Objective: In the Kingdom of Saudi Arabia (KSA), non-communicable diseases (NCDs) cause 73% of deaths, with high body mass index (BMI) as the leading risk factor. Among adolescents, 79% reported physical inactivity (PA), 30% and 10% were living with overweight/obesity and prediabetes, respectively. Little is known about the influence of school environments in shaping healthy […]
Genome-Wide Association Study of Genetic Variants Associated with Lower Extremity Amputation Risk in Peripheral Artery Disease
Peripheral artery disease (PAD) is a global health burden affecting over 200 million individuals and is frequently complicated by limb-threatening ischemia, leading to major amputations. Despite known clinical risk factors, the genetic basis underlying amputation risk in PAD remains poorly defined. In this study, we performed a multi-pronged genome-wide association study (GWAS) to identify genetic […]
CIZ1-LOSS CAUSES FEMALE-SPECIFIC AUTOSOMAL NEURODEVELOPMENTAL DISORDER THROUGH DEFECTIVE X-INACTIVATION MAINTENANCE
We report an autosomal recessive neurodevelopmental disorder exclusively affecting females carrying biallelic loss-of-function variants in CIZ1, a gene encoding a nuclear matrix protein essential for the maintenance of X-chromosome inactivation. Eight unrelated affected females were identified, whereas male siblings with biallelic variants were asymptomatic. We showed that loss of CIZ1 compromises the maintenance of X-chromosome […]
“Move the ultrasound scanning machine to where the woman is”: Stakeholder perspectives and experiences of task-sharing antenatal ultrasound scanning with trained midwives in Blantyre, Malawi.
In 2018, Malawi adopted the World Health Organization antenatal care (ANC) recommendation of at least one ultrasound scan (USS) for pregnant women before 24 weeks gestation. A shortage of trained providers and USS machines, however, has significantly hindered implementation. A qualitative study explored diverse stakeholder perspectives on integrating USS into ANC services through task-sharing with […]
Estimating geographic access to health care services for children unvaccinated against diphtheria, tetanus, pertussis across low- and middle-income countries in 2021
Achieving routine immunization for all children remains a major challenge in many low- and middle-income countries. In 2021, 18.1 million children globally missed their first dose of the diphtheria-tetanus-pertussis vaccine (DTP1), highlighting gaps in immunization and healthcare services. The Global Immunization Agenda 2030 aims for 90% coverage of essential childhood and adolescent vaccines and a […]
Multi-polygenic scores for externalizing behavior in schoolchildren
Background: Externalizing behavior refers to emotional and behavioral problems or disorders characterized by conducts directed outward at an individual’s environment. Polygenic scores (PGSs) indexing the individual genetic susceptibility for this behavior still explain a small proportion of the phenotypic variance. To increase this phenotypic variance explained for externalizing behavior we used a multi-PGS approach combining […]
Unraveling dynamic factors in Dialectic Behavioural Treatment for Adolescents (DBT-A): a study protocol
Dialectical Behavioural Therapy for Adolescents (DBT-A) is an effective treatment for adolescents exhibiting features of borderline personality disorder (BPD). However, some do not benefit, potentially leading to major negative outcomes later in life. Previous quantitative studies have highlighted the importance of dynamic (changeable) factors in determining treatment success, including the therapeutic alliance, emotional dynamics between […]
An economic evaluation of a specialist mental health service for healthcare workers in the East of England
Background Healthcare workers experience disproportionately high rates of depression, anxiety, and posttraumatic stress compared with the general population. Within the NHS, work related stress and mental health related sickness absence has increased over the past decade, a trend intensified by COVID-19. The mental health support offers are patchy across the UK, and the evidence base […]
BMPR-II biomarkers for testing therapeutic efficacy in pulmonary arterial hypertension: The StratosPHere 1 study.
Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease where deficiency of the TGF/BMP pathways have causal roles in hereditary and idiopathic forms. It is an attractive candidate for therapeutic intervention but there is an unmet need for clinically-relevant and practical biomarkers that can measure target engagement. A major challenge has been the inaccessibility of […]
Machine Learning and Micro Capture-C resolve GWAS associations revealing endothelial stress pathways in Coronary Artery Disease
Resolving the gene targets of non-coding genetic variation is the major bottleneck in translating genome wide association studies into mechanistic understanding of complex diseases such as coronary artery disease (CAD). Combining new Transformer-based Machine Learning (ML) approaches trained on cardiovascular epigenetics with high-resolution, allele-specific genomic and transcriptomic technologies we create a highly scalable platform to […]