The effectiveness of interventions to support informal stroke carers: a systematic review.

Purpose: Stroke affects one in four adults in the UK, with over a third relying on informal carers. The burden of care can have detrimental effects on the mental and physical health of carers, which may impact the rehabilitative process. Despite this, interventions have focused on the physical demands of caregiving, prioritising the stroke survivor.

Unlocking the power of L1 regularization: A novel approach to taming overfitting in CNN for image classification.

Convolutional Neural Networks (CNNs) stand as indispensable tools in deep learning, capable of autonomously extracting crucial features from diverse data types. However, the intricacies of CNN architectures can present challenges such as overfitting and underfitting, necessitating thoughtful strategies to optimize their performance. In this work, these issues have been resolved by introducing L1 regularization in the basic architecture of CNN when it is applied for image classification.

A Break from the Norm? Parametric Representations of Preference Heterogeneity for Discrete Choice Models in Health.

BackgroundAny sample of individuals has its own unique distribution of preferences for choices that they make. Discrete choice models try to capture these distributions. Mixed logits are by far the most commonly used choice model in health.

Autophagy and Bacterial infections.

Autophagy is an evolutionarily conserved cellular process that is prominent during bacterial infections. In this review article, we discuss how direct pathogen clearance via xenophagy and regulation of inflammatory products represent dual functions of autophagy that coordinate an effective antimicrobial response. We detail the molecular mechanisms of xenophagy, including signals that indicate the presence of an intracellular pathogen and autophagy receptor-mediated cargo targeting, while highlighting pathogen counterstrategies, such as bacterial effector proteins that inhibit autophagy initiation or exploit autophagic membranes for replication.

Movement fluency metrics during multi-phase sit-to-walk and reach-to-grasp: Test-retest reliability and agreement between laboratory-based and portable 3D motion analysis systems.

Background: International consensus recommends use of kinematic metrics of movement during standardized functional tasks after stroke to ascertain whether rehabilitation is driving behavioral restitution or compensation. Quality of human movement can be characterized by fluency metrics including smoothness and hesitation. Before using these metrics in stroke rehabilitation it is important to find whether 'reference values', from healthy adults, are repeatable.

Semantic memory in healthy apolipoprotein ε4 carriers: A systematic review.

The Apolipoprotein epsilon 4 (APOE ε4) genetic variant is notoriously linked to enhanced risk of developing Alzheimer's Disease (AD). Several studies have examined how this allele could influence cognitive functioning in healthy adults, and whether ε4 carriers show a subtle cognitive decline that would indicate preclinical AD pathology. Research has predominantly focused on episodic memory, where ε4 carriers are usually impaired, while semantic memory functioning has received less attention.

Extreme weather events and dengue in Southeast Asia: A regionally-representative analysis of 291 locations from 1998 to 2021.

Background: Climate change, leading to more frequent and intense extreme weather events (EWEs), could significantly impact dengue transmission. However, the associations between EWEs and dengue remains underexplored in the Southeast Asia (SEA) region. We investigated the association between selected EWEs (i.

: a transposon facilitating the movement of the virulence factor ToxA in fungal wheat pathogens.

There is increasing evidence that mobile genetic elements can drive the emergence of pathogenic fungal species by moving virulence genes horizontally. The 14 kbp transposon was shown to move the necrotrophic effector, horizontally between wheat pathogens, namely , , and . All three species utilize the ToxA protein to infect wheat.

The NEON (Nerve rEpair Or Not) trial: a randomized controlled trial of microsurgical repair versus nerve alignment for digital nerve injury.

Background: Digital nerves provide sensibility to the fingers. They are commonly injured through accidental sharp laceration. The aim of the NEON (Nerve rEpair Or Not) study was to investigate whether microsurgical suture repair of lacerated digital nerves is superior to nerve alignment alone without suture repair.

Characterisation of the Historic Demographic Decline of the British European Polecat Population.

The European polecat (Mustela putorius) has a widespread distribution across many countries of mainland Europe but is documented to be declining within these ranges. In Britain, direct persecution led to a severe decline of the polecat population during the 19th century. Unlike European mainland populations, it is now recovering across much of its former British range.

