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.

Proteomic changes upon treatment with semaglutide in individuals with obesity.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways.

Hessian QM9: A quantum chemistry database of molecular Hessians in implicit solvents.

A significant challenge in computational chemistry is developing approximations that accelerate ab initio methods while preserving accuracy. Machine learning interatomic potentials (MLIPs) have emerged as a promising solution for constructing atomistic potentials that can be transferred across different molecular and crystalline systems. Most MLIPs are trained only on energies and forces in vacuum, while an improved description of the potential energy surface could be achieved by including the curvature of the potential energy surface.

Cu- or Ag-containing Bi-Sb-Te for in-line roll-to-roll patterned thin-film thermoelectrics.

The Selective Metallization Technique shows promise for roll-to-roll in-line patterning of flexible electronics using evaporated metals, but challenges arise when applied to sputtering functional materials. This study overcomes these challenges with simultaneous sputtering of Bi-Sb-Te and evaporation of metal (Ag or Cu) for thermoelectric layers when using Selective Metallization Technique. Large-scale manufacturing is demonstrated through roll-to-roll processing of a 0.

Impact of bone quality on surgical decision-making in total hip arthroplasty: a qualitative analysis in the UK.

Introduction: For total hip arthroplasty (THA) to be successful, surgeons need to make several decisions ranging from implant choice to impaction force. It is unclear, however, whether and how bone quality affects surgeon's decision-making and how surgeons evaluate bone quality.

Objectives: This inductive/deductive qualitative hybrid study aims to explore the impact of bone quality on the decision-making of surgeons performing elective primary THA.

Development of a family-centred core outcome set for infants with developmental dysplasia of the hip treated with a brace.

Aims: This study aims to define a set of family-centred core outcomes for infants undergoing brace treatment to facilitate consistent reporting for future high-quality research.

Methods: Family-centred outcomes will be identified through a literature review and a scoping survey involving key stakeholders, including parents, healthcare professionals, and researchers. These outcomes will then be rated for their perceived importance in a two-stage modified Delphi process with the same stakeholders.

When "loss-of-function" means proteostasis burden: Thinking again about coding DNA variants.

Each human genome has approximately 5 million DNA variants. Even for complete loss-of-function variants causing inherited, monogenic diseases, current understanding based on gene-specific molecular function does not adequately predict variability observed between people with identical mutations or fluctuating disease trajectories. We present a parallel paradigm for loss-of-function variants based on broader consequences to the cell when aberrant polypeptide chains of amino acids are translated from mutant RNA to generate mutated proteins.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

A molecular toxicological study to explore potential health risks associated with ultrafine particle exposure in cold and humid indoor environments.

Environmental pollutants including ultrafine particulate matter (UFPs) and adverse meteorological conditions pose significant public health impacts, particularly affecting respiratory health. This study aims to elucidate the synergistic effects of cold-humid conditions and UFPs exposure on respiratory health, utilizing Carbon Black Nanoparticles (CB-NPs) as surrogates for UFPs. Through comprehensive lung function tests, histopathological examinations, and biomarker analyses, this research focuses on the modulation of oxidative stress signaling pathways and NF-κB activation.

Measurement of CP Violation Observables in D^{+}→K^{-}K^{+}π^{+} Decays.

A search for violation of the charge-parity (CP) symmetry in the D^{+}→K^{-}K^{+}π^{+} decay is presented, with proton-proton collision data corresponding to an integrated luminosity of 5.4  fb^{-1}, collected at a center-of-mass energy of 13 TeV with the LHCb detector. A novel model-independent technique is used to compare the D^{+} and D^{-} phase-space distributions, with instrumental asymmetries subtracted using the D_{s}^{+}→K^{-}K^{+}π^{+} decay as a control channel.

A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown.

Tocilizumab and rituximab for systemic sclerosis interstitial lung disease: a real-world cohort analysis.

Objectives: Systemic sclerosis (SSc)-interstitial lung disease (ILD) is one of the leading causes of mortality in SSc. Data from randomised controlled trials (RCTs) supports rituximab and tocilizumab monotherapy but there is limited data regarding their use for those who fail standard immunomodulatory therapies.

Methods: SSc patients treated with rituximab or tocilizumab were retrospectively identified in a single centre cohort.

Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children.

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.

Basic Science and Pathogenesis.

