Who Is the Most Stressed During COVID-19 Isolation? Data From 27 Countries -
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+****************** ***************************** ****************** ************************ ***** This is old, not peer-reviewed version of the manuscript. For published version, please visit: https://doi.org/10.1111/aphw.12234 *********************************************** ****************** ************** *********** **** To limit the rapid spread of COVID-19, countries have asked their citizens to stay at home. As a result, demographic and cultural factors related to home life became especially relevant to predicting population well-being during isolation. This pre-registered worldwide study analyses the relationship between the number of adults and children in a household, marital status, age, gender, individualism-collectivism and perceived stress. We used the COVIDiSTRESS Global Survey data of 54,245 online participants from 27 countries. The data was collected worldwide between March 30 and April 6, 2020. Our results provide evidence that higher levels of stress are associated with younger age, being a woman, being single, staying with more children, and living in collectivistic cultures. We discuss our findings by emphasizing the need for the public health to focus on both physical and psychological well-being of these groups, as they may be especially susceptible to experiencing elevated levels of stress.
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In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
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+The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
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A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
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+Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
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A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
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+The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
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Can Information about Pandemics Increase Negative Attitudes toward Foreign Groups? A Case of COVID-19 Outbreak -
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+Pathogen threat can translate into a willingness to distance oneself from others on a psychological level. Building on this notion, we predicted that the ongoing coronavirus pandemic can affect attitudes toward foreign nationalities. We explored the intergroup consequences of the current epidemiological situation in two studies involving a total of 652 participants. In correlational Study 1, we showed a positive relationship between media exposure in the United Kingdom (UK) and in Poland, and prejudice to four foreign nationalities. Study 2 showed that negative affect toward Italians (i.e., a nation struggling with the most severe COVID-19 outbreak at the time of the study) was indirectly predicted by exposure to news about coronavirus through the increase in anxiety, but this effect was not observed when a generalized measure of prejudice was considered. Overall, our studies revealed that prejudice and anxiety are sensitive to the current epidemiological situation, and our findings suggest that the outbreak of COVID-19 may translate into severe social consequences and increased psychological distancing to nations most affected by the pandemic.
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Stress and worry in the 2020 coronavirus pandemic: Relationships to trust and compliance with preventive measures across 48 countries in the COVIDiSTRESS global survey -
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+The COVIDiSTRESS global survey collects data on early human responses to the 2020 COVID-19 pandemic from 173,429 respondents in 48 countries. The open science study was co-designed by an international consortium of researchers to investigate how psychological responses differ across countries and cultures, and how this has impacted behaviour, coping and trust in government efforts to slow the spread of the virus. Starting in March 2020, COVIDiSTRESS leveraged the convenience of unpaid online recruitment to generate public data. The objective of the present analysis is to understand relationships between psychological responses in the early months of global coronavirus resreictions, and help understand how different government measures succeed or fail in changing public behaviour. There were variations between and within countries. Although Western Europeans registered as more concerned over COVID-19, more stressed, and having slightly more trust in the governments’ efforts, there was no clear geographical pattern in compliance with behavioural measures. Detailed plots illustrating between-countries differences are provided. Using both traditional and Bayesian analyses, we found that individuals who worried about getting sick worked harder to protect themselves and others. However, concern about the coronavirus itself did not account for all of the variance in experienced stress during the early months of coronavirus restrictions. More alarmingly, such stress was associated with less compliance. Further, those most concerned over the coronavirus trusted in government measures primarily where policies were strict. While concern over a disease is a source of mental distress, other factors including strictness of protective measures, social support, and personal lockdown conditions must also be taken into consideration to fully appreciate the psychological impact of COVID-19 and to understand why some people fail to follow behavioral guidelines intended to protect themselves and others from infection.
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A Technological View of Artificial Intelligence in US Healthcare -
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+Since the onset of COVID-19 in the United States, hospitals became increasingly burned out—nurses reported higher levels of stress, exhaustion, and a depressive mood (Zerbini 20). Patients flooded operating rooms, ventilators were in high-demand and medical professionals worked long hours. The use of Artificial Intelligence (AI) has made a large difference. Artificial Intelligence, as defined by leading technology company IBM, is a field that combines computer science and robust datasets to enable problem-solving to make predictions or classifications (19). A researcher from the University College London and the Lancet Digital Health found that as a result, AI usage in healthcare has significantly reduced the burden on medical professionals (McCall 20). Founder of the Dutch digital health company, Sonohaler, Dr. Bohr explains that Artificial Intelligence is increasingly being used in healthcare and is expected to cut healthcare costs by 150 billion dollars by 2026. In addition, it is forecasted that the AI-healthcare market is expected to grow to 6.6 billion dollars (20). However, there are risks and drawbacks. From the University of Cambridge, in the United Kingdom, Dr. Hamid explains that AI in healthcare offers various risks and opportunities (18). As artificial intelligence is utilized at a higher frequency in the healthcare industry, it’s important to make considerations regarding its effectiveness and its future implementation. While AI in the US healthcare industry can pose potential cybersecurity risks, it serves as an important technological advancement for improving patient care such as monitoring diabetes and improving patient experience but important considerations should be made regarding the safe utilization, patient opinion, and development of artificial intelligence as it is used more in healthcare.
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Healthcare system barriers impacting the care of Canadians with myalgic encephalomyelitis: a scoping review -
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+Background: Myalgic encephalomyelitis (ME, also known as chronic fatigue syndrome or ME/CFS) is a debilitating, complex, multi-system illness. Developing a comprehensive understanding of the multiple and interconnected barriers to optimal care will help advance strategies and care models to improve quality of life for people living with ME in Canada. Objectives: To: (1) identify and systematically map the available evidence; (2) investigate the design and conduct of research; (3) identify and categorize key characteristics; and (4) identify and analyze knowledge gaps related to healthcare system barriers for people living with ME in Canada. Methods: The protocol was preregistered in July 2022. Peer-reviewed and grey literature was searched, and patient partners retrieved additional records. Eligible records were Canadian, included people with ME/CFS and included data or synthesis relevant to healthcare system barriers. Results: In total, 1821 records were identified, 406 were reviewed in full, and 21 were included. Healthcare system barriers arose from an underlying lack of consensus and research on ME and ME care; the impact of long-standing stigma, disbelief, and sexism; inadequate or inconsistent healthcare provider education and training on ME; and the heterogeneity of care coordinated by family physicians. Conclusions: People living with ME in Canada face significant barriers to care, though this has received relatively limited attention. This synthesis, which points to several areas for future research, can be used as a starting point for researchers, healthcare providers and decision-makers who are new to the area or encountering ME more frequently due to the COVID-19 pandemic.
