The promise of molecular science in brain health. What breakthroughs are anticipated in the next 20 years?

Brain health means optimal physiological brain function across the normal life-course. It encompasses not only healthy brain aging but also brain diseases, their diagnosis and treatment. In all these areas, molecular science has advanced our understanding.

Economic evaluation of extended panel analysis in cancer patients with historical NHS diagnostic germline genetic testing - A modeling study based on real-world data.

Background: The South West Thames Centre for Genomics implemented a wider diagnostic Next Generation Sequencing (NGS) gene panel for eligible cancer patients undergoing diagnostic testing whilst restricting data analysis and reporting for BRCA1/BRCA2/PALB2/CHEK2 1100delC only as per contemporaneous guidelines. This study investigated the cost-utility of reanalyzing existing diagnostic grade extended panel data for truncating germline pathogenic variants (GPVs) in known moderate risk cancer susceptibility genes (CSGs) and performing follow-up genetic testing for first-degree relatives if patients have an identified CSG allele.

Methods: Reanalysis of existing NGS data was undertaken in 889 samples from cancer patients contemporaneously eligible through the NHS England National Genomic Test Directory (NGTD) codes R207 (ovarian) or R208 (breast) who had tested negative for BRCA1/BRCA2/PALB2 and CHEK2 1100delC founder variant.

Bruck syndrome in pregnancy.

Bruck syndrome is a rare, autosomal-recessive condition associated with features of both arthrogryposis and osteogenesis imperfecta. It is characterised by congenital large joint contractures with pterygia and bone fragility, leading to fractures and deformities, along with a short stature caused by progressive skeletal deformities. There are fewer than 50 described cases of Bruck syndrome in the literature, with no reported cases in pregnancy.

Can ChatGPT make surgical decisions with confidence similar to experienced knee surgeons?

Background: Unicompartmental knee replacements (UKRs) have become an increasingly attractive option for end-stage single-compartment knee osteoarthritis (OA). However, there remains controversy in patient selection. Natural language processing (NLP) is a form of artificial intelligence (AI).

Development and validation of prediction models for fetal growth restriction and birthweight: an individual participant data meta-analysis.

Background: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes.

Objectives: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data.

CMR is vital in the management of cardiology inpatients: a tertiary centre experience.

To review the utility of cardiovascular magnetic resonance (CMR) in the management of hospital inpatients, we performed a retrospective review of all inpatient CMR scans performed over a six-month period at a tertiary referral cardiology centre. Patient demographics, indication for CMR imaging, results of the CMR scans and whether the results changed patient management were recorded. Change in management included medication changes, subsequent invasive procedures, or avoidance of such, and hospital discharge.

Percentage mammographic density or absolute breast density for risk stratification in breast screening: Possible implications for socioeconomic health disparity.

Objectives: Obesity levels and mortality from breast cancer are higher in more deprived areas of the UK, despite lower breast cancer incidence. Supplemental imaging for women with dense breasts has been proposed as a potential improvement to screening, but it is not clear how stratification by percentage mammographic density (%MD) would be reflected across socioeconomic groups. This study aims to clarify the associations between breast composition (dense and fatty tissue) and socioeconomic status in a multi-ethnic screening population.

The PS4-likelihood ratio calculator: flexible allocation of evidence weighting for case-control data in variant classification.

Background: The 2015 American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant classification framework specifies that case-control observations can be scored as 'strong' evidence (PS4) towards pathogenicity.

Methods: We developed the PS4-likelihood ratio calculator (PS4-LRCalc) for quantitative evidence assignment based on the observed variant frequencies in cases and controls. Binomial likelihoods are computed for two models, each defined by prespecified OR thresholds.

Lenacapavir to prevent HIV infection: current prices versus estimated costs of production.

Background: Despite improvements in treatment and oral pre-exposure prophylaxis (PrEP) access, 1.3 million people acquired HIV in 2022. Six-monthly lenacapavir PrEP could benefit tens of millions of people at high risk of infection.

