Targeted Polymer-Peptide Conjugates for E-Selectin Blockade in Renal Injury.

Background/objectives: Leukocytes play a significant role in both acute kidney injury (AKI) and chronic kidney disease (CKD), contributing to pathogenesis and tissue damage. The process of leukocyte infiltration into the inflamed tissues is mediated by the interactions between the leukocytes and cell adhesion molecules (CAMs, i.e.

Genome-wide association analysis of composite sleep health scores in 413,904 individuals.

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

British Society of Gastroenterology National Evaluation of Colonoscopy Quality: Findings from the National Endoscopy Database.

Background And Aims: Analysis of national colonoscopy quality using automatically uploaded data from a national database, including exploring performance variation.

Methods: Data on all colonoscopies performed in the UK 01/03/2019-29/02/2020 and recorded in the National Endoscopy Database were analysed. Unadjusted key performance indicators were calculated and proportions of endoscopists achieving national standards were determined.

Cross-sectional relationships of circadian misalignment and rest-activity rhythms with occupational attainment in UK Biobank participants.

Circadian misalignment and disrupted rest-activity rhythms have been linked to adverse health and educational outcomes, yet few studies have considered their relationships with economic outcomes. We investigate associations between multiple accelerometer-measured circadian misalignment traits (Composite Phase Deviation and the Sleep Regularity Index) and rest-activity rhythm traits (Inter-daily Stability, Intra-daily variability and relative amplitude), with occupational attainment, measured using the average wage paid to an individual's occupation. We use data from 20 356 UK Biobank participants who wore an accelerometer (2013-16), provided employment data for the year they wore the accelerometer, and supplied covariate data at recruitment (2006-10).

Comparative Efficacy and Safety of Endoscopic Modalities for Colorectal Cancer Screening in Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis.

Background & Aims: Long-standing inflammatory bowel disease (IBD) increases the risk of colonic neoplasia, necessitating effective screening strategies. This network meta-analysis compared the efficacy and safety between different endoscopic modalities in the high-definition (HD) era.

Methods: We searched CENTRAL, ClinicalTrials.

Update from 2010 (standard operating procedure): protocol for the 2024 British Society of Gastroenterology Guidelines on colorectal surveillance in inflammatory bowel disease.

Introduction: The evolving landscape of inflammatory bowel disease (IBD) necessitates refining colonoscopic surveillance guidelines. This study outlines methodology adopted by the British Society of Gastroenterology (BSG) Guideline Development Group (GDG) for updating IBD colorectal surveillance guidelines.

Methods And Analysis: The 'Grading of Recommendations, Assessment, Development and Evaluation' (GRADE) approach, as outlined in the GRADE handbook, was employed.

Association between Accelerometer-Measured Irregular Sleep Duration and Longitudinal Changes in Body Mass Index in Older Adults.

Irregular sleep duration may disrupt circadian rhythms and contribute to metabolic, behavioral, and mood changes, potentially increasing the risk for obesity. However, quantitative data on the relationship between sleep duration irregularity and weight change are lacking. In this prospective study, we analyzed data from 10,572 participants (mean age: 63 years) in the UK Biobank who wore accelerometers for a week between 2013-2015 and had two body mass index (BMI; kg/m) measurements on average 2.

Exploring caregiver experiences of communicating with children about differences of sex development (DSD).

Objective: Explore the caregiver experience of communicating about differences of sex development (DSD) with their children. Evidence-based guidance regarding how, when, and what information is shared by caregivers is lacking and is needed to inform optimal information sharing strategies for this population.

Methods: Qualitative semi-structured interviews were conducted with 15 caregivers of children with DSD, recruited from 3 multidisciplinary DSD clinics.

Brighter nights and darker days predict higher mortality risk: A prospective analysis of personal light exposure in >88,000 individuals.

Light enhances or disrupts circadian rhythms, depending on the timing of exposure. Circadian disruption contributes to poor health outcomes that increase mortality risk. Whether personal light exposure predicts mortality risk has not been established.

Addressing disparities in the long-term mortality risk in individuals with non-ST segment myocardial infarction (NSTEMI) by diabetes mellitus status: a nationwide cohort study.

Aims/hypothesis: The aim of this study was to investigate how diabetes mellitus affects longer term outcomes in individuals presenting to hospital with non-ST segment elevation myocardial infarction (NSTEMI).

Methods: We analysed data from 456,376 adults hospitalised between January 2005 and March 2019 with NSTEMI from the UK Myocardial Ischaemia National Audit Project (MINAP) registry, linked with Office for National Statistics death reporting. We compared outcomes and quality of care by diabetes status.

Dendritic Cell-Targeted Nanoparticles Enhance T Cell Activation and Antitumor Immune Responses by Boosting Antigen Presentation and Blocking PD-L1 Pathways.

Dendritic cells (DCs) within the tumor microenvironment (TME) have an insufficient capacity to activate T cells through antigen presentation. Furthermore, the programmed cell-death ligand 1 (PD-L1), abundantly expressed on tumor-associated DCs, binds the programmed cell-death 1 (PD-1)-positive T cells and suppresses their immune function. The binding of PD-L1 to CD80 (B7.

Post-COVID changes and disparities in cardiovascular mortality rates in the United States.

Introduction: The COVID-19 pandemic disrupted healthcare delivery and increased cardiovascular morbidity and mortality. This study assesses whether cardiovascular mortality rates in the US have recovered post-pandemic and examines the equity of this recovery across different populations.

Methods: We analyzed data from the CDC WONDER database, covering US residents' mortality from 2018-2023.

Sleep inertia drives the association of evening chronotype with psychiatric disorders: epidemiological and genetic evidence.

Evening chronotypes (a.k.a.

The variation in post-endoscopy upper gastrointestinal cancer rates among endoscopy providers in England and associated factors: a population-based study.

Background: Post-endoscopy upper gastrointestinal cancer (PEUGIC) is an important key performance indicator for endoscopy quality. We examined variation in PEUGIC rates among endoscopy providers in England and explored associated factors.

Methods: The was a population-based, retrospective, case-control study, examining data from National Cancer Registration and Analysis Service and Hospital Episode Statistics databases for esophageal and gastric cancers diagnosed between 2009 and 2018 in England.

Defining Success in the Delivery of Fertility-Related Care for Patients with Differences of Sex Development.

Introduction: Individuals with differences of sex development (DSD) experience complex, often competing, medical and psychosocial challenges surrounding fertility. The study aimed to characterize how "success" in fertility-related care is conceptualized and attained among individuals with a DSD, their parents or caregivers, healthcare providers, and other stakeholders.

Methods: As part of a larger study, DSD stakeholders (n = 110) participated in semi-structured interviews covering the clinical care of patients with DSD.