Colorectal carcinogenesis in the Lynch syndromes and familial adenomatous polyposis: trigger events and downstream consequences.

Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path_APC) and pathogenic mismatch repair gene (path_MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path_APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years.

A meta-analysis of the effects of plyometric training on muscle strength and power in martial arts athletes.

Background: Plyometric training (PT) was explored as an effective intervention for enhancing muscle strength and power. However, its specific impact on these attributes in martial arts athletes had not been systematically evaluated. Therefore, the objective of this meta-analysis was to provide a quantitative assessment of the impact of PT on muscle strength and power in martial arts athletes.

Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting.

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation.

Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation.

Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels.

Background: HuR/ELAV1, a ubiquitous RNA-binding protein, belongs to the RNA-binding protein family and is crucial for stabilizing and regulating the translation of various mRNA targets, influencing gene expression. Elevated HuR levels are associated with multiple disorders, including cancer and neurodegenerative diseases. Despite the identification of small molecule inhibitors targeting HuR, their detailed characterization remains limited.

Single-cell RNA sequencing highlights the role of distinct natural killer subsets in sporadic amyotrophic lateral sclerosis.

Background: Neuroinflammation plays a major role in amyotrophic lateral sclerosis (ALS), and cumulative evidence suggests that systemic inflammation and the infiltration of immune cells into the brain contribute to this process. However, no study has investigated the role of peripheral blood immune cells in ALS pathophysiology using single-cell RNA sequencing (scRNAseq).

Methods: We aimed to characterize immune cells from blood and identify ALS-related immune alterations at single-cell resolution.

Mediation of the effect of prenatal maternal smoking on time to natural menopause in daughters by birthweight-for-gestational-age z-score and breastfeeding duration: analysis of two UK birth cohorts born in 1958 and 1970.

Background: Prenatal maternal smoking, lower birthweight, and shorter breastfeeding duration have all been associated with an earlier age at menopause in daughters. We estimated the extent to which birthweight-for-gestational-age z-score and breastfeeding duration mediate the effect of prenatal maternal smoking on time to natural menopause in daughters.

Methods: Using pooled data from two prospective birth cohort studies - the 1970 British Cohort Study (n = 3,878) followed-up to age 46 years and the 1958 National Child Development Study (n = 4,822) followed-up to age 50 years - we perform mediation analysis with inverse odds weighting implemented in Cox proportional-hazards models.

"We're all in the same storm, but not all of us are in the same boat": qualitative exploration of UK response-focused civil servants experiences of working from home during COVID-19.

Introduction: The experiences of UK Government response-focused employees, who were considered frontline workers during the coronavirus response, are missing from current literature. Meeting the demands of being on the frontline, whilst also adjusting from a normal and practiced way of working to having to work from within one's home, may bring a plethora of new barriers and facilitators associated with providing an effective pandemic response.

Method: This interview study collected and analysed data from 30 UK Civil servants who worked on the COVID-19 pandemic response from their own homes.

Relationship between handgrip strength and timed up-and-go test on hospitalization costs in older adults: a population-based study.

Background: Weak handgrip strength and slow timed up-and-go (TUG) time are known risk factors for hospitalization among older adults; however, few studies have investigated the relationships between these physical tests and future hospitalization costs.

Methods: We used data from 13,613 participants in the population-based Singapore Chinese Health Study who underwent assessment for handgrip strength and TUG time at a mean age of 74 years. Hospitalization costs for the subsequent year, among those who survived for at least one year thereafter, were ascertained via linkage with administrative healthcare finance data.

Osteology and functional morphology of a transitional pterosaur Dearc sgiathanach from the Middle Jurassic (Bathonian) of Scotland.

Pterosaurs were the first vertebrates to evolve active flight. The lack of many well-preserved pterosaur fossils limits our understanding of the functional anatomy and behavior of these flight pioneers, particularly from their early history (Triassic to Middle Jurassic). Here we describe in detail the osteology of an exceptionally preserved Middle Jurassic pterosaur, the holotype of Dearc sgiathanach from the Isle of Skye, Scotland.

Predictors of specialist care referrals (SCR) following emergency department review or hospital admission in adults with previous acute COVID-19: a prospective UK cohort study.

Background: Long-COVID research to date focuses on outcomes in non-hospitalised vs. hospitalised survivors. However Emergency Department attendees (post-ED) presenting with acute COVID-19 may experience less supported recovery compared to people admitted and discharged from hospital (post-hospitalised group, PH).

Neonatal indicator data in Tanzania District Health Information System: evaluation of availability and quality of selected newborn indicators, 2015-2022.

Background: The Every Newborn Action Plan (ENAP) indicators are essential in monitoring neonatal healthcare coverage and quality. The District Health Information System (DHIS2), an open-source platform in over 80 countries, supports health data collection and analysis, enabling progress tracking at national and subnational levels. This study evaluates the availability and quality of maternal and newborn health indicators, explicitly focusing on ENAP indicators within Tanzania's DHIS2.

Enhancing trauma triage in low-resource settings using machine learning: a performance comparison with the Kampala Trauma Score.

Background: Traumatic injuries are a leading cause of morbidity and mortality globally, with a disproportionate impact on populations in low- and middle-income countries (LMICs). The Kampala Trauma Score (KTS) is frequently used for triage in these settings, though its predictive accuracy remains under debate. This study evaluates the effectiveness of machine learning (ML) models in predicting triage decisions and compares their performance to the KTS.

Cost-Utility Analysis of LifeVest® in Post-Myocardial Infarction Patients at Risk of Sudden Cardiac Death in England.

Background: Patients with a left ventricular ejection fraction ≤ 35% are at increased risk of sudden cardiac death (SCD) within the first months after a myocardial infarction (MI). The wearable cardioverter defibrillator (WCD) is an established, safe and effective solution which can protect patients from SCD during the first months after an MI, when the risk of SCD is at its peak. This study aimed to evaluate the cost-effectiveness of WCD combined with guideline-directed medical therapy (GDMT) compared to GDMT alone, after MI in the English National Health Service (NHS).

Hallmarks of Appetite: A Comprehensive Review of Hunger, Appetite, Satiation, and Satiety.

Purpose Of Review: The present review describes the available literature on the physiologic mechanisms that modulate hunger, appetite, satiation, and satiety with a particular focus on well-established and emerging factors involved in the classic satiety cascade model.

Recent Finding: Obesity is a significant risk factor for numerous chronic conditions like cancer, cardiovascular diseases, and diabetes. As excess energy intake is considered by some to be the primary driver of weight gain, tremendous collective effort should be directed toward reducing excessive feeding at the individual and population levels.

Hormone circuit explains why most HPA drugs fail for mood disorders and predicts the few that work.

Elevated cortisol in chronic stress and mood disorders causes morbidity including metabolic and cardiovascular diseases. There is therefore interest in developing drugs that lower cortisol by targeting its endocrine pathway, the hypothalamic-pituitary-adrenal (HPA) axis. However, several promising HPA-modulating drugs have failed to reduce long-term cortisol in mood disorders, despite effectiveness in other hypercortisolism conditions such as Cushing's syndrome.

Genome-wide analysis of TCP family genes and their constitutive expression pattern analysis in the melon (Cucumis melo).

Background: TCP proteins are plant-specific transcription factors that play essential roles in various developmental processes, including leaf morphogenesis and senescence, flowering, lateral branching, hormone crosstalk, and stress responses. However, a comprehensive analysis of genome-wide TCP genes and their expression patterns in melon is yet to be done.

Objective: The present study aims to identify and analyze the TCP genes in the melon genome and understand their putative functions.

Adjunctive therapea - a promising method in the treatment of periodontal disease.

Objectives: The aim of the study is to compare the clinical efficacy of the application of "Armenicum" paste as an adjunct to SRP for the non-surgical treatment of patients with periodontitis.

Methods: The current RCT prospective study was conducted on 157 patients with chronic periodontitis. The patients were blind randomly assigned into two groups: Group A (SRP + Armenicum" paste) 81 patients (42 males and 39 females, 37 to 68 years) and Group B (SRP) 76 patients (39 males and 37 females, 37 to 68 years).

Unleashing creativity in people with Parkinson's disease: a pilot study of a co-designed creative arts therapy.

Background: Conventional medical management, while essential, cannot address all multifaceted consequences of Parkinson's disease (PD). This pilot study explores the potential of a co-designed creative arts therapy on health-related quality of life, well-being, and pertinent non-motor symptoms.

Methods: We conducted an exploratory pilot study with a pre-post design using validated questionnaires.

Glucose Lowering through Weight management (GLoW): a randomised controlled trial of the clinical and cost effectiveness of a diabetes education and behavioural weight management programme vs a diabetes education programme in adults with a recent diagnosis of type 2 diabetes.

Aims/hypothesis: UK standard care for type 2 diabetes is structured diabetes education, with no effects on HbA, small, short-term effects on weight and low uptake. We evaluated whether remotely delivered tailored diabetes education combined with commercial behavioural weight management is cost-effective compared with current standard care in helping people with type 2 diabetes to lower their blood glucose, lose weight, achieve remission and improve cardiovascular risk factors.

Methods: We conducted a pragmatic, randomised, parallel two-group trial.

AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility.

Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker.

Associations of inferior frontal sulcal hyperintensities on brain MRI with cerebral small vessel disease, cognitive function, and depression symptoms.

Inferior frontal sulcal hyperintensities (IFSH) observed on fluid-attenuated inversion recovery (FLAIR) MRI have been proposed as indicators of elevated cerebrospinal fluid waste accumulation in cerebral small vessel disease (CSVD). However, to validate IFSH as a reliable imaging biomarker, further replication studies are required. The objective of this study was to investigate associations between IFSH and CSVD, and their potential repercussions, i.

Optimal network sizes for most robust Turing patterns.

Many cellular patterns exhibit a reaction-diffusion component, suggesting that Turing instability may contribute to pattern formation. However, biological gene-regulatory pathways are more complex than simple Turing activator-inhibitor models and generally do not require fine-tuning of parameters as dictated by the Turing conditions. To address these issues, we employ random matrix theory to analyze the Jacobian matrices of larger networks with robust statistical properties.

The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics.

The evolution of eukaryotes is a fundamental event in the history of life. The closest prokaryotic lineage to eukaryotes, the Asgardarchaeota, encode proteins previously found only in eukaryotes, providing insight into their archaeal ancestor. Eukaryotic cells are characterized by endomembrane organelles, and the Arf family GTPases regulate organelle dynamics by recruiting effector proteins to membranes upon activation.