Re-annotation of SARS-CoV-2 proteins using an HHpred-based approach opens new opportunities for a better understanding of this virus -
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+Since the publication of the genome of SARS-CoV-2 - the causative agent of COVID-19 - in January 2020, many bioinformatic tools have been applied to annotate its proteins. Although efficient methods have been used, such as the identification of protein domains stored in Pfam, most of the proteins of this virus have no detectable homologous protein domains outside the viral taxa. As it is now well established that some viral proteins share similarities with proteins of their hosts, we decided to explore the hypothesis that this lack of homologies could be, at least in part, the result of the documented loss of sensitivity of Pfam Hidden Markov Models (HMMs) when searching for domains in “divergent organisms”. To improve the annotation of SARS-CoV-2 proteins, we used here the HHpred protein annotation tool and an available custom HH-suite database of HMMs specific to Homo sapiens proteins. To avoid “false positive predictions” as much as possible, we designed a robustness procedure to evaluate the HHpred results. In total, 6 robust similarities involving 6 distinct SARS-CoV-2 proteins were detected. Of these 6 similarities, 3 are already known and well documented, and one is in agreement with recent crystallographic results. We then examined carefully the two similarities that have not yet been reported in the literature. We first show that the C-terminal part of Spike S (the protein that binds the virion to the cell membrane by interacting with the host receptor, triggering infection) has similarities with the human prominin-1/CD133; after reviewing what is known about prominin-1/CD133, we suggest that the C-terminal part of Spike S could both improve the docking of Spike S to ACE2 (the main cell entry receptor for SARS-CoV-2) and be involved in the delivery of virions to regions where ACE2 is located in cells. Secondly, we show that the SARS-CoV-2 ORF3a protein shares similarities with human G protein-coupled receptors (GPCRs) belonging mainly to the “Rhodopsin family”. We conclude that the approach described here (or similar approaches) opens up new avenues of research to better understand SARS-CoV-2 and could be used to complement virus annotations, particularly for less-studied viruses.
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Engineering customized viral receptors for various coronaviruses -
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+Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus amplification for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as amplification of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.
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Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection -
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+A highly transmissible SARS-CoV-2 variant JN.1 is rapidly spreading throughout the nation, becoming the predominant strain in China and worldwide. However, the current immunity against the circulating JN.1 at population level has yet to be fully evaluated. We recruited representative cohorts with stratified age groups and diverse combinations of vaccination and/or infection in recent months, and promptly assessed humoral immunity for these subjects predominantly exhibiting hybrid immunity. We report that at 11 months following BA.5-wave breakthrough infection (BTI), these vaccinated individuals generally showed above-the-threshold yet low level of neutralizing activity against JN.1, with slightly greater potency observed in children and adolescents compared to adults and seniors. Meanwhile, XBB/EG.5-wave reinfection post-BTI significantly boosted the neutralizing antibodies against Omicron variants, including JN.1 in both adults (13.4- fold increase) and seniors (24.9-fold increase). To better understand respiratory mucosal protection against JN.1 over an extended period of months post-BTI, we profiled the humoral immunity in bronchoalveolar lavage samples obtained from vaccinated subjects with or without BTI, and revealed increased potency of neutralizing activity against the BA.5 and JN.1 variants in the respiratory mucosa through natural infection. Notably, at 11 months post-BTI, memory B cell responses against prototype and JN.1 were detectable in both blood and respiratory mucosa, displaying distinct memory features in the circulation and airway compartments. XBB/EG.5-wave reinfection drove the expansion of JN.1-specific B cells, along with the back-boosting of B cells responding to the ancestral viral strain, suggesting the involvement of immune imprinting. Together, this study indicates heterogeneous hybrid immunity over 11 months post-BTI, and underscores the vulnerability of individuals, particularly high-risk seniors, to JN.1 breakthrough infection. An additional booster with XBB-containing vaccine may greatly alleviate the onward transmission of immune-evasive SARS-CoV-2 variants.
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B cell maturation restored ancestral germlines to control Omicron BA.2.86 -
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+The unceasing interplay between SARS-CoV-2 and the human immune system has led to a continuous maturation of the virus and B cell response providing an opportunity to track their evolution in real time. We longitudinally analyzed the functional activity of almost 1,000 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people, and from individuals with hybrid and super hybrid immunity (SH), developed after three mRNA vaccine doses and two breakthrough infections. The most potent neutralization and Fc functions against highly mutated variants, including BA.2.86, were found in the SH cohort. Despite different priming, epitope mapping revealed a convergent maturation of the functional antibody response. Neutralization was mainly driven by Class 1/2 nAbs while Fc functions were induced by Class 3/4 antibodies. Remarkably, broad neutralization was mediated by restored IGHV3-53/3-66 B cell germlines which, after heterogenous exposure to SARS-CoV-2 S proteins, increased their level of somatic hypermutations. Our study shows the resilience of the human immune system which restored previously expanded germlines and activated naive B cells to broaden the antibody repertoire of antibodies to control future SARS-CoV-2 variants.
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Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated -
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+Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. This study analyses the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-{gamma}) in both CD4+ and CD8+ T-cells. In conclusion, the AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
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Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans -
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+Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10 -3 and 1.1x10 -3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.
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The Effect of Analytical Thinking on Irrational Behaviors in Times of COVID-19: the Mediating Role of Misinformation Beliefs -
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+The present study was to investigate the influence of analytical thinking on irrational behaviors evoked by COVID-19 (including excessive epidemic prevention and hoarding behavior) and the mediating role of misinformation beliefs related to COVID-19 (including social and pseudoscientific beliefs) in a public health crisis. 1968 Chinese participants completed the Analytical Thinking Test, Misinformation Beliefs Questionnaire and Irrational Behavior Questionnaire online. The results showed that (1) Analytical thinking had a negative prediction on both excessive epidemic prevention and hoarding behavior; (2) misinformation beliefs, even social misinformation beliefs, partly mediated the relationship between the analytical thinking and irrational behaviors. These findings provide some useful references for effectively reducing people’s irrational behaviors during a public health crisis.
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A Descriptive Study of Patient Quality Care via Telehealth During COVID-19 -
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+The COVID-19 pandemic has seen a rise in reported symptoms of anxiety or depressive disorders, difficulty sleeping or eating, and an increase in alcohol and substance use primarily resulting from isolation and job loss. Social distancing guidelines created the perfect opportunity for mental healthcare organizations across all mental health care settings and levels of care to connect with individuals and families suffering from mental abnormalities virtually; however, widespread adoption of telehealth programs by mental health practitioners continues to fall short. This study uses a non-experimental descriptive survey design to answer descriptive questions on how participants rated their experience with telehealth as a standalone service delivery method in private practice settings. When patients experience quality care, they are more likely to return for future services and refer others. Quality experiences do correlate with positive financial performance, and this study describes how patients are rating their experience. The survey in this study contained Likert Scale questions, and the researcher used cross-tabulation and pivot tables to describe how participants responded to the survey. Results from this study are intended to provide insight into telehealth acceptance and effectiveness. This study also provides a foundation for further research to discover participant perceptions and examine participant responses as it relates to telehealth as a standalone mode of treatment in a private practice setting.
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Promoting Daily Well-being in Adolescents using mHealth -
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+Adolescents are at increased risk for developing mental health problems. The Grow It! app is an mHealth intervention aimed at preventing mental health problems through improving coping by cognitive behavioral therapy (CBT)-inspired challenges as well as self-monitoring of emotions through Experience Sampling Methods (ESM). Yet, little is known about daily changes in well-being and coping during a stressful period, like the COVID-19 pandemic. The current study aimed to elucidate daily changes in positive and negative affect, and adaptive coping, and to better understand the within-person’s mechanisms of the Grow It! app. The sample consisted of 12-25-year old Dutch adolescents in two independent cohorts (cohort 1: N = 476, Mage=16.24, 76.1% female, 88.7% Dutch; cohort 2: N = 814, Mage=18.45, 82.8% female, 97.2% Dutch). ESM were used to measure daily positive and negative affect and coping (cohort 1: 42 days, 210 assessments per person; cohort 2: 21 days, 105 assessments). The results showed that, on average, adolescents decreased in daily positive affect and adaptive coping, and increased in their experienced negative affect. A positive relation between adaptive coping and positive affect was found, although independent of the CBT-based challenges. Latent class analysis identified two heterogeneous trajectories for both positive and negative affect, indicating that the majority of participants with low to moderate-risk on developing mental health problems were likely to benefit from the Grow It! app.
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Prospective, directional associations between Social Media Intensity, Loneliness, and Anxiety among Peruvian Adolescents during the COVID-19 Pandemic -
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+The impact of social media on adolescent mental health is an area of intense interest and controversy, especially since the COVID-19 pandemic has increased youth’s reliance on online communications. Current evidence, mostly from cross-sectional studies in the Global North, is mixed. Thus, the aim of this study was to investigate the relationship between social media and mental health in adolescents in Perú across 15 months of COVID-19 lockdowns. In this observational study, we first examined associations between social media intensity (SMI), feelings of loneliness, and anxiety at the beginning of the pandemic (May 2020) in 1603 early adolescents (10 – 14 years). Hypotheses of a positive association between all outcomes, particularly for girls, were derived from exploring one half of the sample (n =807), preregistered, and then confirmed in the second half of the sample (n = 806). In May 2020, SMI was associated with more frequent loneliness for girls, and SMI was associated with more frequent anxiety for both sexes. In a longitudinal follow up (n = 455) we then investigated prospective and directional associations across three waves (May 2020, November 2020, and July 2021). Longitudinal analyses revealed a more complex pattern. Across 15 months of COVID-19 in Perú, feelings of loneliness in girls were associated with an increase in SMI. In contrast, higher SMI among girls was associated with an increase in feelings of anxiety. We did not find the reverse relationships. Our findings with early adolescents in low-and middle-income urban settings in Latin America, an underrepresented population, underscore the importance of longitudinal research and contribute to understanding these important issues globally.
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Public Health Communication Reduces COVID-19 Misinformation Sharing and Boosts Self-Efficacy -
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+During pandemics, circulation of misinformation has optimal conditions as information spreads fast while uncertainty is high. While health authorities play a key role in providing advice for protective behaviors, little is known on how health authorities can mitigate the spread of misinformation on social media. In two experiments in Denmark, we assess the effect of an accuracy nudge and two video interventions from the Danish Health Authorities used in a real-world public health campaign circulated on social media in Denmark during the COVID-19 pandemic. Our findings show that providing citizens with elaborate, actionable and concrete advice decrease misinformation sharing by boosting citizens’ sense of self-efficacy. Furthermore, while accuracy nudges may less effective during times with high uncertainty, public health authorities can provide citizens with competences through scaleable video interventions on social media.
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How did UK social distancing restrictions affect the lives of women experiencing intimate partner violence during the COVID-19 pandemic? A qualitative exploration of survivor views -
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+Background: An increase of domestic abuse cases was reported at the start of the COVID-19 pandemic, with many people living with abuse facing additional barriers to seeking support. Available evidence suggests women are overrepresented in the reported cases of intimate partner violence (IPV) and we aimed to learn more about how their lives were impacted by social distancing restrictions. Methods: We conducted a qualitative interview study, using reflexive thematic analysis. Interviews were conducted between April 2021 and March 2022. 18 women in the UK with past experiences of IPV provided informed consent and participated in this study. Results: We identified five themes related to the experiences of COVID-19 lockdown restrictions on the lives of the participants. Firstly, lockdown meant being confined to a place where abuse was escalating in frequency and intensity. Participants described fear, isolation, and loss of control during the early stages of the pandemic from the combination of abuse and pandemic-related changes to daily life. However, psychosocial wellbeing and identity underwent a transformation when abuse ended during lockdown, with many participants using the word “freedom” when reflecting on their experience of living through the COVID-19 pandemic. We identified key barriers that prevented access to support for IPV, including “cancelled” services and missed opportunities to intervene during interactions in lockdown with frontline workers. Paradoxically, some participants found other forms of support were more readily available, such as provision of online psychological support and social groups. Conclusions: In this study, we explored the views of female survivors of IPV in the UK during the COVID-19 pandemic. Our results highlight the importance of combined public awareness campaigns and community intervention points for victims to safely seek help during social distancing restrictions. Having the time and space to reflect on healing after escaping abuse was described by women in our study as a benefit from their lives in lockdown, which is a factor that could be incorporated into future initiatives developed to support people subjected to violence and abuse.
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Impacts of Inequality and Poverty on COVID-19 in Indonesia -
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+Purpose: The purpose of this study was to investigate how inequality and poverty contributed to COVID-19 cases and mortality using panel regression. Design/methodology/approach: The data cover semiannual observations during the COVID-19 period spanning from 2019 to 2022 in 34 provinces in Indonesia. This study split samples into high- and low-inequality provinces and apply the fixed effect panel regression on COVID-19 cases and mortality. Findings: The results suggest that the effect of inequality on the spread of COVID-19 was greater in low-inequality provinces. Whereas poverty and unemployment positively influenced the total cases in high-inequality provinces. The variable of unmet health facility had a negative impact on COVID-19 cases, but education positively influenced COVID-19 cases. There were identical results for all the variables when looking at COVID-19 mortality, except for unemployment. Unemployment showed a positively significant influence on COVID-19 mortalities in all samples, whereas it only influenced COVID-19 cases in high-inequality provinces. Originality/value: the most crucial outcome of this study concerns the distinctive implications for different types of inequality and their impact on COVID-19.
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Is resisting Covid-19 vaccination a “problem”? A critical policy inquiry of vaccine mandates for healthcare workers -
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+As the COVID-19 global vaccination campaign was launched in December of 2020, vaccination became mandatory for many healthcare workers (HCWs) worldwide. Large minorities resisted the policy, and the responses of authorities to this resistance led to damaged professional reputations, job losses, and suspension or termination of practice licenses. The joint effect of dismissals, early retirements, career changes, and vaccine injuries disabling some compliant HCWs from adequate performance, has exacerbated existing crises within health systems. Nevertheless, the position of leading health authorities has been that the benefits of a fully vaccinated healthcare labour force - protecting health systems, vulnerable patient populations, and even HCWs themselves – achieved through mandates, if necessary, outweigh its potential harms. Informed by critical policy and discourse traditions, we examine the expert literature on vaccine mandates for HCWs. We find that this literature neglects evidence countering claims about the safety and effectiveness of COVID-19 vaccines, dismisses the science supporting the contextual nature of microbial virulence, miscalculates patient and system-level harms of vaccination policies, and ignores or legitimizes the coercive elements built into their design. We discuss the implications of our findings for the sustainability of health systems, for patient care, and for the well-being of HCWs, and suggest directions for ethical clinical and policy practice.
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Genotypic-phenotypic landscape computation based on first principle and deep learning -
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+The relationship between genotype and fitness is fundamental to evolution, but quantitatively mapping genotypes to fitness has remained challenging. We propose the Phenotypic-Embedding theorem (P-E theorem) that bridges genotype-phenotype through an encoder-decoder deep learning framework. Inspired by this, we proposed a more general first principle for correlating genotype-phenotype, and the Phenotypic-Embedding theorem provides a computable basis for the application of first principle. As an application example of the P-E theorem, we developed the Co-attention based Transformer model to bridge Genotype and Fitness (CoT2G-F) model, a Transformer-based pre-train foundation model with downstream supervised fine-tuning (SFT) that can accurately simulate the neutral evolution of viruses and predict immune escape mutations. Accordingly, following the calculation path of the P-E theorem, we accurately obtained the basic reproduction number (R) of SARS-CoV-2 from first principles, quantitatively linked immune escape to viral fitness, and plotted the genotype-fitness landscape. The theoretical system we established provides a general and interpretable method to construct genotype-phenotype landscapes, providing a new paradigm for studying theoretical and computational biology.
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Phase 3 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine - Conditions: COVID-19 Interventions: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection Sponsors: Novavax Not yet recruiting
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Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection. - Conditions: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection Interventions: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) Sponsors: Sheng-Teng Huang Completed
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SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19) - Conditions: COVID-19 Interventions: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets Sponsors: JKT Biopharma Co., Ltd. Not yet recruiting
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INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old - Conditions: COVID-19 Pandemic; COVID-19 Vaccines Interventions: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia Recruiting
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Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2 - Conditions: SARS CoV 2 Infection Interventions: Biological: IMNN-101 Sponsors: Imunon Not yet recruiting
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Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults - Conditions: COVID-19 Interventions: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo Sponsors: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited Not yet recruiting
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Effectiveness of a Nasal Spray on Viral Respiratory Infections - Conditions: Acute Respiratory Tract Infection; Flu, Human; COVID-19; Common Cold Interventions: Device: Nasal Spray HSV Treatment Sponsors: CEN Biotech; Urgo Research, Innovation & Development Recruiting
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GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects - Conditions: COVID-19 Interventions: Drug: GS-441524; Drug: Placebo Sponsors: National Center for Advancing Translational Sciences (NCATS); Leidos Biomedical Research, Inc.; ICON Government and Public Health Solutions, Inc Not yet recruiting
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The Aerobic Exercise Capacity and Muscle Strenght in Individuals With COVID-19 - Conditions: COVID-19 Pneumonia; COVID-19 Interventions: Device: Kardiopulmonary exercise test (Quark KPET C12x/T12x device connected to the Omnia version 1.6.8 COSMED system); Device: Peripheral muscle strength measurement (microFET3 (Hoggan Health Industries, Fabrication Enterprises, lnc) and JAMAR hydraulic hand dynamometer (Sammons Preston, Rolyon, Bolingbrook).; Device: Standard exercise tolerance test (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.); Device: Aerobic exercise training (a bicycle ergometer and recorded through the ergoline rehabilitation system 2 Version 1.08 SPI.) Sponsors: Selda Sarıkaya; Zonguldak Bulent Ecevit University Completed
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UNAIR Inactivated COVID-19 Vaccine INAVAC as Heterologue Booster (Immunobridging Study) in Adolescent Subjects - Conditions: COVID-19 Pandemic; COVID-19 Vaccines Interventions: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia Active, not recruiting
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World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt - Conditions: Mucormycosis; Rhinocerebral (Etiology); COVID-19 Interventions: Procedure: debridment Sponsors: Nasser Institute For Research and Treatment Completed
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Mindfulness-based Mobile Applications Program - Conditions: COVID-19; Cell Phone Use; Nurse; Mental Health Interventions: Device: mindfulness-based mobile applications program Sponsors: Yu-Chien Huang Completed
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Attention Training for COVID-19 Related Distress - Conditions: Anxiety Interventions: Behavioral: Attention Bias Modification; Behavioral: Attention Control Training; Behavioral: Neutral training Sponsors: Palo Alto University Not yet recruiting
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Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial - Conditions: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 Interventions: Drug: Hyperbaric oxygen Sponsors: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk Not yet recruiting
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From PubMed
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What kind of a problem is loneliness? Representations of connectedness and participation from a study of telepresence technologies in the UK - Loneliness is represented in UK policy as a public health problem with consequences in terms of individual suffering, population burden and service use. However, loneliness is historically and culturally produced; manifestations of loneliness and social isolation also require social and cultural analysis. We explored meanings of loneliness and social isolation in the UK 2020-2022 and considered what the solutions of telepresence technologies reveal about the problems they are used to address….
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Therapeutic role of miR-19a/b protection from influenza virus infection in patients with coronary heart disease - Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary…
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Simple virus-free mouse models of COVID-19 pathologies and oral therapeutic intervention - The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies…
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Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice - CONCLUSION: Our results indicate significant immunogenicity and neutralization efficacy induced by PastoCovac Plus and Sinopharm, but not by Noora and SpikoGen. This suggests the need for additional comparative assessment of the potency and efficacy of these four vaccines in vaccinated subjects.
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Potential Therapeutic Strategies and Drugs That Target Vascular Permeability in Severe Infectious Diseases - Severe infection pathogenicity is induced by processes such as pathogen exposure, immune cell activation, inflammatory cytokine production, and vascular hyperpermeability. Highly effective drugs, such as antipathogenic agents, steroids, and antibodies that suppress cytokine function, have been developed to treat the first three processes. However, these drugs cannot completely suppress severe infectious diseases, such as coronavirus disease 2019 (COVID-19). Therefore, developing novel drugs that…
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Preliminary report on therapeutic potential of coal-derived carbon quantum dots against SARS-CoV-2 virus - Due to the pandemic of COVID-19 and subsequent emerging of new mutant strains, there has been a worldwide hunt for therapeutic and protective agents for its inhibition. In this short communication, for the first time, we report the coal-derived carbon quantum dot (CQD) for the possible therapeutic application against SARS-CoV-2. The synthesized C1-CQD is observed to be safe towards the normal cell line at highest dose, while effectively inhibiting growth of SARS-CoV2 (>95%) with IC(50) value of…
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SARS-CoV-2 Membrane protein regulates the function of Spike by inhibiting its plasma membrane localization and enzymatic activity of Furin - The presence of a multibasic cleavage site in the Spike protein of SARS-CoV-2 makes it prone to be cleaved by Furin at the S1/S2 junction (aa. 685-686), which enhances the usage of TMPRSS2 to promote cell-cell fusion to form syncytia. Syncytia may contribute to pathology by facilitating viral dissemination, cytopathicity, immune evasion, and inflammation. However, the role of other SARS-CoV-2 encoding viral proteins in syncytia formation remains largely unknown. Here, we report that SARS-CoV-2 M…
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Role of telerehabilitation in the rehabilitation of children with cerebral palsy during COVID-19: A review - Individuals with cerebral palsy (CP) have limited mobility and are unable to actively participate in tasks that are part of their daily living. Thus, continuous therapeutic sessions are required to keep such individuals active and engaged in the environment. Due to the coronavirus disease of 2019 (COVID-19) lockdowns, rehabilitation for children with CP was inhibited which consequently put them at risk of losing their functional gains which were obtained through previous in-person therapies. In…
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Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies to protect individuals at high risk of COVID-19 are critical but are currently a largely unmet need. We evaluated the oral antiviral drug ensitrelvir, which specifically targets the SARS-CoV-2 3CL protease, for its efficacy as a pre-exposure prophylactic treatment. Aged BALB/c mice were subcutaneously treated…
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Priming congruence and COVID-19 vaccination intention: a mediation analysis - CONCLUSIONS: Implications of these results are discussed in light of the socially situated cognition perspective and the congruence of (a) a societal context of communication toward the vaccine and the unvaccinated, (b) the participant’s degree of adherence to that communication, (c) the theme of priming, whether or not related to feeling connected to others. Implications of materialism priming are discussed, and the effect of commitment on intention to get vaccinated.
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A subunit-based influenza/SARS-CoV-2 Omicron combined vaccine induced potent protective immunity in BALB/c mice - Infection with influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant risk to human life, health, and the global economy. Vaccination is one of the most effective strategies in the fight against infectious viruses. In this study, we, for the first time, have evaluated the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 and administered to BALB/c mice. Results showed that…
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Nudging Public Health Behaviors to Prevent COVID-19: A Systematic Review - Many countries have implemented strict preventive measures and mandatory policies to curb virus transmission during the COVID-19 pandemic. Some have adopted softer approaches, such as nudge-based intervention, to influence public health behavior. This systematic review, conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines, aims to determine if the nudge-based intervention can effectively influence people’s preventive behavior during the…
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Imatinib treatment improves hyperglycaemic dysregulation in severe COVID-19: a secondary analysis of blood biomarkers in a randomised controlled trial - SARS-CoV-2 can induce insulin resistance, which is, among others, mediated by adipose tissue dysfunction and reduced angiotensin-converting enzyme 2 (ACE2) enzymatic activity. In SARS-CoV-2-infected mice, the tyrosine kinase inhibitor imatinib attenuates inflammation and improves insulin sensitivity. Here, we report the effects of imatinib on incident hyperglycaemia, circulating levels of glucoregulatory proteins, longitudinal insulin sensitivity and ACE-2 enzymatic activity in 385 hospitalized…
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IFN-gamma decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3beta signaling pathway - Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8^(+) T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8^(+) T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8^(+) T cells from COVID-19…
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Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters - CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.
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From Patent Search
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Forty-Three Mexican Students Went Missing. What Really Happened to Them? - One night in 2014, a group of young men from a rural teachers’ college vanished. Since then, their families have fought for answers. - link
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Lucy Prebble’s Dramas of High Anxiety - In plays such as “The Effect” and TV shows such as “I Hate Suzie” and “Succession,” the writer has become an expert at getting deep inside worried characters’ heads. - link
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Joe Biden’s Last Campaign - Trailing Trump in polls and facing doubts about his age, the President voices defiant confidence in his prospects for reëlection. - link
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The Legacy of RuPaul’s “Drag Race” - The drag star brought the form mainstream, and made an empire out of queer expression. Now he fears “the absolute worst.” - link
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The Israeli Settlers Attacking Their Palestinian Neighbors - With the world’s focus on Gaza, settlers have used wartime chaos as cover for violence and dispossession. - link
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From Vox
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Good news! Scientists are throwing a sex party … for giant marine snails. -
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+A young queen conch. | Jennifer Doerr/NOAA SEFSC Galveston
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+Queen conchs in the Florida Keys are struggling to mate. Scientists are going to help them mingle.
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+The sex life of a conch is, for a snail, quite thrilling. In the spring and summer, the queen conch — a large, ornate species of marine snail — hunts for a mate in the warm, shallow waters of Florida and the Caribbean. Rather than slime along the ocean floor like many other mollusks do, conch (commonly pronounced “konk,” with a hard “k”) hop using a claw-shaped structure attached to their gooey innards. During mating season, conch will leap toward one another and pair up.
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+Things escalate from there.
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+“Have you seen a conch penis?” Andrew Kough, a marine biologist at the Shedd Aquarium in Chicago, asked me on the phone. (I had not.) “It’s insane.”
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+Positioned next to a female, shells touching, the male queen conch will extend a long, worm-like penis, also known as a verge, into her shell opening to deliver sperm. This can take many hours. Once they uncouple, the female will eventually lay her eggs on the seafloor in a crescent-shaped sac that looks a bit like dried ramen. A few days later, free-swimming baby conchs will hatch and float around for a while before settling in the sand, forming the next generation of queen conch.
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+ Curtesy of Shedd Aquarium
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+A juvenile conch with its eyes poking out.
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+At least, that’s how it’s supposed to go.
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+In the last few decades, the sex lives of queen conchs have run into trouble. In Florida and other parts of the Caribbean, conchs are struggling to find mates, struggling to pair up, and thus failing to produce new conchs. Part of the problem is that the population is far smaller than it once was due to decades of overfishing and increasingly destructive hurricanes. That means they simply have trouble finding other conchs to mate with. Meanwhile, conchs in nearshore waters of the Florida Keys — affectionately referred to as the Conch Republic — are failing, for largely unknown reasons, to develop gonads, which are needed for sexual reproduction.
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+These problems are putting the future of queen conchs in danger. Earlier this year, the US listed them as federally threatened, meaning they could become at risk of extinction in the near future.
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+ Allison Bailey/SOPA Images/LightRocket via Getty Images
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+A queen conch in Grand Cayman, an island in the Cayman Islands.
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+But there’s now some good news for sex-starved conchs. This spring, a team of scientists will gather up queen conchs in shallow waters off the Florida Keys, where they’re isolated and failing to breed, and move them farther offshore where there are healthier conch populations. The idea is to give these queen conchs a better shot at finding a mate and, in doing so, help them recover.
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+The project, led by the Florida Fish and Wildlife Conservation Commission (FWC), is an example of what it often takes to save imperiled species in a world changed by humans. Conchs are now so rare that putting an end to overfishing isn’t enough. To survive, they need scientists to play matchmaker.
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+Meet the ridiculously goofy, delightful queen conch
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+The spiraled shell of a queen conch is beautiful and elegant. The animal’s soft body, however, is sort of the opposite of that. It looks like a jumble of flesh onto which have been stuck two giant googly eyes.
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+Fixed to the end of tentacle-like stocks, those eyes poke out of the conch’s shell like a periscope from a submarine. Though cartoonish, they’re useful. Conchs are likely more visual than most other snails, according to Gabriel Delgado, a conch researcher, and they use these eyes — which have rods and cones, as do a human’s — to find mates and avoid predators.
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+The queen conch is one of several dozen conch species worldwide, all of which are moderately large to very large marine snails. They’re found in and around the Caribbean, where they play a valuable role in the ecosystem: Conchs eat algae that can otherwise smother coral. (They tend to hang out in groups, which is why Delgado, an associate researcher at FWC, sometimes describes them as “marine cows.”) Queen conchs also provide homes for critters including a small fish, known as the conchfish, that lives within their shells.
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+Queen conchs are also prized by humans. These snails not only have attractive shells that tourists love to buy but also protein-rich flesh that people love to eat. (It’s not uncommon to find conch on the menu in seafood restaurants across the country.) Plus, these animals are easy to collect: Conchs live in shallow water, and they can’t really put up a fight.
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+These traits helped turn queen conch into the second-largest fishery in the Caribbean — and ultimately led to their woes.
