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User feedback shaped the final version, which can be accessed free from the App Store and Google Play. TGX-221 inhibitor Early implementation has demonstrated patient and provider satisfaction. Obstacles to full implementation of Decide + Be Ready remain within the Military Health System. We lay out a roadmap for dissemination, implementation, and evaluation and explore the applications of the decision aid for health professions education in the realm of shared decision-making. Finally, we recommend consideration of decision aids for other health care decisions as a way to achieve patient-centered care, improve health outcomes, and potentially reduce costs.G-quadruplex (G4) DNA structures have emerged as important regulatory elements during DNA metabolic transactions. While many in vitro studies have focused on the kinetics of G4 formation within DNA single-strands, G4 are found in vivo in double-stranded DNA regions, where their formation is challenged by the complementary strand. Since the energy of hybridization of Watson-Crick structures dominates the energy of G4 folding, this competition should play a critical role on G4 persistence. To address this, we designed a single-molecule assay allowing to measure G4 folding and persistence times in the presence of the complementary strand. We quantified both folding and unfolding rates of biologically relevant G4 sequences, such as the cMYC and cKIT oncogene promoters, human telomeres and an avian replication origin. We confirmed that G4s are found much more stable in tested replication origin and promoters than in human telomere repeats. In addition, we characterized how G4 dynamics was affected by G4 ligands and showed that both folding rate and persistence time increased. Our assay opens new perspectives for the measurement of G4 dynamics in double-stranded DNA mimicking a replication fork, which is important to understand their role in DNA replication and gene regulation at a mechanistic level.

Digital health can transform the management of atrial fibrillation (AF) and enable patients to take a central role in detecting symptoms and self-managing AF. There is a gap in understanding factors that support sustained use of digital health tools for patients with AF. This study identified predictors of Alivecor® KardiaMobile ECG monitor usage among patients with AF enrolled in the iPhone®Helping Evaluate Atrial fibrillation Rhythm through Technology (iHEART) randomized controlled trial.

We analysed data from 105 English and Spanish-speaking adults with AF enrolled in the intervention arm of the iHEART trial. The iHEART intervention included smartphone-based electrocardiogram self-monitoring with Alivecor® KardiaMobile and triweekly text messages for 6 months. The primary outcome was use of Alivecor® categorized as infrequent (≤5 times/week), moderate (>5 times and ≤11 times/week), and frequent (>11 times/week). We applied multinomial logistic regression modelling to characterize frequency and predictors of use. Of the 105 participants, 25% were female, 75% were White, and 45% were ≥65 years of age. Premature atrial contractions (PACs) [adjusted odds ratio (OR) 1.23, 1.08-1.40, P = 0.002] predicted frequent as compared to infrequent use. PACs (adjusted OR 1.17, 95% confidence interval 1.06-1.30, P = 0.003), lower symptom burden (adjusted OR 1.06, 1.01-1.11, P = 0.02), and less treatment concern (adjusted OR 0.96, 0.93-0.99, P = 0.02) predicted moderate as compared to infrequent use.

Frequent use of AliveCor® is associated with AF symptoms and potentially symptomatic cardiac events. Symptom burden and frequency should be measured and incorporated into analyses of future digital health trials for AF management.

Frequent use of AliveCor® is associated with AF symptoms and potentially symptomatic cardiac events. Symptom burden and frequency should be measured and incorporated into analyses of future digital health trials for AF management.Emerging evidence links genes within human-specific segmental duplications (HSDs) to traits and diseases unique to our species. Strikingly, despite being nearly identical by sequence (>98.5%), paralogous HSD genes are differentially expressed across human cell and tissue types, though the underlying mechanisms have not been examined. We compared cross-tissue mRNA levels of 75 HSD genes from 30 families between humans and chimpanzees and found expression patterns consistent with relaxed selection on or neofunctionalization of derived paralogs. In general, ancestral paralogs exhibited greatest expression conservation with chimpanzee orthologs, though exceptions suggest certain derived paralogs may retain or supplant ancestral functions. Concordantly, analysis of long-read isoform sequencing datasets from diverse human tissues and cell lines found that about half of derived paralogs exhibited globally lower expression. To understand mechanisms underlying these differences, we leveraged data from human lymphoblastoid cell lines (LCLs) and found no relationship between paralogous expression divergence and post-transcriptional regulation, sequence divergence, or copy number variation. Considering cis-regulation, we reanalyzed ENCODE data and recovered hundreds of previously unidentified candidate CREs in HSDs. We also generated large-insert ChIP-sequencing data for active chromatin features in an LCL to better distinguish paralogous regions. Some duplicated CREs were sufficient to drive differential reporter activity, suggesting they may contribute to divergent cis-regulation of paralogous genes. This work provides evidence that cis-regulatory divergence contributes to novel expression patterns of recent gene duplicates in humans.

To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease.

For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years.

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