about state policy through an online deliberative process spanning seven weeks. Drawing on literature on small stories in deliberation, we trace stories related to a policy proposal about paying parents to educate children at home. Our analysis demonstrates thatā¦
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Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients - CONCLUSION: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumorās local immune condition, and supports clinical decision-making in tumor therapies.
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The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes - INTRODUCTION: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes.
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Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera - In response to the urgent need for potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapeutics, this study introduces an innovative nucleoside tailoring strategy leveraging ribonuclease targeting chimeras. By seamlessly integrating ribonuclease L recruiters into nucleosides, we address RNA recognition challenges and effectively inhibit severe acute respiratory syndrome coronavirus 2 replication in human cells. Notably, nucleosides tailored at the ribose 2ā-positionā¦
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Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis - Damage of the endothelial glycocalyx (eGC) plays a central role in the development of vascular hyperpermeability and organ damage during systemic inflammation. However, the specific signalling pathways for eGC damage remain poorly defined. Aim of this study was to combine sublingual video-microscopy, plasma proteomics and live cell imaging to uncover further pathways of eGC damage in patients with coronavirus disease 2019 (COVID-19) or bacterial sepsis. This secondary analysis of the prospectiveā¦
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Laboratory approach for vaccine-induced thrombotic thrombocytopenia diagnosis in the Netherlands - CONCLUSION: Our study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti-PF4-inducing, FcÉ£RIIa-dependent platelet activation, suggesting an HIT-like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology (ānon-HIT likeā) leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies.
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Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model - INTRODUCTION: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins.
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Elderberry interaction with pazopanib in a patient with softātissue sarcoma: A case report and literature review - Elderberry flower extract is marketed as an herbal supplement with purported benefits in boosting the immune system. The use of elderberry increased during the coronavirus pandemic. However, the interaction of elderberry with cytotoxic medicines has remained elusive. Pazopanib is a multikinase inhibitor approved for patients diagnosed with soft-tissue sarcoma. The present study reported on the case of a middle-aged woman diagnosed with localized intermediate-grade sarcoma of the left sartoriusā¦
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Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19 - We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown thatā¦
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Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and Repress Coronavirus Replication, Validating Mac1 as an Antiviral Target - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed. Here, we describe small-molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation-mediated innate immune responses. Three high-throughput screening hits had the same 2-amide-3-methylester thiophene scaffold. We studied the compound binding mode using X-ray crystallography, allowing us to designā¦
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Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics - CONCLUSION: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.
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From Patent Search
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Jessica Tisch, the Ex-N.Y.P.D. Official Trying to Tame New Yorkās Trash - The city has lived in filth for decades. Can Jessica Tisch, a scion of one of the countryās richest families, finally clean up the streets? - link
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Maggie Rogersās Journey from Viral Fame to Religious Studies - The singer-songwriterās sudden celebrity made her a kind of minister without training. So she went and got some. - link
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Battling Under a Canopy of Russian and Ukrainian Drones - The commander of one of Ukraineās most skilled units sent his men on a dangerous mission that required them to elude a swarm of aerial threats. - link
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Park Chan-wook Gets the Picture He Wants - With āThe Sympathizer,ā the director of āOldboyā and āThe Handmaidenā comes to American television. - link
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Joe Biden and U.S. Policy Toward Israel - After six months of war, has Israelās killing of World Central Kitchen aid workers compelled the President to do more to save lives in Gaza? - link
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From Vox
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College enrollment is up. The financial aid mess could bring it crashing down. -
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+Students head to class on the campus of Brown University in Providence, Rhode Island. | John Tlumacki/The Boston Globe via Getty Images
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+The number of first-time filers has dropped 40 percent since the new FAFSAās bungled rollout.
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+A report released earlier this year from the National Clearinghouse Research Center found that higher education is finally experiencing a reversal in enrollment declines for the first time since the pandemic began.
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+In fall 2023, there were about 176,000 more undergraduates enrolled, a 1.2 percent increase over fall 2022ās total enrollment at colleges nationwide. The trend could continue as applications continue to increase.
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+College enrollment began retreating in certain parts of the country after a peak in 2010, so the increase is a welcome change as industry watchers continue to fear āthe enrollment cliffā ā shrinking class sizes year after year that have led to layoffs and consolidation and, ultimately, the shuttering of schools. A variety of factors have driven up enrollment this year: More older students matriculated, certificate and vocational programs at community colleges attracted more pupils, and those who had dropped out in previous years returned to complete their degrees.
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+āThe undergraduate enrollment increase is significant. Itās the first time that we have seen this happen in our tracking, which goes back to 2015,ā said Jeremy Cohen, a research associate at the National Student Clearinghouse Research Center.
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+But as the annual May 1 enrollment deadline nears for many colleges, the tumultuous rollout of the new FAFSA, which has caused massive delays in the admissions schedule for families and schools, could destroy the gains.
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+As of late March, 40 percent fewer first-time filers had completed the FAFSA ā it stands for the Free Application for Federal Student Aid ā compared with the same time last year, according to the National College Attainment Network, which analyzed new data from the Department of Education. In all, an estimated half a million to 700,000 fewer high school seniors will complete the FAFSA compared to the class of 2023, the NCAN told Inside Higher Education.
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+āItās bad. There are a lot of words not fit to print to describe how bad the FAFSA rollout has been and the impact thatās going to have on student enrollment,ā said Katharine Meyer, a Brookings Institution fellow at the Brown Center on Education Policy. āI remain cautious to see what the fall 2024 [enrollment] numbers look like, to see if [the enrollment gains] are a shift in the trend, or if [2023] just ended up being a nice year.ā
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+The debate over whether college is worth the cost is ongoing, and the FAFSA processing delays further complicate it. If students canāt access grants and loans for the coming academic year, college will be out of reach, particularly for low-income students. Ultimately, the promise of financial security ā one of the most touted benefits of earning a post-secondary degree ā could be elusive for many, especially students who stand to benefit the most from a college degree.
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+Enrollment-dependent institutions will suffer, too. Itās why higher education experts are putting pressure on the Department of Education to fix these errors quickly.
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+āWe are urging the department to take immediate steps to address these issues. In the meantime, we are encouraging colleges and universities to be flexible with their enrollment deadlines, so we donāt inadvertently lose students in this process,ā said Hironao Okahana, the assistant vice president and executive director of the Education Futures Lab at the American Council on Education, which tracks higher education trends. āWe still believe that there is learning that happens at the post-secondary level that develops critical thinking and other aspects that are really important in democratic society, writ large.ā
+
+
+āThat value proposition itself is still there, and we have work to do as a sector to make sure that those opportunities are provided equitably,ā he added.
+
+
+Hereās what we know about enrollment trends and why the FAFSA complications might completely erase any gains this fall.
+
+
+With some colleges set to charge students $100,000 for room, board, and other expenses each year, thereās already a perception, among students and families, that higher education is unaffordable ā a reality forcing some students to not attend altogether. Now, the chaotic rollout of the FAFSA has become a new major roadblock.
+
+
+Congress directed the Department of Education to revamp the historically complicated FAFSA form to make it simpler for families to file and get financial aid awards. But the rollout grew disastrous beginning in January after thousands of students reported technical glitches that prevented them from completing the new form. While 40 percent fewer students completed the form this year, 27 percent fewer students submitted the form, according to data released by the Department of Education this week. The submission rate includes forms that still need to be corrected due to a variety of processing errors.
+
+
+After weeks of technical challenges that prevented families from completing the new form, the Department of Education announced that it would begin to transmit tax information to schools. Colleges are supposed to use this information to create financial aid packages for students, but even this step has presented new difficulties.
+
+
+School leaders have reported receiving inaccurate tax information for thousands of applicants. The Department of Education recently announced that 200,000 of the 1.5 million applications that it had sent to schools before March 21 had miscalculation errors. The latest hiccups could delay the admissions process further, well past the typical May 1 enrollment deadline that many schools have already extended.
+
+
+āI expect to see this have a really stark impact on enrollment that will likely be concentrated among community college students, who tend to be lower income, and lower-income students in general,ā Meyer said.
+
+
+Community colleges saw the biggest enrollment increases last fall, adding 118,000 students ā a 2.6 percent gain over the prior year, according to the National Clearinghouse report. Older students, those ages 21 and above who enrolled as first-year students, drove the enrollment increase. Community colleges that offered vocational training and dual-enrollment programs attracted more students, reversing pandemic declines.
+
+
+But the FAFSA complications could shift where students choose to go to school as they think through what they can afford, Meyer said. This means more students could opt for affordable options that might not meet their academic needs. Other students may choose to forgo college entirely.
+
+
+Students who plan to enroll as first-year students arenāt the only group who stand to be affected. āWhile much attention has focused on how this will impact first-time students and enrollment of new college classes, which it undoubtedly will, the effects on current students should not be overlooked,ā said Cohen. āBecause students who rely on financial aid need to fill out the FAFSA every year, delays or uncertainty in aid packages could lead to students who might otherwise continue their education stopping out instead.ā
+
+
+Enrollment-dependent institutions are also vulnerable. āThere are institutions where the difference of 100 students is actually the difference between staying open and closing,ā said Meyer. āThere are students who are already enrolled in these precarious institutions that could only end up closing in the next year or two because of this.ā
+
+
+Wisconsinās Northland College, which enrolls around 526 students, recently declared financial exigency due to declining enrollment and rising costs and is deciding whether to close. The College of Saint Rose in Albany, New York, announced it would close at the end of the 2023ā24 academic year due to enrollment ācaused by both a shrinking pool of high school graduates and the prolonged negative impact of COVID-19,ā which made it struggle to manage operating expenses.
+
+
+āIn the long run, I think thereās every hope and expectation that this FAFSA simplification will deliver on its promise to get more low-income students into college,ā said Meyer. āBut the class of 2024 is being rocked really hard.ā
+
+
āCivil Warā has little to say about America ā but a lot to say about war -
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+Cailee Spaeny (left) and Wagner Moura as journalists in Alex Garlandās Civil War. | Murray Close/A24
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+
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+You might think a movie about a second American civil war would be a thinly veiled Trump story. Itās not āĀ and itās better for it.
+
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+You might think the new movie Civil War is a warning about Americaās deepening political divide. The filmās trailer certainly suggests so, and director Alex Garland seemingly confirmed that was his intent in a recent interview with the Atlantic.
+
+While the United States faces very real threats from extreme polarization and rising political violence, a modern repeat of the Civil War is basically out of the question (especially the filmās version, in which a rebel alliance led by Texas and California confront the federal government). Trying to use such a war to examine how American polarization could collapse our democracy would almost certainly be a doomed enterprise.
+
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+Thankfully, Civil War is not the film I was led to believe. The movie begins near the end of the conflict, providing little context about how things got so bad in fictional America. There are stray hints ā the president (Nick Offerman) is in his third term and has disbanded the FBI ā but nothing that could help the viewer understand why the United States collapsed into bloodshed. Contrary to marketing, and perhaps even the directorās intent, Civil War has virtually nothing to say about real-world American politics.
+
+
+But this doesnāt mean the film is a failure ā far from it. Once you understand that Civil War isnāt about what you think, you can appreciate it for what it actually is: a searing meditation on what happens when political orders collapse and violence takes on a sinister logic of its own.
+
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+In doing so, it channels some of the best modern academic research on violence in civil wars.
+
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+This is your brain on violence
+
+
+Civil War tracks a group of four reporters as they race from the (relative) safety of New York City to Washington, DC, to cover the fall of the president: The combined forces of California and Texas are knocking at the Capitolās doorstep.
+
+
+Yet thereās no real sense of place or specificity in this narrative. With the exception of a rebel base outside Charlottesville, the towns and cities they pass through have no names. The violence the reporters witness on the road is horrific ā weāre talking mass graves, suicide bombings, and torture ā but it generally has no clear political motivation or higher purpose.
+
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+ A24
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+Kirsten Dunst as photojournalist Lee in Civil War.
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+In one scene, a sniper opens fire on the reportersā car, forcing them to take shelter beside two soldiers heās also attacked. When the reporters ask the soldiers which side everyone is on, they scoff ā explaining that heās trying to kill them, and thatās all that matters.
+
+
+That scene clarifies what the movie is really about: not how political order collapses into civil war, but what happens to a society after it does.