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Clinical Features and Vaccine Efficacy Analysis of COVID-19 patients in a Chongqing Shelter hospital in 2022 -
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+Background: The long term impact of coronavirus disease 2019 (COVID19) on many aspects of society emphasizes the necessity of vaccination and nucleic acid conversion time as markers of prevention and diagnosis. However, little research has been conducted on the immunological effects of vaccines and the influencing factors of virus clearance. Epidemiological characteristics and factors related to disease prognosis and nucleic acid conversion time need to be explored. Design and participants: We reviewed published documentation to create an initial draft. The data were then statistically evaluated to determine their link. Given that a Chongqing shelter hospital is typical in terms of COVID-19 patients receiving hospital management and treatment effects, a retrospective analysis was conducted on 4,557 cases of COVID19 infection in a shelter hospital in Chongqing in December 2022, which comprised 2,291 males and 2,266 females. The variables included age, medical history, nucleic acid conversion time, vaccination status, and clinical symptoms. Results: Univariate survival analysis using the Log-rank test (P < 0.05) showed that factors such as age significantly affected nucleic acid conversion time. COX regression analysis indicated a significant association between a history of hypertension and nucleic acid conversion time, which had a hazard ratio of 0.897 (95% CI: 0.811 to 0.992). A statistically significant difference was observed between vaccinated and unvaccinated infected individuals in terms of the presence of symptoms such as cough and sensory system manifestations (P < 0.05). Conclusion: The effect of vaccination against COVID19 on symptoms such as coughing, nasal congestion, muscle aches, runny nose, and sensory system symptoms in COVID19 patients was determined. Typical symptoms, such as runny nose, were generally higher in vaccinated than in unvaccinated ones; previous hypertension was an influential factor in nucleic acid conversion time in patients with COVID19 infection.
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Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelial cells -
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+Respiratory syncytial virus (RSV) can cause severe disease especially in infants; however, mechanisms of age-associated disease severity remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigated whether age regulates RSV epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibited cytopathy and mucus hyperplasia, and neonatal epithelium had more robust viral spread and inflammatory responses than adult epithelium. Mechanistically, RSV-infected neonatal ciliated cells displayed age-related impairment of STAT3 activation, rendering susceptibility to apoptosis, which facilitated viral spread. In contrast, SARS-CoV-2 infection of ciliated cells had no effect on STAT3 activation and was not affected by age. Taken together, our findings identify an age-related and RSV-specific interaction with neonatal bronchial epithelium that critically contributes to severity of infection, and STAT3 activation offers a potential strategy to battle severe RSV disease in infants.
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“Yeah, this graph doesn’t show that”: Analysis of Online Engagement with Misleading Data Visualizations -
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+Attempting to make sense of a phenomenon or crisis, social media users often share data visualizations and interpretations that can be erroneous or misleading. Prior work has studied how data visualizations can mislead, but do misleading visualizations reach a broad social media audience? And if so, do users amplify or challenge misleading interpretations? To answer these questions, we conducted a mixed-methods analysis of the public’s engagement with data visualization posts about COVID-19 on Twitter. Compared to posts with accurate visual insights, our results show that posts with misleading visualizations garner more replies in which the audiences point out nuanced fallacies and caveats in data interpretations. Based on the results of our thematic analysis of engagement, we identify and discuss important opportunities and limitations to effectively leveraging crowdsourced assessments to address data-driven misinformation.
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COVID-19 VACCINE ACCEPTANCE AND HESITANCY IN GHANA: A SYSTEMATIC REVIEW -
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+The propensity to accept vaccines and factors that affect vaccine acceptance and hesitancy will determine the overall success of the COVID-19 vaccination program. Therefore, it is essential for countries to understand the factors that influence vaccine acceptance and hesitancy in order to prevent further future shocks, and it is necessary to have a thorough understanding of these factors. This study, as a result, aims to review selected published works in the domain of study and conduct valuable analysis to determine the most influential factors in COVID-19 vaccine acceptance and hesitancy in Ghana. The review also explored the acceptance rate of COVID-19 vaccines in Ghana. We selected published works from 2021 to April 2023 and extracted, analyzed, and summarized the findings based on the key factors that influence COVID-19 vaccine acceptance and hesitancy in Ghana, the acceptance rate in Ghana, the demographic factors that are often examined, and the study approach used to examine these factors. The study found that positive vaccination perception, safety, belief in vaccine efficacy, knowledge of COVID-19, and a good vaccine attitude influence COVID-19 vaccine acceptance in Ghana. The negative side effects of the vaccines, mistrust in the vaccine, lack of confidence in the safety of the vaccines, fear, and spiritual and religious beliefs all played significant roles in the factors influencing COVID-19 vaccine hesitancy. The demographic parameters frequently included in these studies that have a significant impact include educational attainment, gender, religious affiliation, age, and marital status.
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Religious People View Both Science and Religion as Less Epistemically Valuable Than Non-Religious People View Science -
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+Religious people typically report low perceived conflict between science and religion, but also less trust in science than non-religious people. We address these puzzling findings using insights from goal systems theory. Goal systems theory suggests that, when people have more means of achieving a goal, they perceive each individual means as less instrumental. We translate this “instrumentality hypothesis” to differences in how religious and non-religious people perceive science and religion. Religious people—who use both science and religion as means to gain knowledge—may perceive both as moderately instrumental, and as less instrumental than non-religious people, who do not use religion as a source of knowledge. We support the instrumentality hypothesis in studies where participants evaluate the capacity of science and religion to explain extraordinary phenomena (Study 1), fill gaps in knowledge (Study 2), answer life’s big questions (Study 3), and to help avoid COVID-19 infection (Study 4). We also find that non-religious people overperceive religious people’s trust in religion and underperceive religious people’s trust in science as sources of knowledge (Study 5). Our studies suggest that non-religious people think that religion specifically deters trust in science, but instead, religious people typically avoid extreme epistemic reliance on any single source of knowledge.
