Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Risk prediction tools for pressure injury occurrence: an umbrella review of systematic reviews reporting model development and validation methods.

Background: Pressure injuries (PIs) place a substantial burden on healthcare systems worldwide. Risk stratification of those who are at risk of developing PIs allows preventive interventions to be focused on patients who are at the highest risk. The considerable number of risk assessment scales and prediction models available underscores the need for a thorough evaluation of their development, validation, and clinical utility.

North American avian species that migrate in flocks show greater long-term non-breeding range shift rates.

Background: Many species are exhibiting range shifts associated with anthropogenic change. For migratory species, colonisation of new areas can require novel migratory programmes that facilitate navigation between independently-shifting seasonal ranges. Therefore, in some cases range-shifts may be limited by the capacity for novel migratory programmes to be transferred between generations, which can be genetically and socially mediated.

Venous compression causes chronic cerebral ischaemia in normal pressure hydrocephalus patients.

Background: Cerebral autoregulation is a robust regulatory mechanism that stabilizes cerebral blood flow in response to reduced blood pressure, thereby preventing cerebral ischaemia. Scientists have long believed that cerebral autoregulation also stabilizes cerebral blood flow against increases in intracranial pressure, which is another component that determines cerebral perfusion pressure. However, this idea was inconsistent with the complex pathogenesis of normal pressure hydrocephalus, which includes components of chronic cerebral ischaemia due to mild increases in intracranial pressure.

Acceptability of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine plus dihydroartemisinin-piperaquine in Papua New Guinea: a qualitative study.

Background: In moderate-to-high malaria transmission regions, the World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) alongside insecticide-treated bed nets to reduce the adverse consequences of pregnancy-associated malaria. Due to high-grade Plasmodium falciparum resistance to SP, novel treatment regimens need to be evaluated for IPTp, but these increase pill burden and treatment days. The present qualitative study assessed the acceptability of IPTp-SP plus dihydroartemisinin-piperaquine (DP) in Papua New Guinea, where IPTp-SP was implemented in 2009.

Effectiveness and user experience of nose and throat swabbing techniques for SARS-CoV-2 detection: results from the UK COVID-19 National Testing Programme.

Background: The UK's National Health Service Test and Trace (NHSTT) program aimed to provide the most effective and accessible SARS-CoV-2 testing approach possible. Early user feedback indicated that there were accessibility issues associated with throat swabbing. We report the results of service evaluations performed by NHSTT to assess the effectiveness and user acceptance of swabbing approaches, as well as qualitative findings of user experiences from research reports, surveys, and incident reports.

Implementation strategies: lessons learned during an e-learning intervention to improve dietary behaviors and feeding practices in early childhood education and care.

Background: Early Childhood Education and Care (ECEC) centers play an important role in fostering healthy dietary habits. The Nutrition Now project focusing on improving dietary habits during the first 1000 days of life. Central to the project is the implementation of an e-learning resource aimed at promoting feeding practices among staff and healthy dietary behaviours for children aged 0-3 years in ECEC.

Prevalence and factors associated with childhood malaria and anaemia in Osun state, Nigeria: a baseline household malariometric study.

Background: Under-5 children have been known to bear a significant burden of malaria in endemic countries. Though significant progress has been made towards malaria prevention and control in Nigeria, it is expected that the addition of new malaria prevention strategy, such as perennial malaria chemoprevention (PMC) can contribute to a more rapid decline in malaria cases. This study aimed to determine the prevalence and factors associated with malaria and anaemia among children aged 2-18 months in Osun State.

Comparative effectiveness of physical activity interventions on cognitive functions in children and adolescents with Neurodevelopmental Disorders: a systematic review and network meta-analysis of randomized controlled trials.

Background: Physical activity (PA) interventions have been shown to yield positive effects on cognitive functions. However, it is unclear which type of PA intervention is the most effective in children and adolescents with Neurodevelopmental Disorders (NDDs). This study aimed to compare the effectiveness of different types of PA interventions on cognitive functions in children and adolescents with NDDs, with additional analyses examining intervention effects across specific NDD types including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

Fragmenstein: predicting protein-ligand structures of compounds derived from known crystallographic fragment hits using a strict conserved-binding-based methodology.

Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that 'stitches' the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode.

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.