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<title>27 September, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Near-term forecasting of Covid-19 cases and hospitalisations in Aotearoa New Zealand</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Near-term forecasting of infectious disease incidence and consequent demand for acute healthcare services can support capacity planning and public health responses. Despite well-developed scenario modelling to support the Covid-19 response, Aotearoa New Zealand lacks advanced infectious disease forecasting capacity. We develop a model using Aotearoa New Zealand9s unique Covid-19 data streams to predict reported Covid-19 cases, hospital admissions and hospital occupancy. The method combines a semi-mechanistic model for disease transmission to predict cases with Gaussian process regression models to predict the fraction of reported cases that will require hospital treatment. We evaluate forecast performance against out-of-sample data over the period from 2 October 2022 to 23 July 2023. Our results show that forecast performance is reasonably good over a 1-3 week time horizon, although generally deteriorates as the time horizon is lengthened. The model has been operationalised to provide weekly national and regional forecasts in real-time. This study is an important step towards development of more sophisticated situational awareness and infectious disease forecasting tools in Aotearoa New Zealand.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.25.23296118v1" target="_blank">Near-term forecasting of Covid-19 cases and hospitalisations in Aotearoa New Zealand</a>
</div></li>
<li><strong>Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily During a 10.9 month Observation Period within a Pragmatic Randomized Clinical Trial</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Com-parisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups were not statistically different. Vitamin D3 supplementation reduced healthcare utilization in four major cate-gories: hospitalizations for any reason (rate difference: -0.19 per 1000 person-days, 95%-CI: -0.21 to -0.17 per 1000 person-days, p &lt; 0.0001); ICU admissions for any reason (rate dif-ference: -0.06 per 1000 person-days, 95%-CI: -0.08 to -0.04 per 1000 person-days, p &lt; 0.0001); emergency room visits for any reason (rate difference: -0.26 per 1000 person-days, 95%-CI: -0.46 to -0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to Covid-19 (rate difference: -8.47X10<sup>-3</sup> per 1000 person-days, 95%-CI: -0.02 to -1.05X10<sup>-3</sup> per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are rec-ommended for replication of these utilization findings and analysis of cost differences.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.25.23296104v1" target="_blank">Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily During a 10.9 month Observation Period within a Pragmatic Randomized Clinical Trial</a>
</div></li>
<li><strong>Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Patients with B-cell lymphomas have altered cellular components of vaccine responses due to the malignancies and therapies. The optimal timing of vaccine administration relative to chemotherapy and immunotherapy remains unknown. The SARS-CoV-2 vaccine campaign created a unique opportunity to gather insights into vaccine timing because patients were challenged with a novel antigen across multiple phases of lymphoma management. We studied retrospective and prospective cohorts of patients with lymphoma and CLL who received an mRNA-based vaccine and paired serologic response with treatment dates, clinical immune parameters, and deep immunophenotyping. Reduced serologic response was observed more frequently during active therapies but nonresponders were also identified within observation and post-treatment groups. Clinical immunologic profiling demonstrated that total IgA and IgM near the time of vaccination correlated with ability to coordinate vaccine response. In individuals treated with CART-19, high-parameter immunophenotyping demonstrated that nonresponse was associated with reduced participation in B cell clusters and clusters of T follicular helper cells required for vaccine response. Together these data suggest that predictors of vaccine responsiveness vary by disease and therapeutic group. Further studies of immune health during and after cancer therapies will allow clinicians to individualize the timing of vaccines and define immunologic vulnerabilities.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.26.23295903v1" target="_blank">Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL</a>
</div></li>
<li><strong>Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.25.23296114v1" target="_blank">Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort</a>
</div></li>
<li><strong>Research ethics review during the COVID-19 pandemic An international study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Research ethics review committees (ERCs) worldwide faced daunting challenges during the COVID-19 pandemic. There was a need to balance rapid turnaround with rigorous evaluation of high-risk research protocols in the context of considerable uncertainty. This study explored the experiences and performance of ERCs during the pandemic. We conducted an anonymous, cross-sectional, global online survey of chairs (or their delegates) of ERCs who were involved in the review of COVID-19-related research protocols after March 2020. The survey ran from October 2022 to February 2023 and consisted of 50 items, with opportunities for open text responses. Two hundred and three participants [130 from high-income countries (HICs) and 73 from low- and middle-income countries (LMICs)] completed our survey. Respondents came from diverse entities and organizations from 48 countries (19 HICs and 29 LMICs) in all World Health Organization regions. Responses show little of the increased global funding for COVID-19 research was allotted to the operation of ERCs. Few ERCs had pre-existing internal policies to address operation during public health emergencies, but almost half used existing guidelines. Most ERCs modified existing procedures or designed and implemented new ones but had not evaluated the success of these changes. Participants overwhelmingly endorsed permanently implementing several of them. Few ERCs added new members but non-member experts were consulted; quorum was generally achieved. Collaboration among ERCs was infrequent, but reviews conducted by external ERCs were recognized and validated. Review volume increased during the pandemic, with COVID-19-related studies being prioritized. Most protocol reviews were reported as taking less than three weeks. One-third of respondents reported external pressure on their ERCs from different stakeholders to approve or reject specific COVID-19-related protocols. ERC members faced significant challenges to keep their committees functioning during the pandemic. Our findings can inform ERC approaches towards future public health emergencies. To our knowledge, this is the first international, COVID-19-related study of its kind.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.24.23296056v1" target="_blank">Research ethics review during the COVID-19 pandemic An international study</a>
</div></li>
<li><strong>Highly efficient and sensitive membrane-based concentration process allows quantification, surveillance, and sequencing of viruses in large volumes of wastewater.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wastewater-based epidemiology is experiencing exponential development. Despite undeniable advantages compared to patient-centered approaches (cost, anonymity, survey of large populations without bias, detection of asymptomatic infected peoples etc), major technical limitations persist. Among them is the low sensitivity of the current methods used for quantifying and sequencing viral genomes from wastewater. In situations of low viral circulation, during initial stages of viral emergences, or in countries experiencing heavy rains, the extremely low concentrations of viruses in wastewater may fall below the limit of detection of the current methods. The availability and cost of the commercial kits, as well as the requirement of expensive materials, can also present major blocks to the development of wastewater-based epidemiological survey, specifically in low-income countries. Thereby, highly sensitive, low cost and open-access methods are still needed to increase the predictability of the viral emergences, to survey low-circulating viruses and to allow wastewater-based surveillance. Here, we outline and characterize new protocols for concentrating, quantifying, monitoring, and sequencing SARS-CoV-2 from large volumes (500 mL-1L) of raw wastewater. Our nucleic acid extraction technique (the routine C: 5ml method) does not require sophisticated equipment such as automatons and is not reliant on commercial kits, making it readily available to a broader range of laboratories for routine epidemiological survey. Furthermore, we demonstrate the efficiency, the repeatability, and the high sensitivity of a new membrane-based concentration method (MBC: 500 mL method) for enveloped (SARS-CoV-2) and naked (FRNAPH GGII) viruses. We show that the MBC method allows the quantification and the monitoring of viruses in wastewater with a significantly improved sensitivity. In contexts of low viral circulation, we report quantifications of SARS-CoV-2 in wastewater at concentrations below 100 genome copies per liter and as low as 40 genome copies per liter. In highly diluted samples collected in wastewater treatment plants of French Guiana, we confirmed the accuracy of the MBC method compared to the estimations done with the C method. Finally, we demonstrate that both the C and MBC methods are compatible with SARS-CoV-2 sequencing. We show that the quality of the sequence is correlated with the concentration of the extracted viral genome. Of note, the quality of the sequences obtained with some MBC processed wastewater was improved by dilutions or enzyme substitutions suggesting the presence of specific enzyme inhibitors in some wastewater. To the best of our knowledge, our MBC method is the first efficient, sensitive, repeatable, and up-scalable method characterized for SARS-CoV-2 quantification and sequencing from large volumes of wastewater.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.25.23296071v1" target="_blank">Highly efficient and sensitive membrane-based concentration process allows quantification, surveillance, and sequencing of viruses in large volumes of wastewater.</a>
