CompHEAR: A Customizable and Scalable Web-Enabled Auditory Performance Evaluation Platform for Cochlear Implant Sound Processing Research -
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+Objective: Cochlear implants (CIs) are auditory prostheses for individuals with severe to profound hearing loss, offering substantial but incomplete restoration of hearing function by stimulating the auditory nerve using electrodes. However, progress in CI performance and innovation has been constrained by the inability to rapidly test multiple sound processing strategies. Current research interfaces provided by major CI manufacturers have limitations in supporting a wide range of auditory experiments due to portability, programming difficulties, and the lack of direct comparison between sound processing algorithms. To address these limitations, we present the CompHEAR research platform, designed specifically for the Cochlear Implant Hackathon, enabling researchers to conduct diverse auditory experiments on a large scale. Study Design: Quasi-experimental. Setting: Virtual. Methods: CompHEAR is an open-source, user-friendly platform which offers flexibility and ease of customization, allowing researchers to set up a broad set of auditory experiments. CompHEAR employs a vocoder to simulate novel sound coding strategies for CIs. It facilitates even distribution of listening tasks among participants and delivers real-time metrics for evaluation. The software architecture underlies the platform's flexibility in experimental design and its wide range of applications in sound processing research. Results: Performance testing of the CompHEAR platform ensured that it could support at least 10,000 concurrent users. The CompHEAR platform was successfully implemented during the COVID-19 pandemic and enabled global collaboration for the CI Hackathon (www.cihackathon.com). Conclusion: The CompHEAR platform is a useful research tool that permits comparing diverse signal processing strategies across a variety of auditory tasks with crowdsourced judging. Its versatility, scalability, and ease of use can enable further research with the goal of promoting advancements in cochlear implant performance and improved patient outcomes.
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Long Covid Perspectives: history, paradigm shifts, global challenges -
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+The Covid-19 pandemic is one of the most devastating health disasters in recorded history. In addition to the significant death toll, the pandemic is leaving behind a long tail of prolonged disease and disability. The long-term symptoms, clinical signs and sequelae of SARS-CoV-2 infection are collectively known as Long Covid â a patient-made term that was created and gained consistency in just a few months in Spring to Summer 2020. Long Covid was openly recognized by the World Health Organization (WHO) in August 2020, following intense advocacy by Covid-19 survivors. Long Covid has been described as the first illness identified, named and defined by patients finding one other on social media such as Twitter. As a disease entity named and defined collectively by patients, Long Covid has the potential to change knowledge building in medicine, while centring patient expertise within the biomedical community. This paper will, first, explore the rise of Long Covid as patient-made term, clinical entity and collective, grassroots, international advocacyâresearch movement in early 2020 and beyond. This happened while people with Covid-19 suffered abandonment and lack of care in the pandemicâs disaster context. Second, I will discuss some key paradigm shifts triggered by this ground-breaking patient-driven, collective advocacyâresearch, while sketching links with earlier patient movements, such as around HIV/AIDS. Then, I will explore the role of Long Covid advocacyâresearch in our digital era. This advocacy took place during a pandemic when digital spaces such as Twitter and Facebook were often the only arenas available to Covid-19 survivors. Moreover, I will raise some pressing issues around epistemic injustice in relation to the use of patient-produced data and the recognition of patient contributions to knowledge. Finally, I will address the need to fully acknowledge the nature, scope, and severity of Long Covid, which are detailed in thousands of scientific publications, including in relation to the ongoing spread of SARS-CoV-2.
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Genomic analysis of Staphylococcus aureus isolates from bacteremia reveals genetic features associated with the COVID-19 pandemic -
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+Genomic analyses of bacterial isolates are necessary to monitor the prevalence of antibiotic resistance genes and virulence determinants. Herein, we provide a comprehensive genomic description of a collection of 339 Staphylococcus aureus strains isolated from patients with bacteremia between 2014 and 2022. Nosocomial acquisition accounted for 56.6% of episodes, with vascular catheters being the predominant source of infection (31.8%). Cases of fatality (27.4%), persistent bacteremia (19.5%) and diagnosis of septic emboli (24.2%) were documented. During the COVID-19 pandemic, we observed a 140% increase of the episodes of S. aureus bacteremia per year, with a concomitant increase of the cases from nosocomial origin. This prompted us to investigate the existence of genetic features associated with S. aureus isolates from the COVID-19 pandemic. While genes conferring resistance to {beta}-lactams (blaI-blaR-blaZ), macrolides (ermA, ermC, ermT, mphC, msrA) and aminoglycosides (ant(4')-Ia, ant(9)-Ia, aph(3')-IIIa, aph(2'')-Ih) were prevalent in our collection, detection of the msrA and mphC genes increased significantly in pandemic S. aureus isolates. Similarly, we observed a higher prevalence of isolates carrying the genes encoding the Clumping Factors A and B, involved in fibrinogen binding. Of note, macrolides were extensively used as accessory therapy for COVID-19 and fibrinogen levels were usually elevated upon SARS-CoV-2 infection. Therefore, our results reveal a remarkable adaptation of the S. aureus isolates to the COVID-19 pandemic context and demonstrates the potential of whole-genome sequencing to conduct molecular epidemiology studies.
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Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants -
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+The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins that are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S from SARS-CoV-2 variants has revealed this structural adaptation at high-resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, "in-situ" high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Considered together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of S.
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The SARS-CoV-2 infection (COVID-19) era impact on incidence of sudden deaths due to Myocardial Infarction (Heart Attack) in States and Union Territories of India- A cross-sectional comparative study (2018-2022) -
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+Background-COVID-19 pandemic increased the risk of CVD (cardiovascular disease). There is lack of comparative assessment on the incidence of sudden death due to MI during and before COVID-19. This study aimed to quantify this assessment. Another quest to start this study is that several studies have reported COVID-19 vaccine-associated myocarditis/cardiomyopathy. Methods and results-This study was based on NCRB data from all states and UTs of India who died suddenly due to MI between 1 January 2018 and 31 December 2022. 5 coastal states of India accounts for about 70 % of all MI cases related sudden death. The base year 2018 is having least whereas the last year 2022 is having the largest number of total new MI cases related mortality detected in one individual year. The largest and noteworthy percent change in sudden death due to MI in males is found in 2022 when it increased by 14.26% (is it due to delayed cardiomyopathy due to COVID-19 or its due to Vaccine? This will be a matter of research in coming era). This study revealed that there is 25.80 percent increase in total number of new MI cases related mortality in 2022 in comparison to pre-COVID-19 year of 2018. There is an overall increase of 11.24 percent in sudden death due to MI cases in males during the COVID-19 period. The Male-Sudden death due to Myocardial Infarction increased during COVID-19 year 2022 by 26.71 percent in comparison to 2018 pre- COVID-19 year. Conclusion-Sudden death due to MI increased during COVID-19.
