Unlocking Tomorrow's Health Care: Expanding the Clinical Scope of Wearables by Applying Artificial Intelligence.

As an integral aspect of healthcare, digital technology has enabled modeling of complex relationships to detect, screen, diagnose and predict patient outcomes. With massive datasets, Artificial Intelligence (AI) can have marked impact on three levels: for patients, clinicians, and health systems. In this review, we discuss contemporary AI enabled wearable devices undergoing research in the field of cardiovascular medicine. These include devices such as smart watches, ECG patches and smart textiles such as smart socks and chest sensors for diagnosis, management and prognostication of conditions such as atrial fibrillation (AF) , heart failure (HF) and hypertension as well as monitoring for cardiac rehabilitation. We review the evolution of machine learning algorithms used in wearable devices from random forest models to the use of convolutional neural networks and transformers. We further discuss frameworks for wearable technologies such as the V3 stage process of verification, analytical validation and clinical validation as well as challenges of AI integration in medicine such as data veracity, validity, security and provide a reference framework to maintain fairness and equityy. Lastly clinician and patient perspectives are discussed to highlight the importance of considering end-user feedback in development and regulatory processes.

The emergence of "us and them" in 80 lines of code: modeling group genesis in homogeneous populations.

Psychological explanations of group genesis often require population heterogeneity in identity or other characteristics, whether deep (e.g., religion) or superficial (e.g., eye color). We used agent-based models to explore group genesis in homogeneous populations and found robust group formation with just two basic principles: reciprocity and transitivity. These emergent groups demonstrated in-group cooperation and out-group defection, even though agents lacked common identity. Group formation increased individual payoffs, and group number and size were robust to varying levels of reciprocity and transitivity. Increasing population size increased group size more than group number, and manipulating baseline trust in a population had predictable effects on group genesis. An interactive demonstration of the parameter space and source code for implementing the model are available online.

Computational approaches to the detection and analysis of sequences with intramolecular G-quadruplex forming potential.

Sequences with the potential to form intramolecular G-quadruplexes (G4-structures) are found in highly nonrandom distributions in the genomes of diverse organisms. These sequences are associated with nucleic acid metabolic processes ranging from transcription and translation to recombination and telomere function. Here we review different computational methods for identifying potential G4-forming sequences and provide protocols for their implementation. We also discuss methods for assessing the significance and specificity of associations between the sequences and different biological functions.

Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae.

Although well studied in vitro, the in vivo functions of G-quadruplexes (G4-DNA and G4-RNA) are only beginning to be defined. Recent studies have demonstrated enrichment for sequences with intramolecular G-quadruplex forming potential (QFP) in transcriptional promoters of humans, chickens and bacteria. Here we survey the yeast genome for QFP sequences and similarly find strong enrichment for these sequences in upstream promoter regions, as well as weaker but significant enrichment in open reading frames (ORFs). Further, four findings are consistent with roles for QFP sequences in transcriptional regulation. First, QFP is correlated with upstream promoter regions with low histone occupancy. Second, treatment of cells with N-methyl mesoporphyrin IX (NMM), which binds G-quadruplexes selectively in vitro, causes significant upregulation of loci with QFP-possessing promoters or ORFs. NMM also causes downregulation of loci connected with the function of the ribosomal DNA (rDNA), which itself has high QFP. Third, ORFs with QFP are selectively downregulated in sgs1 mutants that lack the G4-DNA-unwinding helicase Sgs1p. Fourth, a screen for yeast mutants that enhance or suppress growth inhibition by NMM revealed enrichment for chromatin and transcriptional regulators, as well as telomere maintenance factors. These findings raise the possibility that QFP sequences form bona fide G-quadruplexes in vivo and thus regulate transcription.

Unique, shared, and redundant roles for the Arabidopsis SWI/SNF chromatin remodeling ATPases BRAHMA and SPLAYED.

Chromatin remodeling is emerging as a central mechanism for patterning and differentiation in multicellular eukaryotes. SWI/SNF chromatin remodeling ATPases are conserved in the animal and plant kingdom and regulate transcriptional programs in response to endogenous and exogenous cues. In contrast with their metazoan orthologs, null mutants in two Arabidopsis thaliana SWI/SNF ATPases, BRAHMA (BRM) and SPLAYED (SYD), are viable, facilitating investigation of their role in the organism. Previous analyses revealed that syd and brm null mutants exhibit both similar and distinct developmental defects, yet the functional relationship between the two closely related ATPases is not understood. Another central question is whether these proteins act as general or specific transcriptional regulators. Using global expression studies, double mutant analysis, and protein interaction assays, we find overlapping functions for the two SWI/SNF ATPases. This partial diversification may have allowed expansion of the SWI/SNF ATPase regulatory repertoire, while preserving essential ancestral functions. Moreover, only a small fraction of all genes depends on SYD or BRM for expression, indicating that these SWI/SNF ATPases exhibit remarkable regulatory specificity. Our studies provide a conceptual framework for understanding the role of SWI/SNF chromatin remodeling in regulation of Arabidopsis development.