3-Dimensional morphological characterization of neuroretinal microglia in Alzheimer's disease via machine learning.

Alzheimer's Disease (AD) is a debilitating neurodegenerative disease that affects 47.5 million people worldwide. AD is characterised by the formation of plaques containing extracellular amyloid-β (Aβ) and neurofibrillary tangles composed of hyper-phosphorylated tau proteins (pTau).

Association of patient- and hospital-level predictors with patterns of initial treatment in patients with Rheumatoid Arthritis: findings from a national cohort study.

Objectives: To update the first-line conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) prescribing pattern, describe change and variation across demographical and geographical factors in the Rheumatoid arthritis (RA) population, and identify individual and hospital factors associated with it.

Methods: This retrospective cohort study included newly diagnosed RA adult patients from 1 May 2018-1 April 2023 in the UK. We used adjusted multinomial logistic regression with random effect to explore associations with different first-line csDMRAD prescription and to account for hospital-level clustering.

The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain.

Objectives: Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.

Methods: Rats (n ​= ​8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery.

The Role of Boundary Spanning in Building Trust: A Place-Based Study on Engaging Hardly Reached Groups in Community Healthcare Settings.

This paper investigates the impact of boundary spanning activities on building trust as a means of tackling health inequalities in hardly reached communities. Lack of trust has been identified as a barrier to engagement with healthcare services, resulting in poorer health outcomes. Engaging with hardly reached communities is challenging due to the social and symbolic boundaries prevalent in community healthcare settings.

Improved konjac glucomannan/curdlan-based emulsion coating by mung bean protein addition for cherry tomato preservation.

Biopolymer-based emulsion systems have been used for food preservation. In this study, mung bean protein (MBP) was added to konjac glucomannan (KGM)/curdlan-based camellia oil emulsion (KC-CO) to develop KCM-CO emulsion system. KCM-CO emulsions showed good compatibility and stability during storage.

Polyploids broadly generate novel haplotypes from trans-specific variation in Arabidopsis arenosa and Arabidopsis lyrata.

Polyploidy, the result of whole genome duplication (WGD), is widespread across the tree of life and is often associated with speciation and adaptability. It is thought that adaptation in autopolyploids (within-species polyploids) may be facilitated by increased access to genetic variation. This variation may be sourced from gene flow with sister diploids and new access to other tetraploid lineages, as well as from increased mutational targets provided by doubled DNA content.

Classical Reaction Barriers in DFT: An Adiabatic-Connection Perspective.

Classical reaction barriers in density-functional theory are considered from the perspective of the density-fixed adiabatic connection. A 'reaction adiabatic-connection integrand', , is introduced, where λ is the electron-electron interaction strength, for which equals the barrier, meaning the barrier can be easily visualized as the area under a plot of vs λ. For five chemical reactions, plots of reference , calculated from Lieb maximizations at the coupled-cluster level of theory, are compared with approximate , calculated from common exchange-correlation functionals using coordinate scaling, for coupled-cluster densities.

On Lateness: The Ethics of Running Behind Schedule in General Practice.

Introduction: GPs, at least in the United Kingdom, often run behind schedule in their clinics. This lateness is an inherently ethical problem due to the negative consequences it generates.

Methods: The paper outlines these negative consequences, attempts to classify the major reasons for such lateness, explores the ethical status of each of these reasons, and offers suggestions for how the negative consequences might be managed.

VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Robust working memory in a two-dimensional continuous attractor network.

Continuous bump attractor networks (CANs) have been widely used in the past to explain the phenomenology of working memory (WM) tasks in which continuous-valued information has to be maintained to guide future behavior. Standard CAN models suffer from two major limitations: the stereotyped shape of the bump attractor does not reflect differences in the representational quality of WM items and the recurrent connections within the network require a biologically unrealistic level of fine tuning. We address both challenges in a two-dimensional (2D) network model formalized by two coupled neural field equations of Amari type.

Global prevalence of Helicobacter pylori antibiotic resistance among children in the world health organization regions between 2000 and 2023: a systematic review and meta-analysis.

Background: Helicobacter pylori infection causes gastritis, peptic ulcers, and gastric cancer. The infection is typically acquired in childhood and persists throughout life. The major impediment to successful therapy is antibiotic resistance.

Unveiling the Seasonal Transport and Exposure Risks of Atmospheric Microplastics in the Southern Area of the Yangtze River Delta, China.

This study investigates the prevalence and impacts of suspended atmospheric microplastics (SAMPs) in the coastal metropolitan city of Ningbo in the Yangtze River Delta Region, China. The sampling was conducted at both urban centre and urban-rural fringe areas, near the coast but distant from large urban populations. SAMP abundance ranged from 0.

