Confirmation of Covid Infection Status and Reporting of Long Covid Symptoms in a Population-Based Birth Cohort: No Evidence of a Nocebo Effect -
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+Some patients with COVID-19 develop symptoms after the acute infection, known as ‘Long COVID’. We examined whether or not confirmation of COVID-19 infection status could act as a nocebo, using data from questionnaires distributed to the Avon Longitudinal Study of Parents and Children cohort. We examined associations between confirmation of COVID-19 infection status (confirmed by a positive test versus unconfirmed) and reporting of Long COVID symptoms. We explored the roles of sex and anxiety as potential moderators. There was no clear evidence of a strong association between confirmation of COVID-19 infection status and the Long COVID composite score, physical or psychological symptoms, or duration of symptoms. There was no clear evidence of moderation by sex or anxiety. We therefore found no evidence of a nocebo effect. Our data suggest that this psychological mechanism does not play a role in the medical symptomatology experienced by patients with Long COVID.
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Affordable private rental supply and demand: short-term disruption (2016–2021) and longer-term structural change (1996–2021) -
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+This research analyses the ABS Census to reveal changes in the supply of private rental housing affordable and available to lower-income households (Q1 and Q2 households) over both the short term (2016–21) and the longer term (1996–2021). It also provides analysis of how COVID-19 policy and population responses temporarily altered the long-run structural trajectory of the private rental sector (PRS) in Australia. In 2021, the Australian PRS housed more than 2.363 million households, a 17 per cent increase of nearly 340,000 households since the 2016 Census. This growth has been greater than total household growth in each intercensal period since 1996. Between 2016 and 2021 PRS growth was concentrated at mid-market levels; in dwellings renting from around $300–$530 per week ($2021). This continues a major change trend first established in 2011, reinforcing the structural shift to a market concentration of dwellings renting at mid-to-higher levels. The long-term shift in the national distribution of PRS household incomes reveals the growth of households with incomes at mid to high levels ($1,246 a week and above). In 1996, these ‘wealthier’ households comprised 40 per cent of all PRS households (or 489,000 households); in 2021, they comprised 64 per cent (or 1,519,000 households), a 211 per cent increase. In comparison, the total number of PRS households increased by 91 per cent between 1996 and 2021 (from 1,234,000 households to 2,362,000). Over the same time frame, there has been a relatively constant total number of lower income renters in the PRS; 508,000 households in1996 and 488,000 in 2024. Nevertheless, there was a shortage of 348,000 affordable and available private rental homes for very-low income (Q1) households in 2021 and that, as a result, 82 per cent of Q1 PRS households paid unaffordable rents.
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COVID-19 and Changes in Young Adults’ Weight Concerns -
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+The COVID-19 pandemic introduced fundamental challenges to nearly all aspects of college students’ lives, yet changes in key domains of their health, including weight concerns, remain untested. The current study utilized a longitudinal project comprised of 355 young-adult college students (Mage=19.5, 66.8% female, 33.2% male) oversampled for recent substance use behavior. Participants completed multiple assessments (mode=5) from September 2017 to September 2021. Piecewise growth-curve models tested whether COVID-19 onset was associated with changes in the trajectories of young adults’ weight concerns. Analyses also examined participants’ sex as a moderator of these trajectories. On average, participants reported a significant increase in weight concern levels around the start of COVID-19, although weight concern slopes were not significantly different before and after COVID-19. Additionally, moderation analyses showed that females (but not males) had a significant increase in weight concern levels after COVID-19 onset.
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Mathematical Modeling of Impacts of Patient Differences on Renin-Angiotensin System and Applications to COVID-19 Lung Fibrosis Outcomes -
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+Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating the effects of these factors. Recent evidence suggests patient-specific alteration of RAS homeostasis with premorbidity and the expression level of angiotensin converting enzyme 2 (ACE2) during COVID-19. However, conflicting evidence suggests decreases, increases, or no changes in RAS after SARS-CoV-2 infection. In addition, detailed mechanisms connecting the patient-specific conditions before infection to infection-induced RAS alteration are still unknown. Here, a mathematical model is developed to quantify the systemic contribution of heterogeneous factors of RAS during COVID-19. Three submodels are connected–an ABM COVID-19 in-host lung tissue model, a RAS model, and a fibrosis model to investigate the effects of patient-group-specific factors in the systemic alteration of RAS and collagen deposition in the lung. The model results indicate cell death due to inflammatory response as a major contributor to the reduction of ACE and ACE2. In contrast, there are no significant changes in ACE2 dynamics due to viral-bound internalization of ACE2. Reduction of ACE and ACE2 reduces the homeostasis of RAS, including angiotensin II (ANGII), in the lung tissue. At the same time, the decrease in ACE2 increases systemic ANGII and results in severe lung injury and fibrosis. The model explains possible mechanisms for conflicting evidence of RAS alterations in previously published studies, and simulated results are consistent with reported RAS peptide values for SARS-CoV-2-negative and SARS-CoV-2-positive patients. We observed decreased RAS peptides for all patient groups with aging in both sexes. In contrast, large variations in the magnitude of reduction were observed between male and female patients in the older and middle-aged groups. We also predicted that feedback of ANGII{middle dot}AT1R to renin could restore ANGI homeostasis but fails to restore homeostasis values of RAS peptides downstream of ANGI. In addition, the results show that ACE2 variations with age and sex significantly alter RAS peptides and lead to collagen deposition with slight variations depending on age and sex. This model may find further applications in patient-specific calibrations of tissue models for acute and chronic lung diseases to develop personalized treatments.
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Maternal Psychological Distress & Mental Health Service Use during the COVID-19 Pandemic -
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+Background: Mental health problems are increasingly recognized as a significant and concerning secondary effect of the COVID-19 pandemic. Research on previous epidemics/pandemics suggest that families, particularly mothers, may be at increased risk, but this population has yet to be examined. The current study (1) described prevalence rates of maternal depressive and anxiety symptoms from an online convenience sample during the COVID-19 pandemic, (2) identified risk and protective factors for elevated symptoms, and (3) described current mental health service use and barriers. Methods: Participants (N = 641) were mothers of children age 0-8 years, including expectant mothers. Mothers completed an online survey assessing mental health, sociodemographic information, and COVID-19-related variables. Results: Clinically-relevant depression was indicated in 33.16%, 42.55%, and 43.37% of mothers of children age 0-18 months, 18 months to 4 years, and 5 to 8 years, respectively. Prevalence of anxiety was 36.27%, 32.62%, and 29.59% for mothers across age groups, respectively. Binary logistic regressions indicated significant associations between risk factors and depression/anxiety across child age groups. Limitations: Cross-sectional data was used to describe maternal mental health problems during COVID-19 limiting the ability to make inferences about the long-term impact of maternal depression and anxiety on family well-being. Conclusions: Maternal depression and anxiety appear to be elevated in the context of COVID-19 compared to previously reported population norms. Identified risk factors for depression and anxiety across different child age ranges can inform targeted early intervention strategies to prevent long-term impacts of the COVID-19 pandemic on family well-being and child development.
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Adaptations of microbial genomes to human body chemistry -
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+Water and oxygen availability vary in normal physiology and disease, so evolutionary adjustments of protein sequences to optimally use these chemical resources would represent a competitive advantage for host-associated microbial genomes. In this study, reference proteomes for taxa derived from the Genome Taxonomy Database (GTDB) were combined with 16S rRNA-based taxonomic abundances in order to calculate chemical metrics for community reference proteomes. This permits new insight into community-level genomic adaptation to specific chemical conditions in body sites. Surprisingly, reference proteomes for gut communities appear to be shaped by the physiological function of water absorption in the intestine more than by reducing conditions. Reference proteomes of gut communities in COVID-19 and inflammatory bowel disease (IBD) patients are generally more reduced than controls despite higher relative abundances of aerotolerant organisms and lower abundances of Faecalibacterium and other obligate anaerobes. The trend of chemical reduction in patients is supported by multi-omics (i.e., metagenomic and metaproteomic) data for COVID-19 and can be attributed to relatively oxidized protein sequences for obligate anaerobes compared to aerotolerant genera in gut communities. Genomic adaptation to transiently oxygenated conditions, reflected in more oxidized protein sequences, may be an evolutionary strategy for obligate anaerobes to compete with aerotolerant organisms in the chemical context of gut inflammation.
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Prior exposure to malaria decreases SARS-CoV-2 mediated mortality in K18-hACE2 mice without influencing viral load in lungs -
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+Abstract: Background: Epidemiological evidence for decreased prevalence and/or mortality due to SARS-CoV-2 infections in countries endemic for malaria have been reported. However, such associational studies in human population are limited by known and several unknown confounding factors. The current study, the first of its kind, was designed to seek experimental evidence to test the hypothesis if prior exposure to Plasmodial infections cross-protect against SARS-CoV-2 challenge infection in a murine model, K-18 human ACE2 transgenic mice. Methods: Mice that had recovered from Plasmodium chabaudi infection 40 days earlier were challenged with a virulent strain of SARS-CoV-2 and viral load in lungs as well as mortality were scored and compared with K18 hACE2 mice that had not experienced prior malaria. Results: The viral load in lungs 6 days post challenge were comparable in malaria recovered mice and controls suggesting no significant generation of anti-viral immunity. However, mice with prior malaria exposure were significantly protected against SARS-CoV-2 induced mortality. Significant differences were observed in several host immune responses between the two groups when cytokines, chemokines and transcription factors were quantified in lungs. The plasma levels of several cytokines and chemokines were also significantly different between the two groups. Conclusion: The results of the study suggest that prior exposure to malaria protects mice against viral induced mortality in K18 hACE2 transgenic mice challenged with a virulent isolate of SARS- CoV-2 in the absence of demonstrable host immunity inhibiting viral growth in lungs.
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Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters -
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+This study aims to comprehensively characterize the SARS-CoV-2 BA.5 variants using K18 hACE2 transgenic mice and golden hamsters as model organisms. Previous research on SARS-CoV-2 has utilized both mouse and hamster models, leading to conflicting results concerning the virus's lethality. In our study, the finding suggests that H11-K18 hACE2 golden hamsters closely mimic the disease progression observed in human COVID-19 cases caused by BA.5 variants, demonstrating consistent severity and symptoms comparable to severe infections. Additionally, hamsters exhibit heightened respiratory viral replication, accurately reflecting the clinical viral kinetics observed in humans. The study emphasizes the critical importance of selecting an appropriate animal model for SARS-CoV-2 research, while also providing robust support for the hypothesis that BA.5 variants contribute to fatal outcomes in COVID-19 cases. These findings highlight the pivotal role of the golden hamster model in advancing our understanding of the pathogenic mechanisms underlying SARS-CoV-2 variants, as well as in the development of targeted therapeutic strategies.
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Predicting Antibody and ACE2 Affinity for SARS-CoV-2 BA.2.86 and JN.1 with In Silico Protein Modeling and Docking -
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+The emergence of the Omicron sublineage of SARS-CoV-2 virus BA.2.86 (nicknamed “Pirola”) has raised concerns about its potential impact on public health and personal health as it has many mutations with respect to previous variants. We conducted an in silico analysis of neutralizing antibody binding to BA.2.86. Selected antibodies came from patients who were vaccinated and/or infected. We predicted binding affinity between BA.2.86 and antibodies. We also predicted the binding affinity between the same antibodies and several previous SARS-CoV2 variants (Wuhan and Omicron descendants BA.1, BA.2, and XBB.1.5). Additionally, we examined binding affinity between BA.2.86 and human angiotensin converting enzyme 2 (ACE2) receptor, a cell surface protein crucial for viral entry. We found no statistically significant difference in binding affinity between BA.2.86 and other variants, indicating a similar immune response. These findings contradict media reports of BA.2.86s high immune evasion potential based on its mutations. We discuss the implications of our findings and highlight the need for modeling and docking studies to go above and beyond mutation and basic serological neutralization analysis. Future research in this area will benefit from increased structural analyses of memory B-cell derived antibodies and should emphasize the importance of choosing appropriate samples for in silico studies to assess protection provided by vaccination and infection. This research contributes to understanding the BA.2.86 variants potential impact on public health. Moreover, we introduce new methodologies for predictive medicine in ongoing efforts to combat the evolving SARS-CoV-2 pandemic and prepare for other hazards.
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Information bias of vaccine effectiveness estimation due to informed consent for national registration of COVID-19 vaccination -
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+Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iteratively imputing corrected vaccination status. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.
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Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster -
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+SARS-CoV-2-neutralizing antibodies were substantially expanded one month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remained unknown. Here, we addressed this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from 39 adult participants obtained at ~1 month and ~3 months post an XBB.1.5 MV booster. Our findings indicate that the resultant neutralizing antibody titers were robust and generally maintained at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.
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COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast -
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+SARS-CoV-2 infection and the resulting coronavirus disease (COVID-19) complicate pregnancies as the result of placental dysfunction which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests maternal response to infection is responsible for placental dysfunction. We hypothesized that maternal circulating extracellular vesicles (EVs) are altered by COVID-19 during pregnancy and contribute to placental dysfunction. To examine this, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their functional effect on trophoblast cells in vitro. We found the timing of infection is a major determinant of the effect of COVID-19 on circulating EVs. Additionally, we found differentially expressed EV mRNA cargo in COVID-19 groups compared to Controls that regulates the differential gene expression induced by COVID-19 in the placenta. In vitro exposure of trophoblasts to EVs isolated from patients with an active infection, but not EVs isolated from Controls, reduced key trophoblast functions including hormone production and invasion. This demonstrates circulating EVs from subjects with an active infection disrupt vital trophoblast function. This study determined that COVID-19 has a long-lasting effect on circulating EVs and circulating EVs are likely to participate in the placental dysfunction induced by COVID-19.
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A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry -
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+Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Our study contributes to understanding the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.
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Non-Consensual Sex among Japanese Women in the COVID-19 Pandemic: A Large-Scale Nationwide Survey-Based Study -
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+Background: Non-consensual sex including rape and sexual assault has been a global concern and may have been influenced by the COVID-19 pandemic, however the information on this topic is limited. Therefore, our objective was to survey the incidence rate of non-consensual sex among Japanese women aged 15-79 years between April to September 2020, following the COVID-19 pandemic in Japan. Materials and Methods: We utilized the data obtained from a nationwide, cross-sectional internet survey conducted in Japan between August and September 2020. Sampling weights were applied to calculate national estimates, and multivariable logistic regression was performed to identify factors associated with non-consensual sex. Data was extracted from a cross-sectional, web-based, self-administered survey of approximately 2.2 million individuals from the general public, including in men and women. Results: Excluding men and responses with inconsistencies, the final analysis included 12,809 women participants, with 138 (1.1%) reporting experiencing non-consensual sex within a five-month period. Being aged 15–29 years and having a worsened mental or economic status were associated with experiencing non-consensual sex. Conclusions: Early intervention to prevent individuals from becoming victims of sexual harm should be extended to economically vulnerable and young women, especially during times of societal upheaval such as the COVID-19 pandemic. Additionally, Japan should prioritize the implementation of comprehensive education on the concept of sexual consent.
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RISK OF THROMBOEMBOLISM AFTER COVID-19 VACCINATION AND COVID-19 INFECTION -
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+Background: Vaccine safety monitoring systems worldwide have reported cases of venous thromboembolism and arterial thromboembolism following a COVID-19 vaccination. However, evidence shows that the association between thromboembolism and SARS-CoV-2 infection is stronger, compared to SARS-CoV-2 vaccination. Hence, weighing the risks and benefits of vaccination should also encounter the roles of vaccination in reducing infection rate, and potentially indirectly lowering the risk of thromboembolism caused by infection. Methods: We conducted a self-controlled case series study (SCCS) from Dec 1st 2020 to 31st August 2022 (before the bivalent vaccine was available) to examinate the association between the first two doses Pfizer/Moderna vaccination and thrombotic events among patients in Corewell Health East (CHE, formerly known as Beaumont Health) healthcare system. We also investigated the effect SARS-CoV-2 infection on the risk of thrombosis events and observed a significant increased risk using the SCCS design. However, because of misclassification bias, SCCS indeed overestimated incidence rate ratio (IRR) of acute event after infection, we then proposed a case-control study addressing this misclassification issues and obtained odd ratio comparing effect of exposure on thrombosis and a subset of controls group. Finally, we analyzed the risk of thromboembolism between vaccinated and unvaccinated groups by a simple diagram, explaining possible factors that affects the probability of experiencing an acute thromboembolism event after a COVID-19 vaccination. Results: Using EHR data at Corewell East, we found an increased risk of thrombosis after the first two doses of COVID-19 vaccination, with incidence rate ratios after the first dose is 1.16 (CI: [1.04, 1.29]), and after the second dose of 1.19 (CI: [1.07,1.32]). The association between thromboembolism and SARS-Cov-2 infection depends on prior vaccination status, as the conditional OR among unvaccinated and vaccinated groups are 1.77 (CI: [1.48, 2.1]) and 1.34 (CI: [1.09, 1.66]) respectively. Encountering the vaccine efficacy (VE), receiving the COVID-19 vaccine decreases the risk of thromboembolism, and the benefits of COVID-19 vaccines are much stronger in the period of high infection rate.
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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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World Health Organization (WHO) , COVID19 Case Series of Post Covid 19 Rhino Orbito Cerebral Mucormycosis in Egypt - Conditions: Mucormycosis; Rhinocerebral (Etiology); COVID-19 Interventions: Procedure: debridment Sponsors: Nasser Institute For Research and Treatment Completed
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Treatment of Post-COVID-19 With Hyperbaric Oxygen Therapy: a Randomized, Controlled Trial - Conditions: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition; Post-COVID Condition; Post COVID-19 Condition, Unspecified; Long COVID; Long Covid19 Interventions: Drug: Hyperbaric oxygen Sponsors: Erasmus Medical Center; Da Vinci Clinic; HGC Rijswijk Not yet recruiting
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Mindfulness-based Mobile Applications Program - Conditions: COVID-19; Cell Phone Use; Nurse; Mental Health Interventions: Device: mindfulness-based mobile applications program Sponsors: Yu-Chien Huang Completed
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Correlation of Antibody Response to COVID-19 Vaccination in Pregnant Woman and Transplacental Passage Into Cord Blood. - Conditions: Covid-19 Interventions: Diagnostic Test: COVID-19 Spike Protein IgG Quantitative Antibody (CMIA) Sponsors: Vachira Phuket Hospital Recruiting
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UNAIR Inactivated COVID-19 Vaccine as Homologue Booster (Immunobridging Study) - Conditions: COVID-19 Pandemic; COVID-19 Vaccines; COVID-19 Virus Disease Interventions: Biological: INAVAC (Vaksin Merah Putih - UA- SARS CoV-2 (Vero Cell Inactivated) 5 μg Sponsors: Dr. Soetomo General Hospital; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia; Indonesia-MoH Recruiting
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High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk - Conditions: Cardiovascular Diseases; Long Covid19 Interventions: Other: High Definition-transcranial Direct Current Stimulation; Dietary Supplement: Chlorella Pyrenoidosa Sponsors: Federal University of Paraíba; City University of New York Recruiting
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Safety and Immunogenicity of a Sub-unit Protein CD40.RBDv Bivalent COVID-19 Vaccine, Adjuvanted or Not, as a Booster in Volunteers. - Conditions: COVID-19 Interventions: Drug: CD40.RBDv vaccin (SARS-Cov2 Vaccin) Sponsors: ANRS, Emerging Infectious Diseases; LinKinVax; Vaccine Research Institute (VRI), France Not yet recruiting
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SGB for COVID-induced Parosmia - Conditions: COVID-19-Induced Parosmia Interventions: Drug: Stellate Ganglion Block; Drug: Placebo Sham Injection Sponsors: Washington University School of Medicine Recruiting
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Investigating the Effectiveness of Vimida - Conditions: Long COVID; Post COVID-19 Condition Interventions: Behavioral: vimida Sponsors: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock Not yet recruiting
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Effects of Physiotherapy Via Video Calls in Patients With COVID-19 - Conditions: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function Interventions: Behavioral: Exercise training Sponsors: Chulabhorn Hospital Active, not recruiting
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Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome Interventions: Behavioral: Exercise session; Behavioral: Control session Sponsors: University of Nove de Julho Not yet recruiting
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From PubMed
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A case report of QTc prolongation: Drug induced or myocarditis in Severe Acute Respiratory Syndrome Coronavirus 2 - Remdesivir is a nucleotide prodrug of an adenosine analog. It binds to the viral Ribonucleic Acid (RNA)-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely. Remdesivir has demonstrated in vitro and in vivo activity against Severe Acute Respiratory Syndrome Coronavirus 2; it also acts in vitro neutralization activity against the Omicron variant and its subvariants. We reported a 54-years-old woman admitted with Coronavirus disease 2019. Considering…