</div></li>
<li><strong>Comparative performance of COVID-19 test methods in healthcare workers during the omicron wave</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction: The COVID-19 pandemic presents unique requirements for accessible, reliable testing, and many testing platforms and sampling techniques have been developed. However, not all test methods have been systematically compared to each other or a common gold standard, and the performance of tests developed in the early epidemic have not been consistently re-evaluated in the context of newly emerging SARS-CoV-2 variants.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Methods: We conducted a repeated measures study with adult healthcare workers presenting for SARS-CoV-2 testing. Participants were tested using seven test modalities: PCR with samples from the nasopharynx, oropharynx, and saliva; and BinaxNOW and iHealth antigen–based rapid detection tests (AgRDT) sampling the oropharynx and the nares. Test sensitivity was compared using any positive PCR test as the gold standard.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Results: 325 individuals participated in the study. PCR tests were the most sensitive with saliva PCR at 0.957 ± 0.048, nasopharyngeal PCR at 0.877 ± 0.075, and oropharyngeal PCR at 0.849 ± 0.082. Standard nasal rapid antigen tests were less sensitive but roughly equivalent at 0.613 ± 0.110 for BinaxNOW brand and 0.627 ± 0.109 for iHealth. Oropharyngeal rapid antigen tests were the least sensitive with BinaxNOW and iHealth brands at 0.400 ± 0.111 and 0.311 ± 0.105 respectively.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Conclusion: PCR remains the most sensitive testing modality for COVID-19, with saliva PCR being significantly more sensitive than oropharyngeal PCR and equivalent to nasopharyngeal PCR. Saliva testing has patient comfort and financial benefits, making it a preferred testing modality. Nasal AgRDTs are less sensitive than PCR though more accessible and convenient.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.25.23296099v1" target="_blank">Comparative performance of COVID-19 test methods in healthcare workers during the omicron wave</a>
</div></li>
<li><strong>Impact of COVID-19 Pandemic on Sleep Including HRV and Physical Activity as Mediators: A Causal ML Approach</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Sleep quality is crucial to both mental and physical well-being. The COVID-19 pandemic, which has notably affected the population9s health worldwide, has been shown to deteriorate people9s sleep quality. Numerous studies have been conducted to evaluate the impact of the COVID-19 pandemic on sleep efficiency, investigating their relationships using correlation based methods. These methods merely rely on learning spurious correlation rather than the causal relations among variables. Furthermore, they fail to pinpoint potential sources of bias and mediators and envision counterfactual scenarios, leading to a poor estimation. In this paper, we develop a Causal Machine Learning method, which encompasses causal discovery and causal inference components, to extract the causal relations between the COVID-19 pandemic (treatment variable) and sleep quality (outcome) and estimate the causal treatment effect, respectively. We conducted a wearable-based health monitoring study to collect data, including sleep quality, physical activity, and Heart Rate Variability (HRV) from college students before and after the COVID-19 lockdown in March 2020. Our causal discovery component generates a causal graph and pinpoints mediators in the causal model. We incorporate the strongly contributing mediators (i.e., HRV and physical activity) into our causal inference component to estimate the robust, accurate, and explainable causal effect of the pandemic on sleep quality. Finally, we validate our estimation via three refutation analysis techniques. Our experimental results indicate that the pandemic exacerbates college students9 sleep scores by 8%. Our validation results show significant p-values confirming our estimation.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291008v2" target="_blank">Impact of COVID-19 Pandemic on Sleep Including HRV and Physical Activity as Mediators: A Causal ML Approach</a>
</div></li>
<li><strong>Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic exposed, with few exceptions, a global deficiency in delivering systematic, data-driven guidance to protect citizens and coordinate vaccination programs. At the same time, medical histories are routinely recorded in most healthcare systems and are instantly available for risk assessment. Here, we demonstrate the utility of medical history in determining the risk for 1,883 diseases across clinical specialties and facilitating the rapid response to emerging health threats at the example of COVID-19. We developed a neural network to learn disease-specific risk states from routinely collected health records of 502,460 UK Biobank participants, demonstrating risk stratification for nearly all conditions, and validated this model on 229,830 individuals from the All of US cohort. When integrated into Cox Proportional Hazard Models, we observed significant discriminative improvements over basic demographic predictors for 1,774 (94.3%). After transferring the unmodified risk models to the All of US cohort, the discriminate improvements were replicated for 1,347 (89.8%) of 1,500 investigated endpoints, demonstrating model generalizability across healthcare systems and historically underrepresented groups. We then show that these risk states can be used to identify individuals vulnerable to severe COVID-19 and mortality. Our study demonstrates the currently underused potential of medical history to rapidly respond to emerging health threats by systematically estimating risk for thousands of diseases at once at minimal cost.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.10.23286918v3" target="_blank">Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats</a>
</div></li>
<li><strong>The Application of Label-free Detection Using a Tapered Optical Fiber System for Head and Neck Cancer and Infectious Biomolecules</strong> -
<div>
Introduction: Head and neck squamous cell carcinoma (HNSCC) is associated with high morbidity and mortality due to late detection. Tapered optical fiber sensors (TOFS) are biosensors with the potential application as a point-of-care device for detection of HNSCC biomarkers. TOFS uses optical fibers as transduction elements and antigen-antibody binding for the detection of target biomolecules. The present TOFS system was designed to achieve high specificity, sensitivity, and repeatability. To explore its application in HNSCC, we targeted the proinflammatory cytokine IL-8, known for its role in promoting tumorigenicity, metastasis, and angiogenesis in HNSCC. To validate our proof-of-concept experiment, a viral surrogate of SARS-CoV-2, Human Coronavirus OC43 (HCoV-OC43), was also tested. Methods: Our TOFS system contains four main parts: the tapered optical fiber, reservoir (cell), laser light source, and photodetector. The fiber is bitapered with a narrow waist region that anchors antibodies to detect target biomolecules. Light is transduced by the laser to the fiber where it travels through the down-taper region to the tapered waist followed by the up-tapered region and ultimately transmitted to the photodetector. The tapered waist facilitates the transformation of a single mode light to multiple modes, which reverts to a single mode of light as it continues through the up-taper region. Biomolecules introduced to the waist region alter the effective refractive index, which is reflected in the phase change of the wavelength. This is detected by the photodetector and quantified using Fouier analysis. Our tapered fibers were designed with antigen-antibody complexes targeting IL-8 and HCoV-OC43 to validate our TOFS design across two different antigens. Results: TOFS with tethered mouse anti-human IgG (28nm) bound to dissolved IL-8 (14 nm) produces a measurable phase shift. As little as 10pg/ml or 7.1X105 IL-8 molecules/l was detected by the prototype device and the phase change represented in real-time the binding dynamic of IL-8 to the tethered IgG. To validate our proof-of-concept experiment, HCoV-OC43 dissolved in saliva was detected with a sensitivity of 50 viruses/mL. Conclusions: TOFS device is a highly sensitive system capable of detecting proteins, viruses, and other biomolecules. Selectivity of the system is guaranteed by specific antigen-antibody binding, supported by the detection of IL-8 and HCoV-OC43 at the femtomolar level. The long-term goal for TOFS is its application as a point-of-care device used for detection, monitoring, and surveillance of HNSCC as well as detection of other pathogens in the clinical setting.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.25.559133v1" target="_blank">The Application of Label-free Detection Using a Tapered Optical Fiber System for Head and Neck Cancer and Infectious Biomolecules</a>