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MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity. -
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+BackgroundDespite several years since the COVID-19 pandemic was declared, challenges remain in understanding the factors that can predict the severity of COVID-19 disease and complications of SARS-CoV-2 infection. While many large-scale Multiomic datasets have been published, integration of these datasets has the potential to substantially increase the biological insight gained allowing a more complex comprehension of the disease pathogenesis. Such insight may improve our ability to predict disease progression, detect severe cases more rapidly and develop effective therapeutics. MethodsIn this study we have applied an innovative machine learning algorithm to delineate COVID-severity based on integration of paired samples of proteomic and transcriptomic data from a small cohort of patients testing positive for SARS-CoV-2 infection with differential disease severity. Targeted plasma proteomics and an onco-immune targeted transcriptomic panel was performed on sequential samples from a cohort of 23 severe, 21 moderate and 10 mild COVID-19 patients. We applied DIABLO, a new integrative method, to identify multi- omics biomarker panels that can discriminate between multiple phenotypic groups, such as the varied severity of disease in COVID-19 patients. ResultsAs COVID-19 severity is known among our sample group, we can train models using this as the outcome variable and calculate features that are important predictors of severe disease. In this study, we detect highly correlated key variables of severe COVID-19 using transcriptomic discriminant analysis and multi-omics integration methods. ConclusionsThis approach highlights the power of data integration from a small cohort of patients offering a better biological understanding of the molecular mechanisms driving COVID-19 severity and an opportunity to improve prediction of disease trajectories and targeted therapeutics.
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Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data -
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+Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic novel lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.
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Deciphering Abnormal Platelet Subpopulations in Inflammatory Diseases through Machine Learning and Single-Cell Transcriptomics -
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+Introduction: The transcriptional heterogeneity of activated platelets, play a significant role in contributing to negative outcomes in sepsis, COVID-19, and autoimmune diseases such as systemic lupus erythematosus (SLE). Despite this, our understanding of these heterogeneous platelet responses remains limited. In this study, we aim to investigate the diverse transcriptional profiles of activated platelets in these diseases, with the goal of deciphering this platelet heterogeneity for new therapeutic strategies to target abnormal and pathogenic platelet subtypes. Materials and methods: We obtained the single cell transcriptional profiles of blood platelets from patients with COVID-19, sepsis, and SLE. Utilizing machine learning algorithms, Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB), we discerned the distinct transcriptomic signatures indicative of fatal versus survival clinical outcomes. Our methodological framework incorporated source data annotations and platelet markers and used SingleR and Seurat for detailed profiling. Additionally, we implemented Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and visualization, aiding in the detection of various platelet subtypes and their correlation with disease status and patient outcomes. Results: Our study identified distinct platelet subpopulations that are associated with disease severity. We demonstrated that alterations in platelet transcription patterns can exacerbate endotheliopathy, potentially heightening the risk of coagulation in fatal patients. Moreover, these changes can also influence lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. Conclusions: Enhanced transcriptional heterogeneity in activated platelets is linked to adverse outcomes in conditions such as sepsis, COVID-19, and autoimmune diseases. The discovery of these unique platelet subpopulations paves the way for innovative therapeutic strategies targeting platelet activation, which could potentially improve patient outcomes.
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Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro -
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+Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ~20% of the treated cases. The persistence of an intermediary form of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious intermediate decayed slowly with a half-life of ~1 day, suggesting that its persistence could outlive the treatment course to re-ignited SARS-CoV-2 infection as the drug is eliminated. Additional studies are needed to define the nature of this viral intermediate, but our findings point to a particular direction for future investigation and offer a specific treatment recommendation that should be tested clinically.
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Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster -
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+Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly mutated BA.2.86 lineage and against the backdrop of pronounced immune imprinting, it is important to characterize the antibody responses following vaccination, particularly in the elderly. Here, we show that the monovalent XBB.1.5-adapted booster vaccination substantially enhanced both binding and neutralising antibody responses against a panel of variants, including BA.2.86, in an older population with four or more previous vaccine doses. Furthermore, neutralizing antibody titers to XBB.1.5 and BA.2.86 were boosted more strongly than titers to historical variants were. Our findings thereby suggest increased vaccine induced protection against both antigenically matched variants, as well as the more distant BA.2.86 variant, and support current vaccine policies recommending a monovalent XBB.1.5 booster dose to older individuals.
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Appraising the decision-making process concerning COVID-19 policy in postsecondary education in Canada: A critical scoping review protocol -
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+Responses to COVID-19 in Canadian postsecondary education have overhauled usual norms and practices, with policies of unclear rationale implemented under the pressure of a public health emergency. However, despite the unprecedented nature of these policies and their dramatic impact on millions of lives, the decision-making process leading to them has not been documented or appraised. Drawing from macro and micro theories of public policy, specifically the critical tradition in policy studies exemplified by Carol Bacchiâs approach âWhat is the problem represented to beâ (WPR), we will conduct a scoping review of COVID-19 policies in Canadian postsecondary education, guided by Arksey and OâMalleyâs framework for scoping reviews and by the team-based approach of Levan and colleagues. Data will include diverse and publicly available documents to capture multiple stakeholdersâ perspectives on the phenomenon of interest, and will be retrieved from university, newsletter, and legal websites through combinations of search terms adapted to specific data types. Two reviewers will independently screen, chart, analyse and synthesize the data and disagreements will be resolved through full team discussion. By identifying, summarizing, and appraising the evidence, our review should inform practices that can contribute to effective and equitable public health policies in postsecondary institutions moving forward.
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Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating -
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+The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals.
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Integrated histopathology, spatial and single cell transcriptomics resolve cellular drivers of early and late alveolar damage in COVID-19 -
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+The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding of the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data of COVID-19 donor lungs with spatial transcriptomic data stratifying histopathological stages of diffuse alveolar damage (DAD). We identify changes in cellular composition across progressive DAD, including waves of molecularly distinct macrophages and depleted epithelial and endothelial populations throughout different types of tissue damage. Predicted markers of pathological states identify immunoregulatory signatures, including IFN-alpha and metallothionein signatures in early DAD, and fibrosis-related collagens in organised DAD. Furthermore, we predict a fibrinolytic shutdown via endothelial upregulation of SERPINE1/PAI-1. Cell-cell interaction analysis revealed macrophage-derived SPP1/osteopontin signalling as a key regulator during early DAD. These results provide the first comprehensive, spatially resolved atlas of DAD stages, highlighting the cellular mechanisms underlying pro-inflammatory and pro-fibrotic pathways across alveolar damage progression.