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Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes - The COVID-19 pandemic caused by the SARS-CoV-2 virus has greatly affected global health. Emerging evidence suggests a complex interplay between Alzheimer’s disease (AD), diabetes (DM), and COVID-19. Given COVID-19’s involvement in the increased risk of other diseases, there is an urgent need to identify novel targets and drugs to combat these interconnected health challenges. Lysophosphatidic acid receptors (LPARs), belonging to the G protein-coupled receptor family, have been implicated in…
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Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level - The SARS-CoV-2 virus, belonging to the Coronavirus genus, which poses a threat to human health worldwide. Current therapies focus on inhibiting viral replication or using anti-inflammatory/immunomodulatory compounds to enhance host immunity. This makes the active ingredients of traditional Chinese medicine compounds ideal therapies due to their proven safety and minimal toxicity. Previous research suggests that andrographolide and baicalin inhibit coronaviruses; however, their synergistic…
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Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage - Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of…
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Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection - Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants in-vitro, by utilizing…
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Design, synthesis and biological evaluation of novel 1,2,4a,5-tetrahydro-4H-benzo[b][1,4]oxazino[4,3-d][1,4]oxazine-based AAK1 inhibitors with anti-viral property against SARS-CoV-2 - Coronavirus entry into host cells hinges on the interaction between the spike glycoprotein of the virus and the cell-surface receptor angiotensin-converting enzyme 2 (ACE2), initiating the subsequent clathrin-mediated endocytosis (CME) pathway. AP-2-associated protein kinase 1 (AAK1) holds a pivotal role in this pathway, regulating CME by modulating the phosphorylation of the μ subunit of adaptor protein 2 (AP2M1). Herein, we report a series of novel AAK1 inhibitors based on previously reported…
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Role of epinephrine in attenuating cytokine storm, decreasing ferritin, and inhibiting ferroptosis in SARS-CoV-2 - CONCLUSION: Epinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart…
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Challenges Experienced by Saudi Patients With Cancer and Their Family Caregivers in Using Digital Healthcare Technology Platforms in the COVID-19 Pandemic - COVID-19 has provided a unique boost to the use of digital healthcare technology, putting many vulnerable people at risk of digital exclusion. To promote digital healthcare equity, it is important to identify the challenges that may inhibit cancer patients and family caregivers from benefiting from such technology. This study explored the challenges that cancer patients and family caregivers experience in using digital healthcare technology platforms during the COVID-19 pandemic. A qualitative…
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Inhibition of SARS-CoV-2 replication by a ssDNA aptamer targeting the nucleocapsid protein - The nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer’s…
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Transcriptional regulation of SARS-CoV-2 receptor ACE2 by SP1 - Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively,…
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Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo - CONCLUSION: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.
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Targeting host-virus interactions: in silico analysis of the binding of human milk oligosaccharides to viral proteins involved in respiratory infections - Respiratory viral infections, a major public health concern, necessitate continuous development of novel antiviral strategies, particularly in the face of emerging and re-emerging pathogens. In this study, we explored the potential of human milk oligosaccharides (HMOs) as broad-spectrum antiviral agents against key respiratory viruses. By examining the structural mimicry of host cell receptors and their known biological functions, including antiviral activities, we assessed the ability of HMOs…
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Integrated network pharmacology and experimental validation-based approach to reveal the underlying mechanisms and key material basis of Jinhua Qinggan granules against acute lung injury - CONCLUSIONS: In summary, our finding clarified the underlying mechanisms and material basis of JHQG therapy for ALI by integrated network pharmacology and experimental validation-based strategy.
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Molnupiravir inhibits human norovirus and rotavirus replication in 3D human intestinal enteroids - Human norovirus (HuNoV) and human rotavirus (HRV) are the leading causes of gastrointestinal diarrhea. There are no approved antivirals and rotavirus vaccines are insufficient to cease HRV associated mortality. Furthermore, treatment of chronically infected immunocompromised patients is limited to off-label compassionate use of repurposed antivirals with limited efficacy, highlighting the urgent need of potent and specific antivirals for HuNoV and HRV. Recently, a major breakthrough in the in…
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Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways - Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues….
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From Patent Search
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+ 22 February, 2024
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+Daily-Dose
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Legal Weed in New York Was Going to Be a Revolution. What Happened? - Lawsuits. Unlicensed dispensaries. Corporations pushing to get in. The messy rollout of a law that has tried to deliver social justice with marijuana. - link
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The Snake with the Emoji-Patterned Skin - In the wild, ball pythons are usually brown and tan. In America, breeding them to produce eye-catching offspring has become a lucrative, frenetic, and—for some—troubling enterprise. - link
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Matt Gaetz’s Chaos Agenda - The Florida Republican is among the most brazen and controversial figures in Donald Trump’s G.O.P. He’s also among the most influential. - link
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The Trials of Alejandro Mayorkas - The Secretary of Homeland Security has been forced to respond to an unprecedented flow of migrants to the U.S.-Mexico border. Why are Republicans in Congress impeaching him for it? - link
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From House Arrest to the Oscars Circuit - Bobi Wine, the leader of the Ugandan opposition—and the star of a film nominated for Best Documentary Feature—meets Hollywood. - link
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From Vox
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Are Ukraine’s defenses starting to crumble? -
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+Ukrainian soldiers in the outskirts of Avdiivka on February 14, 2024. | Vlada Liberova/Libkos/Getty Images
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+What Ukraine’s biggest setback in months tells us about the future of the war.
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+This week, Russian forces made their most significant breakthrough in nine months — but at a heavy cost.
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+Ukrainian military commanders estimate that 47,000 Russians were killed or injured in the battle, which is significantly higher than the pre-war population of Avdiivka of around 32,000. The estimated death toll in the battle, 17,000, would be higher than the Soviet army’s during the 10-year war in Afghanistan.
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+Those numbers are impossible to verify and very possibly exaggerated, but there’s no doubt the losses were exceedingly high and that this is a point of sensitivity for the Russian government. (This week, a pro-war Russian military blogger died reportedly by suicide after being forced to remove a post criticizing military commanders for the high casualties sustained in the battles.) Britain’s Ministry of Defense also estimates the Russians lost more than 400 tanks in the battle.
