Measurement and data transmission validity of a multi-biosensor system for real-time remote exercise monitoring among cardiac patients

Background: Remote telemonitoring holds great potential to augment management of patients with coronary heart disease (CHD) and atrial fibrillation (AF) by enabling regular physiological monitoring during physical activity. Remote physiological monitoring may improve home and community exercise-based cardiac rehabilitation (exCR) programs and could improve assessment of the impact and management of pharmacological interventions for heart rate control in individuals with AF.Objective: Our aim was to evaluate the measurement validity and data transmission reliability of a remote telemonitoring system comprising a wireless multi-parameter physiological sensor, custom mobile app, and middleware platform, among individuals in sinus rhythm and AF.Methods: Participants in sinus rhythm and with AF undertook simulated daily activities, low, moderate, and/or high intensity exercise. Remote monitoring system heart rate and respiratory rate were compared to reference measures (12-lead ECG and indirect calorimeter). Wireless data transmission loss was calculated between the sensor, mobile app, and remote Internet server.Results: Median heart rate (-0.30 to 1.10 b∙min-1) and respiratory rate (-1.25 to 0.39 br∙min-1) measurement biases were small, yet statistically significant (all P≤.003) due to the large number of observations. Measurement reliability was generally excellent (rho=.87-.97, all P<.001; intraclass correlation coefficient [ICC]=.94-.98, all P<.001; coefficient of variation [CV]=2.24-7.94%), although respiratory rate measurement reliability was poor among AF participants (rho=.43, P<.001; ICC=.55, P<.001; CV=16.61%). Data loss was minimal (<5%) when all system components were active; however, instability of the network hosting the remote data capture server resulted in data loss at the remote Internet server during some trials.Conclusions: System validity was sufficient for remote monitoring of heart and respiratory rates across a range of exercise intensities. Remote exercise monitoring has potential to augment current exCR and heart rate control management approaches by enabling the provision of individually tailored care to individuals outside traditional clinical environments

Devotions for Lent 2023 Hymns of Lent

This Lent, we will continue reflecting on hymns of faith, namely, some of our most beloved Lenten hymns. 10 such hymns have been chosen to fill the 40(+) days of Lent. Therefore, this devotional, different from previous editions, does not proceed on a weekly basis, but merely flows from one hymn to the next. Also different from previous editions, the devotional reflections are specifically based on the stanzas of the selected hymns. Therefore, each day’s reflection features the text of the hymn stanza, a devotion based on that stanza, a prayer, and then a Scripture passage or passages for further meditation. I pray these reflections may be of edification for you during this Lenten season.https://scholar.csl.edu/osp/1022/thumbnail.jp

Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential

Current approaches to staging chronic liver diseases have limited utility for predicting liver cancer risk. Here, we employed single-nucleus RNA sequencing (snRNA-seq) to characterize the cellular microenvironment of healthy and pre-malignant livers using two distinct mouse models. Downstream analyses unraveled a previously uncharacterized disease-associated hepatocyte (daHep) transcriptional state. These cells were absent in healthy livers but increasingly prevalent as chronic liver disease progressed. Copy number variation (CNV) analysis of microdissected tissue demonstrated that daHep-enriched regions are riddled with structural variants, suggesting these cells represent a pre-malignant intermediary. Integrated analysis of three recent human snRNA-seq datasets confirmed the presence of a similar phenotype in human chronic liver disease and further supported its enhanced mutational burden. Importantly, we show that high daHep levels precede carcinogenesis and predict a higher risk of hepatocellular carcinoma development. These findings may change the way chronic liver disease patients are staged, surveilled, and risk stratified

Metabolic Versatility and Antibacterial Metabolite Biosynthesis Are Distinguishing Genomic Features of the Fire Blight Antagonist Pantoea vagans C9-1

Smits THM, Rezzonico F, Kamber T, et al. Metabolic Versatility and Antibacterial Metabolite Biosynthesis Are Distinguishing Genomic Features of the Fire Blight Antagonist Pantoea vagans C9-1. PLoS ONE. 2011;6(7): e22247.Background: Pantoea vagans is a commercialized biological control agent used against the pome fruit bacterial disease fire blight, caused by Erwinia amylovora. Compared to other biocontrol agents, relatively little is currently known regarding Pantoea genetics. Better understanding of antagonist mechanisms of action and ecological fitness is critical to improving efficacy. Principal Findings: Genome analysis indicated two major factors contribute to biocontrol activity: competition for limiting substrates and antibacterial metabolite production. Pathways for utilization of a broad diversity of sugars and acquisition of iron were identified. Metabolism of sorbitol by P. vagans C9-1 may be a major metabolic feature in biocontrol of fire blight. Biosynthetic genes for the antibacterial peptide pantocin A were found on a chromosomal 28-kb genomic island, and for dapdiamide E on the plasmid pPag2. There was no evidence of potential virulence factors that could enable an animal or phytopathogenic lifestyle and no indication of any genetic-based biosafety risk in the antagonist. Conclusions: Identifying key determinants contributing to disease suppression allows the development of procedures to follow their expression in planta and the genome sequence contributes to rationale risk assessment regarding the use of the biocontrol strain in agricultural systems

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Peer reviewe

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques