Investigating the added value of incorporatingmammographic density to an integrated breastcancer risk model with questionnaire-based riskfactors and polygenic risk score.

Introduction: Incorporation of mammographic density to breast cancer risk models could improve risk stratification to tailor screening and prevention strategies according to risk. Robust evaluation of the value of adding mammographic density to models with comprehensive information on questionnaire-based risk factors and polygenic risk score is needed to determine its effectiveness in improving risk stratification of such models.

Methods: We used the Individualized Coherent Absolute Risk Estimator (iCARE) tool for risk model building and validation to incorporate density to a previously validated literature-based model with questionnaire-based risk factors and a 313-variant polygenic risk score (PRS).

Wasm-iCARE: a portable and privacy-preserving web module to build, validate, and apply absolute risk models.

Objectives: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face limitations in portability and privacy due to their need for circulating user data in remote servers for operation. We overcome this by porting iCARE to the web platform.

Wasm-iCARE: a portable and privacy-preserving web module to build, validate, and apply absolute risk models.

Objective: Absolute risk models estimate an individual's future disease risk over a specified time interval. Applications utilizing server-side risk tooling, such as the R-based iCARE (R-iCARE), to build, validate, and apply absolute risk models, face serious limitations in portability and privacy due to their need for circulating user data in remote servers for operation. Our objective was to overcome these limitations.

Moving Toward Findable, Accessible, Interoperable, Reusable Practices in Epidemiologic Research.

Data sharing is essential for reproducibility of epidemiologic research, replication of findings, pooled analyses in consortia efforts, and maximizing study value to address multiple research questions. However, barriers related to confidentiality, costs, and incentives often limit the extent and speed of data sharing. Epidemiological practices that follow Findable, Accessible, Interoperable, Reusable (FAIR) principles can address these barriers by making data resources findable with the necessary metadata, accessible to authorized users, and interoperable with other data, to optimize the reuse of resources with appropriate credit to its creators.

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci.

Aged interleukin-10tm1Cgn chronically inflamed mice have substantially reduced fat mass, metabolic rate, and adipokines.

Interleukin 10tm1Cgn (IL 10tm) mice have been utilized as a model of chronic inflammation and declining health span because of their propensity to develop chronic activation in NFkB pathways, skeletal muscle and cardiac changes, and mitochondrial dysfunction. We hypothesized that older IL 10tm frail mice would have alterations similar to frail, older humans in measured parameters of glucose metabolism, oxygen consumption (VO2), respiratory quotient (RQ), spontaneous locomotor activity, body composition and plasma adipokine levels. To test this hypothesis, we investigated these metabolic parameters in cohorts of 3, 10, and 20 month old IL 10tm female mice and age and gender matched C57Bl/6 mice.

The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases.

Objectives: Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D-frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic diseases (cardiovascular disease, diabetes, hyperlipidemia, hypertension) in this relationship.