Analysis-ready VCF at Biobank scale using Zarr.

Background: Variant Call Format (VCF) is the standard file format for interchanging genetic variation data and associated quality control metrics. The usual row-wise encoding of the VCF data model (either as text or packed binary) emphasizes efficient retrieval of all data for a given variant, but accessing data on a field or sample basis is inefficient. The Biobank-scale datasets currently available consist of hundreds of thousands of whole genomes and hundreds of terabytes of compressed VCF.

The Impact of Gamified Interventions on the Management of Chronic Obstructive Pulmonary Disease: Systematic Literature Review.

Background: Chronic obstructive pulmonary disease (COPD) requires consistent sustained management, including regular physical activity, pulmonary rehabilitation, and self-care adherence. Despite strong clinical guidelines, patient engagement remains a major challenge, leading to suboptimal disease control and increased health care use. Gamified interventions have emerged as potential tools to improve adherence, motivation, and outcomes in chronic disease management.

The maternal postnatal six-week check in women with epilepsy: Does the prevalence or subsequent postpartum health differ from the general postnatal population?

Objectives: To examine the prevalence of the maternal postnatal six-week check (SWC) in women with epilepsy compared to a sample of the postnatal population without epilepsy, and assess whether the SWC is associated with health outcomes in the first year postpartum.

Methods: Clinical Practice Research Datalink Aurum and Hospital Episode Statistics data were used to identify births between January1998-March2020 to women with epilepsy (n = 23,533) and a random sample of births to women without epilepsy (n = 317,369). The adjusted risk ratio (aRR) for not having a SWC in women with compared to without epilepsy was estimated using modified Poisson regression.

Likelihoods for a general class of ARGs under the SMC.

Ancestral recombination graphs (ARGs) are the focus of much ongoing research interest. Recent progress in inference has made ARG-based approaches feasible across of range of applications, and many new methods using inferred ARGs as input have appeared. This progress on the long-standing problem of ARG inference has proceeded in two distinct directions.

The Influence of Contextual Social Deprivation on Poor Health Among Urban Male Residents: A Nationally Respresentative Study in China.

This study aimed to examine whether contextual social deprivation is independently associated with health outcomes. A cross-sectional, multistage sampling design was employed to interview participants from six selected cities in China. A standardized questionnaire was used to collect data on individual socioeconomic characteristics and contextual social deprivation.

The heart of palliative care is relational: a scoping review of the ethics of care in palliative medicine.

Background: Palliative care, perhaps more than any subspecialty in healthcare, is deeply relational and engages patients and families at times of great vulnerability. Ethics of care, or relational ethics, developed through contributions from feminist ethics, offers conceptual tools and ways of thinking that seem especially suited to palliative care practice.

Aim: To identify and describe studies and theoretical analyses applying the ethics of care to palliative care (both adult and paediatric), specifically, its use to guide and improve practice and education for palliative care practitioners.

Factors associated with parental hesitancy towards the human papillomavirus vaccine: a cross-sectional study.

Cervical cancer is the second most common cancer among females in Cameroon, with human papillomavirus (HPV) being the primary cause. While HPV vaccines are highly effective and have been introduced by Cameroon's Ministry of Health (MOH), uncertainties persist regarding the determinants of HPV-related vaccine hesitancy. This study investigated the factors associated with parental HPV and cervical cancer awareness as well as parental HPV vaccine hesitancy in Cameroon.

Determining a role for Patient and Public Involvement and Engagement (PPIE) in genomic data governance for cancer care.

Comprehensive collections of cancer data, including genomic data, are needed to improve cancer risk prediction and treatments. A recent government review, Better, Broader, Safer: Using health data for research and analysis, has argued for high-quality Patient and Public Involvement and Engagement (PPIE) for ethical data use. In this paper we determine a role and justification for PPIE to govern uses of genomic data in fields like cancer.

Diagnostic and prognostic value of ECG-predicted hypertension-mediated left ventricular hypertrophy using machine learning.

