Single-cell transcriptomic atlas of human retina from Chinese donors reveals population-specific cellular diversity.

The human retina exhibits complex cellular heterogeneity which is critical for visual function, yet comprehensive ethnic-specific references are scarce in ophthalmic transcriptomics. The lack of single-cell RNA sequencing (scRNA-seq) data from Asian populations particularly Chinese donors imposes significant limitations in understanding population-specific retinal biology. We constructed the first comprehensive single-cell transcriptomic atlas of the human retina from Chinese donors, generated through high-throughput scRNA-seq of ∼290,000 viable cells obtained from 18 fresh retinal specimens (living donor and post-mortem specimens).

Integrative GWAS and Mendelian randomization study of rheumatoid arthritis based on the 2019 UK Biobank questionnaire.

Introduction: Rheumatoid arthritis (RA) is the most prevalent autoimmune inflammatory joint disorder worldwide. We aimed to identify the genetic variants contributing to RA and investigate the potential influence of related diseases on RA risk.

Methods: We performed genome-wide association studies (GWAS) on RA using the 2019 UK Biobank pain questionnaire.

A scRNA-seq reference contrasting living and early post-mortem human retina across diverse donor states.

Background: Current human retina studies predominantly utilize post-mortem tissue, and the sample accessibility constraints make the characterization of the living human retina at single-cell resolution a challenge. Although single-nucleus RNA-seq expands the utility of frozen samples, it provides a nuclear-centric view, potentially missing key cytoplasmic information and transient biological processes. Thus, it is important to generate resources directly from living human retinal tissue to complement existing datasets.

Identification of RIPK3 as a target of flavonoids for anti-necroptosis in vitro.

Receptor-interacting protein kinase 3 (RIPK3), a key regulator of necroptosis, has emerged as an important target for therapeutic intervention. Flavonoids are natural compounds known for their anti-inflammatory and antioxidant properties, with recent studies highlighting their potential to modulate necroptosis. In this study, we explored the potential of RIPK3 as a target for flavonoids to achieve anti-necroptosis and anti-inflammatory effects.

'Forging healthy communities': a service evaluation of a 12-week community-based exercise, nutrition, behaviour change and peer-support programme.

Background: Physical inactivity is a leading cause of premature mortality and morbidity worldwide. Primary care settings provide an opportunity for effective lifestyle interventions, including physical activity (PA) promotion. This study aims to evaluate the impact of a rural community-based multi-component, 12-week exercise, nutrition, education and peer-support programme on participants health and wellbeing.

Identification of hypertension subtypes using microRNA profiles and machine learning.

Objective: Hypertension is a major cardiovascular risk factor affecting about 1 in 3 adults. Although the majority of hypertension cases (∼90%) are classified as "primary hypertension" (PHT), endocrine hypertension (EHT) accounts for ∼10% of cases and is caused by underlying conditions such as primary aldosteronism (PA), Cushing's syndrome (CS), pheochromocytoma or paraganglioma (PPGL). EHT is often misdiagnosed as PHT leading to delays in treatment for the underlying condition, reduced quality of life and costly, often ineffective, antihypertensive treatment.

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127).

Hip pain is a common musculoskeletal complaint that leads many people to seek medical attention. We conducted a primary genome-wide association study (GWAS) on the hip pain phenotype within the UK Biobank cohort. Sex-stratified GWAS analysis approach was also performed to explore sex specific variants associated with hip pain.

Age and cancer type: associations with increased odds of receiving a late diagnosis in people with advanced cancer.

Purpose: In order to deliver appropriate and timely care planning and minimise avoidable late diagnoses, clinicians need to be aware of which patients are at higher risk of receiving a late cancer diagnosis. We aimed to determine which demographic and clinical factors are associated with receiving a 'late' cancer diagnosis (within the last 12 weeks of life).

Method: Retrospective cohort study of 2,443 people who died from cancer ('cancer decedents') in 2013-2015.

A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches.

Unlabelled: Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood while it has been suggested that self-reported headache and self-reported migraine were genetically correlated. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank and the self-reported migraine phenotype from the 23andMe using the Unified Score-based Association Test (metaUSAT) software for genetically correlated phenotypes ( = 397,385).

Glycated Haemoglobin A1c Variability Score Elicits Kidney Function Decline in Chinese People Living with Type 2 Diabetes.

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.

Assessing the impact of a national clinical guideline for the management of chronic pain on opioid prescribing rates: a controlled interrupted time series analysis.

Background: Opioids can be effective analgesics, but long-term use may be associated with harms. In 2013, the first national, comprehensive, evidence-based pain management guideline was published, from the Scottish Intercollegiate Guideline Network (SIGN 136: Management of Chronic Pain) with key recommendations on analgesic prescribing. This study aimed to examine the potential impact on national opioid prescribing rates in Scotland.

Development and external validation of multivariable risk models to predict incident and resolved neuropathic pain: a DOLORisk Dundee study.

Neuropathic pain is difficult to treat, and an understanding of the risk factors for its onset and resolution is warranted. This study aimed to develop and externally validate two clinical risk models to predict onset and resolution of chronic neuropathic pain. Participants of Generation Scotland: Scottish Family Health Study (GS; general Scottish population; n = 20,221) and Genetic of Diabetes Audit and Research in Tayside Scotland (GoDARTS; n = 5236) were sent a questionnaire on neuropathic pain and followed- -up 18 months later.

Machine learning for classification of hypertension subtypes using multi-omics: A multi-centre, retrospective, data-driven study.

Background: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter.

Predicting Hypertension Subtypes with Machine Learning Using Targeted Metabolites and Their Ratios.

Hypertension is a major global health problem with high prevalence and complex associated health risks. Primary hypertension (PHT) is most common and the reasons behind primary hypertension are largely unknown. Endocrine hypertension (EHT) is another complex form of hypertension with an estimated prevalence varying from 3 to 20% depending on the population studied.

Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension.

Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing's syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics.

Community prescribing trends and prevalence in the last year of life, for people who die from cancer.

Background: People who die from cancer ('cancer decedents') may latterly experience unpleasant and distressing symptoms. Prescribing medication for pain and symptom control is essential for good-quality palliative care; however, such provision is variable, difficult to quantify and poorly characterised in current literature. This study aims to characterise trends in prescribing analgesia, non-analgesic palliative care medication and non-palliative medications, to cancer decedents, in their last year of life, and to assess any associations with demographic or clinical factors.

A computational investigation of COVID-19 transmission inside hospital wards and associated costs.

The COVID-19 pandemic has placed a particular burden on hospitals: from intra-hospital transmission of the infections to reduced admissions of non-COVID-19 patients. There are also high costs associated with the treatment of hospitalised COVID-19 patients, as well as reductions in revenues due to delayed and cancelled treatments. In this study we investigate computationally the transmission of COVID-19 inside a hospital ward that contains multiple-bed bays (with 4 or 6 beds) and multiple single-bed side rooms (that can accommodate the contacts of COVID-19-positive patients).

System-level policies on appropriate opioid use, a multi-stakeholder consensus.

Background: This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies.

Methods: We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level.

Tonic dopamine, uncertainty and basal ganglia action selection.

To make optimal decisions in uncertain circumstances flexible adaption of behaviour is required; exploring alternatives when the best choice is unknown, exploiting what is known when that is best. Using a computational model of the basal ganglia, we propose that switches between exploratory and exploitative decisions are mediated by the interaction between tonic dopamine and cortical input to the basal ganglia. We show that a biologically detailed action selection circuit model, endowed with dopamine dependant striatal plasticity, can optimally solve the explore-exploit problem, estimating the true underlying state of a noisy Gaussian diffusion process.

Factors Associated with the Implementation of Non-Pharmaceutical Interventions for Reducing Coronavirus Disease 2019 (COVID-19): A Systematic Review.

There has been much discussion recently about the importance of implementing non-pharmaceutical interventions (NPIs) to protect the public from coronavirus disease 2019 (COVID-19) infection. Different governments across the world have adopted NPIs (e.g.