"I'm quite proud of how we've handled it": health professionals' experiences of returning additional findings from the 100,000 genomes project.

Participants in the 100,000 Genomes Project (100kGP) could consent to receive additional finding (AF) results, individual variants relating to genes associated with susceptibility to cancer and familial hypercholesterolemia (FH). In the study reported here, qualitative interviews were used to explore the experiences of National Health Service (NHS) professionals from across England who were tasked with returning over 80,000 "no AF" results and 700 positive AF results to 100kGP participants. Interviews were conducted with 45 professionals from a range of backgrounds, including Genetic Counsellors, Clinical Geneticists, FH Clinical Nurse Specialists and Clinical Scientists.

Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2).

Background/objectives: Unfortunately, not all metastatic castration resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing in prostate cancer.

Subjects/methods: In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC.

Therapeutic implications of homologous repair deficiency testing in patients with prostate cancer (Part 2 of 2).

Background/objectives: Unfortunately, not all metastatic castration-resistant prostate cancer (mCRPC) patients receive available life-prolonging systemic therapies, emphasizing the need to optimize mCRPC treatment selections. Better guidelines are necessary to determine genetic testing for prostate cancer.

Subjects/methods: In this two-part expert opinion-based guide, we provide an expert consensus opinion on the utilization of germline and somatic testing to detect HRR alterations in patients with mCRPC.

Clinical cell-surface targets in metastatic and primary solid cancers.

Therapies against cell-surface targets (CSTs) represent an emerging treatment class in solid malignancies. However, high-throughput investigations of CST expression across cancer types have been reliant on data sets of mostly primary tumors, despite therapeutic use most commonly in metastatic disease. We identified a total of 818 clinical trials of CST therapies with 78 CSTs.

Impact of depression and cardiovascular risk factors on cognitive impairment in patients with atrial fibrillation: A Systematic review and meta-analysis.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with significant cardiovascular morbidity and mortality, as well as cognitive impairment (CI). The interplay between AF and CI is complex, involving various pathophysiological changes and numerous risk factors. Among them, depression has emerged as a significant contributor to both AF and CI, further complicating the relationship between these conditions.

Estimating the economic effect of harm associated with high risk prescribing of oral non-steroidal anti-inflammatory drugs in England: population based cohort and economic modelling study.

Objectives: To quantify prevalence, harms, and NHS costs in England of problematic oral non-steroidal anti-inflammatory drug (NSAID) prescribing in high risk groups.

Design: Population based cohort and economic modelling study.

Setting: Economic models estimating patient harm associated with NSAID specific hazardous prescribing events, and cost to the English NHS, over a 10 year period, were combined with trends of hazardous prescribing event to estimate national levels of patient harm and NHS costs.

Use of All of Us data to increase health literacy and research skills in high school students.

Objective: This case study describes how an All of Us engagement project returned value to community by strengthening high school students' capacity to serve as health advocates.

Materials And Methods: Project activities included health literacy education and research projects on the influence of environmental, societal, and lifestyle factors on community health disparities. The research project involved use of the Photovoice method and All of Us data.

The role of specialist palliative care in individuals "living beyond cancer": a narrative review of the literature.

Purpose: Many patients living beyond cancer experience significant unmet needs, although few of these patients are currently reviewed by specialist palliative care teams (SPCTs). The aim of this narrative review was to explore the current and potential role of SPCTs in this cohort of patients.

Methods: A search strategy was developed for Medline, and adapted for Embase, CINAHL, and PsycInfo.

The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

Objectives: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2).

Subjects And Methods: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years.

Cholestasis alters polarization and suppressor function of hepatic regulatory T cells.

Fibrosing cholangiopathies, including biliary atresia and primary sclerosing cholangitis, involve immune-mediated bile duct epithelial injury and hepatic bile acid (BA) retention (cholestasis). Regulatory T-cells (Tregs) can prevent auto-reactive lymphocyte activation, yet the effects of BA on this CD4 lymphocyte subset are unknown. Gene regulatory networks for hepatic CD4 lymphocytes in a murine cholestasis model revealed Tregs are polarized to Th17 during cholestasis.