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Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages -
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+A better understanding of the bifurcation of human B cell differentiation into memory B cells (MBC) and antibody-secreting cells (ASC) and identification of MBC and ASC precursors is crucial to optimize vaccination strategies or block undesired antibody responses. To unravel the dynamics of antigen-induced B cell responses, we compared circulating B cells reactive to SARS-CoV-2 (Spike, RBD and Nucleocapsid) in COVID-19 convalescent individuals to B cells specific to Influenza-HA, RSV-F and TT, induced much longer ago. High-dimensional spectral flow cytometry indicated that the decision point between ASC- and MBC-formation lies in the CD43+CD71+IgG+ Activated B cell compartment, showing properties indicative of recent germinal center activity and recent antigen encounter. Within this Activated B cells compartment, CD86+ B cells exhibited close phenotypical similarity with ASC, while CD86- B cells were closely related to IgG+ MBCs. Additionally, different activation stages of the IgG+ MBC compartment could be further elucidated. The expression of CD73 and CD24, regulators of survival and cellular metabolic quiescence, discerned activated MBCs from resting MBCs. Activated MBCs (CD73- CD24lo) exhibited phenotypical similarities with CD86- IgG+ Activated B cells and were restricted to SARS-CoV-2 specificities, contrasting with the resting MBC compartment (CD73-/CD24hi) that exclusively encompassed antigen-specific B cells established long ago. Overall, these findings identify novel stages for IgG+ MBC and ASC formation and bring us closer in defining the decision point for MBC or ASC differentiation.
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Predicting the Trend of SARS-CoV-2 Mutation Frequencies Using Historical Data -
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+As the SARS-CoV-2 virus rapidly evolves, predicting the trajectory of viral variations has become a critical yet complex task. A deep understanding of future mutation patterns, in particular the mutations that will prevail in the near future, is vital in steering diagnostics, therapeutics, and vaccine strategies in the coming months. In this study, we developed a model to forecast future SARS-CoV-2 mutation surges in real-time, using historical mutation frequency data from the USA. To improve upon the accuracy of traditional time-series models, we transformed the prediction problem into a supervised learning framework using a sliding window approach. This involved breaking the time series of mutation frequencies into very short segments. Considering the time-dependent nature of the data, we focused on modeling the first-order derivative of the mutation frequency. We predicted the final derivative in each segment based on the preceding derivatives, employing various machine learning methods including random forest, XGBoost, support vector machine, and neural network models, in this supervised learning setting. Empowered by the novel transformation strategy and the high capacity of machine learning models, we witnessed low prediction error that is confined within 0.1% and 1% when making predictions for future 30 and 80 days respectively. In addition, the method also led to a notable increase in prediction accuracy compared to traditional time-series models, as evidenced by lower MAE, and MSE for predictions made within different time horizons. To further assess the method's effectiveness and robustness in predicting mutation patterns for unforeseen mutations, we categorized all mutations into three major patterns. The model demonstrated its robustness by accurately predicting unseen mutation patterns when training on data from two pattern categories while testing on the third pattern category, showcasing its potential in forecasting a variety of mutation trajectories. To enhance accessibility and utility, we built our methodology into an R-shiny app (https://swdatpredicts.shinyapps.io/rshiny_predict/), a tool with potential applicability in studying other infectious diseases, thus extending its relevance beyond the current pandemic.
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A Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Combined Modified RNA Vaccine Candidate Against COVID-19 and Influenza. - Conditions: Influenza; COVID-19 Interventions: Biological: Influenza and COVID-19 Combination A; Biological: Licensed influenza vaccine; Biological: COVID-19 Vaccine; Biological: Influenza and COVID-19 Combination B; Biological: Placebo Sponsors: BioNTech SE; Pfizer Not yet recruiting
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Transcranial Pulse Stimulation (TPS) in Post-COVID-19 - Conditions: Post-COVID-19 Syndrome; Fatigue Interventions: Device: Transcranial pulse stimulation Verum; Device: Transcranial pulse stimulation Sham Sponsors: Medical University of Vienna; Campus Bio-Medico University Not yet recruiting
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Evaluate the Efficacy and Safety of âFormosa 1-Breath Free (NRICM101)â in Subjects With the Symptoms of COVID-19 or Influenza-like Disease - Conditions: Influenza Viral Infections; COVID-19 Interventions: Drug: Formosa 1-Breath Free (NRICM101); Drug: Placebo control drug Sponsors: China Medical University Hospital; Tian-I Pharmaceutical,. Co. Ltd.; China Medical University, China; Qualitix Clinical Research Co., Ltd. Not yet recruiting
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A Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Booster Vaccination With Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell) - Conditions: COVID-19 Interventions: Biological: Recombinant COVID-19 (XBB) Trimer Protein Vaccine (Sf9 Cell); Biological: Recombinant COVID-19 Variant Vaccine (Sf9 Cell); Biological: Placebo Sponsors: WestVac Biopharma Co., Ltd.; WestVac Biopharma (Guangzhou) Co., Ltd. Not yet recruiting
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Restoring Energy With Sub-symptom Threshold Optimized Rehabilitation Exercise for Long COVID - Conditions: Long Covid19; Exercise Intolerance, Riboflavin-Responsive Interventions: Behavioral: Restoring Energy with Sub-symptom Threshold Aerobic Rehabilitation Exercise; Behavioral: Light Stretching/Breathing Exercises Sponsors: Columbia University; New York University Recruiting
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A Pilot Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues - Conditions: Multiple Sclerosis; Long COVID; Long Covid19; Obese; Obesity; Obesity, Morbid; Acute Leukemia in Remission Interventions: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary Sponsors: University of Chicago Not yet recruiting
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EXERCISE TRAINING USING AN APP ON PHYSICAL CARDIOVASCULAR FUNCTION INDIVIDUALS WITH POST-COVID-19 SYNDROME - Conditions: Post-Acute COVID-19 Syndrome Interventions: Behavioral: Exercise; Behavioral: Control Sponsors: University of Nove de Julho Not yet recruiting
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A Phase 1 Trial of Recombinant COVID-19 Trivalent Protein Vaccine ïŒCHO CellïŒLYB002V14 in Booster Vaccination - Conditions: SARS-CoV-2; COVID-19 Vaccine Interventions: Biological: 30ÎŒg dose of LYB002V14; Biological: 60ÎŒg dose of LYB002V14; Biological: placebo Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd. Not yet recruiting
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COVID-19 Vaccine Effectiveness Against Recurrent Infection Among Lung Cancer Patients and Biomarker Research - Conditions: COVID-19 Recurrent; Lung Cancer; Vaccination; Antibody; Chemotherapy; Immune Checkpoint Inhibitor Interventions: Biological: Any Chinese government-recommended COVID-19 booster vaccine Sponsors: Peking Union Medical College Hospital Recruiting
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IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS. - Conditions: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation Interventions: Dietary Supplement: Nutritional blend (ImmuneRecov). Sponsors: Federal University of SĂŁo Paulo Recruiting
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Physical Activity Coaching in Patients With Post-COVID-19 - Conditions: Post-COVID-19 Syndrome Interventions: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active Sponsors: University of Alcala; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid Not yet recruiting
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Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training - Conditions: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer Interventions: Device: breathing training Sponsors: Tri-Service General Hospital Active, not recruiting
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From PubMed
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Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants - Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibitionâŠ
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The Antiviral Activity of the Lectin Griffithsin against SARS-CoV-2 Is Enhanced by the Presence of Structural Proteins - Although COVID-19 transmission has been reduced by the advent of vaccinations and a variety of rapid monitoring techniques, the SARS-CoV-2 virus itself has shown a remarkable ability to mutate and persist. With this long track record of immune escape, researchers are still exploring prophylactic treatments to curtail future SARS-CoV-2 variants. Specifically, much focus has been placed on the antiviral lectin Griffithsin in preventing spike protein-mediated infection via the hACE2 receptorâŠ
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Cholesterol 25-Hydroxylase Suppresses Swine Acute Diarrhea Syndrome Coronavirus Infection by Blocking Spike Protein-Mediated Membrane Fusion - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging porcine intestinal coronavirus that can cause acute diarrhea, vomiting, rapid weight loss, and high mortality in newborn piglets. Cholesterol 25-hydroxylase (CH25H) is a molecular mediator of innate antiviral immunity and converts cholesterol to 25-hydroxycholesterol (25HC). Previous studies have reported that CH25H and 25HC have an antiviral effect against multiple viruses. However, the interplay between SADS-CoV infection andâŠ
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Tetherin Restricts SARS-CoV-2 despite the Presence of Multiple Viral Antagonists - Coronavirus infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S), inducing lysosomal degradation of Tetherin, and ORF7a, altering its glycosylation. Similarly, SARS-CoV-2 has also been shown to use ORF7a and Spike to enhance virion release in the presence of Tetherin. Here, weâŠ
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The Functional Implications of Broad Spectrum Bioactive Compounds Targeting RNA-Dependent RNA Polymerase (RdRp) in the Context of the COVID-19 Pandemic - CONCLUSIONS: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins.
