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The purpose of this research was to examine attitude, usefulness, and satisfaction as antecedents of behavioral intentions of the students towards E-pad usage. The primary data was collected from the B-School students of Mangalore, Bangalore, and Udupi. A sample of 187 students in 10 various prestigious B-Schools was used to study the impact of attitude, usefulness, and satisfaction on behavioral intentions towards E-pad usage. The path coefficient value and the T statistics confirm the positive association between the attitude and behavioral intentions, usefulness and behavioral intentions, satisfaction, and behavioral intentions. The multi-group analysis through PLS also suggests that there is a perceptional difference among males and females on attitude, usefulness, satisfaction, and behavioral intentions of the students. The findings have many implications for present behavioral intentions models and promotion progress in the firm. [ABSTRACT FROM AUTHOR]

Background: Detecting atrial fibrillation (AF) after stroke is a key component of secondary prevention, but indiscriminate prolonged cardiac monitoring is costly and burdensome. Multivariable prediction models could be used to inform patient selection., Objective: To determine the performance of available models for predicting AF after a stroke., Methods: We searched for studies of multivariable models that were derived, validated and/or augmented for prediction of AF in patients with a stroke, using Medline and Embase from inception through 20/09/2024. Discrimination measures for tools with c-statistic data from ≥3 cohorts were pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). The risk of bias was assessed using the Prediction Model Risk Of Bias tool (PROBAST)., Results: We included 75 studies with 58 prediction models. 66% had a high risk of bias. Fifteen multivariable models were eligible for meta-analysis. Three models showed excellent discrimination: SAFE (c-statistic 0.856, 95% CI 0.796-0.916), SURF (0.815, 95% CI 0.728-0.893), and iPAB (0.888, 95% CI 0.824-0.957). Excluding high-bias studies, only SAFE showed excellent discrimination (0.856, 95% CI 0.800-0.915). No model showed excellent discrimination when limited to external validation or studies with ≥100 AF events. No clinical impact studies were found., Conclusion: Three of the fifty-eight identified multivariable prediction models for AF after stroke demonstrated excellent statistical performance on meta-analysis. However, prospective validation is required to understand the effectiveness of these models in clinical practice before they can be recommended for inclusion in clinical guidelines., (Copyright © 2025. Published by Elsevier Inc.)