Gut microbiota dysbiosis affects intestinal sensitivity through epithelium-to-neuron signaling: novel insights from a colon organoid-based model to improve visceral pain therapy.

Chronic gastrointestinal pain is a hallmark of most intestinal pathologies, yet effective treatments remain elusive given the complexity of the underlying mechanisms. Aiming to investigate the intestinal epithelium contribution to visceral pain modulation in dysbiosis context, we first demonstrated that intracolonic instillation of microbe-free fecal supernatants from mice with post-inflammatory dysbiosis induced by dextran sodium sulfate (FS) provokes visceral hypersensitivity in recipient mice. Epithelium involvement in the response to FS was analyzed through a novel approach comprising murine epithelial colon organoids and primary dorsal root ganglia (DRG) neurons.

A national cohort study of melanoma BRAF status, testing patterns, patient and tumour characteristics, treatment and survival in England 2016-21.

Background: Inadequacy of testing for melanoma BRAF status results in delayed access to systemic therapy. BRAF mutations and their association with patient/tumour characteristics and survival is poorly understood.

Objectives: To report national data from England on the (1) frequency of molecular BRAF testing, (2) association of patient/tumour characteristics with BRAF mutations and (3) treatment received and survival of patients with BRAF mutations.

The landscape of microbial associations in human cancer.

Oncomicrobes are estimated to cause 15% of cancers worldwide. When cancer whole-genome sequencing (WGS) data are collected, the microbes present are also sequenced, allowing the investigation of potential etiological and clinical associations. Interrogating the microbial community for 8908 patients encompassing 22 cancer types from the Genomics England WGS dataset revealed that only colorectal tumors exhibited unmistakably distinct microbial communities that can reliably be used to distinguish anatomical site [positive predictive value (PPV) = 0.

Gut microbiome communities demonstrate fine-scale spatial variation in a closed, island bird population.

Environmental variation is a key factor shaping microbial communities in wild animals. However, most studies have focussed on separate populations distributed over large spatial scales. How ecological factors shape inter-individual microbiome variation within a single landscape and host population remains poorly understood.

Limited inbreeding avoidance at the gamete level despite inbreeding depression in Atlantic salmon (Salmo salar).

Inbreeding and the associated increase in homozygosity and potential accumulation of deleterious alleles may reduce fitness in a process known as inbreeding depression. Mechanisms to mitigate reproduction between close relatives, ranging from pre-mating mate choice to post-mating gamete selection, have evolved across taxa. In external fertilisers like Atlantic salmon (Salmo salar), where females have limited control over paternity, mechanisms of inbreeding avoidance can be expected to evolve at the gamete level.

Intersectional analysis of visual generative AI: the case of stable diffusion.

Since 2022, Visual Generative AI (vGenAI) tools have experienced rapid adoption and garnered widespread acclaim for their ability to produce high-quality images with convincing photorealistic representations. These technologies mirror society's prevailing visual politics in a mediated form, and actively contribute to the perpetuation of deeply ingrained assumptions, categories, values, and aesthetic representations. In this paper, we critically analyze Stable Diffusion (SD), a widely used open-source vGenAI tool, through visual and intersectional analysis.

Spaces of ranked tree-child networks.

Ranked tree-child networks are a recently introduced class of rooted phylogenetic networks in which the evolutionary events represented by the network are ordered so as to respect the flow of time. This class includes the well-studied ranked phylogenetic trees (also known as ranked genealogies). An important problem in phylogenetic analysis is to define distances between phylogenetic trees and networks in order to systematically compare them.

Genomics uncover resistant and virulent Klebsiella on foods: a potential risk to human health.

Klebsiella pneumoniae is a bacterium of public health importance due to its association with antimicrobial resistance (AMR) and its role as a major cause of both hospital- and community-acquired infections. While Klebsiella species have been detected in foods, our understanding of their diversity and the potential risks they pose from food is limited. This study aims to comprehensively evaluate the Klebsiella species population and their contribution to the burden of AMR, virulence, and heavy metal tolerance from diverse food samples.