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The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation - Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-ÎČ production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-ÎČ signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzymeâŠ
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Antiviral Potential of Azelastine against Major Respiratory Viruses - The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reducedâŠ
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Remdesivir Derivative VV116 Is a Potential Broad-Spectrum Inhibitor of Both Human and Animal Coronaviruses - Coronaviruses represent a significant threat to both human and animal health, encompassing a range of pathogenic strains responsible for illnesses, from the common cold to more severe diseases. VV116 is a deuterated derivative of Remdesivir with oral bioavailability that was found to potently inhibit SARS-CoV-2. In this work, we investigated the broad-spectrum antiviral activity of VV116 against a variety of human and animal coronaviruses. We examined the inhibitory effects of VV116 on theâŠ
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COVID-19 Vaccination and Immunosuppressive Therapy in Immune-Mediated Inflammatory Diseases - The COVID-19 vaccination program has probably been the most complex and extensive project in history until now, which has been a challenge for all the people involved in the planning and management of this program. Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy have required special attention, not only because of the particular haste in carrying out the process but also because of the uncertainty regarding their response to the vaccines. We now haveâŠ
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Antibody Response to SARS-CoV-2 Vaccination in Patients with End-Stage Kidney Disease on Hemodialysis - Patients with end-stage kidney disease on hemodialysis (ESKD-HD) have a high risk of contracting severe COVID-19. Vaccination can help reduce disease severity, but the immune dysregulation observed in these patients may result in an inadequate antibody response. Therefore, we aimed to evaluate the immune response postvaccination in ESKD-HD patients. This prospective cohort study was conducted in two hemodialysis centers in Indonesia. We enrolled ESKD-HD patients (n = 143) pre- andâŠ
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SARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection - Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs. Many efforts have been directed at findingâŠ
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Combating Black Fungus: Using Allicin as a Potent Antifungal Agent against Mucorales - Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstratedâŠ.
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Soluble CD137: A Potential Prognostic Biomarker in Critically Ill Patients - T cell depletion and functional impairment are characteristics of sepsis. CD137 is a costimulatory receptor on activated T cells, while soluble CD137 (sCD137) inhibits CD137 signaling. This study found elevated sCD137 levels in the plasma of patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock compared to healthy controls. The sCD137 levels negatively correlated with the C-reactive protein and positively with procalcitonin and interleukin-6. There was noâŠ
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De Novo Potent Peptide Nucleic Acid Antisense Oligomer Inhibitors Targeting SARS-CoV-2 RNA-Dependent RNA Polymerase via Structure-Guided Drug Design - Global reports of novel SARS-CoV-2 variants and recurrence cases continue despite substantial vaccination campaigns, raising severe concerns about COVID-19. While repurposed drugs offer some treatment options for COVID-19, notably, nucleoside inhibitors like Remdesivir stand out as curative therapies for COVID-19 that are approved by the US Food and Drug Administration (FDA). The emergence of highly contagious SARS-CoV-2 variants underscores the imperative for antiviral drugs adaptable toâŠ
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Amphiphilic Sialic Acid Derivatives as Potential Dual-Specific Inhibitors of Influenza Hemagglutinin and Neuraminidase - In the shadow of SARS-CoV-2, influenza seems to be an innocent virus, although new zoonotic influenza viruses evolved by mutations may lead to severe pandemics. According to WHO, there is an urgent need for better antiviral drugs. Blocking viral hemagglutinin with multivalent N-acetylneuraminic acid derivatives is a promising approach to prevent influenza infection. Moreover, dual inhibition of both hemagglutinin and neuraminidase may result in a more powerful effect. Since both viralâŠ
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From Patent Search
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+Daily-Dose
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How Netanyahuâs Right-Wing Critics See Israelâs Future - Danny Danon, the former Israeli Ambassador to the United Nations, believes thereâs no path forward for a Palestinian state. - link
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An Unpermitted Shooting Range Upends Life in a Quiet Town - Residents of Pawlet, Vermont, were accustomed to calm and neighborly interactions. Then a new resident moved in. - link
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There Are No Safe Places in Gaza - As Israelâs military campaign has expanded into southern Gaza, displaced families have been forced to move again and again. - link
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Coloradoâs Top Court Kicked Trump Off the Ballot. Will the Supreme Court Agree? - A legal scholar analyzes how the nine Justices are likely to view the blockbuster decision. - link
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When Americans Are the Threat at the Border - Many people charged with trafficking in Tucson are U.S. citizens, suffering from the same problems of poverty and addiction that plague the rest of the country. - link
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+
From Vox
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A guide to difficult conversations for people who hate confrontation -
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+Getty Images
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+âWe donât avoid conversations because they donât matter. We avoid them because they do matter.â
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+We humans love to talk. Conversations serve many purposes: to pass the time, to learn about people and the world, to exchange information, to share a laugh. Sometimes the function of discourse is to get what we want: a change in behavior, a raise, a resolution to some disagreement. These higher-stakes conversations can be anxiety-inducing because there is so much that can go wrong. Will our partner get defensive when we ask them not to make jokes at the expense of our family? Will our best friend dismiss us when we say we fear weâve grown apart? We may bite our tongue and hope whateverâs eating us up inside fades.
