Rapid traversal of vast chemical space using machine learning-guided docking screens.

The accelerating growth of make-on-demand chemical libraries provides unprecedented opportunities to identify starting points for drug discovery with virtual screening. However, these multi-billion-scale libraries are challenging to screen, even for the fastest structure-based docking methods. Here we explore a strategy that combines machine learning and molecular docking to enable rapid virtual screening of databases containing billions of compounds.

Clinically available predictors of obstructive sleep apnoea requiring treatment in type 2 diabetes patients in primary care.

Obstructive sleep apnoea is a common yet frequently underdiagnosed condition in patients with type 2 diabetes, particularly in primary care. Early detection is important, as untreated sleep apnoea may contribute to worsened metabolic control and increased cardiovascular risk. This study evaluated 164 patients with type 2 diabetes and found that 75% had obstructive sleep apnoea, with 31% requiring treatment for moderate to severe cases.

Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals.

Recent studies suggest the existence of brain-first and body-first subtypes within the Lewy body disorder (LBD) spectrum, including Parkinson's disease. These studies primarily focused on α-synuclein propagation through the parasympathetic vagal and olfactory bulb routes, leaving the possibility of a sympathetic nervous system spreading route unexplored. In the present study, we analyzed two postmortem datasets, which included 173 and 129 cases positive for Lewy pathology.

Optimizing Xenium In Situ data utility by quality assessment and best-practice analysis workflows.

The Xenium In Situ platform is a new spatial transcriptomics product commercialized by 10x Genomics, capable of mapping hundreds of genes in situ at subcellular resolution. Given the multitude of commercially available spatial transcriptomics technologies, recommendations in choice of platform and analysis guidelines are increasingly important. Herein, we explore 25 Xenium datasets generated from multiple tissues and species, comparing scalability, resolution, data quality, capacities and limitations with eight other spatially resolved transcriptomics technologies and commercial platforms.

Diffusion MRI with double diffusion encoding and variable mixing times disentangles water exchange from transient kurtosis.

Double diffusion encoding (DDE) makes diffusion MRI sensitive to a wide range of microstructural features, and the acquired data can be analysed using different approaches. Correlation tensor imaging (CTI) uses DDE to resolve three components of the diffusional kurtosis: isotropic, anisotropic, and microscopic kurtosis. The microscopic kurtosis is estimated from the contrast between single diffusion encoding (SDE) and parallel DDE signals at the same b-value.

Navigating biodiversity patterns in fragmented seagrass mosaics.

Human-driven fragmentation of natural habitats increasingly threatens biodiversity, particularly in coastal ecosystems like seagrass meadows. Fragmentation breaks continuous habitats into smaller, isolated patches, amplifying edge effects and disrupting community structures and ecosystem functions. This study examines the effects of habitat fragmentation on large (> 1 mm) and small (0.

A functional enzymatic assay as potential readout for a clinical trial of a schistosomiasis vaccine.

An estimated 200 million people are currently infected with schistosomiasis and an additional 800 million reside in high transmission-risk areas in 78 endemic countries. In this report we describe a functional enzymatic assay based on the core calpain antigen (Sm-p80) of the schistosomiasis vaccine, SchistoShield®. A 44 kDa soluble variant of the core Sm-p80 antigen (B7), was assessed for its enzymatic activity using a fluorescent synthetic substrate.

Primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease.

Combined In Situ Transcriptomic and Immunofluorescence to Assess the Effects on DNA Damage and Innate Immune Responses Induced by Bacterial Genotoxin in In Vivo Models.

Understanding complex pathophysiological processes involves studying intercellular responses and phenotypes within the organ microenvironment, preserving the spatial tissue architecture. This chapter explores a practical and cost-effective method for combining techniques such as in situ immunostaining and transcriptomics analysis. These protocols are adaptable to various mRNA targets, antibodies, tissue types, and tissue fixation appealing to a wide scientific community.

Nursing Students' Experiences of and Attitudes to the Sustainable Development Goals: A Scoping Review.

Objectives: To conduct a review based on studies that have investigated nursing students' experiences of and attitudes to the Sustainable Development Goals (SDG).

Design: A scoping review.

Methods: A systematic scoping review was conducted using PubMed, Google Scholar, and Web of Sciences databases covering the years 2014-2024.

Monoallelic expression in human immune cells: linking genotype to phenotype.

Patients with an inborn error of immunity (IEI) often show a complete penetrance of their disease-causing mutation, whereas other forms of IEI show a family pattern where many family members carrying the same mutation remain unaffected. The underlying mechanism, differential allele-specific expression, was recently and elegantly demonstrated by Stewart et al.

Exogenous sex steroid hormones and asthma phenotypes: a study protocol for a prospective cohort analysis with UK-wide primary care data.

Introduction: The role of female sex hormones and their influence on asthma's development and natural history remain uncertain. Our study aims to enhance understanding of exogenous sex hormones' role in asthma development and manifestation, considering phenotypic heterogeneity and focusing on metabolic syndrome-linked asthma that has shown increased severity in females.

Methods And Analysis: A cohort study using primary care data from the Clinical Practice Research Datalink (CPRD) databases linked with additional data sources (Hospital Episode Statistics, ethnicity and deprivation) will include individuals aged 16-70 years, spanning 1 January 2005 to 31 December 2019.

10-year diagnosis-specific antibiotic prescribing trends among paediatric inpatients at two private-sector hospitals in central India: a prospective observational study.

