Potential drug targets for asthma identified through mendelian randomization analysis.

Background: The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options for moderate-to-severe asthma treatment remain limited, highlighting the urgent need for novel therapeutic drug targets. In this study, we aimed to identify new treatment targets for asthma using the Mendelian randomization method and large-scale genome-wide association data (GWAS).

The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy.

KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis of fatty acids and nucleotides. However, the beyond mechanisms of KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related metabolic alterations in cancer cells and explore the prevalence and significance of KRAS mutation in shaping the tumor microenvironment and influencing epigenetic modification via various molecular activities.

An assessment of burden associated with problem joints in children and adults with moderate or severe haemophilia A: analysis of the CHESS-Paediatrics and CHESS II cross-sectional studies.

Background: Clinical research has offered many definitions and fragmented perspectives of joint morbidity in haemophilia. As joint damage, pain and mobility impairment can be present without clinical record of persistent bleeding, a person-centric joint morbidity characterisation remained a priority for the haemophilia community, giving rise to the 'problem joint' concept. As diagnosing and managing joint morbidity is critical, the aim of this study was to analyse the holistic burden of problem joints in people with moderate or severe haemophilia A (HA).

Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics.

Background: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients.

Methods: Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation.

The implementation of safer drug consumption facilities in Scotland: a mixed methods needs assessment and feasibility study for the city of Edinburgh.

Background: Scotland currently has amongst the highest rates of drug-related deaths in Europe, leading to increased advocacy for safer drug consumption facilities (SDCFs) to be piloted in the country. In response to concerns about drug-related harms in Edinburgh, elected officials have considered introducing SDCFs in the city. This paper presents key findings from a feasibility study commissioned by City of Edinburgh Council to support these deliberations.

Understanding and addressing a 'difficult' family in ICU.

Conflicts between ICU staff and patient/relatives are common and are a source of additional stress in an already tense environment. These conflicts vary from disagreements to serious controversies, which may lead to legal process or even violence. Unsuccessful communication is recognised as a common denominator for such disagreements.

Evidence Communication Rules for Policy (ECR-P) critical appraisal tool.

Background: Scientific papers increasingly put forward scientific-based policy recommendations (SPRs) as a means of closing the circle of science, policy and practice. Assessing the quality of such SPRs is crucial, especially within the context of a systematic review. Here, we present ECR-P (Evidence Communication Rules for Policy)-a critical appraisal tool that we have developed, which can be used in assessing not only the quality of SPRs but also the quality of their evidence base and how effectively these have both been communicated.

Association between triglyceride-glucose (TyG) related indices and cardiovascular diseases and mortality among individuals with metabolic dysfunction-associated steatotic liver disease: a cohort study of UK Biobank.

Background: Triglyceride-glucose (TyG) related indices, which serve as simple markers for insulin resistance, have been closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular disease (CVD), and mortality. However, the prognostic utility of TyG-related indices in predicting the risk of CVD and mortality among patients with MASLD remains unclear.

Methods: Data of 97,331 MASLD patients, with a median age of 58.

Genetic insight into dissecting the immunophenotypes and inflammatory profiles in the pathogenesis of Sjogren syndrome.

Background: Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS).

Improving care experiences for premenstrual symptoms and disorders in the United Kingdom (UK): a mixed-methods approach.

Background: Poor care experiences are reported for premenstrual disorders, which may result in negative outcomes such as distress, reduced healthcare engagement, and delays to diagnosis. This research aimed to explore healthcare experiences for premenstrual symptoms in the United Kingdom and identify areas for potential improvements based on participant responses.

Method: An online survey was delivered, with participants recruited via social media.

Determining timeframes to death for imminently dying patients: a retrospective cohort study.

Background: Clinicians are frequently asked 'how long' questions at end-of-life by patients and those important to them, yet predicting timeframes to death remains uncertain, even in the last weeks and days of life. Patients and families wish to know so they can ask questions, plan, make decisions, have time to visit and say their goodbyes, and have holistic care needs met. Consequently, this necessitates a more accurate assessment of empirical data to better inform prognostication and reduce uncertainty around time until death.

Using group model building to frame the commercial determinants of dietary behaviour in adolescence - findings from online system mapping workshops with adolescents, policymakers and public health practitioners in the Southwest of England.

Background: In England, 23% of children aged 11 start their teenage years living with obesity. An adolescent living with obesity is five times more likely to live with obesity in adult life. There is limited research and policy incorporating adolescents' views on how they experience the commercial determinants of dietary behaviour and obesity, which misses an opportunity to improve services and policies that aim to influence the prevalence of childhood obesity.

A systemic approach to identifying sustainable community-based interventions for improving adolescent mental health: a participatory group model building and design protocol.

Background: The deteriorating mental health of children and young people in the United Kingdom poses a challenge that services and policy makers have found difficult to tackle. Kailo responds to this issue with a community-based participatory and systemically informed strategy, perceiving mental health and well-being as a dynamic state shaped by the interplay of broader health determinants. The initiative works to explore, define and implement locally relevant solutions to challenges shaping the mental health and well-being of young people.

Ion homeostasis and coordinated salt tolerance mechanisms in a barley (Hordeum vulgare L.)doubled haploid line.

Salinization poses a significant challenge in agriculture. Identifying salt-tolerant plant germplasm resources and understanding their mechanisms of salt tolerance are crucial for breeding new salt-tolerant plant varieties. However, one of the primary obstacles to achieving this goal in crops is the physiological complexity of the salt-tolerance trait.

Poorer objective but not subjective driving performance in drivers vulnerable to sleep loss effects during extended wake.

Sleepiness-related errors are a leading cause of driving accidents, requiring drivers to effectively monitor sleepiness levels. However, there are inter-individual differences in driving performance after sleep loss, with some showing poor driving performance while others show minimal impairment. This research explored if there are differences in self-reported sleepiness and driving performance in healthy drivers who exhibited vulnerability or resistance to objective driving impairment following extended wakefulness.

Shape-matching-based fracture reduction aid concept exemplified on the proximal humerus-a pilot study.

Purpose: Optimizing fracture reduction quality is key to achieve successful osteosynthesis, especially for epimetaphyseal regions such as the proximal humerus (PH), but can be challenging, partly due to the lack of a clear endpoint. We aimed to develop the prototype for a novel intraoperative C-arm-based aid to facilitate true anatomical reduction of fractures of the PH.

Methods: The proposed method designates the reduced endpoint position of fragments by superimposing the outer boundary of the premorbid bone shape on intraoperative C-arm images, taking the mirrored intact contralateral PH from the preoperative CT scan as a surrogate.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Small Fibre Pathology in Fibromyalgia: A review.

Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP.

Chemosensory Cues Modulate Women's Jealousy Responses to Vocal Femininity.

Jealousy responses to potential mating rivals are stronger when those rivals display cues indicating higher mate quality. One such cue is vocal femininity in women's voices, with higher-pitched voices eliciting greater jealousy responses. However, cues to mate quality are not evaluated in isolation.

Electron Tomography of Organelles and Vesicles in the Investigation of SNARE Function and Localization.

Electron tomography can provide additional morphological information not easily obtained by conventional transmission electron microscopy of thin sections. It uses a goniometer stage in the electron microscope to tilt the specimen and collect a series of 2D images from different orientations, which are combined to provide a 3D volume tomogram and a colored reconstruction of the morphological feature(s) of interest. Here we describe the protocols for its use in visualizing changes in organelle morphology after depletion of the SNARE proteins VAMP7 and VAMP8 and to study VAMP7 localization on endolysosomes/lysosomes.

Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.

Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.