Objective: Four hypertension-mediated left ventricular hypertrophy (LVH) phenotypes have been reported using cardiac magnetic resonance (CMR): normal LV, LV remodelling, eccentric and concentric LVH, with varying prognostic implications. The electrocardiogram (ECG) is routinely used to detect LVH; however, its capacity to differentiate between LVH phenotypes is unknown. This study aimed to classify hypertension-mediated LVH from the ECG using machine learning and test for associations of ECG-predicted phenotypes with incident cardiovascular outcomes.

The association of ethnicity and migration status with agenda for change pay band in National Health Service healthcare workers: Results from the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH).

Objectives: Ethnic minority and migrant healthcare workers (HCWs) constitute 24% of the UK's National Health Service. Migration status, often overlooked in Human Resources records, is associated with their placement within the Agenda for Change (AfC) pay bands. Therefore, we analysed the association between ethnicity, migration status, and AfC pay bands using data from the UK-REACH cohort study.

Perioperative immunotherapy strategies for resectable non-small cell lung cancer.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare, via a network meta-analysis, the effectiveness and safety of different immunotherapy agents that are administered in a perioperative setting to people with resectable non small-cell lung cancer To perform indirect comparisons in order to generate a clinically meaningful hierarchy of perioperative strategies of immunotherapy administration for overall survival in operable people with resectable non small-cell lung cancer.

Synergies Among Clinicians, Academia, and Industry in the Age of Artificial Intelligence.

In the rapidly evolving landscape of gastrointestinal health care, the integration of artificial intelligence (AI) presents unprecedented opportunities for enhancing patient outcomes, improving efficiency, and driving innovation. Effective collaboration among clinicians, academia, and industry is crucial to harness the full potential of AI technologies. Clinicians offer invaluable insights from real-world practice, ensuring that AI solutions address genuine clinical needs and improve patient care.

Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption.

The major spliceosome contains five small nuclear RNAs (snRNAs; U1, U2, U4, U5 and U6) essential for splicing. Variants in RNU4-2, encoding U4, cause a neurodevelopmental disorder called ReNU syndrome. We investigated de novo variants in 50 snRNA-encoding genes in a French cohort of 23,649 individuals with rare disorders and gathered additional cases through international collaborations.

Long-term health outcomes of bilateral salpingo-oophorectomy in BRCA1 and BRCA2 pathogenic variant carriers with personal history of breast cancer: a retrospective cohort study using linked electronic health records.

Background: Carriers of BRCA1 and BRCA2 pathogenic variants are at elevated risk of developing breast and ovarian cancers. To mitigate ovarian cancer risk, bilateral salpingo-oophorectomy (BSO) is commonly recommended for unaffected carriers and those with personal breast cancer history. Assessing BSO's long-term health outcomes in carriers with previous breast cancer history is essential.

Genomic landscape of diffuse glioma revealed by whole genome sequencing.

Diffuse gliomas are the commonest malignant primary brain tumour in adults. Herein, we present analysis of the genomic landscape of adult glioma, by whole genome sequencing of 403 tumours (256 glioblastoma, 89 astrocytoma, 58 oligodendroglioma; 338 primary, 65 recurrence). We identify an extended catalogue of recurrent coding and non-coding genetic mutations that represents a source for future studies and provides a high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and extrachromosomal DNA.

Delineating Mpl-dependent and -independent phenotypes of Jak2 V617F-positive MPNs in vivo.

The Jak2 V617F mutation stands as the main driver of myeloproliferative neoplasms (MPNs) by constitutively activating signaling through several type I cytokine receptors, namely the erythropoietin receptor, the thrombopoietin receptor (TpoR)/myeloproliferative leukemia (Mpl) protein, and the granulocyte colony-stimulating factor receptor. Among these, TpoR assumes a pivotal role in hematopoietic stem cell renewal and differentiation, being positioned as a key driver of MPNs alongside mutated Jak2. However, the impact of TpoR/Mpl absence in the context of Jak2 V617F in vivo has been explored only through a transgenic Jak2 V617F mouse model, in which regulation of Jak2 expression does not depend on its natural promoter.

Integrative proximal-ubiquitomics profiling for deubiquitinase substrate discovery applied to USP30.

The growing interest in deubiquitinases (DUBs) as drug targets for modulating critical molecular pathways in disease is fueled by the discovery of their specific cellular roles. A crucial aspect of this fact is the identification of DUB substrates. While mass spectrometry-based proteomic methods can be used to study global changes in cellular ubiquitination following DUB activity perturbation, these datasets often include indirect and downstream ubiquitination events.

Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.

Background: Functional disorders (FDs) are characterized by persistent somatic symptoms and are highly comorbid with internalizing disorders (IDs). To provide much-needed insight into FD etiology, we evaluated FD and ID familial coaggregation and shared familiality.

Methods: Lifelines is a three-generation cohort study, which assessed three FDs (myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS], irritable bowel syndrome [IBS], and fibromyalgia [FM]) and six IDs (major depressive disorder [MDD], dysthymia [DYS], generalized anxiety disorder [GAD], agoraphobia [AGPH], social phobia [SPH], and panic disorder [PD]) according to diagnostic criteria.

BSG/ACPGBI guidance on the management of colorectal polyps in patients with limited life expectancy.

Background: Determining optimal management of colorectal polyps in patients with limited life expectancy of under 10 years can be difficult, due to challenges balancing an uncertain natural history of polyp progression to symptomatic malignancy versus the increased risk and consequences of polypectomy complications.

Aim: This British Society of Gastroenterology and Association of Coloproctologists of Great Britain and Ireland guidance aims to help clinicians and patients consider these risks to aid decision-making for polypectomy versus a conservative approach.

Methods: A guidance development group comprising 28 members was established, including gastroenterologists, colorectal surgeons, elderly care physicians, anaesthetists, epidemiologists, nurse endoscopists, a general practitioner and patient representatives.

Saturation genome editing of reveals distinct dominant and recessive neurodevelopmental disorders.

Recently, variants in an 18 nucleotide region in the centre of were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thousands of individuals worldwide. is a non-protein-coding gene that is transcribed into the U4 small nuclear RNA (snRNA) component of the major spliceosome. ReNU syndrome variants disrupt spliceosome function and alter 5' splice site selection.

Go Figure: Transparency in neuroscience images preserves context and clarifies interpretation.

Visualizations are vital for communicating scientific results. Historically, neuroimaging figures have only depicted regions that surpass a given statistical threshold. This practice substantially biases interpretation of the results and subsequent meta-analyses, particularly towards non-reproducibility.

Dietary Factors and Cognitive Function: with a Focus on Subjective Cognitive Decline.

Purpose Of The Review: Age-related cognitive decline is an important global challenge. Substantial evidence suggests that diet may prevent or delay cognitive aging. This narrative review examines recent literature on how dietary factors influence cognitive function, with a focus on subjective cognitive decline (SCD).

Association of Daily Steps with Incident Nonalcoholic Fatty Liver Disease: Evidence from the UK Biobank Cohort.

Purpose: Low physical activity has been shown to be associated with a higher risk of nonalcoholic fatty liver disease (NAFLD). However, the strength and shape of this association are currently uncertain due to a reliance on self-reported physical activity measures. This report aims to investigate the relationship of median daily step count with NAFLD using accelerometer-derived step count from a large prospective cohort study.

Reply to: What evidence is required to justify the NHS Health Check programme?

Medications that reduce blood pressure and cholesterol are among the most cost-effective healthcare interventions available, but their delivery remains suboptimal. In 2009, the National Health Service (NHS) Health Check was introduced to increase the detection and treatment of major cardiovascular risk factors in people aged 40-74 years. In a prospective observational study using the UK Biobank, we compared health outcomes between NHS Health Check attenders and matched non-attenders.