Implementation of a multicomponent medication adherence promotion system is associated with a decrease in late T-cell-mediated rejection.

Poor immunosuppression adherence in pediatric recipients of liver transplant (LT) contributes to late T-cell-mediated rejection (TCMR) in ~90% of cases and increases the risk of mortality. A medication adherence promotion system (MAPS) was found to reduce late rejection in pediatric recipients of kidney transplants. Using quality improvement methodology, we adapted and implemented the MAPS in our LT clinic.

Same People, Different Results: Categorizing Cancer Registry Cases Across the Rural-Urban Continuum.

Background: Many rural-urban indexes are utilized in cancer research. This variation introduces inconsistencies between studies. Recommendations on index use have prioritized geographical unit over feasibility of inclusion in analysis.

Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock.

Background: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]).

Genetic analysis of reveals high gene flow in the South-West Indian Ocean.

(Gray, 1849), abundant in the South-West Indian Ocean (SWIO), constitutes a vital resource for both subsistence and commercial fisheries. However, despite this socioeconomic importance, and recent indications of overfishing, little is known about the population structure of in the region. To inform sustainable management strategies, this study assessed the spatio-temporal population structure and genetic variability of at 20 sites in the SWIO (Kenya, Tanzania, Mozambique, Madagascar, Mauritius, Rodrigues, and the Seychelle Islands) by complementary analysis of mitochondrial DNA (mtDNA) noncoding region (NCR) sequences and microsatellite markers.

Distinct effects of racial and socioeconomic disparities on biliary atresia diagnosis and outcome.

Objectives: To identify and distinguish between racial and socioeconomic disparities in age at hepatology care, diagnosis, access to surgical therapy, and liver transplant-free survival in patients with biliary atresia (BA).

Methods: Single-center retrospective cohort study of 69 BA patients from 2010 to 2021. Patients were grouped into White and non-White cohorts.

Virtual Access to STEM Careers: In the Field Experiments.

The Virtual Access to STEM Careers (VASC) project is an intertwined classroom and virtual reality (VR) curricular program for third through fourth graders. Elementary school students learn about and take on the roles and responsibilities of STEM occupations through authentic, problem-based tasks with physical kits and immersive VR environments. This article reports on a round of curriculum and virtual environment development and in-classroom experimentation that was guided by preliminary results gathered from our initial VASC prototyping and testing.

Radiation Oncology Ransomware Attack Response Risk Analysis Using Failure Modes and Effects Analysis.

Purpose: There have been numerous significant ransomware attacks impacting Radiation Oncology in the past 5 years. Research into ransomware attack response in Radiation Oncology has consisted of case reports and descriptive articles and has lacked quantitative studies. The purpose of this work was to identify the significant safety risks to patients being treated with radiation therapy during a ransomware attack scenario, using Failure Modes and Effects Analysis.

A platform-independent AI tumor lineage and site (ATLAS) classifier.

Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.

Estimating the health impact of nicotine exposure by dissecting the effects of nicotine versus non-nicotine constituents of tobacco smoke: A multivariable Mendelian randomisation study.

The detrimental health effects of smoking are well-known, but the impact of regular nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing daily use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]).

New Insights on Liver-Directed Therapies in Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) has been increasing over the past decades, but improvements in systemic and locoregional therapies is increasing survival. Current locoregional treatment options include ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and stereotactic body radiotherapy (SBRT). There is ongoing research regarding the combination of systemic and local therapies to maximize treatment effect as well as in new non-invasive, image-guided techniques such as histotripsy.

Utility of Postoperative Phone Calls in Reducing Unplanned Health Care Utilization.

Introduction: Postoperative phone calls ideally proactively identify concerns. This study aimed to determine whether postoperative phone calls after elective outpatient pediatric urology surgery were associated with differences in postoperative healthcare utilization.

Methods: This retrospective cross-sectional study included patients undergoing elective outpatient pediatric urologic surgery in selected months of 2019-2021.