Development and validation of a virtual teaching method for minimally invasive surgery skills: a prospective cohort study.

Introduction: The COVID-19 pandemic led to a significant reduction in operative exposure for surgical trainees, necessitating alternative training methods to mitigate the impact on surgical education. This study sought to evaluate whether minimally invasive surgery (MIS) skills could be taught remotely using widely available technology with objective assessments of proficiency.

Methods: This was a pilot observational study with a comparative assessment of face-to-face (F2F) and virtual training of novice learners in MIS skills.

How Do We Better Serve Excluded Populations When Delivering Digital Health Technology? Inclusion Evaluation of a Digital Musculoskeletal Self-Management Solution.

Background: Digital self-management platforms have been proposed as a solution to better support people manage their musculoskeletal (MSK) condition. However, research studies often explicitly exclude people who can't access internet connected devices. An important consideration is that digital exclusion (for people without access to an internet connected device) from these new digital options will worsen already existing inequality and inequity in healthcare.

What is the effect of bariatric surgery on health-related quality of life in people with obesity? Observational cohort analysis of the United Kingdom National Bariatric Surgery Registry.

Background: Previous small studies investigating health-related quality of life (HRQoL) following bariatric surgery have demonstrated heterogenous effects. This study aimed to use National Bariatric Surgery Registry (NBSR) records to investigate the relationship between weight and HRQoL in people undergoing bariatric surgery in the UK.

Materials And Methods: In this observational study using United Kingdom National Bariatric Surgery Registry (NBSR) records between 1st June 2017 and 23rd November 2022, patients undergoing primary bariatric surgery with one baseline and at least one follow-up visit within 1 year from surgery were eligible for inclusion.

Ex vivo host transcriptomics during Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans infection of PBMCs from South African volunteers.

Cryptococcus neoformans, Cryptococcus gattii and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of HIV-related deaths globally, with the majority occurring in Africa. The human immune response to C.

Sport PRactice and its Effects on aortic size and valve function in bicuspid Aortic valve Disease: a cross-sectional report from the SPREAD study.

Objective: Concerns exist about the possible detrimental effects of exercise training on aortic size and valve function in individuals with bicuspid aortic valve (BAV). This multicentre international study aimed to determine the characteristics of aortic size and valve function in athletes versus non-athletes with BAV and athletes with tricuspid aortic valve (TAV).

Methods: We enrolled competitive athletes with BAV and age- and sex-matched athletes with TAV and non-athletes with BAV.

Balancing key stakeholder priorities and ethical principles to design a trial comparing intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy: FERN qualitative study.

Objectives: As part of the FERN feasibility study, this qualitative research aimed to explore parents' and clinicians' views on the acceptability, feasibility and design of a randomised controlled trial (RCT) of active intervention versus expectant management in monochorionic (MC) diamniotic twin pregnancies with early-onset (prior to 24 weeks) selective fetal growth restriction (sFGR). Interventions could include laser treatment or selective termination which could lead to the death or serious disability of one or both twins.

Design: Qualitative semi-structured interviews with parents and clinicians.

Investigating Splice Defects in Using Targeted Long-Read Sequencing.

Biallelic variants in are associated with retinitis pigmentosa (RP) and Type 2 Usher Syndrome (USH2), leading to impaired vision and, additionally, hearing loss in the latter. Although the introduction of next-generation sequencing into clinical diagnostics has led to a significant uplift in molecular diagnostic rates, many patients remain molecularly unsolved. It is thought that non-coding variants or variants of uncertain significance contribute significantly to this diagnostic gap.

A local review of section 17 leave forms in conjunction with the Mental Health Act Code of Practice: recommendations for future practice.

Aims And Method: The aim of this project was to set out recommendations for the section 17 leave form to reflect guidance provided in the Mental Health Act 1983: Code of Practice, following local Care Quality Commission feedback. We reviewed guidance in the Code and publicly available leave forms to identify items to include in the leave form. Then, we determined which publicly available leave forms included each item and reviewed whether the item should be included in the leave form and whether any reformulation was needed.