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+âWe donât avoid conversations because they donât matter,â says Michael Yeomans, an assistant professor at Imperial College Business School who studies decision-making in conversation. âWe avoid them because they do matter.â
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+Steering clear of potentially consequential conversations can be detrimental to relationships. Left unaddressed, even minor concerns can brew into resentment, anger, and depression â often to the complete surprise of the other party. If you never have potentially thorny chats, you risk never learning the appropriate way to navigate interpersonal conflict, and those you interact with never have the opportunity to change their ways.
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+Hope is not lost. There are tactics you can employ to deftly share your concerns without accusation, embarrassment, or outrage. All thatâs needed is a plan, an objective outlook, and an understanding of what your conversation partner will be most receptive to.
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+What to do before you have the conversation
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+Before bringing up a gripe or potential point of contention, decide if itâs even worth discussing. Are you just in a bad mood and are likely to feel differently tomorrow? Is the issue something that youâre unable to change and may only ruffle feathers? (Like telling your partner you find their parents annoying.) Take a beat and consider the alternatives to the discussion, suggests Erin Wehrman, an associate professor at Missouri State University whose research focuses on interpersonal and family communication. Whatâs the best possible outcome from broaching this conversation? Whatâs the worst? If the worst that could happen is you argue for a few minutes, you may consider bringing up your concerns.
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+Taking time to reflect may allow you to be more objective in assessing the situation. Try to focus on the facts of the situation, Wehrman says, instead of filling in the blanks and assuming the other personâs intentions. Your cousin made a comment and it made you angry. A neighbor parked in front of your house and you felt disrespected. âMy story about why people do the things that they do,â Wehrman says, âthat is my story, thatâs opinion.â Collecting and presenting the facts gives your conversation partner the opportunity to explain their perspective without needing to go on the defensive.
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+You may be feeling nervous about angering or disappointing the person you want to speak to â âthis is normal, and emotions are very normal,â Wehrman says. âItâs just part of our bodyâs reaction to stress.â She suggests preparing exactly what youâll say and then considering a few potential ways the other person might respond. Have a plan for each outcome. If they respond to your concerns defensively, you might take a different approach (more on this later) than if they are validating and receptive. Remind yourself that improving a relationship involves advocating for yourself.
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+How to prepare for the conversation
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+If you decide the issue is worth discussing, youâll want a plan based on your goals. What do you hope to accomplish? Then consider how the other person might react based on different ways of broaching the conversation. You want to avoid venting, for instance, if youâd like the other person to change their behavior in some way, like becoming more mindful of the language theyâre using in front of your children. âTry to avoid using them as a listening board for your own emotions because that translates to very different goals,â says Chris Segrin, head of the University of Arizonaâs department of communication and a behavioral scientist whose specialty is interpersonal relationships. âI want to get this off my chest, off my mind, versus thereâs something I would like to see different, some change.â
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+Think about the setting, too. You wonât want to initiate a deep conversation at the dinner table with extended family or after theyâve worked a 16-hour shift, says licensed marriage and family therapist Kiaundra Jackson. âIf they are in a good mood, if theyâre smiling, if they just ate,â she says, âthis might be a good time to have that difficult conversation.â Just be sure to ask if theyâre open to chatting before interrupting their favorite TV show.
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+Then make a plan for when youâll walk away. If anyone starts yelling or name-calling, youâll suggest taking a breather and revisiting the conversation later, Wehrman says.
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+Segrin suggests rehearsing what youâll say ahead of time, either mentally or with a trusted neutral party.
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+How to start the conversation
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+Getting the ball rolling can be the most stressful part of any difficult conversation. Be sure to use âIâ statements. Telling someone theyâve done something wrong puts the blame on them â and theyâll likely get defensive, Segrin says.
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+If youâre at a loss, here are some expert-approved statements to help initiate the conversation:
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+I see youâre eating dinner right now, but I wanted to talk to you about something. Is now a good time?
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+Ever since we hung out last week, I havenât stopped thinking about that comment you made about [X]. I wanted to talk to you about that because itâs been bothering me.
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+Sorry I havenât brought this up before, but Iâd really like to talk about [X].
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+Iâve noticed you [react a certain way] when I [do something]. From my perspective, it seems likeâŠ
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+Skills to use to make sure the conversation runs smoothly
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+There are many trust-building and relationship-strengthening strategies to employ even in the most difficult conversations, Yeomans says. Simply being receptive to the other personâs concerns promotes a culture of respect instead of aggression. âIâm always shocked when people donât realize that when they are aggressive in a disagreement that other people respond with aggressiveness,â Yeomans says. âIf you start off nice, people will take that cue from you.â
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+To signal receptiveness and promote productive conversations, Yeomans has developed a âreceptiveness recipe.â Strategies include actively acknowledging the other personâs perspective, highlighting areas where you both agree, softening your claims by using language like âI thinkâŠâ or âI see it this wayâŠ,â using positive statements such as âI think itâs helpful whenâŠâ instead of âYou shouldnât be doing this,â and sharing personal stories. Even when you disagree with a siblingâs view on how to care for your parents, itâs crucial to demonstrate youâve actually listened to their argument (âI understand where youâre coming fromâ; âI see your pointâ), addressed common concerns (âI do agree that Mom needs extra supportâ), and avoided being too forceful when suggesting alternatives (âI think it would be helpful to find a part-time home aid; Iâve heard from friends in similar situations that their parents still had independence, but assistance when neededâ). These tactics can be particularly helpful to have in your back pocket if a loved one approaches you with a thorny conversation you werenât prepared for.
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+Donât expect to persuade your conversation partner to totally see things your way. Instead, aim to learn more about how your loved one feels or views the situation and vice versa, Yeomans says. âI want to understand your perspectiveâ or âI want to understand where youâre coming fromâ is more constructive than trying to strong-arm someone into changing their mind completely.
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+Continually check in with yourself and the other person throughout the discussion to weigh whether everyone feels comfortable continuing, Jackson says. Ask if they want to take a break or revisit at another time. If things are getting heated, suggest stepping away for a few minutes to get some air or picking up the conversation again in a few days.
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+Again, think about the conditions for when youâll walk away from a combative person. If a line is crossed, you can say, âI can tell this is important to you, but I donât really want to continue to talk about this right now.â
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+How to wrap up a difficult conversation
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+If the conversation reaches a point of resolution, first confirm with whomever youâre talking with that they, too, feel satisfied. âNever assume that you have an agreement with them,â Segrin says. Try asking, âWould you agree that tomorrow youâll bring waste bags on your walk with your dog?â or âHow comfortable are you with the plan to not discuss personal details about our relationship with friends anymore?â Give them the space to express their takeaways from the conversation. âToo many people have failed to wrap these up by just assuming I said my piece, everythingâs going to magically fix itself â not really,â Segrin says. âAsk them explicitly, âDo you feel like we have come to an agreement about how this might change in the future and how comfortable you are with that?â See if youâre going to get a buy-in from them.â
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+Show your appreciation for your conversation partner by thanking them for taking your concerns seriously, even if you didnât come to an agreement, Wehrman says. (You can say, âI know we donât see eye-to-eye on this, but I appreciate you letting me have a turn to talk.â)
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+Always remain focused on the future, Segrin says. Blame is retroactive and does nothing to change what already occurred. âIf you want change, thatâs a future orientation,â Segrin says. âSo keep it on the future and donât get carried away with pointing fingers about whoâs responsible for what happened in the past.â
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Police are solving fewer crimes. Why? -
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+Chief Eddie Garcia of the Dallas Police Department poses for a portrait at DPD headquarters in Dallas, Texas, on February 16, 2022. | Cooper Neill/Washington Post via Getty Images
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+
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+Three years after demands for police reform, police are solving fewer crimes. What happened?
