Cluster effect for SNP-SNP interaction pairs for predicting complex traits.

Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions.

External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab.

Objective: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy).

Design: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant.

Cross-cultural comparison of low back pain in the nursing workforce: A pilot study.

Aim: This study aimed to analyse cross-cultural differences in the prevalence of low back pain (LBP) and other back pain of general nurses in direct inpatient care in the Czech Republic (CZ) and Great Britain (GB).

Methods: The survey was used using an extended standardized Nordic Musculoskeletal Questionnaire and self-created additional questions. The data were analysed with Stata 15 using a significance level of 0.

Loss of reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes.

There are multiple independent genetic signals at the () locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss remains unknown.

Optical Coherence Tomography Measures Predicting Fractional Flow Reserve: The OMEF Study.

Background: Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to evaluate the value of OCT in predicting fractional flow reserve (FFR).

Methods: We performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel.

Ion carrier modulated MRI contrast.

An ion-responsive MRI contrast agent based on a POPC liposomal scaffold is generated that displays a large amplitude relaxivity switch. Entrapment of MR active Gd-DOTA within cholesterol-doped, , membrane rigidified, liposomes dampens the MR response through diminished water exchange across the lipid bilayer. Relaxivity is re-established by integration of ion carriers in the liposome membrane to mediate solvated ion flux.

PITX2 deficiency leads to atrial mitochondrial dysfunction.

Aims: Reduced left atrial PITX2 is associated with atrial cardiomyopathy and atrial fibrillation (AF). PITX2 is restricted to left atrial cardiomyocytes (aCMs) in the adult heart. The links between PITX2 deficiency, atrial cardiomyopathy, and AF are not fully understood.

Leveraging 3D Atrial Geometry for the Evaluation of Atrial Fibrillation: A Comprehensive Review.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with significant morbidity and mortality. Managing risk of stroke and AF burden are pillars of AF management. Atrial geometry has long been recognized as a useful measure in achieving these goals.

Comparison of Patients Classified as High-Risk between International Cardiovascular Disease Primary Prevention Guidelines.

Cardiovascular disease (CVD) primary prevention guidelines classify people at high risk and recommended for pharmacological treatment based on clinical criteria and absolute CVD risk estimation. Despite relying on similar evidence, recommendations vary between international guidelines, which may impact who is recommended to receive treatment for CVD prevention. To determine the agreement in treatment recommendations according to guidelines from Australia, England and the United States.

The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines.

Objective: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research.

Design: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM.

Cyclin F-EXO1 axis controls cell cycle-dependent execution of double-strand break repair.

Ubiquitination is a crucial posttranslational modification required for the proper repair of DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). DSBs are mainly repaired through homologous recombination (HR) when template DNA is present and nonhomologous end joining (NHEJ) in its absence. In addition, microhomology-mediated end joining (MMEJ) and single-strand annealing (SSA) provide backup DSBs repair pathways.

Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction.

Aims: Disruption of the predictable symmetry of the healthy heart may be an indicator of cardiovascular risk. This study defines the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases.

Methods And Results: The analysis includes 44 796 UK Biobank participants (average age 64.

Transfusion Camp: The UK experience and its value in improving knowledge of transfusion medicine among postgraduate trainees.

Objectives: To report the UK experience of rolling out Transfusion Camp.

Background: Transfusion Camp is a structured education programme developed in Toronto, with the aim of reducing knowledge gaps in transfusion medicine in postgraduate trainees. It consists of didactic lectures viewed online by the participants, then interactive, locally delivered seminars.

SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.

While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis.

Quantitative Computed Tomography Angiography for the Evaluation of Valvular Fibrocalcific Volume in Aortic Stenosis.

Background: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods.

Objectives: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression.

Extending mechanical thrombectomy service provision to 24/7: a break-even analysis.

Background: Comprehensive stroke centres across England have developed investment proposals, showing the estimated increases in mechanical thrombectomy (MT) treatment volume that would justify extending the standard hours to a 24/7 service provision. These investment proposals have been developed taking a financial accounting perspective, that is by considering the financial revenues from tariff income. However, given the pressure put on local health authorities to provide value for money services, an affordability question emerges.

Sacubitril/Valsartan Versus Enalapril in Chronic Chagas Cardiomyopathy: Rationale and Design of the PARACHUTE-HF Trial.

Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF.

The characteristics of CTCF binding sequences contribute to enhancer blocking activity.

While the elements encoding enhancers and promoters have been relatively well studied, the full spectrum of insulator elements which bind the CCCTC binding factor (CTCF), is relatively poorly characterized. This is partly due to the genomic context of CTCF sites greatly influencing their roles and activity. Here we have developed an experimental system to determine the ability of minimal, consistently sized, individual CTCF elements to interpose between enhancers and promoters and thereby reduce gene expression during differentiation.

Hif-2α programs oxygen chemosensitivity in chromaffin cells.

The study of transcription factors that determine specialized neuronal functions has provided invaluable insights into the physiology of the nervous system. Peripheral chemoreceptors are neurone-like electrophysiologically excitable cells that link the oxygen concentration of arterial blood to the neuronal control of breathing. In the adult, this oxygen chemosensitivity is exemplified by type I cells of the carotid body, and recent work has revealed one isoform of the hypoxia-inducible transcription factor (HIF), HIF-2α, as having a nonredundant role in the development and function of that organ.