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COVID-19 ORF3a Viroporin Influenced Common and Unique Cellular Signalling Cascades in Lung, Heart and Brain Choroid Plexus Organoids with Additional Enriched MicroRNA Network Analyses for Lung and Brain Tissues -
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+Tissue specific implications of SARS-CoV-2 encoded accessory proteins are not fully understood. SARS-CoV-2 infection can severely affect three major organs - the heart, lung, and brain. We analysed SARS-CoV-2 ORF3a interacting host proteins in these three major organs. Further we identified common and unique interacting host proteins, their targeting miRNAs (lung and brain), and delineated associated biological processes reanalysing RNA-seq data from the brain (COVID-19 infected/uninfected Choroid Plexus Organoids study), lung tissue from COVID-19 patients/healthy subjects, and cardiomyocyte cells based transcriptomics analyses. Our in silico studies showed ORF3a interacting proteins could vary depending upon tissues. Number of unique ORF3a interacting proteins in brain, lung and heart were 10, 7 and 1 respectively. Though common pathways influenced by SARS-CoV-2 infection were more, unique 21 brain and 7 heart pathways were found. One unique pathway for heart was negative regulation of calcium ion transport. Reported observations of COVID-19 patients with the history of hypertension taking calcium channel blockers (CCBs) or dihydorpyridine CCBs had elevated rate of intubation or increased rate of intubation/death respectively. Also likelihood of hospitalization of chronic CCB users with COVID-19 was more in comparison to long term Angiotensin Converting Enzyme inhibitors/Angiotensin Receptor Blockers users. Further studies are necessary to confirm this. miRNA analysis of ORF3a interacting proteins in brain and lung revealed, 2 of 37 brain miRNAs and 1 of 25 lung miRNAs with high degree and betweenness indicating their significance as hubs in the interaction network. Our study could help in identifying potential tissue specific COVID-19 drug/drug repurposing targets.
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Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2 -
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+Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fc{gamma}-receptor (Fc{gamma}R)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is not clear. Here we studied 1,213 S-binding mAbs derived from longitudinal sampling of B-cells collected from eight COVID-19 convalescent patients and identified 72 (5.9%) mAbs that enhanced infection in a VSV-SARS-CoV-2-S-Wuhan pseudovirus (PV) assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least five months post-infection. Enhancement of PV infection by NTD-binding mAbs was not observed using intestinal (Caco-2) and respiratory (Calu-3) epithelial cells as infection targets and was diminished or lost against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire from two of the convalescent subjects identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum (i.e., functionally secreted antibody). Functional analysis of these mAbs demonstrated robust activation of Fc{gamma}RIIIa associated with antibody binding to recombinant S proteins. Taken together, these findings suggest functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display diverse attributes that include Fc{gamma}R activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.
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ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) - Condition: Covid19 Interventions: Other: Placebo; Drug: Metformin Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center Recruiting
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Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom - Condition: Post-COVID-19 Syndrome Interventions: Behavioral: Exercise Therapy; Behavioral: Psychotherapy Sponsors: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research Not yet recruiting
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A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19 - Condition: COVID-19 Interventions: Drug: HH-120; Drug: placebo Sponsor: Huahui Health Completed
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A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2 - Conditions: COVID-19; SARS-CoV-2 Interventions: Drug: VYD222; Drug: Normal saline Sponsor: Invivyd, Inc. Recruiting
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Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial - Condition: COVID-19 Interventions: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention Not yet recruiting
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Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions: Vaccine-Preventable Diseases; COVID-19 Pandemic; Health-Related Behavior; Health Knowledge, Attitudes, Practice; Narration Interventions: Behavioral: Baseline surveys; Behavioral: Digital Storytelling Intervention; Behavioral: Information Control Intervention Sponsors: Arizona State University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Not yet recruiting
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Non-pharmacological and TCM-based Treatment for Long COVID Symptoms - Condition: Long Covid19 Intervention: Behavioral: Acupuncture and TCM-based lifestyle management Sponsor: The Hong Kong Polytechnic University Not yet recruiting
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Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions: COVID-19 Infection; COVID-19 Vaccine Adverse Reaction Interventions: Biological: LEM-mR203; Biological: Placebo Sponsor: Lemonex Not yet recruiting
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SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People - Condition: COVID-19 Intervention: Drug: SA55 nasal spray Sponsor: Sinovac Life Sciences Co., Ltd. Recruiting
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A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects - Condition: COVID-19 Intervention: Drug: STI-1558 Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd. Not yet recruiting
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A Study to Determine the Tolerability of Intranasal LMN-301 - Condition: COVID-19 Intervention: Biological: LMN-301 Sponsor: Lumen Bioscience, Inc. Not yet recruiting
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Mind Body Intervention for Long COVID - Conditions: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul Intervention: Behavioral: Mind Body Intervention #1 Sponsor: Beth Israel Deaconess Medical Center Not yet recruiting
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Impact of Covid-19 Aerosol Box On Intubation Success Rate - Condition: Intubation; Difficult or Failed Interventions: Device: Intubation using aerosol box; Device: Intubation without aerosol box Sponsor: Universiti Kebangsaan Malaysia Medical Centre Completed
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Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children - Conditions: Fever After Vaccination; Fever; Seizures Fever Interventions: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Routine Childhood Vaccinations Sponsors: Duke University; Kaiser Permanente; Columbia University; Children’s Hospital Medical Center, Cincinnati; Centers for Disease Control and Prevention Not yet recruiting
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SA55 Injection Phase II Study in the Treatment of Mild/Moderate COVID-19 Patients - Condition: Infection of Upper Respiratory Tract Caused by 2019-nCoV Intervention: Drug: SA55 Injection Sponsor: Sinovac Life Sciences Co., Ltd. Recruiting
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From PubMed
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Therapeutic benefits of prophetic medicine remedies in treating hematological diseases (A review article) - Hematological disorders are common medical ailments constituting an important cause of morbidity and mortality worldwide, which may be managed efficiently using different prophetic medicine remedies as adjuvants to current therapeutics. Prophetic medicine includes the body of knowledge about medicine that has been derived from the deeds, customs (sunnah), ahadith (sayings), actions, and agreements of Prophet Muhammad, peace be upon him. This review article aims at exploring the magnitude of…
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The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease - Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2. While numerous crystal structures of the SARS-CoV-2 main…
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Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study - CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.
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A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir - During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have…
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Identification of γ-Fagarine as a novel antiviral agent against respiratory virus (hMPV) infection - Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloida isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to…
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Structural basis for translation inhibition by MERS-CoV Nsp1 reveals a conserved mechanism for betacoronaviruses - All betacoronaviruses (β-CoVs) encode non-structural protein 1 (Nsp1), an essential pathogenicity factor that potently restricts host gene expression. Among the β-CoV family, MERS-CoV is the most distantly related member to SARS-CoV-2, and the mechanism for host translation inhibition by MERS-CoV Nsp1 remains controversial. Herein, we show that MERS-CoV Nsp1 directly interacts with the 40S ribosomal subunit. Using cryogenic electron microscopy (cryo-EM), we report a 2.6-Å structure of the…
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Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm - CONCLUSIONS: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm.
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SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression - Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. miRNAs inhibit translation initiation of their target mRNAs by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5´-cap structure. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for…
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De novo design of a stapled peptide targeting SARS-CoV-2 spike protein receptor-binding domain - Although effective vaccines have been developed against SARS-CoV-2, many regions in the world still have low rates of vaccination and new variants with mutations in the viral spike protein have reduced the effectiveness of most available vaccines and treatments. There is an urgent need for a drug to cure this disease and prevent infection. The SARS-CoV-2 virus enters the host cell through protein-protein interaction between the virus’s spike protein and the host’s angiotensin converting enzyme…
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Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers - An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT(50) values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential…
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Responses of patients with cancer to mRNA vaccines depend on the time interval between vaccination and last treatment - CONCLUSION: Accordingly, our data support that timing of mRNA-based therapy is critical and we suggest that at least a 6-months or 12-months waiting interval should be observed before mRNA vaccination in systemically treated patients.
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Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors - A collaborative, open-science team undertook discovery of novel small molecule inhibitors of the SARS-CoV-2 nsp16-nsp10 2’-O-methyltransferase using a high throughput screening approach with the potential to reveal new inhibition strategies. This screen yielded compound 5a, a ligand possessing an electron-deficient double bond, as an inhibitor of SARS-CoV-2 nsp16 activity. Surprisingly, X-ray crystal structures revealed that 5a covalently binds within a previously unrecognized cryptic pocket…
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Cinnamaldehyde inhibits cytokine storms induced by the ORF3a protein of SARS-CoV-2 via ROS-elimination in activated T cells - Cytokine storms are the cause of complications in patients with severe COVID-19, and it becomes the target of therapy. Several natural compounds were selected to screen the inhibitory effect on T-cell proliferation by Fluorescence-Activated Cell Sorting (FACS) and cytokine production by enzyme-linked immunosorbent assay (ELISA). Open reading frame 3a (ORF3a) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the specific T-cell activation model in vivo and in vitro. The…
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How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery - The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21st century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed…
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Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection - TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to…
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From Patent Search
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Rishi Sunak’s Self-Serving Climate Retreat - The British Prime Minister has rolled back the country’s policies on reducing emissions. To what end? - link
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Sikh Separatism and the Brewing Conflict Between Canada and India - Did India carry out or abet the assassination of a Sikh leader on Canadian soil? - link
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The World According to Elon Musk’s Grandfather - What happened to antisemitic rants before social media. - link
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House Republicans Refuse to Host Zelensky Because They’re Too Busy Fighting One Another - Reflections on a day of self-parody on Capitol Hill. - link
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How the U.S. Lifted Children Out of Poverty and Then Threw Them Back Into It - After the expanded child tax credit expired, America’s child poverty rate doubled. Why was that policy so successful, and what can be done to fill the gap? - link
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From Vox
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Another Covid-19 winter is coming. Here’s how to prepare. -
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+The US government has approved new Covid-19 vaccines and is shipping out free tests ahead of a winter wave of infections. | Yuichiro Chino/Getty Images
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+Free Covid tests are back — and new vaccines are at your local pharmacy too.
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+The United States is in the midst of its worst Covid-19 wave since the beginning of the year and finally deploying some of its most powerful tools against it. The next step will be getting as many Americans as possible to take advantage of them.
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+Last week, the US government approved updated Covid-19 vaccines and advised that effectively every American other than young infants receive one. Starting next week, it will again ship out free Covid-19 tests to any American who orders them. Some local hospital systems have begun reinstituting mask mandates, though widespread requirements are unlikely given how politically toxic masking rules have become. Individuals, particularly those with compromised immune systems, are still advised to wear masks in times of high spread.
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+Covid-19’s spread has been increasing since the middle of the summer, picking up in late June based on wastewater surveillance and climbing steadily through August.
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+Hospitalizations increased in tandem, particularly among the older and more vulnerable populations. The hospitalization rate for Americans over 70 more than doubled from early July to early September. (Younger age groups were less affected by severe disease, which follows the coronavirus’s pattern since it first emerged.) Deaths have risen as a result: The number of weekly Covid-19 deaths had dipped below 500 for the first time in early July but topped 900 again in late August.
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+The summer wave may finally be cresting, however. The amount of Covid-19 detected in wastewater was flat from August 30 to September 6 and then dipped slightly the week of September 13, per Biobot Analytics. Hospitalizations are still up over the past two weeks, but that is a lagging indicator; if spread is indeed slowing as the wastewater data suggests, indicators of serious illness should start to plateau and then decline in the coming weeks.
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+Still, as I wrote in late July, this summer’s increase in Covid-19 activity may merely be a preview of coming attractions. Recent mutations have allowed the coronavirus to regain some of its transmissibility. Public health officials are still expecting a winter wave of viral activity — not only from Covid but influenza and respiratory syncytial virus, or RSV, as well.