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+Given those losses, it’s natural to wonder whether Avdiivka — not even one of the larger cities in Donetsk province, much less Ukraine — was a Pyrrhic victory for the Russians.
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+Yes, in both Bakhmut and Avdiivka, the Russians demonstrated that with enough time, artillery ammunition, and human lives, they can take a small Ukrainian city, almost entirely demolishing it in the process.
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+But is this a sustainable strategy for victory over the second-largest country, in terms of land area, in Europe?
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+“I do not think it’s sustainable, but it is what I think that they’ll do,” retired Lt. Gen. Ben Hodges, former commander of the US Army in Europe, told Vox, saying the war would come down to whether Ukraine could count on continued Western support. “They’ll do it because they can see that we are starting to waver.”
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+The key factor when it comes to understanding Avdiivka is not so much size, location, or strategic significance, but timing. The loss comes at a time when international support for Ukraine, particularly in the United States, is starting to fade. It raises stark questions about what it will take from Kyiv and its international backers to keep Ukraine in the fight.
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+The Ukrainians may be able to stabilize the front line in the coming months, but without significant additional support, Avdiivka is unlikely to be the last city to fall.
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+How significant of a victory is Avdiivka?
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+Avdiivka was “not a mere symbolic Russian victory,” said Franz-Stefan Gady, an Austrian military analyst with the Center for a New American Security (CNAS), who travels regularly to the front lines in Ukraine.
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+The town lies less than 10 miles from the Russian-held city of Donetsk, the capital of the self-proclaimed Donetsk People’s Republic. The loss will put the city much farther out of range for any future Ukrainian counteroffensive. “Ukraine is losing an important strongpoint that anchored Ukrainian defenses in the area. It could potentially open up new avenues of attack for Russian forces,” Gady added.
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+Analysts also pointed out, though, that given the exhaustion of Russian troops after taking the city, they would be unlikely to be able to press further into Ukrainian-held territory. In a recent assessment, the Washington-based think tank Institute for the Study of War said Ukrainian forces would likely be able to set up new defensive positions just a few miles beyond the city, forcing the Russian offensive to culminate here.
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+“Battlefield results are measured in the ability to turn a local success into a bigger one,” Mykola Bielieskov, an analyst with the Kyiv-based National Institute for Strategic Studies, told Vox. “The Russians won’t be able to do that after pushing us out of Avdiivka. They lack reserves and have been exhausted from a five-month fight.”
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+But even though Kyiv and its foreign backers don’t publicize Ukrainian casualty numbers, it’s clear the Ukrainians took heavy losses as well. A recent New York Times account based on interviews with Ukrainian troops describes a chaotic retreat from the city in which hundreds of Ukrainian soldiers may have been captured. Unverified images on social media show some of these prisoners being executed. The outcome is likely to contribute to already serious morale problems at the front and add to Ukraine’s difficulty in recruiting new troops.
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+Avdiivka was a long and draining fight for both sides, and though it’s likely the Russian losses in the battle were far greater, Ukraine may have less of an ability to absorb those losses.
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+Ukraine’s hunger for shells
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+The battle for Avdiivka may have taken place in the fields surrounding the city, but the road to defeat may well have started in Washington, DC.
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+Experts have been warning for months that unless the US Congress allocates new military aid to Ukraine — the last American aid package was sent in December — Ukraine would start to lose the ability to defend the 1,500-kilometer front line.
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+The biggest problem is artillery ammunition: Last summer, Ukraine was firing more artillery shells than Russia per month. Now with supply shortages, it is firing less than a fifth of what the Russians can put out, according to Britain’s Royal United Services Institute.
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+“If you don’t have shells, then courage alone will not be enough to win,” said Yehor Cherniev, a member of the Ukrainian Parliament and deputy chair of its national security committee. Cherniev said it was “cynical” of opponents of military aid to point to losses like Avdiivka as evidence that Ukraine can’t win. “First, they don’t give Ukraine shells, and then they lament that it has lost a populated area and claim that Russia cannot be defeated,” he said.
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+The White House has placed the blame for the defeat squarely on congressional Republicans. National Security Council spokesperson John Kirby told reporters in a call on Monday that Avdiivka was not lost because Ukrainian troops lacked skill or training: “It was because of congressional inaction. We’ve been warning Congress that if they didn’t act, Ukraine would suffer losses on the battlefield, and here you go. That’s what happened this weekend.”
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+Avdiivka may be only a sign of things to come if aid does not resume.
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+Last week, the Senate overwhelmingly passed an aid package that included military funding for Ukraine as well as Israel and Taiwan, and though previous aid packages have passed with substantial majorities, it’s not clear if the bill will even come up for a vote in the GOP-controlled House, given former president and presumptive Republican nominee Donald Trump’s public opposition to more aid.
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+Asked by Vox if Ukraine could continue to rely on US support for the long term, Sen. Chris Murphy (D-CT), a leading advocate of Ukraine aid, replied, “I don’t know. We were all together just a year ago, but Trump is causing Republicans to walk away from Ukraine. I think everybody should be worried. This [US] election will be definitive as to whether or not Ukraine survives.”
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+Republican critics of aid, such as Sen. J.D. Vance (R-OH), counter that no amount of US aid could turn the tide given Russia’s overwhelming advantages in terms of soldiers and industrial capacity.
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+“The West doesn’t make enough munitions to support an indefinite war. Ukraine doesn’t have enough manpower to support an indefinite war,” he told Politico on the sidelines of the Munich Security Conference this week.
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+It is true that Ukraine’s forces face significant personnel shortages, and that the government has been reluctant to pass controversial legislation that would expand conscription and crack down on draft dodging.
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+“They have failed to make the necessary political decisions to do this,” said Hodges. “I think not only is that a problem for them on the battlefield, but it also will begin to undermine some Western support.”
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+The task ahead
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+Stabilizing the front lines after the withdrawal from Avdiivka will be an early test for Gen. Oleksandr Syrskyi, who took over as commander of Ukraine’s armed forces this month. In recent days, the Russians have been concentrating forces for what appears to be an attempt to break through Ukraine’s lines in another area by retaking territory around the southern city of Robotyne, one of the rare successes of Ukraine’s summer counteroffensive.
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+“One of the problems with the end of Ukraine’s counteroffensive is that much of the terrain that was seized was not particularly defensible terrain,” the analyst Rob Lee wrote on Twitter.
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+CNAS’s Gady said it’s likely there could be “more tactical withdrawals in the coming weeks,” as Ukrainian commanders work to stabilize the situation.
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+Beyond the next few weeks, 2024 is likely to be a rebuilding year for Ukraine, as they restore battered units, train new ones, and wait for more aid to arrive. European ammunition production is finally starting to ramp up, though at a much slower rate than Ukrainians hoped last year.