</div></li>
<li><strong>WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific</strong> -
<div>
The authors have withdrawn their manuscript owing to the results of this pre-print being based on experiments performed prior to COVID-19 shutdowns, which required a near complete culling of the mouse colony. Upon re-initiating the colony, the phenotype outlined in the pre-print could no longer be observed and as such we have decided to withdraw the pre-print. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2020.05.20.106930v2" target="_blank">WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific</a>
</div></li>
<li><strong>Assessing the Impact of Language Barriers on Telehealth Utilization And Subsequent Clinical Outcomes in Patients with Cancer During the COVID-19 Pandemic and Beyond</strong> -
<div>
Importance: The COVID-19 pandemic prompted a surge in telehealth utilization. However, language barriers have emerged as a potential obstacle to effective telemedicine engagement, impacting millions of limited English proficient (LEP) individuals. Understanding the role of English proficiency in telehealth outcomes is critical, particularly in cancer care, where consistent follow-up and communication are vital. Objective: The primary objective of this study is to assess the relationship between telehealth use and clinical outcomes in cancer patients while concurrently exploring the effects of English language proficiency on telehealth utilization. Design: This study utilizes a retrospective cohort design, encompassing cancer patients seen at the Chao Comprehensive Cancer Center between March 1, 2020, and December 31, 2022. The study incorporates both in-person and telehealth visits, examining the association between encounter type and clinical outcomes. Setting: The study took place at an NCI-designated cancer center, offering a controlled setting for assessing telehealth utilization and its consequences in cancer care. Participants: The study includes 7,890 patients with more than one outpatient visit during the study period. The majority of our cohort consists of English, Spanish and Vietnamese-speaking patients. Main Outcome(s) and Measure(s): Primary outcomes include the association between telehealth utilization and clinical outcomes, such as hospitalization rates, duration of hospital admissions, rates of readmission, and patient mortality. Results: There was decreased telehealth utilization in non-English speaking cancer patients throughout the pandemic. Increased telehealth utilization was associated with higher rates of admission, irrespective of cancer type. Additionally, telehealth visits were associated with higher rates of subsequent readmissions and longer duration of subsequent admissions compared to in-person visits. Spanish-speaking patients utilizing telehealth had higher rates of re-admission compared to English speakers utilizing telehealth. Patients who died had higher rates of telehealth utilization compared to patients who survived. Conclusions and Relevance: This study highlights the implications of telehealth usage in healthcare outcomes and the role of language barriers in telehealth engagement among cancer patients. The study underscores the need to optimize telehealth usage and minimize its limitations to enhance the quality of cancer care in a telehealth-driven era.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/5g2st/" target="_blank">Assessing the Impact of Language Barriers on Telehealth Utilization And Subsequent Clinical Outcomes in Patients with Cancer During the COVID-19 Pandemic and Beyond</a>
</div></li>
<li><strong>RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variants Monitoring, and Risk Pre-warning</strong> -
<div>
The Resource for Coronavirus 2019 (RCoV19) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.24.558358v1" target="_blank">RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variants Monitoring, and Risk Pre-warning</a>
</div></li>
<li><strong>Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain</strong> -
<div>
The enzymatic activity of the SARS-CoV-2 Nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N-terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5'-cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated. Here we determine high-resolution cryo-electron microscopy structures of catalytic intermediates for the NMPylation and deRNAylation/capping reactions, revealing diverse nucleotide binding poses and divalent metal ion coordination sites to promote its repertoire of activities. The deRNAylation/capping structure explains why GDP is a preferred substrate for the capping reaction over GTP. Altogether, these findings enhance our understanding of the promiscuous coronaviral NiRAN domain, a therapeutic target, and provide an accurate structural platform for drug development.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.25.558837v1" target="_blank">Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain</a>
</div></li>
<li><strong>Using a function-first “scout fragment”-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes</strong> -
<div>
Helicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as genome replication and maintenance, ribosome assembly and translation. Helicases with essential functions only in certain cancer cells have been identified and helicases expressed by certain viruses are required for their pathogenicity. As a result, helicases are important targets for chemical probes and therapeutics. However, it has been very challenging to develop selective chemical inhibitors for helicases, enzymes with highly dynamic conformations. We envisioned that electrophilic "scout fragments", which have been used for chemical proteomic based profiling, could be leveraged to develop covalent inhibitors of helicases. We adopted a function-first approach, combining enzymatic assays with enantiomeric probe pairs and mass spectrometry, to develop a covalent inhibitor that selectively targets an allosteric site in SARS-CoV-2 nsp13, a superfamily-1 helicase. Further, we demonstrate that scout fragments inhibit the activity of two human superfamily-2 helicases, BLM and WRN, involved in genome maintenance. Together, our findings suggest a covalent inhibitor discovery approach to target helicases and potentially other conformationally dynamic mechanoenzymes.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.25.559391v1" target="_blank">Using a function-first “scout fragment”-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes</a>
</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Other: Placebo;   Drug: Metformin<br/><b>Sponsors</b>:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Behavioral: Exercise Therapy;   Behavioral: Psychotherapy<br/><b>Sponsors</b>:   Hannover Medical School;   Health Insurance Audi BKK;   occupational health service Volkswagen AG;   Helmholtz Centre for Infection Research<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SA55 Injection;   Other: Placebo for SA55 injection<br/><b>Sponsor</b>:   Sinovac Life Sciences Co., Ltd.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: HH-120;   Drug: placebo<br/><b>Sponsor</b>:   Huahui Health<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2<br/><b>Interventions</b>:   Drug: VYD222;   Drug: Normal saline<br/><b>Sponsor</b>:   Invivyd, Inc.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells);   Biological: Placebo<br/><b>Sponsors</b>:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration<br/><b>Interventions</b>:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention<br/><b>Sponsors</b>:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-pharmacological and TCM-based Treatment for Long COVID Symptoms</strong> - <b>Condition</b>:   Long Covid19<br/><b>Intervention</b>:   Behavioral: Acupuncture and TCM-based lifestyle management<br/><b>Sponsor</b>:   The Hong Kong Polytechnic University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2)</strong> - <b>Condition</b>:   Systemic Inflammatory Response Syndrome<br/><b>Interventions</b>:   Biological: Allogeneic thyTreg 5.000.000;   Biological: Allogeneic thyTreg 10.000.000<br/><b>Sponsors</b>:   Hospital General Universitario Gregorio Marañon;   Instituto de Salud Carlos III<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: SA55 nasal spray<br/><b>Sponsor</b>:   Sinovac Life Sciences Co., Ltd.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: STI-1558<br/><b>Sponsor</b>:   Zhejiang ACEA Pharmaceutical Co. Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mind Body Intervention for Long COVID</strong> - <b>Conditions</b>:   Long COVID;   Post-Acute Sequelae of COVID-19;   COVID Long-Haul<br/><b>Intervention</b>:   Behavioral: Mind Body Intervention #1<br/><b>Sponsor</b>:   Beth Israel Deaconess Medical Center<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amantadine Therapy for Cognitive Impairment in Long COVID</strong> - <b>Conditions</b>:   Long COVID;   Post-COVID19 Condition;   Post-Acute COVID19 Syndrome<br/><b>Intervention</b>:   Drug: Amantadine<br/><b>Sponsor</b>:   Ohio State University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of Covid-19 Aerosol Box On Intubation Success Rate</strong> - <b>Condition</b>:   Intubation; Difficult or Failed<br/><b>Interventions</b>:   Device: Intubation using aerosol box;   Device: Intubation without aerosol box<br/><b>Sponsor</b>:   Universiti Kebangsaan Malaysia Medical Centre<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia</strong> - <b>Condition</b>:   Parosmia<br/><b>Interventions</b>:   Procedure: Stellate Ganglion Block;   Other: Placebo<br/><b>Sponsor</b>:   Lawson Health Research Institute<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A promising nucleic acid therapy drug: DNAzymes and its delivery system</strong> - Based on the development of nucleic acid therapeutic drugs, DNAzymes obtained through in vitro selection technology in 1994 are gradually being sought. DNAzymes are single-stranded DNA molecules with catalytic function, which specifically cleave RNA under the action of metal ions. Various in vivo and in vitro models have recently demonstrated that DNAzymes can target related genes in cancer, cardiovascular disease, bacterial and viral infection, and central nervous system disease. Compared with…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Hepatic Impairment on the Pharmacokinetics of Nirmatrelvir/Ritonavir, the First Oral Protease Inhibitor for the Treatment of COVID-19</strong> - Nirmatrelvir, a novel, potent, orally bioavailable SARS-CoV-2 main protease (M^(pro) ) inhibitor, coadministered with ritonavir for pharmacokinetic (PK) enhancement is licensed for the treatment of mild to moderate COVID-19 in individuals at increased risk of progression to severe disease. CYP3A4 is the primary metabolic enzyme responsible for nirmatrelvir metabolism; however, when CYP3A4 is inhibited by ritonavir, nirmatrelvir is primarily excreted, unchanged, in urine. Because of intended use…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Xuanbai Chengqi Decoction alleviates acute lung injury by inhibiting NLRP3 inflammasome</strong> - CONCLUSION: The therapeutic mechanism of XCD in ALI treatment may involve alleviating inflammatory responses in lung tissues by inhibiting the activation of the NLRP3 inflammasome-mediated pyroptosis in macrophages.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transcriptomics-inferred dynamics of SARS-CoV-2 interactions with host epithelial cells</strong> - Virus-host interactions can reveal potentially effective and selective therapeutic targets for treating infection. Here, we performed an integrated analysis of the dynamics of virus replication and the host cell transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using human Caco-2 colon cancer cells as a model. Time-resolved RNA sequencing revealed that, upon infection, cells immediately transcriptionally activated genes associated with…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>B cell responses to membrane-presented antigens require the function of the mechanosensitive cation channel Piezo1</strong> - The demand for a vaccine for coronavirus disease 2019 (COVID-19) highlighted gaps in our understanding of the requirements for B cell responses to antigens, particularly to membrane-presented antigens, as occurs in vivo. We found that human B cell responses to membrane-presented antigens required the function of Piezo1, a plasma membrane mechanosensitive cation channel. Simply making contact with a glass probe induced calcium (Ca^(2+)) fluxes in B cells that were blocked by the Piezo1 inhibitor…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Host range, transmissibility and antigenicity of a pangolin coronavirus</strong> - The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NETs induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model</strong> - BACKGROUND: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells and highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, little data is available on the involvement of NETs in secondary events after virus clearance, which can…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2</strong> - The main protease (M^(pro)) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection</strong> - Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computational study on the mechanisms of inhibition of SARS-CoV-2 M<sup>pro</sup> by aldehyde warheads based on DFT</strong> - SARS-CoV-2 main protease, M^(pro), plays a crucial role in the virus replication cycle, making it an important target for antiviral research. In this study, a simplified model obtained through truncation is used to explore the reaction mechanism of aldehyde warhead compounds inhibiting M^(pro) at the level of density functional theory. According to the calculation results, proton transfer (P_T)-nucleophilic attack (N_A) is the rate-determining step in the entire reaction pathway. The water…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Heat shock protein 90 inhibition in the endothelium</strong> - No abstract</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Determinants of <em>de novo</em> B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</strong> - Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recurrent Viral Capture of Cellular Phosphodiesterases that Antagonize OAS-RNase L</strong> - Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions is less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</strong> - Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels. Multiple attempts…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Regulation of human interferon signaling by transposon exonization</strong> - Innate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is Trump Just an Ordinary Republican Now?</strong> - The former President’s rhetoric during his recent trip to Iowa wasn’t any tamer, but he no longer sounds distinct from his G.O.P. rivals. - <a href="https://www.newyorker.com/news/the-political-scene/is-trump-just-an-ordinary-republican-now">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Astra Taylor’s Age of Insecurity</strong> - The activist and writer sees capitalism as an insecurity-producing machine. - <a href="https://www.newyorker.com/news/the-new-yorker-interview/astra-taylors-age-of-insecurity">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Soccer Players Re-Started Spain’s #MeToo Movement</strong> - A journalist describes the history of feminist activism in Spain and why the World Cup controversy marks a new phase. - <a href="https://www.newyorker.com/news/q-and-a/how-soccer-players-restarted-spains-metoo-movement">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Joe Biden’s Visit to a U.A.W. Picket Line Was a Powerful Political Gesture</strong> - By joining striking workers in Michigan, the President sent a message that can’t be delivered from a White House lectern. - <a href="https://www.newyorker.com/news/our-columnists/joe-bidens-visit-to-a-uaw-picket-line-was-a-powerful-political-gesture">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Biden Administration’s Next Big Climate Decision</strong> - The liquefied-natural-gas buildout—and fossil-fuel exports—challenge progress on global warming. - <a href="https://www.newyorker.com/news/daily-comment/the-biden-administrations-next-big-climate-decision">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Scientists will unleash an army of crabs to help save Florida’s dying reef</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/31gRT62Rm9Q9j3MMk0YbgTEyAvA=/221x0:2000x1334/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72692620/adler_3465__1_.0.jpg"/>
<figcaption>
Jason Spadaro, a marine ecologist at the Mote Marine Laboratory and Aquarium, holds a large Caribbean king crab. | Jennifer Adler
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Not all heroes wear capes. Some are crabs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hq0H9M">
With giant pincers and rough, spider-like legs, Caribbean king crabs don’t look like your typical heroes. Yet these crustaceans may be key to solving one of the world’s most pressing environmental problems: the decline of coral reefs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tzAL7E">
In recent decades, warming seas, diseases, and other threats have wiped out <a href="https://www.cell.com/one-earth/fulltext/S2590-3322(21)00474-7">half</a> of the world’s corals and <a href="https://www.climate.gov/news-features/features/mission-iconic-reefs-noaa-aims-restore-florida-keys-climate-resilient-corals">90 percent</a> of those in Florida. And this past summer, the problem accelerated. A <a href="https://www.vox.com/climate/23868423/florida-coral-reef-bleaching-heat-wave-climate-change">devastating heat wave struck the Caribbean</a>, pushing the reef in the Florida Keys — the largest in the continental US — closer to the brink of collapse.