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+The good news is that, at this point, we know the playbook for slowing viral spread, and the government is taking steps to help people follow it. And there are some indications that the US public, in spite of inevitable and understandable pandemic fatigue, is taking the start of this viral season seriously. If people do avail themselves of new vaccines and free tests, the country will be in a better position to weather any winter surge.
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+Updated Covid-19 vaccines and more free tests are now available
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+Vaccination is the most important step any person can take to protect themselves this winter. Updated flu shots are already available, and Pfizer and Moderna have formulated new versions of the mRNA Covid-19 vaccines that proved so effective in preventing deaths and hospitalizations. The FDA gave them its approval last week.
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+The CDC has advised that every American older than 6 months should receive one shot of the updated Covid-19 vaccines. As public health experts told Vox’s Rachel DuRose, there is a growing expectation that an annual Covid shot will be recommended to most Americans in the years to come.
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+For this year’s updated shots specifically, the CDC recommends:
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+All Americans 5 years of age and older receive one dose of either the Pfizer or Moderna vaccine, at least two months after their most recent shot.
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+Americans 6 months to 4 years who have not been previously vaccinated should receive either three doses of Pfizer or two doses of Moderna.
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+Americans 6 months to 4 years who have already been vaccinated should receive at least one dose of Pfizer or Moderna.
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+The Novavax vaccine, which uses a protein-based formulation instead of the mRNA technology, is also available as an alternative for people who choose not to or are unable to receive the Pfizer and Moderna vaccines. Most people should be able to get both the flu and Covid shots at the same time, according to government health officials.
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+Most health insurers will cover a new Covid-19 vaccine for free, although it is worth checking with your plan in advance; there have been reports of people facing $100 or more in out-of-pocket costs when they show up at a pharmacy. Uninsured people or people whose health plan won’t cover the vaccine can still get a free dose from certain health centers, their state or local health department, or at pharmacies participating in the federal program to provide free vaccines.
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+The Biden administration has also announced that every American household will be eligible to order up to four free at-home Covid-19 rapid test kits starting on September 25. The government had previously made tests available for free to everyone in the thick of the pandemic, but rolled back eligibility to only uninsured Americans earlier this year.
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+The administration is trying to get ahead of this year’s cold-and-flu season, after last year’s proved so challenging to the health system. As Dr. William Schaffner of Vanderbilt, formerly the medical director of the National Foundation for Infectious Diseases, told me, last year’s struggles were a function of biology. Flu and RSV in particular spiked much earlier in the fall than they usually did before the pandemic, and the population appeared vulnerable to them after those viruses had been largely dormant while Covid was spreading widely.
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+But this year, Schaffner said, the viruses are less likely to take us by surprise. Instead, the challenge for 2023 will be whether the health system can marshal a strong response to a viral surge that it’s already anticipating. Giving away free tests, for example, should grant people the ability to identify when they are sick with Covid-19, so they can isolate and avoid spreading the virus to other people.
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+The vaccines are the most important tool available to preventing hospitalizations and deaths — and perhaps the area where the government’s test will be greatest, given the anti-vaccine movement that flourished during the pandemic. Less than 1 in 5 Americans got previously updated versions of the vaccine that targeted the omicron variant. Even for people over 65, who are most vulnerable, less than half received the bivalent booster.
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+Based on that low uptake, many public health experts have been fearful that Americans will be skeptical about any future Covid-19 shots. But there is some evidence that the public, perhaps informed by the spread of the coronavirus in the late summer, is more receptive to the new Covid shots heading into this fall and winter.
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+A little more than half of Americans said they were either very or somewhat interested in receiving the updated vaccines, according to a new Reuters/Ipsos poll. That may reflect an overall increase in concern about Covid-19: A recent Gallup survey found that the share of Americans who believe the pandemic is getting worse had grown from 5 percent in May to 30 percent in September.
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+Those numbers indicate public health officials may find Americans more receptive to interventions like testing and vaccines; at the same time, the government is doing its part to make those resources more easily accessible. The opportunity is there for the US to chart a better path out of the pandemic. The next few months will determine whether we can take advantage of it.
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That “free” iPhone 15 could cost a fortune -
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+It pays off to carefully consider your options when taking advantage of new phone deals. | Justin Sullivan/Getty Images
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+How to buy a new phone for less without paying more.
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+Are you in the market for a new phone, or just want to get the latest and greatest? Either way, you’re sure to come across seemingly incredible offers from major carriers offering heavily discounted if not free phones, including the highest-end versions of the newest models. With the new iPhone 15 hitting the shelves, now might be a great time to upgrade what you’ve got. And you’ll want to get the best price for it, of course.
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+That’s easier said than done these days. The major three carriers — AT&T, T-Mobile, and Verizon — are offering up to $1,000 off the price of iPhones and Androids, which covers the price of most of them entirely, from an iPhone 15 Pro to a Samsung Galaxy Z Flip 5. Their manufacturers are offering big (though not as big) discounts, too. Meanwhile, a herd of low-cost carriers are offering phones for full price, but throwing in big service discounts with a purchase.
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+For most of us, a phone is an important and expensive purchase. Any discount is welcome, and free is very tempting. But the biggest discounts might not be the best deals, depending on your needs and, of course, the desires of whoever’s offering them in the first place.
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+Why are the three major carriers offering me so much more than everyone else?
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+Back in the day, your iPhone purchase price was largely subsidized by your carrier when you agreed to a years-long contract. End that contract early and you were on the hook for what could be a considerable cancellation fee. As iPhone prices have gone up, those arrangements have been phased out … sort of. Instead, your phone purchase is financed by the carrier, interest-free, and you’re paying it off in monthly installments on your phone bill for the next several years. But the carrier also gives you bill credits that can be as much as those installments, making it seem as though the phone is cheap or free.
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+Here’s the catch: To get the full discount, you have to trade in your old phone, and in most cases you’ll get a smaller discount for older or broken devices; if you switch to a different carrier or downgrade your plan before those installments end, you’re on the hook for paying whatever’s left — no more bill credits for you. While AT&T evenly distributes the entire discount across a 36-month term, Verizon and T-Mobile give you a chunk of your credit upfront (that’s the trade-in) and finance the remainder. That means you’ll owe them less money if you change providers or plans early. If you stay with the same carrier and plan until the phone is paid off, it won’t make a difference.