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+In 2020, after the police-involved killings of Breonna Taylor and George Floyd, millions of Americans took to the streets for months to demand police reform. Almost three and a half years later, a report of national crime data, compiled and published by the Federal Bureau of Investigation as part of the Uniform Crime Reporting (UCR) Program, indicates that police departments nationwide have changed â for the worse. The data says cops are solving fewer crimes today than they did then.
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+âThe UCR is sort of the best source of crime data thatâs released each year,â crime data analyst Jeff Asher tells Vox. âIt provides a trove of information on whatâs happening nationally.â
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+Asher says UCR data tells us things like whether murder and other violent crime rates are down; the level of staffing in law enforcement; and the percentage of crimes solved (also known as clearance rates).
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+âThe first thing I look at is the murder clearance rate,â Asher says. âAnd the murder clearance rate fell from above 60 percent in 2019 to just 52 percent in 2022.â
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+Asher tells Voxâs daily news podcast, Today, Explained, that murder clearance rates arenât the only figure that fell: âIt was really across the board to some of the lowest levels ever reported for every crime.â
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+According to Asherâs analysis of the UCR data, âFor all violent crimes, the clearance rate went from almost 46 percent in 2019 to 36.7 percent in 2022. The same thing happened with property crimes. Property crime went from a 17 percent clearance rate to a 12 percent clearance rate from 2019 to 2022. And so you look at crime by crime, and with the exception of burglary, every crime has seen really a nosedive in the last three or four years.â
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+So why are fewer crimes being solved by police departments? Asher says itâs harder to explain the trend than to describe it. But he thinks the data may offer some insights. âThere was a substantial decline in the summer of 2020,â he says. âWe can relate the drop in clearance rates to everything thatâs happened in American criminal justice, in policing, in attitudes toward police since the murder of George Floyd in May of 2020.â
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+Asher also points out that 2020 began an exodus of officers leaving law enforcement. âThe majority of big cities had fewer officers in 2022 than they did in 2019,â Asher says. âIf you have fewer officers, you have fewer resources to dedicate to solving crime, which means lower clearance rates. And we do have lots of research that shows that.â
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+Noel King, host of Today, Explained, wanted to know what law enforcement thought about Asherâs analysis of the FBIâs report. How are officers responding to the suggestion that theyâre not doing their jobs as well as they once were? So she talked with Dallas Police Chief Edgardo âEddieâ Garcia, who is also president of the Major Cities Chiefs Association.
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+A partial transcript of their conversation, edited for length and clarity, follows. Listen to the full conversation wherever you find podcasts.
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+Noel King
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+Chief Garcia, weâre chatting today because of an annual FBI report that comes out in the fall. One of the data points in that report has to do with the solve rates for violent crimes. And this year, what the data suggests is that that solve rate fell from about 46 percent in 2019 to about 36.7 percent in 2022, meaning fewer violent crimes are being solved. What do you think is happening here? What do you think is causing this drop?
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+Chief Eddie Garcia
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+I mean, the one thing that we have to say is that solving a violent crime is not an easy task. And as departments face staffing shortages now, I know that there are other chiefs [across the nation], as am I, that are very reticent to move bodies out of patrol, as thatâs the number one priority of any department. So you have amazing detectives doing an amazing job that are working a lot. They are overworked in some areas. As departments face staffing shortages, we always look at that patrol, thereâs no question about it. But, you know, most of us also have a lot of holes to fill in our detective bureaus. And so that is one of the major issues. I believe that if some agencies are seeing drops in their solve rates, I believe we could start there.
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+Noel King
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+Why do you think youâre having staffing problems, personnel shortages?
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+Chief Garcia
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+What is often not talked about is really in these last few years, beginning in 2020, honorable police officers have not felt supported. They have not felt supported by their community at times. They havenât felt supported by their administration at times, and they havenât felt supported by their city governments. Thereâs probably not another profession of honorable men and women, and I say honorable because Iâm not going to sit here and tell you that every police officer deserves to wear this uniform. They do not. But most of our men and women that are working in this profession are honorable men and women. And I donât care what field you go into, if you donât feel supported, if people donât honor the work that you do and sacrifice in your life every day, you know, I donât know if there are many other professions that have had a defund movement. [And] thatâs going to have an impact on honorable men and women joining any profession, much less law enforcement. Thatâs important.
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+Noel King
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+What do you hear specifically from officers? I imagine you sit and you talk to them and youâre alluding to a couple of things. Some real issues have arisen since 2020. The nation goes through an uprising. We see calls to abolish the police altogether. We see slogans like ACAB. When you sit with officers and they tell you itâs harder, what are the specifics? What are they talking about?
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+Chief Garcia
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+I started 32 years ago. And Iâll tell you what, being a police officer 32 years ago is different than it is today. Thereâs a lot more on officersâ plates, quite frankly. Officers are asked to do too much, to deal with a lot of the social ills that are impacting crime. And officers want to get compensated fairly. They feel theyâre overworked, oftentimes. And so those are some of the issues that I hear.
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+But, you know, one of the disconnects that I really believe is occurring now, and I say this because Iâm not a stay-in-the-office chief, but a lot of this division is not being driven by neighborhoods. Thereâs not a neighborhood in the city of Dallas â and I can speak for my other colleagues as well, regardless of language spoken, racial makeup, or economic status â that I have ever heard the words, âWe want to see less of you.â It never happens.
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+And in fact, oftentimes itâs our communities of color that plead with me for more officers. I have invited people to come to community meetings with me where they will hear my community let me have it if they are not seeing patrol officers and presence in their neighborhood. And oftentimes itâs our most vulnerable communities, and itâs not often, but sometimes theyâll accuse police departments of providing more police services to other, more affluent areas than the areas of need. And so thereâs a real big disconnect. And I think people need to get out of their offices and go into neighborhood meetings with police chiefs to hear the same information that I hear at every community meeting that I go to.
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+Noel King
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+I think the reason that FBI data struck a chord, Chief Garcia, is that there is a sense in this country, in parts of this country, that police have stopped doing their jobs. Even if you understand why, you kind of feel like the police are doing less now, if morale is low, that certainly can happen. Do you think thereâs any truth to the sentiment that police are pulling back because they feel overworked, they feel disrespected? And they feel like doing this job is just going to get you in trouble? I mean, what are you hearing?