</p>
<div class="c-float-right">
<div id="wQ0T2G">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z63ikB">
The decline of coral reefs is an enormous problem for wildlife and human communities. Reefs not only provide habitat for as much as a quarter of all marine life, including commercial fish, but they also help <a href="https://www.vox.com/down-to-earth/23046997/hurricane-ian-coral-reefs-climate-change-hurricanes">safeguard coastal communities during severe storms</a>. Simply put, we need coral reefs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gl0XzZ">
Coral reefs, meanwhile, need crabs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WwNwks">
Lucky for them, help is on the way. Scientists are in the process of building a crab army — hundreds of thousands of crustaceans strong — that they’ll unleash on Florida’s reefs, giving this ailing ecosystem a tool to fight back.
</p>
<h3 id="iUILzr">
Crabs to the rescue
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iW1mxp">
If you find crustaceans icky, Jason Spadaro’s lab is not a place you want to visit. Housed in a large, hurricane-proof building on Summerland Key in the Florida Keys, it’s full of tanks that are full of crabs — dozens of them. Some are the size of fingernails; others are as large as dinner plates. They all look a bit like rocks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UkYmJX">
Spadaro, a crab enthusiast and marine ecologist at the Mote Marine Laboratory and Aquarium, is heading up an ambitious plan: to breed a quarter of a million Caribbean king crabs each year. It’s not about cultivating seafood, though these crabs are indeed delicious, Spadaro said. It’s about helping coral reefs survive.
</p>
<div class="c-wide-block">
<figure class="e-image">
<img alt="A person’s open hand with a tiny crab sitting in the middle." src="https://cdn.vox-cdn.com/thumbor/CnfVS0nrjXO8xJUIUkRKIth1EN4=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24952372/adler_3382__1_.jpg"/>
<figcaption>
A juvenile Caribbean king crab.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZRfrvc">
The key is in the crabs’ diets: These critters consume enormous quantities of seaweed, also known as macro algae. Algae has been choking reefs throughout the world and especially in Florida, making it hard for them to grow and recover from damaging events like marine heat waves.
</p>
<h3 id="ZCsKMr">
Algae harms coral. Crabs eat algae.
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YF3GPC">
Algae is one of the few winners in a world dominated by humans. It thrives on our waste, such as sewage and runoff from farmland, which is full of nitrogen and phosphorous — nutrients that algae need to grow.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tasMVL">
As pollution runs into the ocean, algae booms.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wTmZFi">
Meanwhile, animals that eat algae have declined precipitously in recent decades. In the 1980s, an unknown pathogen wiped out longspined sea urchins in the Caribbean. These marine invertebrates — which take the shape of an overfilled pin cushion — eat loads of algae. Similarly, overfishing and the loss of various ecosystems has caused declines in algae-eating fish, such as parrotfish.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="26ChoJ">
Like a fertilized pasture with no cows, a field of algae on a reef with no herbivores grows unencumbered. In the last decade, the extent of algae on reefs globally increased by roughly <a href="https://gcrmn.net/wp-content/uploads/2023/04/GCRMN_Souter_et_al_2021_Status_of_Coral_Reefs_of_the_World_2020_V1.pdf">20 percent</a>, turning them from brilliant fields of color to monochrome patches of green.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Lm4AP4">
This is a serious problem for coral.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pcSaJ4">
When a thick layer of seaweed covers the reef, it’s hard for baby corals — which spend their early days as larvae swimming in the ocean — to find a spot on the seafloor and start a colony. This seaweed not only takes up floor space but it can also <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124162#:~:text=These%20data%20indicate%20that%20macroalgae,settlement%20and%20increasing%20recruit%20mortality.">limit the amount of sunlight</a> that reaches the bottom (coral needs light to grow) and produce chemicals that dissuade corals from settling. Abundant algae also competes with adult colonies for space, crowding them out.
</p>
<div>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/-xula4tWUy-HCTUrNU9letF-RzM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24952349/adler_6935__1_.jpg"/>
<figcaption>
Algae takes over a dead colony of elkhorn coral on a reef in the Florida Keys.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0jnzbB">
Across the Caribbean and in Florida, scientists are pouring their time and resources into restoring reefs by planting (or “outplanting”) bits of coral on the seafloor. Yet without also ridding these ecosystems of algae, Spadaro said, restoration may struggle to succeed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NclYZN">
Enter: crabs.
</p>
<h3 id="AZP0NL">
Hungry crabs to the rescue
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bW4kal">
Caribbean king crabs are voracious algae eaters, eating seaweed at rates “that exceed nearly all other fish or invertebrate grazers in the Caribbean,” researchers wrote in a <a href="https://www.cell.com/current-biology/pdf/S0960-9822(20)31674-2.pdf">2021 study</a> led by Spadaro.
</p>
<div class="c-float-right c-float-hang">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/vNgoHxNh1D_FMMikAxq1t-qDbro=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24952379/adler_3488__1_.jpg"/>
<figcaption>
Spadaro lifts a male crab out of a tank at the Mote Marine Lab.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3oQEaF">
For the study, Spadaro compared typical reefs in the Florida Keys to those he had stocked with Caribbean king crabs at a density of about one animal per square meter. After a year, the crab-filled reefs had about 85 percent less algae compared to reefs he left alone. A follow-up experiment found similar results.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LZxVCZ">
“The effect of crab stocking on seaweed cover was rapid and dramatic,” Spadaro and his co-author wrote. In turn, the decrease in algae appeared to help the coral. The reefs with crabs had a higher density of young corals, the study found, and more fish that are typically associated with coral reefs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UhgCJX">
Results like this indicate that Caribbean king crabs are important allies for coral reefs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jPlyZf">
Making crabs even more appealing is that they’re native to Florida, just in relatively low numbers. (“Everything eats them,” Spadaro said.) Adding them to the reef is unlikely to have any grave unintended consequences for the ecosystem, Spadaro said, especially considering that there are few other herbivores.
</p>
<h3 id="1tNRxT">
How to train a crustacean
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ArvvjD">
Spadaro has roughly a hundred crabs in the Florida Keys, and just shy of 200 at a new breeding facility in Sarasota. He’ll start dropping them into the ocean as soon as the end of the year or in early 2024, he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VbREJX">
But there’s one step before then, and it may involve … hand puppets?
</p>
<div class="c-wide-block">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/dTTib8CVqjw93kcrmnhk6PTX2IU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24952406/adler_3156__1_.jpg"/>
<figcaption>
A male Caribbean king crab.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qq2V4W">
Because the crabs are raised in a lab, they don’t have any experience with predators. So before putting them onto the reef, Spadaro and his team may have to condition them to fear things like octopuses, snappers, and groupers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="w7JMFo">
One way to do this is by using puppets modeled after predators. By putting these puppets in the tanks while poking at the crabs, the crabs learn to move away from the threat. Several months ago, Mote partnered with a local elementary school and had students craft hand puppets, modeled after crab predators, to use in fear conditioning. (Fortunately, the crabs don’t have great vision.)
</p>
<div>
<div class="c-image-grid">
<div class="c-image-grid__item">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/8u74jNuBY8XBeIRemVO169PddNk=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24954814/adler_3341__1_.jpg"/>
<figcaption>
Summer Huber, education specialist at Mote, uses a hand puppet to condition a crab to avoid predators.