Aims: The Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF) longitudinal cohort study is a multi-centre prospective cohort study of patients identified at risk of atrial fibrillation (AF). The aim of the FIND-AF longitudinal cohort study is to provide multi-modal phenotypic characterization of these patients., Methods and Results: A total of 1955 participants identified as at risk of AF by the FIND-AF algorithm from primary care electronic health record (EHR) data, aged 30 years and above and eligible for oral anticoagulation, will be recruited between October 2023 and November 2024 to receive home-based intermittent electrocardiogram monitoring. About 500 participants without diagnosed AF will then undergo cross-sectional phenotypic characterization including physical examination, symptoms assessment, serum blood biomarkers and echocardiography, and non-stress cardiac magnetic resonance imaging. Longitudinal information about cardio-renal-metabolic-pulmonary outcomes will be ascertained from linkages to EHR data. The study is funded by the British Heart Foundation (CC/22/250026). The study has ethical approval (North West-Greater Manchester South Research Ethics Committee reference 23/NW/0180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder's open-access policy., Conclusion: The FIND-AF multi-centre prospective longitudinal cohort study aims to (i) provide evidence for the impact of comorbidities on AF genesis, (ii) uncover actionable targets to prevent AF, and (iii) act as a platform for cohort randomized clinical trials that investigate enhanced detection and prevention of AF., Competing Interests: Conflict of interest: C.P.G. reports personal fees from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Vifor Pharma, Menarini, Wondr Medical, Raisio Group, and Oxford University Press. He has received educational and research grants from BMS, Abbott Inc., the British Heart Foundation, National Institute of Health Research, and Horizon 2020 and from the European Society of Cardiology, outside the submitted work. G.Y.H.L. is a National Institute for Health and Care Research (NIHR) senior investigator and has been a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Anthos. All other authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Chronic kidney disease (CKD) is a major global health problem and its early identification would allow timely intervention to reduce complications. We performed a systematic review and meta-analysis of multivariable prediction models derived and/or validated in community-based electronic health records (EHRs) for the prediction of incident CKD in the community., Methods: Ovid Medline and Ovid Embase were searched for records from 1947 to 31 January 2024. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST) and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation (GRADE)., Results: Seven studies met inclusion criteria, describing 12 prediction models, with two eligible for meta-analysis including 2 173 202 patients. The Chronic Kidney Disease Prognosis Consortium (CKD-PC) (summary c-statistic 0.847; 95% CI 0.827-0.867; 95% PI 0.780-0.905) and SCreening for Occult REnal Disease (SCORED) (summary c-statistic 0.811; 95% CI 0.691-0.926; 95% PI 0.514-0.992) models had good model discrimination performance. Risk of bias was high in 64% of models, and driven by the analysis domain. No model met eligibility for meta-analysis if studies at high risk of bias were excluded, and certainty of effect estimates was 'low'. No clinical utility analyses or clinical impact studies were found for any of the models., Conclusions: Models derived and/or externally validated for prediction of incident CKD in community-based EHRs demonstrate good prediction performance, but assessment of clinical usefulness is limited by high risk of bias, low certainty of evidence and a lack of impact studies., Competing Interests: C.P.G. received honoraria for consulting and/or speeches from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Vifor, Pharma, Menarini, Wondr Medical, Raisio Group and Oxford University Press. All the other authors declared no competing interests. The authors had full responsibility for data collection, data interpretation and writing of the report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Cardiovascular diseases are a leading cause of death and disability globally, with inequalities in burden and care delivery evident in Europe. To address this challenge, The Lancet Regional Health-Europe convened experts from a range of countries to summarise the current state of knowledge on cardiovascular disease inequalities across Europe. This Series paper presents evidence from nationwide secondary care registries and primary care healthcare records regarding inequalities in care delivery and outcomes for myocardial infarction, heart failure, atrial fibrillation, and aortic stenosis in the National Health Service (NHS) across the United Kingdom (UK) by age, sex, ethnicity and geographical location. Data suggest that women and older people less frequently receive guideline-recommended treatment than men and younger people. There are limited publications about ethnicity in the UK for the studied disease areas. Finally, there is inter-healthcare provider variation in cardiovascular care provision, especially for transcatheter aortic valve implantation, which is associated with differing outcomes for patients with the same disease. Providing equitable care is a founding principle of the UK NHS, which is well positioned to deliver innovative policy responses to reverse observed inequalities. Understanding differences in care may enable the implementation of appropriate strategies to mitigate differences in outcomes., Competing Interests: CPG reports personal fees from AstraZeneca, Amgen, Bayer, Boehrinher-Ingelheim, Daiichi Sankyo, Vifor, Pharma, Menarini, Wondr Medical, Raisio Group and 10.13039/501100007723Oxford University Press. He has received educational and research grants from BMS, Abbott inc., the 10.13039/501100000274British Heart Foundation, 10.13039/501100000272National Institute for Health Research, 10.13039/501100007601Horizon 2020, and from the 10.13039/501100000860European Society of Cardiology, outside the submitted work. YMN reports a study grant from Bayer. All other authors declare no competing interests., (© 2023 The Author(s).)