Background: Neuroinflammation is a key component of Alzheimer's Disease (AD) pathology. Triggering receptor expressed on myeloid cells 2 (TREM2) is crucial to microglial involvement in AD, mediating trem2-dependent activation and Disease-Associated Microglia (DAM) polarization. However, GWAS revealed that loss-of-function mutations of its encoding gene are an important risk factor for AD.

Basic Science and Pathogenesis.

Background: Microglial reactivity and neuroinflammation are crucial pathological processes in Alzheimer's Disease (AD). Several attempts to develop a treatment by supressing the immune response in AD have been made, yet these yielded very limited results. Recent studies suggest contrasting effects of microglial reactivity, indicating a biphasic response with both beneficial and deleterious effects at distinct stages of AD.

Clinical Manifestations.

Background: Dementia-related biomarkers can detect pathology years before clinical diagnostic criteria are met. Understanding the relationship between biomarkers and early cognitive changes is crucial as disease-modifying therapies may have maximum benefits when delivered early. We aimed to demonstrate the utility of remote computerised cognitive tests in a large cohort of cognitively normal older individuals, comparing these to standard in-person assessments and investigating their associations with biomarkers.

Basic Science and Pathogenesis.

Background: Pathological alterations in Alzheimer's disease (AD) begin several years before the onset of symptoms. Grey matter mean diffusivity (MD) may be used as a measure of early grey matter damage in AD as it reflects the breakdown of microstructural barriers, which precede volumetric changes and affect cognitive function. In this study, we investigated the changes in MD early on in the disease trajectory, and relate them to the amyloid and tau deposition.

Clinical Manifestations.

Background: Transcultural adaptations of brief cognitive screening tools (BCTs) involve the development of alternate versions that are psychometrically equivalent to the original, while being linguistically and culturally adapted to a new sociodemographic context. The RUDAS (Rowland Universal Dementia Assessment Scale) is less affected by culture, language, and education compared with other BCTs. However, several studies have reported an effect of education on RUDAS scores.

Clinical Manifestations.

Background: Accurate assessment of cognitive impairment in low-income settings may require consideration of complex psychosocial variables (PV). Failure to consider the association of PV with biological factors, such as HIV, could lead to false classification of cognitive impairment. We investigated the impact of PV on cognitive performance in people with HIV (PWH) and without in a low-income area of Cape Town, South Africa.

Clinical Manifestations.

Background: Cortical atrophy in Alzheimer's disease (AD) is typically thought to commence in the medial temporal lobe. However, growing evidence suggests that this may not be true for all patients. Here, we explored atrophy patterns in patients with mild cognitive impairment (MCI) and AD and whether atrophy patterns are associated with specific clinical and neuropathological outcomes.

Clinical Manifestations.

Background: Cognitive assessments are essential for detecting and monitoring cognitive changes in neurological populations. Compared to standard pen-and-paper tests, online cognitive tasks offer a more accessible, scalable, repeatable and cost-effective approach to assessment. Cognitron is an online cognitive assessment platform with previously demonstrated validity and reliability (1).

Evaluation of Phoenix Sepsis Score Criteria: Exploratory Analysis of Characteristics and Outcomes in an Emergency Transport PICU Cohort From the United Kingdom, 2014-2016.

Objectives: To assess characteristics and outcomes of children with suspected or confirmed infection requiring emergency transport and PICU admission and to explore the association between the 2024 Phoenix Sepsis Score (PSS) criteria and mortality.

Design: Retrospective analysis of curated data from a 2014-2016 multicenter cohort study.

Setting: PICU admission following emergency transport in South East England, United Kingdom, from April 2014 to December 2016.

SCXRD, CSP-NMRX and microED in the quest for three elusive polymorphs of meloxicam.

Crystal structure determination is a crucial aspect of almost every branch of the chemical sciences, bringing us closer to understanding crystallization, polymorphism, phase transitions, and the relationship between a structure and its physicochemical and functional properties. Unfortunately, many molecules notoriously crystallize as microcrystalline powders, providing a significant challenge in establishing their structures. In this work, we describe the crystal structure determination of three elusive polymorphs of the anti-inflammatory drug meloxicam (MLX) using three approaches, of which only one was successful for each crystal phase.

The Role of WNT5a and TGF-β1 in Airway Remodelling and Severe Asthma.

Background: Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF-β in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.

Methods: WNT5a and TGF-β protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1-3, n-8 and GINA 4-5, n-14) and healthy subjects (n-9), alongside relevant remodelling markers.

Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice.

Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment.