Molecular basis of human angiotensin-1 converting enzyme inhibition by a series of diprolyl-derived compounds.

Angiotensin-1-converting enzyme (ACE) is a zinc-dependent carboxypeptidase of therapeutic interest for the treatment of hypertension, inflammation and fibrosis. It consists of two homologous N and C catalytic domains, nACE and cACE, respectively. Unfortunately, the current clinically available ACE inhibitors produce undesirable side effects due to the nonselective inhibition of these domains.

Benchmarking Alzheimer's disease prediction: personalised risk assessment using polygenic risk scores across various methodologies and genome-wide studies.

Background: The success of selecting high risk or early-stage Alzheimer's disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer's disease (AD). Our study comprehensively examines AD PRS utility using various methods and models.

Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study.

Aims: To assess outcomes of oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c), where specific treatment guidance is limited.

Materials And Methods: Using hospital-linked UK primary care records (Clinical Practice Research Datalink; 2004-2020), we identified 7084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer and haemochromatosis) preceding diabetes diagnosis (type 3c cohort), initiating oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors or thiazolidinediones), and without concurrent insulin treatment. We stratified by pancreatic exocrine insufficiency [PEI] (n = 5917 without PEI, 1167 with PEI) and matched to 97 227 type 2 diabetes (T2D) controls.

Progression of the faecal microbiome in preweaning dairy calves that develop cryptosporidiosis.

Background: Cryptosporidiosis is a diarrheal disease that commonly affects calves under 6 weeks old. The causative agent, Cryptosporidium parvum, has been associated with the abundance of specific taxa in the faecal microbiome during active infection. However, the long-term impact of these microbiome shifts, and potential effects on calf growth and health have not yet been explored in depth.

Application of a high-throughput swarm-based deep neural network Algorithm reveals SPAG5 downregulation as a potential therapeutic target in adult AML.

Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored.

The association between the healthy lifestyle index and MRI-derived body composition measurements in the UK Biobank study.

A high healthy lifestyle index (HLI) score, which reflects an adequate amount of sleep, no alcohol consumption, no smoking, a moderate to high physical activity level, a high quality diet, and a normal body mass index (BMI), has been associated with reduced risk of morbidity and mortality. We examined the relationship between the HLI and measurements of adipose and lean tissue volumes measured using magnetic resonance imaging (MRI). We studied 33,002 participants in the UK Biobank study, aged 40-69 years at enrolment.

A multi-level analysis of motor and behavioural dynamics in 9-month-old preterm and term-born infants during changing emotional and interactive contexts.

Computational analysis of infant movement has significant potential to reveal markers of developmental health. We report two studies employing dynamic analyses of motor kinematics and motor behaviours, which characterise movement at two levels, in 9-month-old infants. We investigate the effect of preterm birth (< 33 weeks of gestation) and the effect of changing emotional and social-interactive contexts in the still-face paradigm.

A global analysis of dairy consumption and incident cardiovascular disease.

The role of dairy products in cardiovascular disease (CVD) prevention remains controversial. This study investigates the association between dairy consumption and CVD incidence using data from the China Kadoorie Biobank and the UK Biobank, complemented by an updated meta-analysis. Among Chinese participants, regular dairy consumption (primarily whole milk) is associated with a 9% increased risk of coronary heart disease (CHD) and a 6% reduced risk of stroke compared to non-consumers.

Observation of quantum strong Mpemba effect.

An ancient and counterintuitive phenomenon known as the Mpemba effect (water can cool faster when initially heated up) showcases the critical role of initial conditions in relaxation processes. How to realize and utilize this effect for speeding up relaxation is an important but challenging task in purely quantum system till now. Here, we experimentally study the strong Mpemba effect in a single trapped ion system in which an exponentially accelerated relaxation in time is observed by preparing an optimal quantum initial state with no excitation of the slowest decaying mode.

Prevalence of and factors associated with long COVID among diverse healthcare workers in the UK: a cross-sectional analysis of a nationwide study (UK-REACH).

Objectives: To assess the prevalence of UK healthcare workers (HCWs) who reported symptoms of COVID-19 lasting for longer than 5 weeks and examine associated factors with experiencing long COVID in an ethnically diverse cohort.

Design: A cross-sectional study using data from the UK Research study into Ethnicity And COVID-19 Outcomes in HCWs cohort study.

Setting: Data were collected electronically between December 2020 and March 2021.

Evaluating the pathological and clinical implications of errors made by an artificial intelligence colon biopsy screening tool.

Objective: Artificial intelligence (AI) tools for histological diagnosis offer great potential to healthcare, yet failure to understand their clinical context is delaying adoption. IGUANA (Interpretable Gland-Graphs using a Neural Aggregator) is an AI algorithm that can effectively classify colonic biopsies into normal versus abnormal categories, designed to automatically report normal cases. We performed a retrospective pathological and clinical review of the errors made by IGUANA.

Real-world evaluation of physiotherapist-led exercise prehabilitation and rehabilitation during autologous stem cell transplantation in myeloma: a single-centre experience.