Objectives: To analyse, compare and present the 10-year diagnosis-specific antibiotic prescribing trends for paediatric inpatients at a non-teaching hospital (NTH) and a teaching hospital (TH) in India.

Design And Setting: A prospective, observational study of antibiotic prescriptions in paediatric departments of two private-sector hospitals in central India. Inpatients were grouped into clinically confirmed infections, suspected infections and no infections.

Negotiating uncertainties: care-seeking in an algorithmic society.

This article examines how different layers of health-related uncertainties emerge and intersect in an algorithmic society. We aim to understand how people's self-care practices co-evolve with digitalised health systems. Sweden stands out among Western countries due to the population's high digital consumption of medical and health products.

Follow-up of incidentally detected mild to moderate ascending aortic dilation and risk factors for rapid progression in a Swedish middle-aged population.

Background: Thoracic aortic aneurysm is a life-threatening disease due to the risk for acute aortic syndromes, and subjects with dilated ascending aortas are recommended surveillance imaging to assess the need for preventive surgery. Our objectives were to investigate the progression of dilated ascending aortas and risk factors for rapid progression in a prospectively enrolled general population-based cohort of subjects aged 50-65 years.

Methods: From the 5058 subjects prospectively enrolled in the general population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) in Linköping, we followed all 74 subjects (22% female, mean age 59±4 years) with ascending aortic dilation (≥40 mm) identified by CT angiography, thoracic CT or transthoracic echocardiography.

Transcriptome analysis to decipher the molecular underpinnings of response to treatment in systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterised by variable treatment responses. We investigated the transcriptional landscape associated with treatment response and resistance in SLE.

Methods: Blood was collected from 92 active patients with SLE at baseline and after 6 months (n=32 paired samples) of treatment with cyclophosphamide (n=40), rituximab (n=20), belimumab (n=23), mycophenolate mofetil (n=8) or azathioprine (n=1) and was subjected to RNA sequencing.

Time trends in Gleason score distribution among Gleason score 8 and 9-10 cancers.

Reporting of prostate cancer grade has drifted to higher reported grades over the past decades. In prostate cancers diagnosed on needle biopsy of 1 72 112 men reported to The National Prostate Cancer Register of Sweden 2000-2020, we also noted a grade shift among high-grade cancers. We applied multinomial logistic regression to assess time trends.

Mechanical and rheological properties of Pluronic F127 based-hydrogels loaded with chitosan grafted with hyaluronic acid and propolis, focused to atopic dermatitis treatment.

Hydrogels for biomedical applications have been widely studied once they are able to enhance the wound-healing process, as well as facilitate the controlled release and loading of drugs. In this context, Pluronic F127 (PF127) has a major role as it was shown to have exceptional versatility, once it holds unique gelation properties, as it is thermoreversible and is liquid in lower temperatures, and changes to gel in higher temperatures. Moreover, the gelation behavior of PF127 is influenced by its concentration and can be further modulated by incorporating different compounds, including drugs.

Phenotyping exertional breathlessness using cardiopulmonary cycle exercise testing in people with chronic airflow limitation.

Background: Exertional breathlessness is a cardinal symptom of people with chronic airflow limitation (CAL) and can be evaluated using cardiopulmonary exercise testing (CPET).

Research Question: Does abnormally high exertional breathlessness in relation to the rate of oxygen uptake (V'O) and minute ventilation (V') indicate different underlying pathophysiological mechanisms and clinical characteristics in people with CAL?

Study Design And Methods: Analysis of people aged ≥40 years with CAL (post-bronchodilator FEV/FVC upper limit of normal) by V'O alone, abnormal by both V'O and V' (B-V'O+V'), or normal by both V'O and V' (B-normal).

Proposed enhanced recommendations for interpretation of electrocardiographic screening of athletes.

While there is ongoing debate about the role of the 12‑lead Electrocardiogram (ECG) in the routine screening of young athletes during pre-participation evaluations, studies continue to support the use of ECG within properly organized settings. This paper aims to offer considerations for enhancing the International ECG recommendations for the interpretation of the ECGs of young athletes through an emphasis on 1) percentile outliers, 2) computerized ECG technology and 3) clarification of terminology. We specifically highlight criteria for early repolarization, left atrial abnormality, right bundle branch block, ST shifts, and high and low voltage QRS.

CHOLECYSTECTOMY IS A RISK FACTOR FOR MICROSCOPIC COLITIS: A NATIONWIDE POPULATION-BASED MATCHED CASE CONTROL STUDY.

Background And Aims: Studies have linked bile-acid malabsorption and microscopic colitis (MC), with some MC patients responding to treatment with bile-acid sequestrants. However, the literature on cholecystectomy as a risk factor for MC is inconclusive. Therefore, we investigated the relationship between cholecystectomy and MC on a nationwide scale to provide more definitive insights.

Plasma metabolite profiles of meat intake and their association with cardiovascular disease risk: A population-based study in Swedish cohorts.

Background: Higher meat intake has been associated with adverse health outcomes, including cardiovascular disease (CVD). This study investigated plasma metabolites associated with meat intake and their relation with cardiometabolic biomarkers, subclinical CVD markers, and incident CVD.

Methods: Associations between self-reported meat intake and 1272 plasma metabolites were investigated in the SCAPIS cohort (n = 8819; ages 50-64).