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+The US reportedly has artillery systems and ammunition ready to send to Ukraine immediately if and when Congress approves funding, and is also leaning toward supplying long-range ATACMS missiles, which it has so far declined to send, and which the Ukrainians say will give them a better ability to disrupt Russian supplies and logistics.
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+As bleak as the picture has often been on land in recent months, the Ukrainians have been having better luck on the Black Sea, where the bulk of the Russian fleet has been pushed back by Ukrainian missile and drone strikes and where Ukrainian grain exports by ship are back to near pre-war levels.
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+As promising as those developments may be, this is ultimately a war over territory that comes down to Ukraine’s ability to defend it.
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+Russia has its own supply issues, which forced it to recently begin purchasing mass quantities of ammunition from North Korea, and has also been reluctant to call a second mass mobilization to bring more troops to the front. But Russia’s ability to sustain heavy losses also shouldn’t be underestimated. A recent analysis from the International Institute for Strategic Studies estimated that even after losing around 8,800 fighting vehicles in the war so far, Russia will probably still be able to sustain its assault on Ukraine at current attrition rates for another two to three years.
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+It’s clear that this will be a much longer war and a contest of industrial capacity and political will as much as military maneuvers. But even getting to that marathon will require Ukraine getting past a very difficult period in the coming months.
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+Gady said a complete collapse of Ukraine’s defenses was not entirely out of the question, but still unlikely: “There are going to be a couple months where the situation is really dire for Ukraine, but I think they can hold.”
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American drivers are now even more distracted by their phones. Pedestrian deaths are soaring. -
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+A driver is captured using a phone behind the wheel in New York in this 2016 in photo. The problem of distracted drivers has only gotten worse, one set of data from millions of drivers shows. | Spencer Platt/Getty Images
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+During the pandemic, distracted driving increased, and it hasn’t gone down since.
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+Until relatively recently, good data on the problem of distracted driving has been hard to find. The government estimates that 3,522 people died because of it in 2021, but experts say the official number probably majorly undercounts the number of deaths, in part because police are rarely able to definitively prove that a driver was distracted right before a crash.
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+In the last few years, though, the data on distracted driving has gotten better. Cambridge Mobile Telematics is a company that partners with major insurance companies to offer downloadable apps that drivers can use to save money on their rates. Via the apps, Cambridge Mobile Telematics (CMT) uses mobile phone sensors to measure driving behavior, including whether a person is speeding, holding their phone, or interacting with an unlocked screen while driving (the company says it doesn’t collect information on what the drivers are doing on their phones). Its work gives the company insight into the driving behaviors of more than 10 million people.
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+CMT recently analyzed driver behavior during millions of car trips. What it found should be troubling to anyone who uses a road in the US: During the pandemic, American drivers got even more distracted by their phones while driving. The amount of distracted driving hasn’t receded, even as life has mostly stabilized.
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+The company found that both phone motion and screen interaction while driving went up roughly 20 percent between 2020-2022. “By almost every metric CMT measures, distracted driving is more present than ever on US roadways. Drivers are spending more time using their phones while driving and doing it on more trips. Drivers interacted with their phones on nearly 58% of trips in 2022,” a recent report by the company concludes. More than a third of that phone motion distraction happens at over 50 mph.
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+We’re also spending nearly three times more time distracted by our phones than drivers in the United Kingdom and several other European countries. US drivers spent an average of 2 minutes 11 seconds on their phones per hour while driving, compared to 44 seconds per hour for UK drivers, CMT found. The company compared the driving behaviors of US and European drivers because road fatalities in the United States surged during the pandemic and European fatalities did not. In 2020, 38,824 people died on US roads. In 2021, that number rose to 42,915 people, and the highest number of pedestrians were killed in 40 years. In 2022, the overall deaths stayed high, around 42,795, among them 7,508 pedestrians.
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+“The way individuals are driving their vehicles in the US is distinct from the way they’re driving in Europe,” says Ryan McMahon, senior vice president of strategy for Cambridge Mobile Telematics. That extra time Americans are spending on their phones while driving increases risk: In more than a third of crashes the company analyzed, McMahon says, the driver had their phone in their hand a minute prior to collision.
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+The large increase in risky driving behaviors in the US started basically as soon as the pandemic began. “We saw this incredible increase in distracted driving. You could almost track it by the day schools started to shut down,” McMahon says. “When mobility changed, risk increased dramatically.”
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+The individual and collective consequences of our cellphone compulsions are stark: The most distracted drivers are over 240 percent more likely to crash than the safest drivers, according to the report.
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+The report also notes how the rise of smartphone use roughly corresponds to the rise in pedestrian fatalities: About 4,600 people were killed while walking in 2007, the year the iPhone was introduced. By 2021, with 85 percent of Americans owning smartphones, the number rose to 7,485.
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+Why American drivers got more distracted during the pandemic
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+McMahon and other experts on distracted driving have some theories. Culture may play a role: The shift to working from home, the fact that Americans work longer hours and vacation less, and the expectation that they need to be available to their colleagues even while driving is a notion many Europeans would scoff at. (As someone currently living in Europe after a lifetime in the United States, my highly subjective observation is that people really do seem less work-crazed in Europe. And while phone-checking while driving definitely happens, I see it a lot less than I do in the US.)
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+“I do think this notion of work in our country, and [the idea that] you have to be available 24-7 has also exacerbated it,” says Pam Shadel Fischer, a senior director at the Governors Highway Safety Association, who’s been working for decades to reduce risky and impaired driving. “It’s absolutely a cultural issue.”
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+The most compelling theories, though, are structural and psychological. In the United States, infrastructure is built around cars, and Americans generally have fewer public transportation options than Europeans do. They spend more time in their cars, commuting, doing chores, and taking children to school than people in European countries, and they are far more likely to make these daily trips on roads that are straight, flat, and built for easy car travel: a perfect recipe for boredom.
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+While it’s difficult to generalize too much about Europe, anyone who’s lived or visited there can attest to the differences inherent in roads built before the age of the auto, where pedestrians are considered important road users. The road design, the topography, and the presence of people on foot demand drivers’ attention. “You see more distraction happening when people are more familiar with roads,” McMahon says.
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+The type of car also may matter a lot. In the US, the CMT analysis notes, 94 percent of car drivers said they were driving cars with automatic transmissions. Only 33 percent of UK drivers answered the same. Manual shifting requires more active engagement with the vehicle.
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+It’s also possible that Americans are getting more comfortable with risk precisely because their vehicles keep getting safer for the people driving them (if not for people outside of them). “We’ve got all these safety features,” Shadel Fischer says. They convince drivers that “‘everything is fine! The car will take care of me, no big deal.’ They overestimate what those safety features are designed to do.”
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+Another challenge is that there are frequently no negative consequences for using your phone while driving. It’s easy for people to do because they’ve done it before with no problem — until it causes a crash.
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+What could make drivers put down their phones?
