COLOFIT: Development and Internal-External Validation of Models Using Age, Sex, Faecal Immunochemical and Blood Tests to Optimise Diagnosis of Colorectal Cancer in Symptomatic Patients.

Background: Colorectal cancer (CRC) is the third most common cancer in the United Kingdom and the second largest cause of cancer death.

Aim: To develop and validate a model using available information at the time of faecal immunochemical testing (FIT) in primary care to improve selection of symptomatic patients for CRC investigations.

Methods: We included all adults (≥ 18 years) referred to Nottingham University Hospitals NHS Trust between 2018 and 2022 with symptoms of suspected CRC who had a FIT.

Medication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years.

Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.

12-month neurological and psychiatric outcomes of semaglutide use for type 2 diabetes: a propensity-score matched cohort study.

Background: While semaglutide, approved for type-2 diabetes mellitus (T2DM), is being investigated as a treatment for brain disorders, concerns over adverse neuropsychiatric events have emerged. More data are therefore needed to assess the effects of semaglutide on brain health. This study provides robust estimates of the risk of neurological and psychiatric outcomes following semaglutide use compared to three other antidiabetic medications.

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.

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.

Diagnostic Accuracy of Four-Dimensional Computed Tomography in Preoperative Localization of Primary Hyperparathyroidism After Negative or Inconclusive Sestamibi: A Systematic Review and Meta-analysis.

Objective: The aim of the study is to assess the diagnostic accuracy of 4-dimensional computed tomography (4D-CT) scans for patients with primary hyperparathyroidism (pHPT) after negative or inconclusive Technetium-99m sestamibi single-photon emission computed tomography scan.

Methods: A literature search of several databases was conducted from inception to August 2023. Eligible studies reported adult patients (>18 years old) who underwent 4D-CT after negative or inconclusive sestamibi results.

Pan-European atmospheric lead pollution, enhanced blood lead levels, and cognitive decline from Roman-era mining and smelting.

Ancient texts and archaeological evidence indicate substantial lead exposure during antiquity that potentially impacted human health. Although lead exposure routes were many and included the use of glazed tablewares, paints, cosmetics, and even intentional ingestion, the most significant for the nonelite, rural majority of the population may have been through background air pollution from mining and smelting of silver and lead ores that underpinned the Roman economy. Here, we determined potential health effects of this air pollution using Arctic ice core measurements of Roman-era lead pollution, atmospheric modeling, and modern epidemiology-based relationships between air concentrations, blood lead levels (BLLs), and cognitive decline.

Emergency care knowledge, utilization, and barriers in Northern Tanzania: A community-based survey.

Background: Emergency care systems are critical to improving care for time-sensitive emergency conditions. The growth and development of these systems in Sub-Saharan Africa is becoming a priority. Layperson knowledge and recognition of emergency symptoms and subsequent care-seeking behavior are key to achieving timely access to care and appropriate treatment.

Genetic variation of hemolysin co-regulated protein 1 affects the immunogenicity and pathogenicity of Burkholderia pseudomallei.

Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B.

Stroke severity shapes extracellular vesicle profiles and their impact on the cerebral endothelial cells.

Ischaemic stroke is a leading cause of death and disability. Circulating extracellular vesicles (EVs) post-stroke may help brain endothelial cells (BECs) counter ischaemic injury. However data on how EVs from ischaemic stroke patients, considering injury severity, affect these cells are limited.

Structure-Activity Relationships for s-Block Metal/Co(III) Heterodinuclear Catalysts in Cyclohexene Oxide Ring-Opening Copolymerizations.

In homogeneous catalysis, uncovering structure-activity relationships remains very rare but invaluable to understand and rationally improve performances. Here, generalizable structure-activity relationships apply to a series of heterodinuclear polymerization catalysts featuring Co(III) and s-block metals M(I/II) (M= Na(I), K(I), Ca(II), Sr(II), Ba(II)). These are shown to apply to polycarbonate production by the ring-opening copolymerizations (ROCOP) of cyclohexene oxide (CHO) and carbon dioxide (CO2), conducted at high (20 bar) and low (1 bar) CO2 pressures, and to polyester production by copolymerization of cyclohexene oxide and phthalic anhydride (PA).

Characterization of TFIIE-regulated genes by transcriptome analysis.

Background/aim: Previous studies on general transcription factor II E (GTF2E) showed that it is associated with certain groups of diseases, such as colon cancer and trichothiodystrophy, but the global effect of GTF2E on cellular processes is still not widely characterized. This study aimed to investigate and characterize the effect of GTF2E on the transcription level of genes and identify the cellular processes and diseases associated with GTF2E.

Materials And Methods: The human colorectal carcinoma cell line HCT116 used in the study was transfected at a 30 nM concentration with siGTF2E1 or nontarget negative siRNA.

The pivotal role of sleep in mediating the effects of life stressors and healthy habits on allostatic load in mid-life adults.

Objectives: We assessed the modulation of allostatic load (AL) by engagement in healthy habits and life stressors, mediated through resilience and the perceived influence of the stressors. Sleep was included as third mediator given extensive evidence associating to all the analysed factors.

Methods: Structural equation models to assess the modulation of AL by either traumatic or psychosocial stressors and healthy habits were generated with data from 620 mid-life adults (age 51.

The global implications of a Russian gas pivot to Asia.

Recent years have seen unprecedented shifts in global natural gas trade, precipitated in large part by Russia's war on Ukraine. How this regional conflict impacts the future of natural gas markets is subject to three interconnected factors: (i) Russia's strategy to regain markets for its gas exports; (ii) Europe's push towards increased liquified natural gas (LNG) and the pace of its low carbon transition; and (iii) China's gas demand and how it balances its climate and energy security objectives. A scenario modelling approach is applied to explore the potential implications of this geopolitical crisis.

Linzagolix rapidly reduces heavy menstrual bleeding in women with uterine fibroids: An analysis of the PRIMROSE 1 & 2 trials.

Objective: To study the timing of the effect of linzagolix, an oral GnRH antagonist, on significant reduction in heavy menstrual bleeding (HMB) in women with uterine fibroids.

Design: The study used pooled data from PRIMROSE1 and PRIMROSE2, two double-blind, similar placebo-controlled trials of linzagolix in US and Europe, respectively. Eligible participants were randomized equally across four treatment arms (linzagolix 100mg and 200mg, with and without concomitant hormonal add-back therapy [ABT] consisting of 1 mg estradiol and 0.

A systematic review and meta-analysis of endovascular treatment of carotid blowout syndrome.

Unlabelled: Carotid Blowout Syndrome (CBS) is a rare and life-threatening condition that necessitates prompt intervention to prevent fatal hemorrhage. This study compares the outcomes of two primary endovascular approaches: reconstructive interventions, which aim to preserve carotid artery function using stents or balloon angioplasty, and deconstructive interventions, which involve vessel occlusion to halt bleeding. A systematic review and meta-analysis were performed by searching multiple databases for relevant studies published from January 2000 to August 2023.

Incongruent virtual reality cycling exercise demonstrates a role of perceived effort in cardiovascular control.

In this study we have used a highly immersive virtual reality (VR) cycling environment where incongruence between virtual hill gradient (created by visual gradient and bike tilt angle) and actual workload (pedalling resistance) can experimentally manipulate perception of exercise effort. This therefore may provide a method to examine the role of effort perception in cardiorespiratory control during exercise. Twelve healthy untrained participants (7 men, age 26 ± 5 years) were studied during five visits.

Place-based household vouchers for locally supplied fruit and vegetables: the Fresh Street pilot cluster randomised controlled trial.

Background: Households in areas of socio-economic deprivation are more likely to consume diets low in fruit and vegetables. Fresh Street is a place-based fruit and vegetable voucher scheme with vouchers redeemable with local independent (non-supermarket) vendors. Paper vouchers are offered to all households in a geographical area regardless of household type, size, or income with no requirement to demonstrate need.

ARSACS: Clinical Features, Pathophysiology and iPS-Derived Models.

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease caused by mutations in the SACS gene. The first two mutations were identified in French Canadian populations 20 years ago. The disease is now known as one of the most frequent recessive ataxias worldwide.

HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies.

HLA-E is a nonclassical, nonpolymorphic, class Ib HLA molecule. Its primary function is to present a conserved nonamer peptide, termed VL9, derived from the signal sequence of classical MHC molecules to the NKG2x-CD94 receptors on NK cells and a subset of T lymphocytes. These receptors regulate the function of NK cells, and the importance of this role, which is conserved across mammalian species, probably accounts for the lack of genetic polymorphism.

The online version of an evidence-based hand exercise programme for people with rheumatoid arthritis: An effectiveness-implementation study.

Background: The Strengthening and Stretching for Rheumatoid Arthritis of the Hand (SARAH) program is an evidence-based exercise program for adults with hand function difficulties due to rheumatoid arthritis. A self-guided online version of the program has been developed for direct access by patients.

Purpose: To evaluate the delivery of the online program in routine therapy care and its impact on clinical outcomes, before making it widely available.

A Digital Parenting Intervention With Intimate Partner Violence Prevention Content: Quantitative Pre-Post Pilot Study.

Background: Intimate partner violence (IPV) and violence against children are global issues with severe consequences. Intersections shared by the 2 forms of violence have led to calls for joint programming efforts to prevent both IPV and violence against children. Parenting programs have been identified as a key entry point for addressing multiple forms of family violence.

Midwives' experience of managing emergencies during labour and birth in a community setting: a mixed-methods systematic review.

Background: For women at low risk of complications during labour and birth, in the United Kingdom, planned birth in a 'community' setting (at home or a freestanding midwifery unit) is generally safe, and intrapartum emergencies are uncommon. Limited exposure may affect midwives' experience of managing an emergency.

Aim: Identify and synthesise available evidence about midwives' experiences of managing intrapartum emergencies during labour in a community setting.

Thalamic deep brain stimulation for central poststroke pain syndrome: an international multicenter study.

Objective: The effectiveness and optimal stimulation site of deep brain stimulation (DBS) for central poststroke pain (CPSP) remain elusive. The objective of this retrospective international multicenter study was to assess clinical as well as neuroimaging-based predictors of long-term outcomes after DBS for CPSP.

Methods: The authors analyzed patient-based clinical and neuroimaging data of previously published and unpublished cohorts from 6 international DBS centers.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.