Comparing surgical outcomes of robotic and laparoscopic or open ileal pouch-anal anastomosis: a systematic review and meta-analysis.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical approach for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) seeking bowel continuity. While laparoscopy improves recovery, robotic-assisted surgery may offer advantages in pelvic procedures. However, its comparative efficacy remains unclear.

Home-Based Care for Hypertension in Rural South Africa.

Background: Poorly controlled hypertension is a common problem worldwide, particularly in low-resource settings.

Methods: We conducted an open-label, randomized, controlled trial of a home-based model of hypertension care in South Africa. Adults with hypertension were assigned to receive home-based care, which consisted of patient monitoring of blood pressure, home visits from a community health worker (CHW) for data collection and medication delivery, and remote nurse-led decision making supported by a mobile application (CHW group); enhanced home-based care, which consisted of the same intervention but with blood-pressure machines transmitting readings automatically (enhanced CHW group); or standard care with clinic-based management (standard-care group).

Perspective on Regional Sea-level Change and Coastal Impacts.

We synthesize sea-level science developments, priorities and practitioner needs at the end of the 10-year World Climate Research Program Grand Challenge 'Regional Sea-Level Change and Coastal Impacts'. Sea-level science and associated climate services have progressed but are unevenly distributed. There remains deep uncertainty concerning high-end and long-term sea-level projections due to indeterminate emissions, the ice sheet response and other climate tipping points.

On-Cell Saturation Transfer Difference NMR Spectroscopy on Ion Channels: Characterizing Negative Allosteric Modulator Binding Interactions of P2X7.

P2X7 receptors are important drug targets involved in pathologies ranging from psychiatric disorders to cancer. Being membrane embedded receptors, they are more challenging for structural characterization, and at present, we only have a small number of X-ray and cryo-EM structures for P2X7 bound to antagonists. We demonstrate that saturation transfer difference (STD) NMR on live mammalian cells (on-cell STD NMR) overexpressing P2X7 receptors allows further structural insight on the complexes of P2X7 with two potent negative allosteric modulators, namely, AZ10606120 and JNJ-47965567, via the determination of the binding epitope mapping of the interactions, e.

Effect of intra-articular adipose-derived mesenchymal stromal cell versus placebo injection on pain and function in patients with knee osteoarthritis: the ADIPOA2 phase 2b randomised clinical trial.

Objectives: This study aims to evaluate the efficacy of intra-articular autologous adipose-derived ex vivo expanded mesenchymal stromal cells (ADSC) on patient-reported outcome (pain and function) in symptomatic mild-to-moderate tibiofemoral knee osteoarthritis (OA).

Methods: Participants were randomised in a prospective, double-blind, controlled phase 2b study to receive 1 single intra-articular injection in 3 separate groups: ADSC low dose 2 × 10 cells; ADSC high dose 10 × 10 cells; or saline placebo. The primary outcome was the rate of OsteoArthritis Research Society International (OARSI)/Outcome MEasures in Rheumatology (OMERACT) 'strict responders' defined by improvements from baseline reported to 0 to 100 mm scale in Western Ontario and McMaster University Osteoarthritis index (WOMAC) pain or physical function subscores ≥50% with minimal absolute changes ≥20 mm at 6 months.

The clinical effectiveness of clarithromycin versus endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps (MACRO): a pragmatic, multicentre, three-arm, randomised, placebo-controlled phase 4 trial.

Background: A paucity of evidence regarding use of endoscopic sinus surgery and antibiotics in managing chronic rhinosinusitis has contributed to a five-times variation in endoscopic sinus surgery rates, as well as variation in the use of antibiotics. The main aim of the present trial was to compare the clinical effectiveness of endoscopic sinus surgery or 3 months of clarithromycin treatment alongside intranasal medication in adults with chronic rhinosinusitis with or without nasal polyps.

Methods: In this pragmatic, three-arm, randomised, placebo-controlled phase 4 trial, participants were recruited from 20 secondary and tertiary care sites in the UK.