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+A tech industry giant genuinely interested in improving lives and mitigating the harm and disruption caused by its products could find a way to disable distracting devices, leaving them available only for, say, GPS and emergency calls. “I’m convinced that the solution is the technology,” Shadel Fischer says. “We shouldn’t have to do anything.”
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+On the policy front, activists like Jennifer Smith, whose mother was killed in Oklahoma in 2008 by a driver talking on his cellphone, have been working with states to pass laws to end distracted driving. Forty-four states have some sort of distracted driving laws on the books, and 27 states have bans on hand-held cellphone use.
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+In the distracted driving report, Cambridge Mobile Telematics looked at how driver behavior changed after a state passed a “hands-free” law and found that it led to a 13 percent reduction in phone motion while driving in the first three months after a law took effect. But those changes tended to diminish over time, and there’s wide variation among the states both in terms of public awareness of the laws and traffic enforcement, which declined in some states during the pandemic. Without high public awareness or enforcement — which is difficult to do well because it relies on law enforcement officers witnessing the distracted driving and enforcing the laws equitably — getting good compliance can be difficult.
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+That’s why policymakers are taking a multi-pronged approach to the issue, trying to find ways to educate the public and make the laws enforceable. “It will take a long, sustained effort to change driver behavior if we want to have fewer deaths in this country,” says Michelle May, manager of the Highway Safety Program at Ohio’s Department of Transportation.
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+Ohio’s “hands-free” law went into effect last year; since then, May says, the state has used telematics data and tracked an 8.1 percent decline in driver distractions. But May expects the effort to reduce phone use while driving will be a long-term effort, akin to the effort to reduce drunk driving and getting people to wear seatbelts.
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+Financial incentives can also help. Car insurance rates have skyrocketed in recent years, becoming a leading cause of inflation and contributing to the financial burdens associated with car ownership, which disproportionately affects low-income and working-class Americans. The use of telematics-based apps by insurance companies offers drivers an opportunity to save money on their insurance rates. Research into the use of the apps suggests that drivers who regularly receive feedback on their driving habits tend to use their phones less while driving. The data can also help state departments of transportation better locate areas with more distracted driving, which could in turn help influence road design. “We’ve found that simple things like using paint to narrow the lanes gives people the illusion that they’ve got to slow down,” Shadel Fischer says. “The road design does play a role in how we act.”
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+In other words, there are ways to address the problem but they rely heavily on a bunch of solutions working with one another, at a time when our road safety system appears to be breaking down. “Every single piece has to work in concert with the other or it won’t be successful because we’re up against such a huge scale of a behavioral problem,” Smith says.
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+The stakes couldn’t be higher, though, and getting this right will undoubtedly take some combination of policy intervention, industry investment, and a willingness among drivers to put their phones down and pay attention.
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+Until then, the status quo is an advanced country with incredibly high rates of road death, where, over time, almost everyone will know someone who lost their life in a car crash. “Somehow, we’re just accepting 42-45,000 people in the US dying in this manner every year,” McMahon says. “It’s preventable.”
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AI-generated video is here to awe and mislead -
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+CFOTO/Future Publishing via Getty Images
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+OpenAI’s Sora is designed to be a “world simulator.” Right now it’s having trouble breaking a glass.
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+A tiny fluffy monster kneels in wonder beside a lit candle. Two small pirate ships battle inside a churning cup of coffee. An octopus crawls along the sandy floor of the ocean. A Dalmatian puppy leaps from one windowsill to another. These are among a series of demo videos of OpenAI’s Sora, revealed last week, which can turn a short text prompt into up to a minute of video.
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+The artificial intelligence model is not yet open to the public, but OpenAI has released the videos, along with the prompts that generated them. This was quickly followed by headlines calling Sora “eye-popping” and “terrifying” and “jaw-dropping.”
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+OpenAI researchers Tim Brooks and Bill Peebles told the New York Times that they picked “sora,” Japanese for “sky,” to emphasize the “idea of limitless creative potential.” There is another term, though, that OpenAI uses to describe Sora: a potential “world simulator,” one that, over time, could create “highly-capable simulators of the physical and digital world, and the objects, animals and people that live within them.”
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+It’s not there yet. While the available demo videos of Sora at work can feel uncanny and realistic, OpenAI’s technical paper on the model notes its many “limitations.” While Sora can sometimes accurately represent the changes on a canvas when a paint-laden brush sweeps across it or create bite marks in a sandwich after showing a man taking a bite, Sora “does not accurately model the physics of many basic interactions,” such as a glass breaking. People and objects can spontaneously appear and disappear, and like many AI models, Sora can “hallucinate.”
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+Some AI experts, like Gary Marcus, have raised doubts about whether a model like Sora could ever learn to faithfully represent the laws of physics. But just as DALL-E and ChatGPT improved over time, so could Sora. And if its goal is to become a “world simulator,” it’s worth asking: What is the world that Sora thinks it’s simulating?
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+Unknown worlds
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+OpenAI has made that question kind of tough to answer, as the company has not disclosed much about what data was used to train Sora. But there are a couple of things we can infer. First, though, let’s look at how Sora works.
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+Sora is a “diffusion transformer,” which is a fancy way of saying that it combines a couple different AI methods in order to work. Like many AI image generators (think DALL-E or Midjourney), Sora creates order from chaos based on the text prompt it receives, gradually learning how to turn a bunch of visual noise into an image that represents that prompt. That’s diffusion. The transformer bit has to do with how those still images relate to each other, creating the moving video. And Sora, OpenAI says, is designed to be a video-generating generalist.
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+In order to do this, Sora would need a lot of data to learn from, reflecting a wide variety of styles, topics, duration, quality, and aspect ratios. OpenAI said in its technical paper that its development “takes inspiration from large language models which acquire generalist capabilities by training on internet-scale data.” While not directly saying this, it’s probably safe to guess that Sora, too, learned from some training data that was taken from the internet.
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+It’s also possible, argued Nvidia AI researcher Jim Fan, that Sora was trained on a data set that incorporates a large amount of “synthetic” data from the latest version of Unreal Engine, a 3D graphics creation tool that is best known for powering the visuals in video games. OpenAI also has some agreements with companies that could provide large amounts of data for training purposes, like Shutterstock. As for the data that OpenAI did not, in the past, use with the agreement of its creator or publisher, well, there are some pending copyright lawsuits.
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+Biased worlds
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+AI bias is not new, and as Vox has explained before, it can be tough to combat. It creeps into training data and algorithms that power AI models in a lot of different ways. Since we don’t know what data Sora was trained on, and the tool is not available for the public to test, it’s hard to speak in much detail about how biases might be reflected in the videos it creates.
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+Sam Altman, OpenAI’s CEO, has said that he believes AI will eventually learn to rid itself of bias.