</figcaption>
</figure>
</div>
<div class="c-image-grid__item">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/YUK7XZEYitkPcfE1yHQlR5LcV84=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24952386/adler_3266__1_.jpg"/>
</figure>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tAP9Sg">
Corals face a large number of threats, including ocean warming, that even the hungriest of crabs can’t fix, yet crabs are an important part of efforts to revive ailing reefs. Scientists have, over decades, figured out how to grow and plant corals to replenish reefs, Spadaro said, but “now we need to help them survive.”
</p></li>
<li><strong>The Republican debate is fake</strong> -
<figure>
<img alt="Donald Trump is surrounded by life-size “minions” — yellow humanoid helpers from the Despicable Me movie franchise — in an a symbolic approximation of his primary opposition." src="https://cdn.vox-cdn.com/thumbor/JObpMOeLfI6bKKumtTHiwqbkJzI=/0x0:2667x2000/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72692544/trump-and-minions.0.jpg"/>
<figcaption>
Donald Trump with what might as well be his primary opposition. | Douglas Gorenstein/NBC/NBCU Photo Bank/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
With Trump dominating the GOP primary, the debate is a cosplay of a competitive election — and a distraction from an ugly truth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="npMuXT">
Tonight’s Republican primary debate is not a real event. It is a performance, a show, a pantomime: a shiny object with virtually no relevance to the outcome of the 2024 presidential primary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KkzV8F">
<a href="https://www.vox.com/donald-trump">Donald Trump</a> is solidly over 50 percent in the national polling averages, and no one else in the primary field has anything that looks like momentum. No opponent has been able to find a line of attack that could hurt him; many of them aren’t even trying. The great GOP establishment hope, that Trump’s legal problems might torpedo his campaign, was a mirage. If anything, the four indictments helped him in the primary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UR3SSj">
At this point, the only things that could stop Trump are his death or incapacitation. Everyone in the political world — including the debate’s organizers and non-delusional rival candidates — is aware of this fact. Trump isn’t participating in the debates because he doesn’t need to: He would be lowering himself to share a stage with people who pretend to be rivals, but are really just the warm-up act for his coronation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hcF7nc">
That doesn’t mean the debate is entirely pointless. The other candidates get something out of being on that stage, like improving their future political prospects or satisfying a need for attention. And if you squint, you might get an actually interesting window into the policy debates that will define a post-Trump Republican party.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wsElGW">
But, of course, we are not yet even close to “post-Trump.” In presenting it as an actual presidential debate, rather than a discussion between somewhat prominent Republicans, the debate’s organizers are <em>lying to you</em>. With Trump absent, and facing no serious challengers, this is all make-believe politics — a ritual the party goes through to cover up the dark reality of what the party has become.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9cyioh">
The debate is fake. Donald Trump’s grip on the GOP is not.
</p>
<h3 id="S1jqPC">
What the “debate” really is
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QMLSRs">
The case for taking the debate seriously amounts to seeing it as a kind of play-in competition: The candidates are duking it out for the right to become the One True Challenger to Donald Trump.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ljyimW">
To understand why this isn’t true, it’s worth charting the trajectory of the candidate who previously held that mantle: <a href="https://www.vox.com/ron-desantis">Florida Governor Ron DeSantis</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="diSYHf">
In mid-February, DeSantis was within striking difference, coming in<a href="https://projects.fivethirtyeight.com/polls/president-primary-r/2024/national/"> roughly 2 percentage points below Trump</a> in the FiveThirtyEight national poll average. But since then, his numbers have been on a striking downward trajectory. A <a href="https://www.npr.org/2023/09/05/1197578367/desantis-gop-presidential-campaign-has-struggled-and-it-hasn-t-gotten-any-smooth">disastrously run campaign</a>, hampered by the candidate’s robotic and unlikeable personality, has tanked the primary electorate’s interest in the Florida governor.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GRCvoX">
Today, he is a whopping 41 percentage points behind Trump in FiveThirtyEight’s average. That’s only slightly better than <a href="https://projects.fivethirtyeight.com/polls/president-primary-d/2024/national/">Robert F. Kennedy Jr.’s 49-point deficit</a> in his fake bid to unseat <a href="https://www.vox.com/joe-biden">President Biden</a>. A recent poll in the critical early state of New Hampshire<a href="https://www.theguardian.com/us-news/2023/sep/21/ron-desantis-fifth-new-hampshire-trump-ramaswamy-haley-christie"> put DeSantis in fifth place</a>. His presidential campaign has been so humiliating that it’s actually hurting him back home: The once-captive Florida Republican party is<a href="https://www.politico.com/news/2023/09/22/desantis-florida-republicans-governor-elections-00117514"> rebelling against a governor</a> who now looks like a weakling.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="agFZRw">
And despite all of this, DeSantis is <em>still in second place. </em>His closest rival, businessman <a href="https://www.vox.com/2024-elections/23720391/vivek-ramaswamy-affirmative-action-woke-capitalism-ideas">Vivek Ramaswamy</a>, sits at around 6 points in the national polling average. DeSantis didn’t lead to the rise of another Trump challenger, as the play-in theory would predict. Instead, it revealed that Trump’s hold on the party is as strong as ever — and it would take a miracle for anyone to break it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9nVg9T">
As such, the Republican debate is not really a presidential debate at all.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kYVqgb">
Debates are, in theory, venues for candidates to present themselves to the public in the hope of winning their party’s nomination. But since the campaign is all but decided, to the point where Trump could completely skip the last debate with no consequence, that isn’t what’s happening.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jkdwlc">
Instead, the debate has been consumed by its secondary functions: lesser candidates jockeying for influence or attention.
</p>
<figure class="e-image">
<img alt="Vivek Ramaswamy and Nikki Haley on the debate stage. Ramaswamy holds up peace signs on each hand while Haley is blank-faced behind her podium." src="https://cdn.vox-cdn.com/thumbor/XEflk8ofc0SFHB7TXG2EyRs7tjM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24954728/1619654364.jpg"/> <cite>Getty Images</cite>
<figcaption>
Vivek Ramaswamy and Nikki Haley at the first Republican debate.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IbbWVd">
Establishment candidates who perform well might be set up for a future run, either for the presidency or some lower federal office (see<a href="https://www.nbcnews.com/politics/2024-election/nikki-haley-debate-moment-carry-forward-2024-presidential-rcna103074"> Nikki Haley</a>). Trump-friendly candidates might do the same, or jump in line for a spot in his second administration (<a href="https://www.livemint.com/politics/news/donald-trump-endorses-vivek-ramaswamy-as-a-possible-vice-president-candidate-11693447257582.html">see Vivek Ramaswamy</a>). Others might have weirder goals: Chris Christie seems desperate to get a measure of revenge on Trump,<a href="https://newrepublic.com/article/140728/least-donald-trump-still-humiliating-chris-christie"> his longtime tormentor</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LFBfOj">
These are all potentially interesting storylines for political junkies. But in a true primary debate, the stakes are much higher: There are often a large percentage of undecided voters looking for a reason to pick one member of their party over another. This time, it’s very clear that Trump is going to walk to the nomination. The idea that any of these candidates can say “in my administration” or “when I’m president” with a straight face is absurd.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nU4pGs">
New York Magazine’s Eric Levitz <a href="https://nymag.com/intelligencer/2023/09/trump-milley-death-fbi-threats.html?utm_source=tw&amp;utm_campaign=nym&amp;utm_medium=s1">recently argued</a> that Trump’s undeniable authoritarian tendencies have put the mainstream press in a difficult position: Either it describes him accurately, and sounds like a “partisan rag,” or else it deceptively treats Trump and the Republican party he controls as essentially normal. Too often, he writes, they make the latter choice — acting like “an amnesiac, or an abusive household committed to keeping up appearances, losing itself in the old routines, in an effortful approximation of normality until it almost forgets what it doesn’t want to know.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="y8Dih2">
The breathless coverage of the presidential debate fits this description to a T. We are all pretending that this is something like what we’ve seen in the past, a normal event held by a normal party, when it’s actually a pageant masking the true nature of the Trump-enthralled GOP: <a href="https://www.vox.com/policy-and-politics/22274429/republicans-anti-democracy-13-charts">a political vehicle of a strongman</a> whose second term would represent <a href="https://www.vox.com/2023/5/13/23708595/trump-second-term-cnn-town-hall">an existential threat to American democracy</a>.