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+Overfishing is a problem, but it’s not the only one
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+Decades of fishing for conch in the Caribbean — much of which is exported to the US for restaurants — has massively depleted the ocean of these animals. “Overfishing has caused population collapses throughout the range of the conch, leaving adult densities below that which would indicate successful reproduction,” according to a 2022 assessment by the National Oceanic and Atmospheric Administration (NOAA).
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+In Florida, however, overfishing is largely a problem of the past. Before 1985, fishing queen conch caused the population to crash until it was “threatened with extermination,” as newspapers wrote at the time. But that year, in light of these declines, all conch fishing was banned. In the four decades since, the queen has been well protected.
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+ Courtesy of Shedd Aquarium
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+Young conchs in a bed of seagrass.
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+Nonetheless, these animals haven’t recovered. The most recent estimate, from 2022, suggests there are roughly 126,000 adult conchs in the Keys, Delgado said. That’s below an estimate from the 1990s. Three populations in Florida have disappeared altogether, according to NOAA. On average, the density of the animals is too low “for successful reproduction to be maintained throughout the region and for Florida to have a healthy self-recruiting population,” NOAA says.
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+Absent fishing, the barrier to recovery is largely linked to climate: Superstorms bury the mollusks alive and ocean warming can mess with their physical development. Before Hurricane Irma struck the Keys, in the fall of 2017, FWC measured roughly 700,000 adult queen conchs across the island chain. That’s well above the number of animals when the fishing ban went into effect. After the storm, however, researchers counted half as many; they believe the hurricane buried conchs under sand, killing them. Hurricane Ian, which hit Florida in 2022, also knocked the population back, Delgado said.
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+Then there’s the breeding problem. Many of the conchs that hang out in shallow waters near shore in the Keys, and especially the females, are incapable of reproducing. They’re not properly developing gonads, organs that produce eggs and sperm, Delgado’s research shows. The current theory, Delgado said, is that the temperatures there are just too extreme. Because the water is so shallow, it gets very cold in the winter and increasingly hot in the summer (climate change is exacerbating marine heat waves). Scientists are still untangling just how that could be impairing their development.
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+This means that, near the shoreline, there are very few conchs that can successfully reproduce. Those that can have trouble finding a mate. Delgado says it’s as though there were an apocalypse and only a few people survived, each on a different continent. “They’re going to have a hard time finding each other,” he said.
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+ Courtesy of the Florida Fish and Wildlife Conservation Commission
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+A queen conch out of the water.
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+If humans have caused this conch apocalypse, humans can also help.
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+A solution to help conchs mingle
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+While conchs near shore are reproductively challenged, those farther offshore — close to the coral reef — are doing much better. In some regions, there are dozens of conchs in close proximity. They’re able to find each other, breed, and make babies, Delgado said.
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+In the coming weeks, Delgado’s team plans to search for conchs in shallow waters in the central Florida Keys, with funding from the Fish and Wildlife Foundation of Florida, an environmental nonprofit. The scientists will tag those they find and relocate them to a healthier group offshore. It’s essentially like dropping individuals who are alone and isolated in the country into a big city. Deeper water offshore is also less prone to temperature extremes, Delgado said, which means the relocated conchs should not have trouble developing the gonads needed for reproduction.
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+ Courtesy of Shed Aquarium
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+Queen conch with its eyes pointing out.
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+Delgado wants to find at least 200 conchs to relocate. If all goes to plan, each of those animals will find their match (or more likely matches) in their new home. The researchers will then monitor the reproduction of those snails.
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+This intervention is not, by itself, going to save Florida’s conchs. It’s more of a pilot project that will help scientists understand the value of relocation services in helping a species recover. If these efforts do grow the offshore conch community, the state may continue to help conch mate in the years to come, perhaps on a much larger scale — especially if climate change continues to disrupt their sex lives.
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Don’t ignore Sudan’s horrific conflict -
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+A man stands by as a fire rages in a livestock market area in al-Fasher, the capital of Sudan’s North Darfur state, on September 1, 2023, in the aftermath of bombardment by the paramilitary Rapid Support Forces (RSF). | AFP via Getty Images
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+More than 8 million people have been displaced during the war, and more than 13,000 people have been killed.
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+The world has no shortage of horrible stories — from the terror of October 7 and the widespread suffering in Gaza caused by Israel’s war to the ongoing refugee crisis in Syria, to Russia’s continuing assault on Ukraine.
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+But the reports coming out of Sudan these days are particularly appalling.
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+According to the UN, more than 8 million people have been displaced during the war, and more than 13,000 people have been killed. Almost half the population, 25 million people, are in need of humanitarian assistance — and they shouldn’t be lost in a sea of global suffering.
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+Almost one year ago, rival military factions in Sudan began fighting in the streets of the capital Khartoum, reigniting civil conflict that echoes the terrible ethnically motivated violence in the country’s Darfur region that shocked the world two decades ago.
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+The current civil war — between the government’s Sudanese Armed Forces (SAF) led by General Abdel Fattah al-Burhan and the Rapid Support Forces (RSF) led by General Mohamed Hamdan Dagalo (called Hemedti) — has spread from the capital to other regions of the country, including Darfur in the west.
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+There, the majority-Arab RSF fighters are being accused of widespread, targeted killing and sexual violence against ethnic minorities in the region.
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+On top of that horror, the SAF and al-Burhan — the de facto leader of the country — have said they will suspend cross-border humanitarian aid delivery from neighboring Chad into RSF-controlled areas. The SAF claims, with some evidence, that weapons and supplies from the UAE make their way to the RSF via the eastern Chad-West Darfur border. But blocking aid would exacerbate the humanitarian crisis within Sudan.
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+While it might be easy to see this violence as cyclical or intractable, it would be a mistake to do so.
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+The tragedy in Sudan
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+Both the RSF and the SAF have shown “utter disregard for the laws of war,” as Human Rights Watch wrote in September, with both forces using shells and other explosives in densely populated civilian areas, while the RSF has looted supplies and raped women and children as young as 14 in the West Darfur city of Geneina.
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+The conflict started in Khartoum and the neighboring city of Omdurman but quickly spread into Darfur and east to Port Sudan, where al-Burhan and the SAF have set up a de facto capital, as the RSF now controls much of Khartoum.
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+Basic infrastructure and services are now essentially nonexistent in Khartoum.
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+“Large, large numbers of people moved out of the worst of the fighting in Khartoum and surrounding areas and have moved into towns and cities in eastern Sudan,” Susan Stigant, the Africa director for the US Institute of Peace, told me in an interview.
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+“That’s putting a tremendous amount of pressure on any of the capacities in those areas in terms of food, in terms of basic services, just in terms of places for people to be able to sleep. Port Sudan is just overflowing” with refugees.
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+Hundreds of thousands of people have moved from different parts of the Darfur region — particularly West Darfur — into refugee camps in eastern Chad, where conditions are incredibly difficult.
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+“People fled with nothing into a place where humanitarian response was not ready for that scale of emergency,” Trish Newport, head of emergency programs at Medecins Sans Frontieres (MSF), told me.
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+Some ethnic minority groups in Darfur, such as the Masalit, have been targeted by the RSF, much as they were in 2003.
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+A long path out of conflict
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+This battle for power had its seeds decades ago in the political machinations of Sudan’s former dictator Omar al-Bashir.
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+And though the RSF evolved from the Janjaweed militias Bashir empowered in the Darfur region 20 years ago and is accused of perpetuating somewhat similar crimes, this is not an inevitable historical repetition.
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+There seemed to be a break for Sudan after decades of autocratic rule and conflict in 2019, when the RSF and SAF together overthrew al-Bashir. Though there was broad popular and civil society mobilization for a change in leadership, “[Bashir] wasn’t overthrown by the popular movement directly,” Stigant said — it was a military coup that put him out of power. The short-lived transition to a civilian government ended with a second coup in 2021, leading to the power struggle between the RSF and the SAF.
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+The diplomatic and humanitarian responses to the Sudan conflict have been completely insufficient to meet the desperate need — both to stop Sudanese people’s suffering and to prevent the fighting from destabilizing other countries, Stigant said. “If you look at the Horn of Africa more broadly, there appears to be a reordering of the politics and the power. If, for example, the Rapid Support Forces push east in an offensive, then they’re getting uncomfortably close to the borders of Eritrea and Ethiopia.”
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+Sudan has seen significant conflict over the decades. Sudanese civil society has repeatedly demanded civilian rule, both in the lead-up to al-Bashir’s disposal and after al-Burhan’s second coup in 2021. “There was a courageous nationwide social movement that pushed for a power-sharing arrangement between civilians and the military and security in 2019 and 2020,” Stigant said. But “the power was never shifted away from the military and the security elites, and we wanted to talk about [the transition] in the way that the Sudanese envisioned it and that I think many people hoped that it would go.”
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+Since last April, there have been some efforts to try and broker a ceasefire in Sudan, but none has held. And stopping the violence will be critical to restoring critical humanitarian aid to Sudan’s people and a democratic transition — something that the Sudanese have demonstrated for and demanded.
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+The African region is critically undercovered in the media, and the Sudan war has suffered that fate, but the conflict and humanitarian situation will only continue to spiral if the international community keeps ignoring it.
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Trumpists don’t need to fear a multiracial America -
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+A woman holds a sign expressing Latino support for Republican presidential candidate Donald Trump at his campaign rally at the Orange County Fair and Event Center, April 28, 2016, in Costa Mesa, California. | David McNew/AFP via Getty Images
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+High Hispanic turnout could actually benefit Trump, according to recent polls.
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+Since Barack Obama’s reelection in 2012, many conservatives have grown increasingly afraid of the republic they claim to love.
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+That year, America’s first Black president won about the same share of the white vote as Michael Dukakis in 1988, when the Democratic nominee lost 40 states. But for Obama, this was more than enough. Thanks to demographic change and high turnout among Black voters, he won the White House comfortably, even as roughly 60 percent of white voters backed his opponent.
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+Faced with Obama’s victory, many liberals celebrated the apparent emergence of a durable Democratic majority. Many conservatives, meanwhile, eulogized their dearly departed nation. “The demographics are changing. It’s not a traditional America anymore,” Bill O’Reilly declared on Fox News’s election night broadcast, as returns began looking unfavorable for Romney. “The white establishment is now the minority.”
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+The GOP leadership implored their party to reconcile itself to this new reality. In its “autopsy” of the Romney campaign, the Republican National Committee argued that “If Hispanic Americans hear that the GOP doesn’t want them in the United States, they won’t pay attention to our next sentence.” It counseled Republicans to embrace immigration reform.
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+But others on the right took the opposite view. In their eyes, moderating on immigration would only deepen the dispossession of “traditional America.” Conservatives needed to arrest demographic change, not acquiesce to it. Republicans had to keep left-leaning groups out of the country and those already here, away from the polls.
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+Right-wing intellectuals, meanwhile, rationalized contempt for liberal democratic norms. In a 2016 essay, Michael Anton argued that the “ceaseless importation of Third World foreigners with no tradition of, taste for, or experience in liberty” was turning the electorate “more left, more Democratic, less Republican, less republican, and less traditionally American with every cycle.” The left was therefore “on the cusp of a permanent victory,” and allowing the Democratic Party to wield power any longer would be tantamount to national suicide. A few months later, Anton became a senior White House official.
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+In the years since Trump’s election, many Republicans have embraced this apocalyptic outlook on immigration — and a related irreverence for democratic niceties.
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+And yet, during the same period, the right’s strategic fears of demographic change and majority rule have become increasingly misplaced. In recent elections and opinion polls, Republicans have made substantial gains with nonwhite voters, even as they’ve embraced a militantly nativist agenda. Indeed, in a New York Times/Sienna poll released over the weekend, Hispanic voters actually favor Trump over Joe Biden by a six-point margin.
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+At the same time, the GOP’s growing support among working-class voters has given the party an interest in making it easier for people to vote. Whereas high turnout used to reliably benefit the Democratic Party, today it is arguably the Republicans who have an interest in widespread voter participation.
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+The conservative movement still faces long-term demographic challenges, with the Christian right claiming scant support among America’s rising generations. But that is not a problem that can be solved by restricting immigration, passing voter ID laws, or advertising your movement’s enthusiasm for autocracy. To the contrary, such actions are likely to be counterproductive.
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+Of course, none of this will be persuasive to white nationalists, who view demographic change as bad by definition. Yet white conservatives who have no problem with ethnic diversity per se, and simply worry that their values will be politically irrelevant in a multiracial America, should calm down.
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+Conservatives are radicalizing against immigration and democracy
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+A few years ago, the idea that a rootless, cosmopolitan elite was attempting to replace America’s white majority through lax immigration enforcement was a far-right conspiracy theory. Today, it is something approaching Republican orthodoxy.
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+Mike Johnson, the GOP speaker of the House, has espoused a version of “the great replacement” theory, albeit one shorn of explicit racial content. In May 2022, Johnson declared that Democrats “intentionally open our borders” because they want to “TURN ILLEGALS INTO VOTERS!”
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+Republican Sen. J.D. Vance expressed similar sentiments that same year, explaining that Democrats “have decided that they can’t win reelection in 2022 unless they bring in a large number of new voters to replace the voters that are already here.” Missouri Sen. Eric Schmitt has also accused Democrats of “fundamentally trying to change the country” through immigration.
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+Earlier this month, Elon Musk posted that “Almost every illegal is a Dem voter. Therefore, the Dem Party will not take action until they lose more votes due to ushering in vast numbers of illegals than they gain.”
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+For his part, Donald Trump gestured at the theory in remarks to the Conservative Political Action Conference (CPAC) over the weekend, saying that his “first and most urgent action” as president would be to “send Joe Biden’s illegal aliens back home.”
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+This rhetoric is incomprehensible unless one posits that by “illegals,” Republicans really mean “recent nonwhite immigrants.” Undocumented immigrants cannot vote by definition. And evidence for widespread voter fraud among such immigrants is nonexistent. What is true is that asylum-seekers and undocumented immigrants are heavily nonwhite, that nonwhite voters are heavily Democratic, and that conservatives have lost some political and cultural influence as the US population has grown more diverse.
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+The right’s fundamental complaint then is not with undocumented immigration or voter fraud, but rather, the political implications of legal forms of immigration and voter participation. Tucker Carlson copped to this position on Fox News in 2021, when he argued that “the immigration Act of 1965” was a worse “attack on democracy” than the January 6 insurrection. “That law completely changed the composition of America’s voter rolls, purely to benefit the Democratic Party,” Carlson said. “That seems like kind of an assault on democracy, a permanent one.”
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+If conservatives want to keep presumptively Democratic-leaning groups out of the country, they’ve also grown preoccupied with keeping them away from the polls by curtailing voting rights and accessibility. Trump continues to mount a personal crusade against mail-in voting, telling Fox News’s Laura Ingraham this month that states where voters can mail their ballots “automatically have fraud.” Not all Republicans endorse that particular conspiracy theory, but 13 red states enacted new voting restrictions in 2023.
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+Not all conservatives were born in the USA
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+When Trump conquered the GOP, the party became more virulently nativist – and also, more popular with Hispanic Americans.
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+In 2016, Trump won 29 percent of the Hispanic vote, which was roughly comparable to Mitt Romney’s showing in 2012, according to the Democratic data firm Catalist. But four years later, his share of the demographic swelled to 37 percent.
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+Initially, many attributed Trump’s gains to unique features of the 2020 cycle. Latinos were disproportionately likely to lose work as a result of shutdowns, and might therefore have backed the less COVID-conscious candidate out of fear of unemployment.
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+But subsequent elections and polling indicate that many Hispanic voters have durably realigned. In the 2022 midterm elections, Republican candidates won roughly the same share of Latinos as Trump had two years earlier.
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+And there’s reason to believe that this result actually masked a broader rightward shift among Hispanic voters writ large. According to a June 2023 report from Equis, a progressive research organization, Latino voters who cast a ballot in 2020 – but sat out the 2022 election — favor a Republican over Biden by a 54 percent to 34 percent margin.
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+As noted above, Trump leads Biden with Hispanic voters by 6 points in the latest Times/Siena poll. And other surveys have produced similar results. A CNBC poll released in December found Latinos supporting Trump over Biden by a 5-point margin. The following month, a USA Today/Suffolk University poll produced the same result.
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+These findings should be taken with a grain of salt. Bidenwon 63 percent of Latino voters just four years ago; it would be extremely unusual for a demographic group to swing by more than 13 points in the span of a single election cycle. Nevertheless, the broader polling data indicates that Trump has expanded his support among Hispanic voters substantially.
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+Public opinion data also suggests that Republicans could win an even larger share of Latinos if they had a slightly less hateful standard-bearer. In recent surveys, Hispanic voters have tended to express a preference for Republicans over Democrats on inflation and handling the economy, while roughly two-thirds say Biden has accomplished not that much, little, or nothing in office.
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+On immigration policy, however, the demographic’s views remain to the left of the American public’s writ large. It’s reasonable to suspect, therefore, that a GOP nominee who didn’t want to deport longtime US residents en masse might win a larger share of the voting bloc. And in fact, Trump’s main primary rival, Nikki Haley, boasts a 12-point lead over Biden among Hispanic voters, in the new Times/Siena poll.
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+To be sure, Hispanic voters still say the Democratic Party cares more about people like them than Republicans do. And they hold many left-of-center views on issues as varied as environmental regulation, health care, and gun control. Yet the GOP has made essentially no effort to counter the impression that it cares little about Latinos as a group. And the fact that Hispanic Americans are torn between liberal impulses on some policy questions, and conservative ones on others, makes them no different than many other voting blocs. The same could be said of working-class whites in the industrial Midwest. Yet that group’s liberal views on abortion and health care policy have not prevented them from voting for Republicans by landslide margins.
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+Recent immigrants are no more inherently hostile to Republican politics than third- or fourth-generation ones. To the contrary, foreign-born Latinos tend to be less supportive of abortion rights than the US public as a whole, while foreign-born Black immigrants are more opposed to marriage for same-sex couples.
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+Naturalized US citizens are also more likely than native-born ones to say that they are “very proud” to be American, to be religiously observant, and to care for their elders. It is therefore conceivable that increasing restrictions on immigration would accelerate the American public’s drift away from social conservatism.
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+Of course, none of this will matter much to conservatives who oppose nonwhite immigration out of sheer racism. Nor will it provide comfort to those who believe that immigrants drive down native-born Americans’ wages or (more plausibly) increase their housing costs. But those who share Michael Anton’s fear that allowing more nonwhite people into the country will hand Democrats a “permanent victory” should know that this simply is not true.
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+Voter suppression doesn’t necessarily help Republicans win elections.
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+If the GOP’s hostility toward immigrants is plausibly counterproductive in political terms, this is even more true of the party’s attempts to make voting more difficult.
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+For much of the modern era, Democrats have enjoyed disproportionate support among young, low-income, and nonwhite Americans, who all have a lower propensity to vote than US adults as a whole. For this reason, high levels of voter turnout tended to increase the party’s odds of victory.
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+But Trump’s ascendance accelerated a decades-long, leftward shift among college-educated voters, a group that has an exceptionally high propensity to vote. In 2012, Obama won 46 percent of college-educated white voters; eight years later, Biden won 54 percent of the demographic.
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+This has dramatically changed the relationship between turnout and partisan advantage. In a 2022 paper, political scientists at the universities of Auburn, Rice, and Texas A&M documented this shift. Drawing on correlations between partisan preference and propensity to vote obtained from survey data, the researchers simulated the impact that higher or lower rates of turnout would have had on recent US elections.
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+They found that Obama would have won by even larger margins had voter turnout been higher in 2008 and 2012, as voters who were on the fence about participating in those elections leaned Democratic. By 2016, however, Democrats ceased to derive an unambiguous benefit from higher levels of voter participation. Four years later, the partisan implications of higher turnout flipped: Had vote participation been 20 percent higher in 2020, then a pool of Trump-leaning marginal voters would have made their voices heard, and the Democratic Party’s vote share would have fallen by 0.6 percent, while a 20 percent reduction in turnout would have increased Biden’s margin by nearly a percentage point.
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+These findings have been borne out by subsequent polls and election results.
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+In 2023, Democrats routed Republicans in low-turnout special elections. This was partly due to the overrepresentation of college graduates in such elections; according to polling from the New York Times and Siena college, special election voters were about 10 percent more college educated than registered voters as a whole. But the Democrats’ advantage among high-propensity voters is deeper than the education divide. Within every demographic category in the Times/Siena poll, Democrats perform better with high-turnout voters than low-turnout ones. In other words: A white, college-educated voter who consistently casts a ballot in every federal election is much more likely to be Democratic than a white, college-educated American who rarely votes.
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+As noted above, Hispanic voters who sat out the 2022 midterm appear to be much more Republican than those who showed up at the polls that year. And this is true of the broader electorate. In December’s Times/Siena poll, Trump led Biden by 2 points among registered voters, but trailed the president by that same margin among likely voters. The more recent version of that poll shows Trump ahead with both likely voters and all registered ones, but he once again did worse with the former than the latter.
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+Last October, a Grinnell College survey found that 2020 Trump voters were 4 points less likely to say they were definitely going to cast a ballot this year than 2020 Biden voters. Around the same time, multiple surveys from Marquette University Law School found Biden performing 4 points better among likely voters than registered ones.
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+All this suggests that it is Republicans who have a political interest in making it easier for people to vote.
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+This is a difficult reality for both progressives and conservatives to digest. The left has a much stronger investment in the ideal of popular sovereignty than the right does. And for decades, partisan interest reinforced this ideological divergence. As far back as 2002, Mitch McConnell was arguing that “voting is a privilege” from the Senate floor.
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+But now, any reform that marginally increases the difficulty of casting a ballot threatens to deter more Republicans than Democrats. Of course, there are still ways for the GOP to disenfranchise left-leaning voters specifically. Slashing resources for heavily Democratic precincts, or disenfranchising felons in states where the formerly incarcerated population is disproportionately Black, can benefit Republicans electorally. But voting restrictions that apply to all universally, such as reductions in voting hours or voter ID laws, may actually hurt the GOP’s cause.
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+The right should take a deep breath
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+All this said, conservatives do have cause for fearing that demographic change is rendering them a permanent minority on key policy questions. But this has less to do with immigration than generational replacement. Millennials and zoomers are much more socially liberal than their forebears. The Christian right’s agenda is already deeply unpopular in the US and is poised to grow steadily more so over time.
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+But that is not a problem that immigration or voting restrictions can solve. Fully dispensing with democracy altogether — and attempting to entrench a theocratic regime — is no more plausible an endeavor. You aren’t going to be able to dictatorially rule over a nation whose mass public and educated elite both overwhelmingly oppose you, and where every major center of economic growth is dominated by the political opposition.
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+Thus, the right simply has no alternative but to adapt to America’s changing demographic and cultural landscape. But as the developments of the past eight years demonstrate, this won’t require forfeiting all that conservatives hold dear. To the contrary, Republicans have managed to diversify their coalition even as they implemented a wildly unpopular revolution in abortion policy, and became more rightwing on immigration. Judging by recent polls, if the party were merely capable of nominating Nikki Haley — an extremely conservative politician by conventional metrics — it would be poised for a Reagan-esque popular-vote landslide.
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+So conservatives should stop hyperventilating about their “great replacement” or the left’s “permanent victory.” For the right, demography is not doom. Republicans are doing just fine. The party may need to make some adjustments in order to thrive in an increasingly multiracial America. But it is possible to assemble a rainbow coalition of reactionaries. Indeed, if polls are to be believed, Trump is on his way to doing just that.
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From The Hindu: Sports
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Amazing Ruler, La Maqueen, Vyasa, Cascais, Corinthian, and Multisided catch the eye -
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2012 series against England was turning point of my career: Ashwin - Twelve years later, Ashwin looked back at the turning point of his remarkable career, which now features 507 Test wickets.
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World Olympic boxing qualifier - Busto Arsizio (Italy)
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Daria Kudashova ousts sixth seed Fanny Ostlund -
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Angad Vir Singh Bajwa tops skeet in National trials -
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From The Hindu: National News
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99 kg of hashish worth ₹108 crore seized near Mandapam during bid to smuggle to Sri Lanka -
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BJP challenges INDIA bloc parties on A. Raja’s remarks - Former Union Minister Ravi Shankar Prasad said the BJP ‘vehemently condemned’ Raja’s remarks, which he termed ‘Maoist ideology’
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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 and written by Nalme Nachiyar.
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Sandeshkhali violence: NCW chief meets President Murmu, recommends President’s rule in West Bengal - National Commission for Women chairperson Rekha Sharma said the situation in West Bengal’s Sandeshkhali is still very dire
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BRS, BSP to contest Lok Sabha polls together -
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From BBC: Europe
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In Ukraine, the show must go on - even underground - Kharkiv National Opera and Ballet is reopening underground, away from Russian drones and missiles.
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Moment astronauts hug as they arrive at space station - The Endeavour spacecraft docked with the ISS after blasting off from Florida.
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Tesla plant halts production after suspected arson - The factory, near Berlin, has been the subject of protests by eco activists, who deny involvement.
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German call leak due to ‘individual error’ - minister - One participant in an air force meeting used an insecure line - allowing Russia to intercept the call.
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Russian Black Sea ship ‘sunk in drone attack’ - Ukraine said sea drones were used to target Russia’s Sergei Kotov patrol ship near the Kerch Strait.
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From Ars Technica
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NASA cancels a multibillion-dollar satellite servicing demo mission - Congress kept throwing money at the OSAM-1 mission, but it faced continual delays. - link
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This rare 11th century Islamic astrolabe is one of the oldest yet discovered - “A powerful record of scientific exchange between Arabs, Jews, & Christians over 100s of years.” - link
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Hackers exploited Windows 0-day for 6 months after Microsoft knew of it - Technically, Microsoft doesn’t consider such bugs as vulnerabilities. It patched it anyway. - link
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European crash tester says carmakers must bring back physical controls - In 2026, Euro NCAP points will be deducted if some controls aren’t physical. - link
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The AI wars heat up with Claude 3, claimed to have “near-human” abilities - Willison: “No model has beaten GPT-4 on a range of widely used benchmarks like this.” - link
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From Jokes Subreddit
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There was a man who had 3 girlfriends -
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+There was a man who had 3 girlfriends, but he did not know which one to marry. So he decided to give each one $5000 and see how each of them spent it.
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+The 1st one went out and got a total makeover with the money. She got new clothes, a new hairdo, manicure, pedicure, the works, and tells the man, “I spent the money so I could look pretty for you because I love you so much.”
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+The 2nd one went out and bought new golf clubs, a CD player, a television, and a stereo and gave them to the man. She said, “I bought these gifts for you with the money because I love you so much.” The 3rd one takes the $5000 and invests it in the stock market, doubles her investment, returns the $5000 to the man and reinvests the rest. She says, “I am investing the rest of the money for our future because I love you so much.”
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+The man thought hard about how each of the women spent the money.
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+Finally, being a man he decided to marry the one with the biggest tits.
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Many years ago, a rich man is having lunch with his doctor friend -
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+when they start discussing their sex lives.
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+“Sex with the wife is terrible! I can’t even get it up anymore” says the rich man.
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+“That’s sad to hear”, replies the doctor, “but all hope is not lost. You see, there’s this experimental pill called Viagra that’s just come out. It’s guaranteed to get you hard and erect for up to four hours.”
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+“Wow, that’s great! Can you get me some?”
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+“I could, but it’s an experimental drug. It’s quite expensive, like $20,000 a pill!”
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+“Oh, well I guess I have no choice, I have to try it because nothing else works.”
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+They make the arrangement for payment and the next day the wealthy man sees the doctor to get his pill. The doctor then instructs him.
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+“Take this an hour before you have sex, so the medication has time to be absorbed into your system. Afterwards you’ll be good for the next four hour until the medication wears off.
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+“Ok,” says the wealthy man.
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+Later that evening the doctor receives a call from the wealthy man.
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+“Doc, I took the pill an hour before I expected my wife to be home, but she just called and said she got a last minute invite to a gala and will be five hours late! What do I do? This thing cost me a lot of money and it’s going to be wasted!”
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+“Well”, says the doctor, “Is the maid around? Maybe you could get with her?”
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+“The maid!? Why? I don’t need Viagra to fuck her!”
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+Karen: Doctor, I’ve not been feeling well lately
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+Doctor: Well, I’ve looked at your lab reports and I’m afraid I have some bad news… Karen: Don’t give me this lab nonsense, you bureaucratic paper pusher! I don’t believe Western medicine anyways! I’ve been following homeopathic medicine, faith-based approaches, and healing crystals all my life, and they never let me down. Now, will you do things my way, or do I need to talk to the hospital management? Doctor: Sure, sure, lady. We’ll do things your way. Does an astrology-based approach work for you? Karen: That’s better! Of course, it would! Doctor: What’s your birth sign? Karen: Cancer. Doctor: Well what a fucking coincidence.
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Did you hear that Reddit is using post content, to train AI? -
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+With that said, crunchy ice cream because the bones are purple when a hat goes bark. If not for never, when will follow complete? Yes’nt sound drains the beholder of fuzzy water-slide lingo.
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Curtesy of Shedd Aquarium
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Allison Bailey/SOPA Images/LightRocket via Getty Images
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Courtesy of Shedd Aquarium
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Courtesy of the Florida Fish and Wildlife Conservation Commission
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Courtesy of Shed Aquarium
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