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+Chief Garcia
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+You hit the nail on the head. That is absolutely an issue. They want to ensure that when chaos ensues, theyâre going to be judged fairly. And one of the dynamics, if the pendulum swings too far, oftentimes officers will feel, is this worth it? Listen, Iâll tell you this, proactive policing is absolutely necessary. I can make an officer answer a 911 call for service, that I can do, but I canât make officers be proactive. And the only reason honorable men and women will be proactive is if they feel supported. So when officers donât feel supported, when they donât have morale, what it causes oftentimes is a community to go to their corner, the police go to their corner, and yet thereâs no one in the middle keeping us safe.
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+And those are things that come not just from my officers or other people that Iâve spoken to, but from community members themselves. And so certainly that exists. You know, we have a crime plan here in the city of Dallas and in our offices. I go around the country and I talk to individuals about what weâre trying to do differently in Dallas with the crime plan. The first thing that I say to people is, âPlease do not screw up a perfectly good crime plan [by not having] your finger on the pulse.â [If] your men and women donât feel supported, if they donât feel theyâre going to be treated fairly once chaos ensues, thereâs no crime plan thatâs going to work. So your point is 100 percent valid. And thatâs something that we need to work hard on.
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+Noel King
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+What do you think itâs going to take to turn this around?
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+Chief Garcia
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+It takes strong leadership. It takes strong support from city government. I have a very supportive city council, which absolutely is necessary. I have an incredibly supportive city manager. And quite frankly, I have arguably the most supportive mayor of public safety I think there is in the country. And it starts with that. It starts with great community trust and great community understanding. We have to build the department. We canât lose sight of the fact that we need to grow. Nothing will ever amount to having a human being sitting at a desk, sitting in a patrol car, offering that and providing that service. So we need to grow and solve rates will then increase. And to your point, 90 to 100 percent [solve rates] is definitely something we should strive for. But itâs not necessarily realistic.
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+There are several reasons. Communities donât speak to us. One of the reasons [they donât speak to us] is lack of accountability in the system, in keeping violent criminals in custody. We have witnesses in the city of Dallas that fear for their lives when they come forward, only to see the individual that they came forward to be a witness against â to see them back out on the street does not lend credibility to the system. And it certainly doesnât make them feel safe when they come forward. So we have that to worry about, which is a humongous issue. We need accountability. And thatâs hugely important. That trust the community has in its police department will have people come forward to speak to us about whatâs occurring because we canât solve these crimes alone oftentimes. You know, the community is not a monolith. Obviously, we have to get better as professionals. Little question about it. But in my experience, at nearly 32 years and now going into the new year, Iâll be in my ninth year as a police chief, whether in California, here in Dallas, our communities have never and still do not want us to go away.
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How to dig yourself out of credit card debt -
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+
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+Paige Vickers/Vox
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+Plus, how to make sure you get your fair share of a mortgage investment in the case of a divorce.
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+On the Money is a monthly advice column. If you want advice on spending, saving, or investing â or any of the complicated emotions that may come up as you prepare to make big financial decisions â you can submit your question on this form. Here, we answer two questions asked by Vox readers, which have been edited and condensed.
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+I struggled with my mental health over the past few years, and as a result have racked up a considerable amount of credit card debt. Iâm also a freelancer, so my ability to work and increase my income depends somewhat on my mental health. Iâve gotten to a point with my mental health where I can put in more hours to increase my income, but Iâm finding tackling this mountain of debt to be daunting, especially since my income fluctuates month to month. Any advice on how to dig myself out of this hole?
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+If youâre looking for tried-and-true methods of tackling debt, consider the snowball method or the avalanche method. Both involve putting as much of your income as possible toward a single outstanding debt while making the minimum payments on all other debts â and once your first outstanding balance is paid off in full, you can repeat the process with a second debt.
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+The snowball method starts with the smallest debt and works its way up. The avalanche method starts with the highest-interest debt and works its way down. Either method can be successful, in part because it allows you to successively increase the speed at which you pay off your subsequent debts. The snowball gets bigger as every credit card is paid off; the avalanche increases in strength as you eliminate your high-interest balances. Both of these methods allow you to see rapid results, which is one of the reasons they work so well.
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+Since your income fluctuates, you may wonder how much money you can afford to put toward your debt every month â and you might end up reducing the amount of money you put toward your debt, in part because you might be anxious about having enough leftover cash to tackle your future financial needs.
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+Hereâs how I solved that problem when I was in a similar situation:
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+About 10 years ago, I had $17,000 in credit card debt. While some of the purchases I made on those credit cards were undoubtedly discretionary, itâs worth noting that much of my debt â like many of our outstanding debts â came from a mismatch between income and necessities. I had just started earning enough money as a freelance writer to begin to seriously tackle my debt situation, and my parents offered me a $14,000 no-interest loan (the maximum they could give me without tax implications) to help me pay everything off as quickly as possible while avoiding credit card interest. I paid my parents back in $800-a-month installments, and paid off the rest of the debt using the snowball method.
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+To help ensure that I would have enough available cash to meet my financial obligations, I set up three savings accounts in addition to my checking account. Every time I got a freelance payment, I put 20 percent into the savings account marked âtaxes,â 20 percent into the account marked âdebt,â and 10 percent into the account marked âsavings.â
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+It took me 19 months to pay off my debt. I was in Seattle, in 2015, renting a converted hotel room with no kitchen (my landlord told me to wash my dishes in a bus tub and dump the dirty water down the toilet, but thatâs another story) while earning $40,000 the first year and $60,000 the second. Since I was living on 50 percent of my income and putting the rest toward savings, taxes, and debt payment, that meant I effectively lived on $20,000 the first year and $30,000 the second â and increasing my freelance income gave me the opportunity to move into a better apartment without slowing down my debt repayment plan.
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+Putting in more hours is a good way to increase your freelance income, and Iâm glad youâre in a position to put more time and mental energy toward taking on assignments, but Iâd recommend putting at least some of those hours into finding higher-paying clients. The kinds of freelance clients that pay the best are often the kinds of clients that have policies built in to allow employees and contractors to manage their workloads without becoming overwhelmed by demands and deadlines, which could be a net positive for both your financial and mental health.
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+In return, youâll need to be in a position where you can make those deadlines even when youâre struggling more than usual. I donât know which mental health challenges youâre dealing with right now, and I donât know how they affect your ability to complete your work. You may need to budget your time the way you do your finances and set aside a buffer of hours every week/month that can allow you to take mental health days without falling into deadline debt. You may also want to budget more time for sleep, food prep, and relaxation â or, depending on where youâre currently living, budget time and money to move into a better apartment â and, if youâre anything like the person who wrote me last month, youâll want to avoid impulse buys.