+
+
+Civil War presents a narrative where war takes on a logic of its own. For some, the need to survive pushes them to act in ways they never would have contemplated otherwise. For others, the collapse in order creates opportunities to act on their very worst impulses ā best dramatized in an unforgettable scene in which a bigoted soldier (Jesse Plemons) cruelly interrogates the main characters at gunpoint.
+
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+Under such conditions, social trust collapses altogether; faith in both institutions and other people canāt survive.
+
+
+Civil Warās treatment of journalism basically fits this theme. The movieās reporters, led by steely photojournalist Lee (a fabulous Kirsten Dunst), are generally decent people and stellar professionals. But in a world where no one trusts anyone, a truly neutral institution like journalism has no place. Without any legal system or supreme power to appeal to, theyāre at the mercy of whatever armed faction they come across ā most of whom donāt trust journalists any more than anyone else.
+
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+In conditions of social breakdown, violence consumes all of what makes a society work.
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+What a fake civil war tells us about real ones
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+Civil Warās grim vision reminded me, more than anything else, of an academic book: The Logic of Violence in Civil Wars by Oxford professor Stathis Kalyvas.
+
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+The book, a modern classic in the literature on civil conflict, argues that most people overestimate the degree to which patterns of violence in civil wars are driven by ideology or emotions run amok. Instead, Kalyvas argues, individual decisions are often made based on calculations of rational self-interest ā starting with survival.
+
+
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+Kalyvasās treatment of the relationship between violence and civilian behavior is particularly noteworthy.
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+As we know from American experiences in Iraq and Afghanistan, winning the support of the local civilian population is critically important in determining who wins a civil war. Drawing on data from the 1940s Greek Civil War, Kalyvas argues that civilians make decisions about cooperation based primarily on perceptions of who is in control of the territory in which they live. Basically, theyāre most likely to cooperate if they think that side will have the power to keep them safe and advance their other interests.
+
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+Civilian cooperation then shapes how combatants use force, as informers tell them where their enemies are hiding or who in the civilian population supports the opposing side. How combatants act on this information in turn shapes civiliansā views, affecting their future decisions to cooperate or not. Violence is, in Kalyvasās language, a ājoint processā: Who lives and who dies is determined by the interplay of civilian and combatant actions, all rooted in perceptions of rational self-interest.
+
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+This is basically how the world in Civil War works. Characters make choices not about ideology or partisanship, but about how best to advance their interests in a country defined by whoās trying to kill them and who isnāt. I canāt recall a single scene where anyone makes an ideological statement about the nature of the American civil war and why theyāre fighting it.
+
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+Such a film has little to say about contemporary American politics. But the imagery and places may help American audiences connect more easily to the subtler story itās actually telling: about how people in real-life civil wars make life into hell for the people caught up in them.
+
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+It is less a film about political polarization, or even the headline-dominating wars in Gaza and Ukraine, than one about the long and bloody counterinsurgency wars that defined the war on terror era.
+
+
+In that respect, Civil War should make Americans think less about our own contemporary problems and more about the suffering we so recently inflicted on others.
+
The Chinese backlash over Netflixās 3 Body Problem, explained -
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+A pivotal scene from Netflixās 3 Body Problem shows the violence of the Chinese Cultural Revolution. | Ed Miller/Netflix
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+
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+It says more about Netflix than it does about China.
+
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+Netflix is banned in China ā part of the governmentās ongoing efforts to limit both foreign influence and Chinese citizensā access to information about their own country. But that hasnāt stopped Chinese viewers, as well as Chinese state media, from weighing in on its highly anticipated adaptation of the Hugo Award-winning 2008 Chinese sci-fi novel The Three-Body Problem. Many people arenāt happy, yet thereās more to this particular backlash than just fan disgruntlement.
+
+
+The first of an esteemed trilogy sometimes known as Remembrance of Earthās Past, the novel The Three-Body Problem is a high-concept fictionalization of a longstanding scientific enigma known as āthe three-body problem.ā Itās heavy on the science, and author Liu Cixin, a native of mainland China, takes a long view of existential problems that mirror those weāre currently grappling with today, most notably the ethics surrounding our response to advanced artificial intelligence.
+
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+One of the novelās central themes is the question of who gets to decide the future for the rest of humanity. It takes an anti-authoritarian approach thatās bolstered by the authorās experience of authoritarianism in China. One of its central characters functions as a strong critique of the Communist Revolution, and the whole novel arguably critiques the modern-day Communist Party. This critique takes center stage, quite literally, in a controversial opening scene from the book that references a violent period of Chinaās history rarely shown in China itself.
+
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+Despite this, the novel The Three-Body Problem not only cleared Chinaās broad book ban on anti-government messaging (although before Xi Jinpingās subsequent tightening of censorship across the cultural front) but has become beloved in its home nation. It won multiple awards and gets held up by many as an example of Chinaās literary excellence and as a major influence in the development of Chinese science fiction. In 2023, another acclaimed and lavish series adapting the book, Three Body, was released by Chinese streaming service Tencent (the show is also currently streaming with English subtitles on Viki; the first two eps are also on YouTube). Three Body has won praise from viewers at home and abroad for staying faithful to the book and its themes; on the popular review forum MyDramaList, for example, the Tencent series has a viewer rating of 8.3/10.
+
+
+This is important context to understand the conversations that have taken place on Weibo and other Chinese social media platforms since the Netflix adaptationās release on March 21. As the show continues to dominate Netflix ratings globally, many English-language media outlets have begun covering the āpolarisedā discussion on Chinese social media around the show ā perhaps painting the situation as more complicated than it is. On Weibo, the state-run media account Global Times accused foreign media of inflating the negative reactions to the show in order to foment political drama and make Chinese viewers appear unreasonably nationalist.
+
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+It could be easy for an audience unfamiliar with Chinese media to assume that the Netflix adaptation is breaking through Chinese government censorship with a brave, controversial stance on the countryās past ā but thatās not entirely true. While the government under Xi Jinping has drastically ramped up itsrestrictionsonspeech, this doesnāt paint a fully accurate picture of how everyday people in China interact with those restrictions. Whatās fascinating about this 3 Body debate is how much it reveals about how Chinese viewers metabolize culture and cultivate their historical awareness.
+
+
+Depictions of nationalistic outrage on Chinese social media are probably being exaggerated
+
+
+The New York Times recently published a news column about it:
+
+
+
+āInstead of pride and celebration, the Netflix series has been met with anger, sneer and suspicion in China. The reactions show how years of censorship and indoctrination have shaped the public perspectives of Chinaās relations with the outside world. They donāt take pride where itās due and take offense too easily. They also take entertainment too seriously and history and politics too lightly.ā
+
+
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+This is certainly a strong argument, and the author, who has spent years reporting from China, including covering its censorship system before, cites examples of criticisms. But a quick Weibo search for ā3 body Netflixā shows that itās not the whole picture; itās also easy to find Chinese viewers praising the show and criticizing it in equal parts. For example, one recent post celebrates the way the Netflix version has popularized Liu Cixinās work and Chinese sci-fi to fans around the world. Another post embeds a British vloggerās commentary on the flaws with the Netflix adaptation, underscoring that criticism of the show is universal.
+
+
+Most of those criticisms would occur to anyone with a passing understanding of the book. Netflixās changes make the storyline blander and more inexplicably British, deliberately erasing most of the Chinese characters and relocating the main action to London. The exception to this rule is the subplot surrounding Ye Wenjie, a traumatized scientist who grows up in the shadow of Chinaās brutal Cultural Revolution. Ye Wenjie is arguably a villain who serves as our primary reference point for understanding China. Itās unsurprising, then, that many Chinese people arenāt happy that an adaptation of a beloved work of Chinese science fiction has erased most of the bookās portrayal of Chinese scientific prowess, relocated the plot to another country, and turned the storyline into something primarily critical of the Chinese government.
+
+
+The Times piece goes on to suggest that Chinese viewers have a dim grasp of what the Cultural Revolution ā the violent decade of Mao Zedongās rule between 1966 and 1976 ā did to the country, but an example from the same column of a widely circulated article critical of the era complicates that point. Information about the Cultural Revolution sometimes does circulate ā only to then be restricted:
+
+
+
+Someone on social media recently reposted an old article about Ye Qisong, one of the founders of the study of physics in modern China. In 1967, around the time that the struggle session of the series took place, Mr.Ā Ye, who shared the same family name of the physicist in the opening scene, was detained, beaten and forced to confess crimes he didnāt commit. He went crazy and wandered the streets in Beijing, begging for food and money. The article was circulated widely online before it was censored.