</p></li>
<li><strong>Trump could now be on the hook for up to $250 million for fraud</strong> -
<figure>
<img alt="In the fading light, the golden facade of the tower’s ground floor glitters, black letters spelling out “Trump Tower” over glass revolving doors. Above the sign are large windows with golden panes; through them a massive US flag is visible. Three figures, blurs dressed in black, walk past the entrance." src="https://cdn.vox-cdn.com/thumbor/MHyK0tW9-j1vK8Ghw4_qGgLnHcM=/272x0:3883x2708/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72692005/GettyImages_1249661823.0.jpg"/>
<figcaption>
Trump Tower in March 2023. | Leonardo Munoz/AFP/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Trump has been found liable for fraud in New York.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9ih1lE">
Former <a href="https://www.vox.com/donald-trump">President Donald Trump</a>, two of his sons, and several of his companies have been <a href="https://s3.documentcloud.org/documents/23991872/ny-ruling-on-trump-business-fraud.pdf">found liable for fraud</a> in state court for inflating the value of his businesses in New York.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mkbSl5">
As a result of the <a href="https://cdn.vox-cdn.com/uploads/chorus_asset/file/24955654/new_york_judge_decision_9_26_23.pdf">Tuesday decision</a>, Trump could be on the hook for up to <a href="https://www.axios.com/2022/09/21/trump-fraud-lawsuit-new-york-attorney-general">$250 million</a>. The exact amount for which he will be held liable will be determined at trial expected to begin next week. The judge in the case, Justice Arthur F. Engoron, also nullified the business certificates of Trump and many of his allies, stripping the former president of control of his New York properties.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5yxXGr">
Trump’s lawyers have indicated that they intend to appeal Tuesday’s ruling, and Trump has also sued Engoron in a separate case that could be decided this week. But if those efforts are unsuccessful, Trump will have to proceed to trial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HzWzmF">
If that trial happens, it will likely be brief. Tuesday’s ruling came as part of a summary judgment — a ruling on the facts of the case. Engoron’s decision means the court won’t need to consider further arguments at trial, because a review of Trump’s financial statements was enough to determine that he had repeatedly committed fraud. Trump asked the court to throw out the case and argued that the alleged fraud occurred too long ago for him to be held liable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8YWU7d">
Justice Arthur F. Engoron didn’t buy it, summarizing Trump’s defense as a false claim that “the documents do not say what they say; that there is no such thing as ‘objective’ value; and that essentially the Court should not believe its own eyes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cHnmkV">
It’s a major early loss for Trump in the climax of New York Attorney General Letitia James’ multi-year investigation into his New York business dealings. James’s civil case is separate from the four sets of <a href="https://www.vox.com/trump-investigations">criminal charges Trump faces</a> that span from New York to Georgia. Together, Trump’s civil and criminal cases will dominate much of the <a href="https://www.vox.com/politics/2023/2/23/23611828/2024-republican-presidential-candidates-trump-hurd">2024 Republican primary</a> calendar, and his legal troubles have <a href="https://www.nytimes.com/2023/08/11/us/politics/donald-trump-legal-bills-campaign.html">consumed millions of dollars of his campaign funds</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i3ifMy">
There have been no indications thus far that a judgment against Trump in the New York attorney general’s case will hurt him politically, however. Though a majority of Americans wanted <a href="https://www.reuters.com/article/us-usa-election-poll/two-in-three-americans-want-to-see-trumps-tax-returns-reuters-ipsos-poll-shows-idUSKCN24G14N">more transparency</a> into his business dealings while he was running for president and in office, he’s never offered much — and he hasn’t suffered for it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S4TYyN">
For years, he refused to release his tax returns, as had become the norm for presidents and presidential candidates, apparently shielding <a href="https://www.nytimes.com/interactive/2020/09/27/us/donald-trump-taxes.html">years of tax avoidance</a> from public scrutiny before the records were leaked. He still won the <a href="https://www.vox.com/presidential-election">2016 election</a> and now enjoys a <a href="https://www.realclearpolitics.com/epolls/2024/president/us/2024_republican_presidential_nomination-7548.html">historically large lead</a>, one that has <a href="https://www.vox.com/trump-investigations/2023/8/25/23845591/donald-trump-charges-january-6-trial-hitler-putsch-trial">seemed to increase with each of his criminal indictments</a>, in the Republican primary.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AfFAEe">
In a statement <a href="https://truthsocial.com/@realDonaldTrump/111134129680540625">posted to his social network</a> following the decision, Trump was dismissive of the ruling, writing he’d “done business perfectly,” and arguing that the case was a distraction from discussions of law and order. That message <a href="https://truthsocial.com/@realDonaldTrump/111134203338820494">was followed</a> by <a href="https://truthsocial.com/@realDonaldTrump/111134204068967035">reminders of his massive primary lead</a>.
</p>
<h3 id="X24o7B">
Why Trump was found liable
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bkQ73T">
James argued that the court had to consider only two “simple and straightforward” questions before ruling Tuesday night: whether Trump’s annual statements of his financial condition between 2011 and 2021 were false or misleading, and whether he and his associates invoked those statements repeatedly or persistently when conducting business transactions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UDvh76">
Engoron found Tuesday that the answer to both of those questions is “yes” based on the evidence that James’s office presented. (The judge also fined Trump’s lawyers $7,500 each for rehashing arguments that he had previously rejected.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9Rbvr7">
James cited many examples of ways in which Trump inflated the value of his assets.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N6fEkD">
For example, she accused Trump of lying about the square footage of his Manhattan Trump Tower apartment — where his wife Melania and son Barron spent time during the early part of his presidency — to inflate its value by about $100 million to $200 million annually from 2012 to 2016.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MUisZh">
She also argued that Trump valued his Mar-a-Lago estate in Florida as if he could sell it as a single-family residence, rather than as the social club that it is required to be under multiple restrictive deeds. And she claimed that he valued undeveloped land at his golf course in Aberdeen, Scotland, based on the assumption that he could construct and sell many more residential homes on that land than permitted by the Scottish government.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kUQgbi">
Engoron found these arguments persuasive, writing “In [the] defendants’ world: rent regulated apartments are worth the same as unregulated apartments; restricted land is worth the same as unrestricted land; restrictions can evaporate into thin air … That is a fantasy world, not the real world.”