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+From there, all you have to do is set aside a certain percentage of each paycheck for debt repayment, set aside another percentage for savings (just in case you have a few lower-than-expected earning months), put a chunk of each paycheck into an account labeled âfreelance taxesâ (20 percent is a good start, but 30 percent is even better), and then use the snowball or avalanche method to pay off each of your outstanding balances.
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+Youâll be out of your debt hole faster than you realize.
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+Is there a way to get a mortgage together and keep track of how much each of you invested so you can get back your fair share of the investment in the event of divorce?
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+Youâll want to talk to a mortgage lawyer about how to draw up this kind of documentation, which will likely involve an ownership contract in addition to your mortgage and title. The contract should allow you to specify each partnerâs equity in the home, as well as the rights to which each of you are entitled in the case of a divorce. Since many states automatically treat marital homes as 50/50 assets, getting your documentation in place as soon as possible is the best way to ensure that you can divide the value of your home proportionally if you need to.
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+That said, thereâs more to the value of a home than the initial investment. Your spouse could argue that their paid and unpaid contributions to the upkeep of the home should be factored into future equity distributions, and if one of you puts more of your income toward day-to-day household expenses â child care, for example, or groceries â you could justifiably claim that these financial contributions should also be treated as investments in the shared home.
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+This is why many states â and many banks â treat homes and mortgages as both shared property and shared responsibility. Itâs also why I checked in with the Chase Home Lending team to confirm that I was offering the right advice. They agreed with my recommendation to consult a mortgage lawyer and added the following insight:
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+Even when a divorce is finalized, your lender may still view both spouses as responsible for the loan until one has been removed or the property has been sold. To resolve this, spouses can also consider refinancing in order to remove one party from the mortgage and title. This process is easiest if done prior to filing for divorce; however, itâs still possible if youâve already filed.
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+Talk to a lawyer, talk to your bank, and make sure you understand both your individual rights and your statesâ marital property laws â and if youâre already concerned that your future divorce might be so acrimonious that you wonât get your fair share, you may want to avoid both marriage and mortgages.
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From The Hindu: Sports
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Divya sparkles in the air pistol final -
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Galloping Ahead and Supernatural please -
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Iâm done with wrestling, says former WFI chief Brij Bhushan - The WFI elections were held on December 21 with Brij Bhushanâs loyalist, Sanjay Singh, and his panel winning the polls by big margins.
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SA vs IND first Test | India chases history in test series in South Africa - South Africa have been victors in seven of Indiaâs eight visits since the first in 1992 with one series drawn in 2010/11, but six of those successes have been by a single win margin.
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Usman Khawaja denied permission to have peace symbol on bat, say reports - The star batter had multiple meetings with Cricket Australia over recent days to find a message that would be appropriate for the second Test this week, local media said.
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From The Hindu: National News
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Telanganaâs assets being shown as Debts: KTR alleges in his presentation countering White Papers of the government - Actual debts are âč3,17,015 crore and not âč6,71,757 crore
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RJDâs Tejashwi Yadav condemns remarks by DMKâs Dayanidhi Maran on workers from Bihar and U.P. - Bihar Deputy CM points out that as the DMK stands for social justice, a leader of the party should not make such remarks
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Clerk suspended for allotting duty to deceased employee during U.P. Governorâs visit -
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Pantoea Tagorei | Visva-Bharati discovers new bacteria, names it after Rabindranath Tagore - The bacteria has immense potential to revolutionise agricultural practices, said microbiologist Bomba Dam, assistant professor at the universityâs botany department who led the research
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Tamil Nadu floods | PMO takes stock of relief and rehabilitation efforts in T.N. - âHigh Level meeting was held today (Sunday) in the PMO to take stock of the post-flood situation in Tamil Nadu and supporting the state in this situation,â government sources said.
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From BBC: Europe
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Czech Republic mourns victims of Prague university mass shooting - Flags fly at half-mast on a day of national mourning after 14 people were killed in Prague on Thursday.
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Russia bans anti-war candidate from challenging Putin - A former TV journalist is barred from standing by officials due to âmistakesâ on her application form.
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Ukraine says it downed three Russian Su-34 warplanes - Moscow has not commented officially on the claim but influential Russian bloggers report losses.
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Ukraine war: New Christmas date marks shift away from Russia - This year Ukraine will celebrate Christmas on 25 December - moving away from the Russian calendar.
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Airbus Atlantic: 700 staff sick after Christmas dinner, health officials say - It is unclear what was on the menu for the festive feast turned nightmare before Christmas.
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From Ars Technica
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Corvids seem to handle temporary memories the way we do - Birds show evidence that they lump temporary memories into categories. - link
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PAX Unplugged 2023: How indie devs build and sell new board games - Tabletop is bigger than ever. Whatâs it like trying to get your game out there? - link
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Matter, set to fix smart home standards in 2023, stumbled in the real market - Gadget makers, unsurprisingly, are hesitant to compete purely on device quality. - link
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US agency tasked with curbing risks of AI lacks funding to do the job - Lawmakers fear the NIST will have to rely on companies developing the technology. - link
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People exaggerate the consequences of saying no to invites - People are more understanding of the reasons for rejections than most of us think. - link
+She says, âWhere did you get this Porsche?â
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+Joe says, âIt was in my garage.â
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+She says, âWhat was it doing in your garage?â
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+Joe says, âWell, I guess God put it there.â
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+She says, âThatâs ridiculous!â
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+Joe says, âWell, yes, it is ridiculous, isnât it, Mary?â
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+(Note: I did not make this up; it is a reworked version of a cartoon involving pie which I saw somewhere on Reddit. I previously posted this here 159 days ago, and some people seemed to like it. I hope you like it, too. Merry Christmas!)
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A teacher tells her student to tell a story with a moral in it. -
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+Little Johnny says, âAll right. I got one. Thereâs a horse and chicken playing in the meadow and the horse falls into the quicksand. He says âHurry up! Go get the farmer! Get me out of here!â The chicken runs back to the farm, but the farmer is nowhere to be seen.â
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+âOh my,â the teacher gasps with a horrified look on her face.
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+âSo the chicken takes the BMW, backs it up near the quicksand, throws a rope to the horse, ties it up to the bumper and pulls the horse out. The horse is so very thankful.â
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+âWhat happened next?â the teacher asks, feeling relieved.
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+âA couple days later⊠the chicken falls into the same quicksand and says, âHurry up! Hurry up! Go get the farmer!â So the horse thinks to himself, âWell⊠I could probably stand over this quicksand.â So, he stands over it and says to the chicken, âGrab hold of my penis!â So the chicken grabs hold of the horseâs penis and gets pulled out.â
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+The teacher is suddenly weirded out by the direction the story is going and asks, âUmm⊠Johnny? Thatâs nice and all, but whatâs the moral of the story?â
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+Without hesitation, Johnny responds with, âThe moral of the story is: if youâre hung like a horse, you donât need a BMW to pick up chicks.â
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