Background: There is emerging evidence for the role of exercise in optimising function, quality of life (QoL) and reducing hospital length-of-stay if commenced prior to undergoing autologous stem cell transplantation (ASCT). A local pilot study of a prehabilitation and rehabilitation intervention during ASCT for myeloma patients indicated promising results and was adapted to translate into local clinical care. The aim of this report is to describe an overview of a newly implemented physiotherapist-led exercise prehabilitation and rehabilitation service delivered as part of the myeloma ASCT pathway, and present real-world findings related to changes in function and QoL.

Fusion, fission, and scrambling of the bilaterian genome in Bryozoa.

Groups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates.

Expedited Conveyance of Out-of-Hospital-Cardiac Arrest patients with STEMI and shockable rhythms to Cardiac Arrest Centres - A Feasibility Pilot Study of the British Cardiovascular Intervention Society conveyance algorithm.

Background And Aims: Guidelines suggest non-traumatic out-of-hospital cardiac arrest (OHCA) be conveyed to cardiac arrest centres (CAC). We hypothesised that (a) a pre-hospital conveyance algorithm based on initial presenting rhythm following OHCA is feasible and (b) that would demonstrate survival advantage.

Methods: This observational pilot study included all consecutive patients with OHCA from suspected cardiac aetiology from the county of Essex, United Kingdom from April 2022-April 2023.

Advancements in understanding the role and mechanism of sirtuin family (SIRT1-7) in breast cancer management.

Breast cancer (BC) is the most prevalent type of cancer in women worldwide and it is classified into a few distinct molecular subtypes based on the expression of growth factor and hormone receptors. Though significant progress has been achieved in the search for novel medications through traditional and advanced approaches, still we need more efficacious and reliable treatment options to treat different types and stages of BC. Sirtuins (SIRT1-7) a class III histone deacetylase play a major role in combating various cancers including BC.

An automated method of streamlining waiting list by clinical risk fast-tracking for patients awaiting TAVR: SWIFT TAVR algorithm.

Introduction: Transcatheter aortic valve replacement (TAVR) is increasingly in demand for treating severe aortic stenosis in a variety of surgical risk profiles. This means increasing wait times and elevated morbidity and mortality on the waitlist. To address this, we developed the SWIFT TAVR algorithm to prioritize patients based on clinical risk and reduce wait times.

Proton Beam Therapy for Pancreatic Tumors: A Consensus Statement from the Particle Therapy Cooperative Group Gastrointestinal Subcommittee.

Objectives: Radiotherapy manages pancreatic cancer in various settings; however, the proximity of gastrointestinal (GI) luminal organs-at-risk (OAR) poses challenges to conventional radiotherapy. Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic tumors.

Subthalamic nucleus oscillations during facial emotion processing and apathy in Parkinson's disease.

Background: Parkinson's disease (PD) is primarily characterized by motor symptoms, but patients also experience a relatively high prevalence of non-motor symptoms, including emotional and cognitive impairments. While the subthalamic nucleus (STN) is a common target for deep brain stimulation to treat motor symptoms in PD, its role in emotion processing is still under investigation. This study examines the subthalamic neural oscillatory activities during facial emotion processing and its association with affective characteristics.

Detecting Xe in an atmospheric tracer experiment.

The Xcounts algorithm for calculating air concentrations of radioactive xenon isotopes (Eslinger et al., 2023) has been extended to estimate Xe in addition to Xe, Xe, Xe, and Xe. The algorithm was applied to 119 samples collected with a SAUNA Q system (Ringbom et al.

In HFpEF, semaglutide reduced a composite of worsening HF or CV death.

GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text].

Examining Intersectionality and Barriers to the Uptake of Video Consultations Among Older Adults From Disadvantaged Backgrounds With Limited English Proficiency: Qualitative Narrative Interview Study.

Background: The rapid shift to video consultation services during the COVID-19 pandemic has raised concerns about exacerbating existing health inequities, particularly for disadvantaged populations. Intersectionality theory provides a valuable framework for understanding how multiple dimensions of disadvantage interact to shape health experiences and outcomes.

Objective: This study aims to explore how multiple dimensions of disadvantage-specifically older age, limited English proficiency, and low socioeconomic status-intersect to shape experiences with digital health services, focusing on video consultations.

Developing an Evidence- and Theory-Informed Mother-Daughter mHealth Intervention Prototype Targeting Physical Activity in Preteen Girls of Low Socioeconomic Position: Multiphase Co-Design Study.

Background: Preteen girls of lower socioeconomic position are at increased risk of physical inactivity. Parental support, particularly from mothers, is positively correlated with girls' physical activity levels. Consequently, family-based interventions are recognized as a promising approach to improve young people's physical activity.

Intraocular Inflammation (IOI) Associated with Faricimab Therapy: One-year Real World Outcomes.

Purpose: To report one-year real-world evidence on intraocular inflammation (IOI) adverse events (AEs) in patients undergoing faricimab therapy in a tertiary care hospital.

Methods: A retrospective review of electronic medical records was conducted for patients receiving faricimab treatment for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) at Moorfields Eye Hospital between September 1st, 2022, and August 31st, 2023. The primary outcome was the incidence of IOI (excluding endophthalmitis).