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Timeless Romance, Supreme Grandeur, Andorra and Jahzara please</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Moonlight Kiss and Sea The Sun show out</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>West Brook, Stravinsky, Monteverdi, Stormy Ocean and Ruling Goddess excel</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asian Games 2022 | Nepal smashes multiple T20I records against Mongolia</strong> - Nepal broke records for highest-ever total in T20I cricket history, the fastest fifty and fastest century by a player in format’s history</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Asian Games 2022 | Indian sailor Vishnu Sarvanan wins bronze</strong> - The seasoned sailor, who competed at the Tokyo Olympics, had a net score of 34 to clinch the bronze in a gruelling 11-race competition.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why should innocent children suffer because of egoistic parents, asks Madras High Court</strong> - Justice P. Velmurugan tells an estranged couple that there is “no mistake that is unpardonable and no agony that is unbearable” and so adults can always bury differences for the sake of their children</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kerala to deploy National Service Scheme units to convert garbage dump sites into beautiful parks</strong> - Spots vulnerable to garbage dumping to be turned into small parks with vertical gardens, installations and other amenities which will be branded as ‘Snehaaramam’ as part of Malinya Muktham Nava Keralam programme.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>65% houses in Joshimath impacted by land subsidence: Govt report</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cauvery Water Management Authority to meet on September 29</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>About 50,000 people to be recruited for govt. service in two years: Stalin</strong> -</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russia shows video to prove top commander is alive</strong> - Ukraine is “clarifying” its recent reports that Russia’s Admiral Sokolov died in a missile attack on Friday.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Germany cracks down on neo-Nazi sect Artgemeinschaft for targeting children</strong> - The authorities say Artgemeinschaft used Nazi-era books “to raise new enemies of the constitution”.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Largest ever Irish drug seizure after ship raided</strong> - Irish authorities say that more than €150m of suspected cocaine has been seized from a cargo ship.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nagorno-Karabakh: More than 40,000 refugees flee to Armenia</strong> - The exodus comes as the Armenian prime minister warns of ethnic cleansing in the region.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>‘They bombed everywhere’: Survivors recount Karabakh attack</strong> - Survivors in a remote village say three children and two adults were killed, including two boys from one family.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Google quietly corrects previously submitted disclosure for critical webp 0-day</strong> - Previous CVE submission failed to mention that thousands of apps were affected. - <a href="https://arstechnica.com/?p=1971345">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Scientists just opened the lid to NASA’s asteroid sample canister</strong> - “There is some black dust-like material that’s visible. We’re hoping that’s from Bennu.” - <a href="https://arstechnica.com/?p=1971340">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Archaeologists: Roman soldiers used this built-in fridge to keep their wine cool</strong> - Fragments of wine glasses, bowls and animal bones offer evidence for their last meal - <a href="https://arstechnica.com/?p=1970546">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-viral drug backfires: COVID drug linked to viral mutations that spread</strong> - Merck’s small-molecule molnupiravir linked to mutated viruses that spread in people. - <a href="https://arstechnica.com/?p=1971307">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>This week’s dead Google products: Google Podcasts, basic Gmail, and more!</strong> - A thrilling roundup of the things Google has killed this week. - <a href="https://arstechnica.com/?p=1971148">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bloke goes into a pub on a hot summer’s day and the barmaid asks what he wants. “I want to bury my face in your cleavage and lick the sweat from between your tits” he says….</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
…“You dirty pig!” shouts the barmaid, “get out before I get my husband.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The bloke apologizes and promises not to repeat his gaffe. The barmaid accepts this and asks him again what he wants. “I want to pull your pants down, spread your arse cheeks and lick all that sweat off your anus.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She says, “You dirty filthy pervert! You’re banned. Get out!!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Again, the bloke apologizes and swears never ever to do it again. “One more chance,” says the barmaid, "Now - what do you want?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I want to turn you upside-down, tear your knickers off and fill your vagina with vodka and then drink every last drop from your hairy cup.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The barmaid is furious at this personal intrusion, and runs upstairs to fetch her husband, who’s sitting quietly watching the telly.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What’s up love?” he asks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“There’s a bloke in the bar who wants to put his head between my tits and lick the sweat off”, she says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I’ll kill him. Where is he?” storms the Husband.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Then he said he wanted to spread my arse cheeks and lick the sweat off my anus” she screams.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Right. He’s dead!” says the husband, reaching for his cricket bat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Then he said he wanted to turn me upside-down, fill my vagina with vodka and then drink it all” she cries!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The husband puts down his cricket bat and returns to his armchair, and switches the telly back on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Aren’t you going to do something about it?” she cries hysterically.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Look love, I’m not messing with any bloke who can flip you upside-down and drink all that alcohol…”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Make_the_music_stop"> /u/Make_the_music_stop </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16th4p2/bloke_goes_into_a_pub_on_a_hot_summers_day_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16th4p2/bloke_goes_into_a_pub_on_a_hot_summers_day_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A family with a little girl has a married couple staying over as guests.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One night, the girl can’t sleep, so she walks in the corridor and passes near the room where the guests are staying. She peeks in and sees the husband lying on his back, the wife bouncing on him, naked. Looks scary!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Next morning, she comes to the woman and asks her:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<strong>Girl</strong>: Excuse me, lady, could I ask you something? Last night, I saw you and your husband in bed, and you were jumping naked on him. Why were you doing this?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<strong>Woman</strong>: Well, adults do that from time to time. It is fun for us, and also, that’s how I get babies.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<strong>Girl</strong>: Ah, okay.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A couple of nights later, the girl once again can’t sleep, and once again passes near the same room. She peeks in, and sees the husband on his back, the wife bobbing her head between his legs. Looks even scarier!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So next morning, she once again comes to the woman:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<strong>Girl</strong>: Excuse me, lady, but I have another question. You told me that when you are jumping on your husband, that’s how you get babies. But last night, I saw you bobbing your head between his legs. What do you get from that?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<strong>Woman</strong>: Jewelry, my girl, jewelry.
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Omeganian"> /u/Omeganian </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16svwph/a_family_with_a_little_girl_has_a_married_couple/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16svwph/a_family_with_a_little_girl_has_a_married_couple/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A young ventriloquist is touring the clubs and one night he’s doing a show in a small club in a small town in Arkansas. With his dummy on his knee, he’s going through his usual dumb blonde jokes when a blonde woman in the fourth row stands on her chair and starts shouting:</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“I’ve heard enough of your stupid blonde jokes. What makes you think you can stereotype women that way? What does the color of a person’s hair have to do with her worth as a human being? It’s guys like you who keep women like me from being respected at work and in the community and from reaching our full potential as a person, because you and your kind continue to perpetuate discrimination against, not only blondes, but women in general…and all in the name of humor!” The ventriloquist is embarrassed and begins to apologize, when the blonde yells, “You stay out of this, mister! I’m talking to that little idiot on your knee!”
</p>
</div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16swpv1/a_young_ventriloquist_is_touring_the_clubs_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16swpv1/a_young_ventriloquist_is_touring_the_clubs_and/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Two scientists walk into a bar.</strong> - <!-- SC_OFF --></p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The first one says, “I’ll have H2O.”
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The second one says, “I’d also like water. Wait, why did you call it H2O? We’re not at work anymore.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The first scientist goes to the bathroom and cries. His assassination attempt has failed.
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Paladin_of_Freedom"> /u/Paladin_of_Freedom </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16t2x2m/two_scientists_walk_into_a_bar/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16t2x2m/two_scientists_walk_into_a_bar/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why do most men like the missionary position for sex..?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
…most men hate fucking up…
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/emzirek"> /u/emzirek </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/16t0hw1/why_do_most_men_like_the_missionary_position_for/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/16t0hw1/why_do_most_men_like_the_missionary_position_for/">[comments]</a></span></p></li>
</ul>
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