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+“It may be a great deal, especially if you were getting ready to upgrade,” Teresa Murray, consumer watchdog for Public Interest Research Group, told Vox. “But not necessarily for everyone.”
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+It is great for the carriers. Even if they lose money upfront by funding part of those phones (they make some money back from selling the trade-ins off to refurbishers, so they’re not losing the entire discount here), they make it back by keeping their customers effectively locked in for several years and upselling them on the pricier plans they have to get to qualify for the full discount. The minor differences between the three carriers’ offers might also be enough to acquire new customers. T-Mobile, for example, gives bill credits for 24 months while the others do it for 36, which means you’re on the hook for a year less. AT&T’s deal extends to some of its cheaper (but not its cheapest) plans. Verizon will give new customers full credit for any iPhone trade-in, regardless of age or condition; the others give less for older or damaged phones — that’s why these deals always say you get “up to” a certain amount off.
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+For carriers, this is where the real money is. When people aren’t buying as many phones as often as they used to, offering a “free” new phone is a great way to give them a push and get them on the most expensive plan.
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+“These companies don’t offer the supposed free iPhones because they want to be nice to you,” Murray said. “They do it for competitive reasons. They want your business long term. And they may want add-ons to make their money back, because nothing’s free.”
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+How do I get these discounts?
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+You can buy the phone directly from the carrier, either online or in-store. You may also be able to get them through other sellers, like the manufacturers. Apple, for instance, has “carrier deals” on its iPhone salespage that are, for the most part, the same as what those carriers are offering on their own sites. (You have to go directly to Verizon to get the new customer discount, for example.)
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+Apple’s site might be a good way to compare the three carriers’ deals, by the way. Some might offer you more for an older device than the others. An iPhone 11 Pro, for instance, will get you the maximum $999 credit from T-Mobile, but only $830 from AT&T and Verizon. Factor in the price of the monthly plans — including taxes and fees, which may add to that cost — you have to be on to get that seemingly better deal.
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+If you buy the phone from Apple’s store, make sure you hit the “finance” option, then “carrier,” and then — and this is very important because you risk not getting the deal if you don’t — make sure you expand, read, and follow your carrier’s “deal details” to the letter. That means choosing the carrier’s installment program at purchase and subscribing to an eligible plan.
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+Why are manufacturers offering any discounts at all when they don’t have cellphone plans to sell me on?
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+You don’t have to buy a phone through a carrier. You can get it directly from a store like Best Buy or a manufacturer, and you won’t be tied to a specific plan or even a carrier if you do. You might not even have to pay full price.
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+That’s because device makers also want people to buy more of their phones more often, so they offer discounts if you trade in your old device. The amount of said “discount” depends on the make and condition of what you’re trading in. The highest-end and newest phone will get you the biggest credit (an iPhone 14 Pro Max currently gets you $650 from Apple and $600 from Samsung, for instance). An older or broken device will get a lot less. An iPhone 6 in great condition will get you $200 from Samsung and “free recycling” (also known as $0) from Apple. Why is Samsung offering more money for an Apple phone than Apple is? Probably because it’s hoping that’ll pay off in the long run if it converts an Apple customer to Samsung.
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+And no, the manufacturers aren’t losing as much (or possibly anything) from those credits as you might think, because they turn around and sell the old phones off to refurbishers. And if you have an Apple Card, you’ll get 3 percent cashback on your Apple purchase because Apple is incentivizing people to get its credit card and spend money with it — money that Apple then gets a cut of.
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+What are “low-cost carriers” and why should I consider them at all when they’re making me pay (gasp) full price?
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+If you don’t need a cellphone plan with all the bells and whistles, you might want to consider a cheaper alternative. Mobile virtual network operators like Mint Mobile and Visible offer pre-paid plans and use the major carriers’ networks. Some are owned by those major carriers; others pay for the use of their networks. You can get plans with data caps or, for slightly more, unlimited plans. The drawback: You might find that your data speeds aren’t as good as with the major carriers, which understandably give their customers priority. So if you need high data speeds and live in a congested area, this might not be the carrier for you.
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+“The comparison I think about is shopping name brands versus store brands,” Murray said.
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+Tom’s Guide and Consumer Reports have some good reviews of these carriers’ pros and cons. Just make sure the prices are still current, since Consumer Reports’ is from 2022 and things may have changed.
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+The low-cost carriers may offer barely there deals, like a few months of free service, if you buy phones through them. But if you have a device to trade in, you’re probably best served by buying it from the manufacturer and getting a trade-in credit, then taking it to a low-cost carrier and signing up.
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+Why wouldn’t I want the best possible deal? A free phone is a free phone!
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+If the conditions are right, then the major carrier deals are mutually beneficial. If you’re planning to stick with a carrier for at least a few years, want or need the most expensive plans with the various bells and whistles, and have a relatively new model phone to trade in, congratulations: Your phone is free, aside from any taxes and activation or connection fees! (One exception: Verizon, which is offering existing customers less than the other two, and new customers potentially more — they can trade in any iPhone in any condition and still get the full $1,000 credit.)
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+But if you don’t want to be tied to one carrier or don’t need everything the priciest plans offer, you might end up paying less in the end when you pay more in the beginning. The money you save with a cheaper plan over the next two or three years may well be more than what the major carriers offered.
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+That said, trying to do the math and keep track of all of those deals to figure out where you come out on top is tricky. WalletHub has a cellphone savings calculator that makes this easier — just make sure that you’re putting in the total price, including taxes and fees, of the devices and monthly charges.
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+What if I need a phone but don’t need the latest model?
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+Now that the 15s are out, new 14s are outdated and cost less. You can still get them for free or at a reduced cost through the same carrier deals if you jump through all the aforementioned hoops, including trading in your old phone.
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+But don’t sleep on refurbished models, which most manufacturers and carriers offer. You won’t get the trade-in deals with them, but they are cheaper to buy outright than the new devices. Apple’s refurbished devices look brand new, have some new components (like the battery), and come with the same year-long warranty the new devices do.
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+In the end, carriers and device manufacturers hire lots of people to figure out the best deal for them. Make sure it’s the best deal for you, too.