Prospective evaluation of lung cancer screening eligibility criteria and lung cancer detection in the Yorkshire Lung Screening Trial.

Introduction: Low dose CT (LDCT) screening for lung cancer reduces lung cancer mortality, but there is a lack of international consensus regarding the optimal eligibility criteria for screening. The Yorkshire Lung Screening Trial (YLST) was designed to evaluate lung cancer screening (LCS) implementation and a primary objective was prospective evaluation of 3 pre-defined eligibility criteria.

Methods: Individuals who had ever smoked, aged 55-80yrs, who responded to written invitation, underwent telephone risk assessment and if eligible by at least one criteria (PLCO≥1.

Cardiovascular events in patients with gout initiating urate-lowering therapy with or without colchicine for flare prophylaxis: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data.

Background: Initiating urate-lowering therapy can trigger gout flares. Gout flares have been associated with a temporally increased risk of cardiovascular events. Therefore, we aimed to estimate the risk of cardiovascular events in patients with gout initiating urate-lowering therapy with flare prophylaxis using colchicine (the drug recommended for gout flare prohphylaxis by many international societies) compared with no prophylaxis.

Impact of hyperkalaemia on renin-angiotensin-aldosterone (RAAS) inhibitor reduction or withdrawal following hospitalisation.

Background: Inhibitors of the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.

High-Throughput Microarray Approaches for Predicting the Stability of Drug-Polymer Solid Dispersions.

Amorphous solid dispersions (ASDs) offer a well-recognized strategy to improve the effective solubility and, hence, bioavailability of poorly soluble drugs. In this study, we developed an extensive library of a significant number of solid dispersion formulations using a library of chemically diverse drugs combined with a water-soluble polymer (polyvinylpyrrolidone vinyl acetate, PVPVA) at different loadings. These formulations were printed as microarrays of solid dispersion formulations, utilizing minimal material amounts (nanograms).

Clinical importance of patient-reported outcome measures in severe asthma: results from U-BIOPRED.

Rationale: Knowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited.

Objectives: To assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care.

Methods: Data of 421 patients with severe asthma (62% female; mean age 51.

Sexual health after childbirth in Dutch women: prevalence, associated factors and perceived need for information: a cross-sectional study.

Background: After childbirth, women often experience changes in sexual health. Little is known about the associated factors for the development of sexual health problems. Therefore, in this study we aim to investigate (1) how many women report changes in sexual health; (2) the prevalence and associated factors of women's postpartum sexual health problems and (3) whether women want to be better informed about postpartum sexual health after childbirth.

Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysis.

Background: The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS).

Root RADAR: how 'rhizocrine' signals allow roots to detect and respond to their soil environment and stresses.

Agricultural intensification coupled with changing climate are causing soils to become increasingly vulnerable to stresses such as drought, soil erosion, and compaction. The mechanisms by which roots detect and respond to soil stresses remain poorly understood. Recent breakthroughs show that roots release volatile and soluble hormone signals into the surrounding soil, then monitor their levels to sense soil stresses.

Predicting the replicability of social and behavioural science claims in COVID-19 preprints.

Replications are important for assessing the reliability of published findings. However, they are costly, and it is infeasible to replicate everything. Accurate, fast, lower-cost alternatives such as eliciting predictions could accelerate assessment for rapid policy implementation in a crisis and help guide a more efficient allocation of scarce replication resources.

GRK5 regulates endocytosis of FPR2 independent of β-Arrestins.

The formyl-peptide receptor 2 (FPR2) is a G-protein-coupled receptor (GPCR) that responds to pathogen-derived peptides and regulates both pro-inflammatory and pro-resolution cellular processes. While ligand selectivity and G-protein-signalling of FPR2 have been well characterized, molecular mechanisms controlling subsequent events such as endocytosis and recycling to the plasma membrane are less understood. Here we show the key role of the GPCR kinase 5 (GRK5) in facilitating FPR2 endocytosis and post-endocytic trafficking.

Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis.

Background: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.

Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.

Psoriatic Arthritis Priority Setting Partnership: patient- and clinician-informed considerations for future UK health service delivery.

Objectives: Little is known about the ideal service delivery model and shortcomings in patient experiences in the NHS for patients with Psoriatic Arthritis (PsA). To identify unmet needs perceived within the current health service delivery model for PsA from the UK Psoriatic Arthritis Priority Setting Partnership (PsA PSP).

Methods: An online survey was conducted in 2020 and distributed to people with PsA, their carers and clinicians to identify research priorities in PsA.