+
+This goes double when it comes to Chinese historical events. Chinese social media influencers regularly amplify and encourage celebration and commemoration of various historical events, but only as they relate to a vision of a unified China, supporting the social and military goals of the CCP.
+
+
+Yet this performed patriotism in no way means that Chinese citizens are unaware of the darker parts of their history; witness one Weibo user who described being stunned and impressed by the opening of the Netflix series, with its historically accurate, unflinching depiction of the Cultural Revolution. Such reactions undercut US-centric mediaās tendency to pigeonhole Chinese citizens as brainwashed or unquestioning of CCP dogma.
+
+
+The conflict at the heart of this is arguably China versus its history
+
+
+In all three versions of the story, the brutality of the Cultural Revolution directly impacts the future of humanity through Ye Wenjie. As a child, Ye Wenjie watches her father, a leading physicist, become a victim of the early Communist Partyās anti-science movement. Because of her association with her father, sheās forced to do years of hard labor, then recruited into a top-secret scientific program. Sheās betrayed repeatedly by other people, all of whom are acting under the auspices of the government to entrap and/or spy on her. Over time, her disillusionment with humanity grows to a breaking point that leads her to make a fatal decision on behalf of all mankind.
+
+
+In other words, the novel and each of its adaptations are clear about the way the Cultural Revolution persecuted the innocent and spawned decades of generational trauma. But each of them portrays the actual violence slightly differently. The English translation of Cixinās novel opens with an unforgettable scene in which Ye Wenjieās father is dragged onto a stage before an incensed crowd of communist supporters, pressured by his wife to renounce basic theories of physics, and then beaten to death for his refusal by a group of overzealous teenage party members ā all while a horrified Ye Wenjie watches from the audience.
+
+
+In the original Chinese version ofCixinās novel, the scene remains entirely the same, but his editor, fearing censorship, asked him to move this section to the middle of the novel rather than the beginning, perhaps hoping that relocating the passage would ameliorate the sting of its criticism. This apparently worked, but when fellow sci-fi writer Ken Liu translated Three-Body into English, Cixin gave him permission to put the passage back at the beginning of the book ā which is how millions of readers around the globe experienced it.
+
+
+The Netflix adaptation follows the English version of the novel: Ye Wenjieās father is violently murdered before our eyes, and this underpins everything else that happens in the drama.
+
+
+The earlier 2023 adaptation from the Chinese streaming service Tencent, however, is an almost page-for-page literal adaptation of the English-language version of the novel in every respect except this one. Instead of showing the public execution of Wenjieās dad, in the Tencent version, heās arrested and betrayed by members of his own family, and he still loses his esteemed career as a physicist ā but heās ultimately never executed, and itās implied instead that he died in ignominy with only Ye Wenjie at his side. This is a stark change that arguably waters down the impact of the book, but we still fully understand that the Cultural Revolution victimized Ye Wenjie and her father; decades later, when other characters learn what she went through, theyāre appalled. Both the Tencent and Netflix versions faithfully adapt Ye Wenjieās later harsh life in the labor camp and the subsequent betrayals she experiences.
+
+
+While the more violent aspects of the regime are often erased, depictions of the bleakness and misguided aims of the Cultural Revolution have become acceptable in Chinese pop culture. For example, last yearās widely acclaimed drama The Youth Memories dealt with the aftermath of the Cultural Revolution on Chinaās ālost generation,ā who were deprived of access to education after the communist takeover. The show takes a lightly but overtly critical stance toward the Revolutionās ban on higher education and treats the lifting of the ban as a major social leap forward.
+
+
+The problems of Netflixās 3 Body Problem have more to do with the Netflixian tendency to make every production feel colorless, flat, and forgettable than with Chinese viewers. A look at Tencentās version, or at shows like The Youth Memories, can give a much more nuanced idea of how Chinese audiences understand their past.
+
+
+
From The Hindu: Sports
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+
Mary Kom steps down as Paris Olympics Chef-de-Mission, cites personal reason - Indian Olympic Association (IOA) President P.T. Usha announced that Mary Kom had asked to be relieved from her position in a letter to addressed to her.
+
Rohit Sharma sets his eyes on playing in upcoming 50-over World Cup, World Test Championship final - The 36-year-old Rohit Sharma was part of Indiaās 2007 T20 World Cup victory, but he counts the 50-over showpiece as the real stuff.
+
Ishan Kishan 2.0: Finding better self than worrying about Twenty20 World Cup place - The 25-year-old was not considered for any of the subsequent national assignments, and India head coach Rahul Dravid had underscored the need for Kishan to play domestic cricket to make his comeback.
+
IPL-17: PBKS vs RR | Rajasthan Royals need better execution of plans against Punjab Kings - Rajasthan Royals will be looking for an improvement in the strategising and execution part against the Punjab Kings.
+
Candidates Chess: Gukesh loses to Alireza; Praggnanandhaa holds Caruana - Following the loss, the 17-year-old Gukesh was down to the joint second spot on four points along with Caruana and Praggnanandhaa.
+
+
From The Hindu: National News
+
+
Congress leader Rahul Gandhi to campaign in Mandya, Kolar on April 17 - The Janata Dal (S), which has entered into an alliance with the BJP, has fielded candidates in both constituencies
+
NITPY students launch app to report poll code violations - The app, which can track real-time responses to complaints, allows residents of Karaikal to report instances of misconduct with photographic evidence
+
Smriti Irani accuses Rahul Gandhi of neglecting development of Amethi for 15 years - Continuing her attack against Rahul Gandhi, the BJP leader said when a minister from Karnataka asked him why he was contesting elections from Wayanad, he replied that the people of Wayanad are more loyal.
+
YouTuber Maridhas ordered to pay costs of ā¹5,000 to TV18 Broadcast Ltd - Madras High Court, however, sets aside an order passed by it in 2022 setting him ex-parte in a 2020 suit seeking damages of ā¹1.5 crore for his allegedly defamatory videos
+
District Central Library to hold TNSPC-Group IV model test -
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+
From BBC: Europe
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Belgium probes Russian interference in EU elections - Two months before Europeans vote in 27 countries, Moscow is accused of trying to influence the vote.
+
Russia floods leave houses almost submerged - Water levels in Orenburg are 2m above critical levels, as the mayor urges mass evacuations.
+
First European citizen jailed under HK security law - The man was convicted of secession after he posted anti-China content on social media.
+
David Cameron heads to Brussels for Gibraltar talks - Following Brexit, the British overseas territory has been operating under temporary rules.
+
Polish MPs debate liberalising right to abortion - Abortion in Poland is heavily restricted, but the new prime minster has pledged to liberalise the law.
+
+
From Ars Technica
+
+
A supernova caused the BOAT gamma ray burst, JWST data confirms - But astronomers puzzled by the lack of signatures of expected heavy elements. - link
+
The Space Force is planning what could be the first military exercise in orbit - āThe vendors will exercise a realistic threat response scenario.ā - link
+
Researchers find a new organelle evolving - A ānitroplastā converts nitrogen from the air to a chemically useful form. - link
+
Three episodes in, the Fallout TV series absolutely nails it - Hyperviolence, strong characters, cool visuals, and some humor make a good show. - link
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Sketchy Botox shots spark multistate outbreak of botulism-like condition - So far at least six people in two states have fallen ill; four of them were hospitalized. - link
+
+
From Jokes Subreddit
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+
Guy : Doctor, my Girlfriend is pregnant but we always use protection and the rubber never broke. How is it possible? -
+
+
+Doctor : Let me tell you a story: "There was once a Hunter who always carried a gun wherever he went.
+
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+One day he took out his Umbrella instead of his Gun and went out. A Lion suddenly jumped in front of him, in order to stare the lion, hunter took out his umbrella and shot the lion and he died
+
+
+Guy : what nonsense! Itās not possible, someone else must have shot the lion
+
+
+Doctor : Good ! You understood the story, next patient please.
+
3 army generals bet who has the bravest soldiers -
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+3 army generals bet who has the bravest soldiers. The first general calls one of his men and commands him: āYou see that tall flag pole? Climb to the top of it and jump down.ā
+
+
+The soldier is hesitant at first, but then begins to climb the pole. When he reaches the top, he jumpsā¦ but breaks a leg.
