Feasibility and Acceptability of a Technology Mediated Fall Risk Prevention Intervention for Older Adults with Mild Cognitive Impairment.

Background: Falls and fall-related injuries are significant public health issues for adults 65 years of age and older. The annual direct medical costs in the US as a result of falls are estimated to exceed $50 billion, and this estimate does not include the indirect costs of disability, dependence, and decreased quality of life. This project targets community dwelling older adults (OA) with mild cognitive impairment (MCI) who are socially vulnerable and thus at high risk for falling.

Applying AI to Care Management and Claims Processing.

This article explores the current and potential applications of AI in care management and health care administration through the experience of Acentra Health. By discussing various AI use cases, this paper highlights how AI can augment the capabilities of healthcare professionals and streamline operations. Ethical considerations, legal compliance, and the future implications of AI in the health care sector are also examined.

Design and quality control of large-scale two-sample Mendelian randomization studies.

Background: Mendelian randomization (MR) studies are susceptible to metadata errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses.

Causal Estimation of Long-term Intervention Cost-effectiveness Using Genetic Instrumental Variables: An Application to Cancer.

Background: This article demonstrates a means of assessing long-term intervention cost-effectiveness in the absence of data from randomized controlled trials and without recourse to Markov simulation or similar types of cohort simulation.

Methods: Using a Mendelian randomization study design, we developed causal estimates of the genetically predicted effect of bladder, breast, colorectal, lung, multiple myeloma, ovarian, prostate, and thyroid cancers on health care costs and quality-adjusted life-years (QALYs) using outcome data drawn from the UK Biobank cohort. We then used these estimates in a simulation model to estimate the cost-effectiveness of a hypothetical population-wide preventative intervention based on a repurposed class of antidiabetic drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors very recently shown to reduce the odds of incident prostate cancer.

3D microperfusion of mesoscale human microphysiological liver models improves functionality and recapitulates hepatic zonation.

Hepatic in vitro models that accurately replicate phenotypes and functionality of the human liver are needed for applications in toxicology, pharmacology and biomedicine. Notably, it has become clear that liver function can only be sustained in 3D culture systems at physiologically relevant cell densities. Additionally, drug metabolism and drug-induced cellular toxicity often follow distinct spatial micropatterns of the metabolic zones in the liver acinus, calling for models that capture this zonation.

Exploring the Bidirectional Causal Pathways Between Smoking Behaviors and Headache: A Mendelian Randomization Study.

Introduction: Although observational data suggest a relationship between headache and smoking, there remain questions about causality. Smoking may increase headache risk, individuals may smoke to alleviate headaches, or smoking and headache may share common risk factors. Mendelian randomization (MR) is a method that uses genetic variants as instruments for making causal inferences about an exposure and an outcome.

Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

Background: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education.

Investigation of the enhanced antitumour potency of STING agonist after conjugation to polymer nanoparticles.

Intravenously administered cyclic dinucleotides and other STING agonists are hampered by low cellular uptake and poor circulatory half-life. Here we report the covalent conjugation of cyclic dinucleotides to poly(β-amino ester) nanoparticles through a cathepsin-sensitive linker. This is shown to increase stability and loading, thereby expanding the therapeutic window in multiple syngeneic tumour models, enabling the study of how the long-term fate of the nanoparticles affects the immune response.

"Organ-in-a-Column" Coupled On-line with Liquid Chromatography-Mass Spectrometry.

Organoids, i.e., laboratory-grown organ models developed from stem cells, are emerging tools for studying organ physiology, disease modeling, and drug development.

Estimating the causal effect of liability to disease on healthcare costs using Mendelian Randomization.

Accurate measurement of the effects of disease status on healthcare costs is important in the pragmatic evaluation of interventions but is complicated by endogeneity bias. Mendelian Randomization, the use of random perturbations in germline genetic variation as instrumental variables, can avoid these limitations. We used a novel Mendelian Randomization analysis to model the causal impact on inpatient hospital costs of liability to six prevalent diseases and health conditions: asthma, eczema, migraine, coronary heart disease, Type 2 diabetes, and depression.

Does testosterone mediate the relationship between vitamin D and prostate cancer progression? A systematic review and meta-analysis.

Purpose: Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of direct causality is sparse and studies have not examined biological mechanisms, which can provide information on plausibility and strengthen the evidence for causality.

Methods: We used the World Cancer Research Fund International/University of Bristol two-stage framework for mechanistic systematic reviews.

Effects of depression on employment and social outcomes: a Mendelian randomisation study.

Background: Depression is associated with socioeconomic disadvantage. However, whether and how depression exerts a causal effect on employment remains unclear. We used Mendelian randomisation (MR) to investigate whether depression affects employment and related outcomes in the UK Biobank dataset.

Educational attainment as a modifier for the effect of polygenic scores for cardiovascular risk factors: cross-sectional and prospective analysis of UK Biobank.

Background: Understanding the interplay between educational attainment and genetic predictors of cardiovascular risk may improve our understanding of the aetiology of educational inequalities in cardiovascular disease.

Methods: In up to 320 120 UK Biobank participants of White British ancestry (mean age = 57 years, female 54%), we created polygenic scores for nine cardiovascular risk factors or diseases: alcohol consumption, body mass index, low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes and stroke. We estimated whether educational attainment modified genetic susceptibility to these risk factors and diseases.

Autophagy modulates cell fate decisions during lineage commitment.

Early events during development leading to exit from a pluripotent state and commitment toward a specific germ layer still need in-depth understanding. Autophagy has been shown to play a crucial role in both development and differentiation. This study employs human embryonic and induced pluripotent stem cells to understand the early events of lineage commitment with respect to the role of autophagy in this process.

Long-term cost-effectiveness of interventions for obesity: A mendelian randomisation study.

Background: The prevalence of obesity has increased in the United Kingdom, and reliably measuring the impact on quality of life and the total healthcare cost from obesity is key to informing the cost-effectiveness of interventions that target obesity, and determining healthcare funding. Current methods for estimating cost-effectiveness of interventions for obesity may be subject to confounding and reverse causation. The aim of this study is to apply a new approach using mendelian randomisation for estimating the cost-effectiveness of interventions that target body mass index (BMI), which may be less affected by confounding and reverse causation than previous approaches.

Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

Objectives: JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA.

Testosterone and socioeconomic position: Mendelian randomization in 306,248 men and women in UK Biobank.

Men with more advantaged socioeconomic position (SEP) have been observed to have higher levels of testosterone. It is unclear whether these associations arise because testosterone has a causal impact on SEP. In 306,248 participants of UK Biobank, we performed sex-stratified genome-wide association analysis to identify genetic variants associated with testosterone.

Effects of increased body mass index on employment status: a Mendelian randomisation study.

Background: The obesity epidemic may have substantial implications for the global workforce, including causal effects on employment, but clear evidence is lacking. Obesity may prevent people from being in paid work through poor health or through social discrimination. We studied genetic variants robustly associated with body mass index (BMI) to investigate its causal effects on employment.