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+“I’m optimistic that we will get to a world where these models can be a force to reduce bias in society, not reinforce it,” he said to Rest of World last year. “Even though the early systems before people figured out these techniques certainly reinforced bias, I think we can now explain that we want a model to be unbiased, and it’s pretty good at that.”
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+AI bias and ethics experts like Timnit Gebru have argued that this is exactly what people should not trust AI companies to do, telling the Guardian last year that we shouldn’t simply trust AI systems, or the people behind them, to self-regulate harms and bias.
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+Made-up worlds
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+A lot of the praise for Sora’s demo videos stems from their realism. And that’s exactly why disinformation experts are concerned here.
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+A new study indicates that AI-generated propaganda created by GPT-3 (i.e., not even the newest GPT model powering the current generation of AI tools) can be just as persuasive as human-written content and takes a lot less effort to produce. Now apply that to video. Even without being able to faithfully replicate Earth physics, there are plenty of ways that a tool like Sora could be used, right now, to hurt and mislead people.
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+“This is definitely slick, but I see two main uses: 1) to sell people more stuff (via ads) 2) to make non-consensual/misleading content to manipulate or harass people online,” wrote Sasha Luccioni, an AI research scientist at HuggingFace, on X. “Genuine question - why is everyone so excited?”
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+OpenAI announced Sora a couple weeks after a wave of explicit, nonconsensual deepfakes of Taylor Swift circulated on social media. The images, as 404 media reported, were created with AI by exploiting loopholes in the systems that are designed to prevent exactly this from happening.
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+To address potential biases and misuses of Sora, OpenAI is allowing only a small group of testers to evaluate its safety risks: “We are working with red teamers — domain experts in areas like misinformation, hateful content, and bias — who are adversarially testing the model,” the company said in a statement on X.
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+A world with podcasting AI dogs, I guess
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+Underneath all this are concerns about what Sora and other tools like it will do to the livelihoods of creative professionals, whose work has been used — often without payment — to train AI tools in order to approximate their jobs.
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+Altman, on X, was taking follower suggestions for new Sora videos in order to show off glimpses of our glorious future, which will evidently be these AI-generated podcasting dogs:
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Mohammed Shami ruled out of IPL, to undergo ankle surgery - Shami, who was recently conferred with the Arjuna Award, has 229 Test, 195 ODI and 24 T20 wickets in his decade-long career.
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Focus on young Indian stars as WPL 2nd edition starts with Mumbai-Delhi face-off - The outings of Harmanpreet Kaur, who will have to tame expectations that are generally placed on the title holders, Mandhana, who has the onerous task of landing RCB a maiden title across WPL and IPL, and the UP Warriorz duo of Alyssa Healy and Chamari Athapaththu, two of the best women batters in contemporary game, will be closely watched.
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With eyes on international events, 600 athletes ski down on Gulmarg slopes - Around 600 athletes will participate in events of Alpine ski, Nordic ski, and snow mountaineering
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IND vs ENG Tests | Ranchi pitch in focus as Rohit and Stokes’ men gear up for the crucial fourth Test -
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Zeel Desai in second round in Thailand -
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From The Hindu: National News
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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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Water supplementation for wildlife, fire control measures implemented in Mudumalai Tiger Reserve -
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First phase of study classes for Hajj pilgrimage launched -
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Food safety officials monitoring cotton candy vendors in Tiruchi district - There are six large manufacturers of cotton candy in the district and the officials have asked them to stop production until further notice
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Union Minister Kishan Reddy dismisses proposal for national festival status to Medaram Jatara - The Union Minister said that there is no existing mechanism to declare any festival as a national festival
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From BBC: Europe
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Footballer Dani Alves guilty of nightclub rape - A court in Spain has sentenced Alves, who played for Barcelona and Brazil, to four and a half years.
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Suspect held after students wounded at German school - Five students are said to have been wounded in an apparent knife attack in Wuppertal, western Germany.
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Kremlin lashes out after Biden aims barb at Putin - Moscow responds to Joe Biden’s remarks about the Russian president at a California fundraiser.
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Rosenberg: How two years of war have changed Russia - The BBC’s Russia Editor reports on a catalogue of drama, bloodshed and tragedy since the war began.
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‘I miss you’: Ukraine’s children orphaned by Russian missile - Dozens of children were orphaned the day a missile hit the village of Hroza in October 2023, killing 59.
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From Ars Technica
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Test flights on tap for Space Perspective’s luxury high-altitude balloon - This Florida-based startup wants to fly thousands of customers up to 100,000 feet. - link
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iMessage gets a major makeover that puts it on equal footing with Signal - How Kybers and ratcheting are boosting the resiliency of Apple’s messaging app. - link
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Unvaccinated Florida kids exposed to measles can skip quarantine, officials say - On Tuesday, nearly 20 percent of the school’s 1,067 students were reportedly absent. - link
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Ala. hospital halts IVF after state’s high court ruled embryos are “children” - Anger and uncertainty spread in wake of Friday’s ruling by the state’s Supreme Court. - link
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Blue Origin has emerged as the likely buyer for United Launch Alliance - Pairing of two launch companies could provide more robust competition to SpaceX. - link
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From Jokes Subreddit
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Why did the monk vow off hot dogs? -
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+He rocked up to the hot dog vendor.
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+“Make me one with everything.”
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+And paid with a fifty.
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+
+The vendor pockets the fifty and gives nothing back.
+
+
+“Whoa,’’ says the monk. “Where’s my change?”
+
+
+“Change comes from within,” replies the vendor.
+
+
+The monk pulls a berretta.
+
+
+“Whoa,” said the hot dog vendor, scared shitless. “I thought you were about inner peace!”
+
+
+“This is my inner piece,” says the monk.
+
+
+“No need for violence,” says the vendor. “You can have the fifty back or I can give you something more valuable I found recently.”
+
+
+Curious, the monk asks, “What did you find?”
+
+
+The vendor holds up a small peppermint chocolate with a hole in the middle, holds it up to the sun until a small light shine through the hole, and says “A light in mint”.
+
+
+The Buddhist chips a tooth on the mint and so he goes to the dentist.
+
+
+The dentist goes to give him Novacaine. But the Buddhist declines.
+
+He says “Doc I have been having really strange dreams for the last month”. Doc asks “Ok. What are the dreams?”. Bloke says “It’s like there is a football World Cup going on. Every night I see a football match but with donkeys! It’s driving me crazy! That’s all I think about all day”.
+
+
+Doc smiles, thinks for a while, and says “Ok. Here is a prescription. Take 2 pills tonight before sleeping and you won’t have any of those dreams any longer.”
+
+
+Bloke thanks the doctor profusely, gets up and walks to the door. He pauses, turns around and asks the doc “Doc if it is ok, can I start the medicine from tomorrow night?”. Doc looks puzzled and asks him “Why? Why not tonight?”. Bloke looks down and whispers “Tonight is the final”.
+
+
+
+