+
+
+The other two generals salute the man for his bravery. The second general calls a soldier and tells him: "See that flag pole? Climb it and do a front-flip onto the ground. The man climbs the pole and performs a flip, as the general wished. Unfortunately, upon impact, the soldier tragically breaks his spine.
+
+
+The generals, again, salute the soldier for his bravery. And finally, itās the third generals turn. He calls a soldier and commands: āSoldier! Take this backpack full of bricks, climb that flag pole and perform a double back-flip onto the ground.ā
+
+
+The soldier laughs and replies:
+
+
+āHaha, boss. Fuck you and your commands!ā
+
+
+The general proudly crosses his arms and exclaims:
+
+So, thereās this guy, Pete, who got into troubles with the local gang. So, the gang members took him and brought him to a 7 feet, 300lbs giant named Ted.
+
+
+They told Ted: āTo this guy, you will fuck him in the ass so heāll learn not to fuck with us.ā
+
+
+Ted replied: āAlright, leave it to me.ā
+
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+The poor Pete asked for mercy: āPlease Mr.Ā Ted, donāt fuck me in the ass.ā
+
+
+Ted replied: āShut up or Iāll break your jaw.ā
+
+
+The gang members brought another guy and told Ted: āTo this guy, cut his hands off so he wonāt steal from us again.ā
+
+
+Ted replied: āAlright, leave it to me.ā
+
+
+Then, they brought another guy and told Ted: āTo this one, cut his testicles off so he wonāt sleep with our women again.ā
+
+
+Ted replied: āAlright, leave it to me.ā
+
+
+Finally, they brought a last guy and told Ted: āTo this one, cut him in pieces and send it to his relatives.ā
+
+
+After the gang members left, Pete said to Ted: āDonāt forget Ted so there isnāt any confusion, Iām the one you have to fuck in the ass.ā
+
A zoo starts having trouble with their prized gorilla -
+
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+Normally a gentle and kind beast, Coco the gorilla started acting out violently, throwing objects at visitors and scaring the children, breaking things in her enclosure and not eating. The zookeepers were puzzled at what had gotten into Coco, and after the vet did a round of tests it was determined that Coco was in heat and sexually frustrated.
+
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+The zoo staff called all the other zoos in the area to try and find Coco a mate, but were unsuccessful. Visitors were avoiding her enclosure, and park attendance was dropping fast, so they were desperate for a solution.
+
+
+The zookeepers all met up at the restaurant in the park to brainstorm ideas, and they eventually came to the conclusion that one of them was going to have to be a hero and pleasure Coco themselves. Understandably, not wanting to have their units mangled or ripped clean off by a 400 pound horny gorilla, volunteers were hard to come by. Just as they were about to scrap the idea, Joe the janitor came around the corner, polishing the floors.
+
+
+Joe was a hulking giant of a man, and hairy to boot. What he gained in size though, he lost in brains. Joe was incredibly stupid.
+
+
+Seeing their potential hero, the zookeepers quickly pooled any cash they had on them and the manager got up from the bar and approached Joe.
+
+
+āHey Joe, youāve heard about Coco right? Well we were wondering if for $250, you would be willing to make love to herā
+
+
+Joe hesitated for a moment and then said
+
+
+āWell, love life has been a bit slow these few years but Iāll hava to go home a tink about it I figureā
+
+
+The manager shakes his hand and dismisses him for the night.
+
+
+The next morning everyone is anxiously waiting for Joeās arrival, and they all crowd around him as he enters the staff room
+
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+āWell I thunked about it long and hard, and I will do it on three conditionsā
+
+
+Everyone letās out a sigh of relief and impatiently ask Joe for his conditions
+
+
+āFirst, I donāt want to have ta kiss er, I never dun seen her brush her teethā
+
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+They all agree, and tell him to continue
+
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+āSecond, if I git er pregnunt I donāt want to have to pay child support. I already got three that I gotta do that forā
+
+
+They all once again agree, trying not to make Joe feel dumb, and press him for his final condition
+
+
+āWell, youāre gonna have to give me a few more days to come up with the $250ā
+
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/25387438/Civil_War___First_Image.jpg)
A24
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