Aims: Multivariable prediction models can be used to estimate risk of incident heart failure (HF) in the general population. A systematic review and meta-analysis was performed to determine the performance of models., Methods and Results: From inception to 3 November 2022 MEDLINE and EMBASE databases were searched for studies of multivariable models derived, validated and/or augmented for HF prediction in community-based cohorts. Discrimination measures for models with c-statistic data from ≥3 cohorts were pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using PROBAST. We included 36 studies with 59 prediction models. In meta-analysis, the Atherosclerosis Risk in Communities (ARIC) risk score (summary c-statistic 0.802, 95% confidence interval [CI] 0.707-0.883), GRaph-based Attention Model (GRAM; 0.791, 95% CI 0.677-0.885), Pooled Cohort equations to Prevent Heart Failure (PCP-HF) white men model (0.820, 95% CI 0.792-0.843), PCP-HF white women model (0.852, 95% CI 0.804-0.895), and REverse Time AttentIoN model (RETAIN; 0.839, 95% CI 0.748-0.916) had a statistically significant 95% PI and excellent discrimination performance. The ARIC risk score and PCP-HF models had significant summary discrimination among cohorts with a uniform prediction window. 77% of model results were at high risk of bias, certainty of evidence was low, and no model had a clinical impact study., Conclusions: Prediction models for estimating risk of incident HF in the community demonstrate excellent discrimination performance. Their usefulness remains uncertain due to high risk of bias, low certainty of evidence, and absence of clinical effectiveness research., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Atrial fibrillation (AF) is associated with a fivefold increased risk of stroke. Oral anticoagulation reduces the risk of stroke, but AF is elusive. A machine learning algorithm (Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF)) developed to predict incident AF within 6 months using data in primary care electronic health records (EHRs) could be used to guide AF screening. The objectives of the FIND-AF pilot study are to determine yields of AF during ECG monitoring across AF risk estimates and establish rates of recruitment and protocol adherence in a remote AF screening pathway., Methods and Analysis: The FIND-AF Pilot is an interventional, non-randomised, single-arm, open-label study that will recruit 1955 participants aged 30 years or older, without a history of AF and eligible for oral anticoagulation, identified as higher risk and lower risk by the FIND-AF risk score from their primary care EHRs, to a period of remote ECG monitoring with a Zenicor-ECG device. The primary outcome is AF diagnosis during ECG monitoring, and secondary outcomes include recruitment rates, withdrawal rates, adherence to ECG monitoring and prescription of oral anticoagulation to participants diagnosed with AF during ECG monitoring., Ethics and Dissemination: The study has ethical approval (the North West-Greater Manchester South Research Ethics Committee reference 23/NW/0180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the Funder's open access policy., Trial Registration Number: NCT05898165., Competing Interests: Competing interests: CPG reports personal fees from AstraZeneca, Amgen, Bayer, Boehrinher-Ingelheim, Daiichi Sankyo, Vifor, Pharma, Menarini, Wondr Medical, Raisio Group and Oxford University Press. He has received educational and research grants from BMS, Abbott, the British Heart Foundation, National Institute of Health Research, Horizon 2020, and from the European Society of Cardiology, outside the submitted work. AJC reports personal fees from Abbott, Bayer, BMS, Sanofi, Milestone, Boston Scientific, InCarda and Menarini. YMN reports a study grant from Bayer. GYHL is consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. GYHL is corincipal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Genomic instability is a prominent hallmark of cancer, however the mechanisms that drive and sustain this process remain elusive. Research demonstrates that numerous cancers with increased levels of genomic instability ectopically express meiosis-specific genes and undergo meiomitosis, the clash of mitotic and meiotic processes. These meiotic genes may represent novel therapeutic targets for the treatment of cancer. We studied the relationship between the expression of the meiosis protein HORMAD1 and genomic instability in squamous cell carcinomas (SCCs). First, we assessed markers of DNA damage and genomic instability following knockdown and overexpression of HORMAD1 in different cell lines representing SCCs and epithelial cancers. shRNA-mediated depletion of HORMAD1 expression resulted in increased genomic instability, DNA damage, increased sensitivity to etoposide, and decreased expression of DNA damage response/repair genes. Conversely, overexpression of HORMAD1 exhibited protective effects leading to decreased DNA damage, enhanced survival and decreased sensitivity to etoposide. Furthermore, we identified a meiotic molecular pathway that regulates HORMAD1 expression by targeting the upstream meiosis transcription factor STRA8. Our results highlight a specific relationship between HORMAD1 and genomic instability in SCCs, suggesting that selectively inhibiting HORMAD1, possibly, through STRA8 signaling, may provide a new paradigm of treatment options for HORMAD1-expressing SCCs.

Genomic instability is a defining characteristic of cancer and the analysis of DNA damage at the chromosome level is a crucial part of the study of carcinogenesis and genotoxicity. Chromosomal instability (CIN), the most common level of genomic instability in cancers, is defined as the rate of loss or gain of chromosomes through successive divisions. As such, DNA in cancer cells is highly unstable. However, the underlying mechanisms remain elusive. There is a debate as to whether instability succeeds transformation, or if it is a by-product of cancer, and therefore, studying potential molecular and cellular contributors of genomic instability is of high importance. Recent work has suggested an important role for ectopic expression of meiosis genes in driving genomic instability via a process called meiomitosis. Improving understanding of these mechanisms can contribute to the development of targeted therapies that exploit DNA damage and repair mechanisms. Here, we discuss a workflow of novel and established techniques used to assess chromosomal instability as well as the nature of genomic instability such as double strand breaks, micronuclei, and chromatin bridges. For each technique, we discuss their advantages and limitations in a lab setting. Lastly, we provide detailed protocols for the discussed techniques., (© 2021. The International CCN Society.)

Herein we describe a catalyst-free regioselective [3 + 3] annulation/oxidation reaction of cyclic amidines such as DBU (1,8-diazabicyclo(5.4.0)undec-7-ene) and DBN (1,5-diazabicyclo(4.3.0)non-5-ene) with activated olefins, i.e ., 2-arylidenemalononitriles and 2-cyano-3-aryl acrylates, to afford tricyclic 2-pyridones and pyridin-2(1 H )-imines, respectively. The mechanism has been proposed based on DFT calculations. In the reaction, the cyclic amidines serve as C,N -bisnucleophiles for the cyclization, while the olefins play a dual role by acting as both reactants and oxidants.

DNA alkylation damage, emanating from the exposure to environmental alkylating agents or produced by certain endogenous metabolic processes, affects cell viability and genomic stability. Fe(II)/2-oxoglutarate-dependent dioxygenase enzymes, such as Escherichia coli AlkB, are involved in protecting DNA from alkylation damage. Inspired by the natural product indenone derivatives reported to inhibit this class of enzymes, and a set of 2-chloro-3-amino indenone derivatives was synthesized and screened for their inhibitory properties against AlkB. The synthesis of 2-chloro-3-amino indenone derivatives was achieved from 2,3-dichloro indenones through addition-elimination method using alkyl/aryl amines under catalyst-free conditions. Using an in vitro reconstituted DNA repair assay, we have identified a 2-chloro-3-amino indenone compound 3o to be an inhibitor of AlkB. We have determined the binding affinity, mode of interaction, and kinetic parameters of inhibition of 3o and tested its ability to sensitize cells to methyl methanesulfonate that mainly produce DNA alkylation damage. This study established the potential of indenone-derived compounds as inhibitors of Fe(II)/2-oxoglutarate-dependent dioxygenase AlkB., (© 2021 John Wiley & Sons Ltd.)

An efficient acid induced rearrangement of a tetrahalo-7,7-dimethoxybicyclo[2.2.1]heptenyl system leading to substituted indenones is reported. This domino reaction involves dehydration, olefin isomerization, ketal hydrolysis, [3,3]-sigmatropic rearrangement and dehydrohalogenation. The resultant vicinal dihalo olefin moiety in the efficiently generated indenone derivatives was utilized to transform into ninhydrin derivatives by employing Ru(III)-catalyzed oxidation.