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Why Volodymyr Zelenskyy had to go to Washington -
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+Ukrainian President Volodymyr Zelenskyy following a meeting with Senate Minority Leader Mitch McConnell (R-KY), Senate Majority Leader Chuck Schumer (D-NY), and a bipartisan group of senators on September 21, 2023 in Washington, DC. | Chip Somodevilla/Getty Images
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+The Ukrainian president seeks support for the same fight, but under different circumstances.
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+Ukrainian President Volodymyr Zelenskyy is visiting the White House and Congress on Thursday — but under decidedly different circumstances than when he arrived less than a year ago.
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+Zelenskyy is seeking to shore up support as Ukraine is struggling to achieve a breakthrough in its counteroffensive. The objective Ukraine is targeting — to essentially divide up Russian-controlled territory — was always going to be extremely challenging. And now time is running short, as fall turns to winter, when fighting will become much more difficult. At the same time,Russia has continued bombarding Ukraine, overnight unleashing missiles on major cities like Kyiv and Kharkiv, and even Lviv, in the west, far from the front lines. Those attacks damaged energy infrastructure, an echo of Moscow’s campaign last year to try to undermine Ukraine’s economy and its population’s resolve.
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+Russia’s invasion continues, as does the suffering and devastation that it has wrought. That hasn’t changed, but the future trajectory of the conflict is a lot less clear — which is why Zelenskyy, after trying to rally the world to Ukraine’s cause at the United Nations in New York, is meeting face-to-face with his backers in Washington.
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+That may be the biggest difference from last year: the question-mark over future Western support for Ukraine, and what that might mean for Ukraine’s ability to sustain its defense against Russia. On the whole, the United States and Europe have continued to provide financially and militarily to Ukraine. Yet the splits are beginning to show. It’s not clear how big or significant they will be, but Zelenskyy doesn’t want to reach the point where Ukraine has to find out.
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+The political dynamics abroad may change the course of war in Ukraine
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+Some House Republicans remain optimistic; Michael McCaul (R-TX), the House chair of the Foreign Affairs Committee, said Thursday that “we will get it done.”
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+But even if this Ukraine aid package does get done, it will likely come after more short-term drama, and maybe even a government shutdown, which is probably not going to make any partners who rely on the US confident about its reliability.
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+And Zelenskyy apparently made no secret to lawmakers as to how much Kyiv relies on that support. As Senate Majority Leader Chuck Schumer (D-NY) said in Thursday floor remarks: “To quote President Zelenskyy in the room, and this is a quote, he said: ‘If we don’t get the aid, we will lose the war.’ That’s a quote from President Volodymyr Zelenskyy. That’s how stark the issue is.”
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+This funding request is also not likely the last US political hurdle for Ukraine. The GOP primary debates have showcased the views of Ukraine skeptics, including the frontrunner, Donald Trump, who claims he has a plan to end the war. This strain in the GOP, then, is probably not going away, and may morph beyond battles over Ukraine funding into fundamentally questioning the US’s position on Ukraine. As Zelenskyy said in an interview this week, if Trump has a peace plan, he should share it. But, Zelenskyy added: If “the idea is how to take the part of our territory and to give Putin, that is not the peace formula.”
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+There are also some worrisome signs among Ukraine’s other partners. Western solidarity has not been perfect throughout Russia’s invasion, but it’s largely held up amid domestic political fights, an energy crisis, and inflation. But none of that is permanent.
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+Right now, Poland, Hungary, and Slovakia have defied EU rules and banned Ukrainian grain exports, saying they are flooding the market and undermining their farmers. Ukraine has filed a complaint at the World Trade Organization against that move, including against Poland, perhaps Kyiv’s staunchest supporter in the Western alliance to date.
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+On Thursday, Poland’s prime minister said it was done sending weapons to Ukraine amid this grain dispute. It’s not clear exactly how the policy will play out; US National Security Advisor Jake Sullivan said Thursday that he believes that Poland continues to stand behind Ukraine. But it shows that support for Ukraine is not unconditional.
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+At the heart of this feud, too, is Russia’s withdrawal from the Black Sea grain deal and its continued blockade of the Black Sea. Ukraine is still trying to get grain out through its sea ports, but it is risky, especially as the region becomes an increasingly volatile front in the war. But Russia can continue to use this as a pressure point, strangling Ukraine’s economy, probing a sore spot in Ukrainian-Polish relations, and potentially disrupting global food prices.
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+And right now, it seems Russia can continue to expose these pressure points.
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+The conflict feels entrenched right now, but the stakes are as high as ever
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+At the United Nations, Zelenskyy called on the world to “act united to defeat the aggressor.” Soon after, Moscow unleashed an aggressive air campaign against Ukrainian cities. Russia almost seemed to be sending a message: Try us.
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+Russia is not exactly winning, but it is also not defeated. Its winter offensive largely failed to achieve its objectives, and there are plenty of doubts as to whether Russia is capable of trying another offensive next year. But Moscow’s defensive lines proved formidable against Ukraine’s advances. Kyiv may be degrading Russian forces and logistics, but Moscow also has tools Ukraine doesn’t have, like the ability to pound Ukrainian forces from the air with attack drones and guided bombs, straining Ukraine’s air defense capabilities and exploiting Kyiv’s lack of air superiority.
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+Russia probably wouldn’t be calling up North Korea if it didn’t really need more munitions and weapons, and sanctions will continue to deplete its ability to wage war in the long-term. But Russia is still finding ways to fight, and even seeking to retake some territory as Ukraine focuses on its counteroffensive. President Vladimir Putin has, so far, survived the biggest challenge to his power to date, and then that challenger’s plane fell out of the sky — a sign, at least for now, that Putin is still in control and will continue waging his war.
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+Yet Ukrainian forces could still make a decisive push into Russian territory in the coming weeks. Last September, Ukraine liberated huge swaths of Kharkiv, and later, in November, forced a Russian retreat in Kherson. That momentum bolstered Western support, and, maybe, along with that Zelenskyy visit, helped convince the West to provide Kyiv things like missile defense systems and battle tanks.
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+Kyiv has adapted and changed throughout the conflict, because it knows the stakes of this war, which are existential. Kyiv switched tactics in its summer counteroffensive when its initial blitz failed, and Ukrainian troops have had success — and might have more still — degrading Russian forces. Ukraine is developing capabilities to take the fight directly to Moscow, with drones and sabotage operations. This is the case Zelenskyy is making in Washington: that Ukraine can win, and it will win. ButKyiv’s backers have to stay the course.
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From The Hindu: Sports
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India vs Australia first ODI | Mohammed Shami shows his class as India restricts Australia - Mohammed Shami, who doesn’t seem to feature in India’s first XI plans for the World Cup, literally made a statement with his second five-wicket haul in ODIs.
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Brave Beauty shine -
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Chance for Neeraj Chopra-led India to showcase its sporting prowess at Asian Games - India’s performance at the Hangzhou Asian Games, where it will compete in 38 disciplines, offers a glimpse into its Olympic prospects.
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ICC Under-19 world cup | Defending champion India to open campaign against Bangladesh - Featuring a total of 16 teams, the U-19 World Cup will be held from January 13 to February 4 in Sri Lanka, with the hosts taking on Zimbabwe in the tournament-opener in Colombo.
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India slams China for denying accreditation to sportspersons from Arunachal Pradesh for Asian Games - As a mark of protest Union Minister Anurag Singh Thakur has cancelled his scheduled visit to China for the Asian Games.
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From The Hindu: National News
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BRS leadership works out truce between Srihari, Rajaiah in Station Ghanpur - Mr. Rajaiah has been sulking over denial of ticket for the next election; Party assures him of a ‘good future’
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Kerala rain: Ongoing wet spell brightens State’s hydel storage prospects - Combined storage in the reservoirs stood at 45% on Thursday, an improvement from the almost-stagnant 37% recorded since mid-August, according to Kerala State Load Despatch Centre data
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Rich tributes paid to historian Sivasankaran Nair - T.P. Sankarankutty Nair, former Professor of History and ex-Director General of the Centre for Heritage Studies, delivered condolence speech
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Lecture on Aditya-L1 mission on Saturday - R. Satheesh Thampi, head of the Planetary Science branch at Space Physics Laboratory, will deliver the lecture
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Rain continues in many parts of Kerala, IMD issues yellow alert for 7 districts - Heavy rainfall predicted in Thiruvananthapuram, Kollam, Pathanamthitta, Alappuzha, Kottayam, Idukki and Ernakulam districts
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From BBC: Europe
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Ukraine’s Volodymyr Zelensky visits Canada for first time since Russia invasion - The Ukrainian president and first lady land in Ottawa, more than 18 months after Russia invaded.
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A shadow of ‘Ukraine fatigue’ hangs over Polish politics - With an election looming, politicians are grappling with how to support Ukraine and prioritise national interests.
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Armenia ready for 40,000 families after Nagorno-Karabakh surrender - PM Nikol Pashinyan says Armenia is prepared but there is “no direct threat” to civilians.
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Nagorno-Karabakh: Conflict between Azerbaijan and Armenians explained - The region is at the heart of a long-running conflict between ethnic Armenians and Azerbaijanis.
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Five to be charged in UK with spying for Russia - Three men and two women are to be charged with conspiracy to conduct espionage, UK prosecutors say.
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From Ars Technica
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Rolling in style: The Priority E-Coast beach cruiser - Ride around town in style on this $1,999 beach cruiser. - link
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Opinion: The Copyright Office is making a mistake on AI-generated art - A rule against copyrighting AI art will be unworkable. - link
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Rocket Report: Two small launchers fail in flight; Soyuz crew flies to ISS - This wasn’t a great week for small launch vehicles. - link
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Incomplete disclosures by Apple and Google create “huge blindspot” for 0-day hunters - No one mentioned that libwebp, a library found in millions of apps, was a 0-day origin. - link
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US to again offer free COVID tests ahead of respiratory virus season - On Monday, households can order 4 free tests with shipments expected to start Oct. 2. - link
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From Jokes Subreddit
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A teacher tells her students to write a sentence defining power. -
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Once everyone has finished, she reads the sentences out to the class:
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“Power is when you can do good,” - Good, Max, nice sentence. That’s an A.
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“Power is when you can do good and punish evil,” - very good, Sarah, beautiful. That’s an A+.
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“Power is when you have a lot of women and can sleep with them,” - whaaaat? Johnny, what kind of filth are you writing? Change it to something proper at once!
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+Johnny thinks for a minute and hands the teacher another piece of paper. She reads:
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“Power is when you have the ability and right to impose your philosophy upon others and to ruin their dreams.”
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+“Doctor I want to have a baby but my husband is adamant that he doesn’t want any children. What can I do?”
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+The doctor tells her that the next time she goes to have sex with her husband, take a sewing needle and poke holes in the tip of the condom.
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+The next day the woman goes back to the doctor and says, “Doctor it didn’t work, after I poked holes in the condom my husband didn’t want to have sex anymore, but I’m sure he didn’t see me do it.”
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+The doctor says, “Yes I saw him earlier. Next time do it before you put the condom on him.”
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Paddy was coming back from his holiday in America. -
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+As he came through Customs, he had two sacks over his shoulder. The Customs officer asked him what he had in the sacks? Paddy replied Mobile phones.
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+The customs officer didn’t believe him and asked to be shown. Paddy opened each sack and sure enough both sacks contained quite a few phones. "What are you going to do with all these mobile phones asked the officer?
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+"Oh, they are not for me. My mate Mick, who is in a band, knew I was going over to America asked me to bring him back Two saxophones.
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+Its his first day in the prison, a while later he sees his cellmate go the the door and yells trough it: “#12!”, and a few people from different cells chuckle. A few hours later another man goes to the door and yells: “#31!”, and a few people start laughing, even the guards smile. Then having gathered up his courage he asks what does the numbers mean. The cellmate looks at him and anwsers: “everyone here has told the same jokes so many times, that we assigned numbers to them and say them instead”. The man thinks for a bit, goes up to the door an yells: “#136!”. And the whole prison erupts in laughter, even the guards are curled up laughing. When the laughter dies down his cellmate looks at him and says: “thats a new one!”
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