NUCLEAR RNA-BINDING PROTEINS MEET CYTOPLASMIC VIRUSES.

Cytoplasmic viruses interact intricately with the nuclear pore complex and nuclear import/export machineries, affecting nuclear-cytoplasmic trafficking. This can lead to the selective accumulation of nuclear RNA-binding proteins (RBPs) in the cytoplasm. Pioneering research has shown that relocated RBPs serve as an intrinsic defence mechanism against viruses, which involves RNA export, splicing and nucleolar factors.

Refining PREVENT prediction models for 10-year risk of cardiovascular disease using measures of anxiety and depression.

Background: Anxiety and depression are associated with cardiovascular disease (CVD). We aimed to investigate whether adding measures of anxiety and depression to the American Heart Association Predicting Risk of Cardiovascular Disease Events (PREVENT) predictors improves the prediction of CVD risk.

Methods: We developed and internally validated risk prediction models using 60% and 40% of the cohort data from the UK Biobank, respectively.

Ethnic disparities in rapid tranquillisation use and justifications in adult mental health inpatient settings: a systematic review and meta-analysis.

Question: Evidence on the likelihood of receiving rapid tranquillisation (RT) across ethnic groups is mixed, with some studies suggesting that ethnic minorities are more likely to receive RT than others. We aimed to investigate the association between ethnicity and RT use in adult mental health inpatient settings and to explore explanations for RT use in relation to ethnicity.

Study Selection And Analysis: We searched six databases, grey sources, and references from their inception to 15 April 2024.

Retinal vascular fingerprints predict incident stroke: findings from the UK Biobank cohort study.

Objective: To investigate the associations between a comprehensive set of retinal vascular parameters and incident stroke to unveil new associations and explore its predictive power for stroke risk.

Methods: Retinal vascular parameters were extracted from the UK Biobank fundus images using the Retina-based Microvascular Health Assessment System. We used Cox regression analysis, adjusted for traditional risk factors, to examine the associations, with false discovery rate adjustment for multiple comparisons.

The impact of clinical phenotypes of coronary artery disease on outcomes in patients with atrial fibrillation: A post-hoc analysis of GLORIA-AF registry.

Background: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist, but the impact of clinical phenotypes of CAD on outcomes in AF patients in the non-vitamin K antagonist oral anticoagulant drugs (NOACs) era is less well understood.

Methods: This was a post-hoc of the GLORIA-AF registry, a global, multicenter, prospective AF registry study. Patients were divided into three groups: prior history of myocardial infarction (MI)/unstable angina group (Group 1); stable angina group (Group 2); and a control group without stable angina or history of MI/unstable angina.

Active cycle of breathing technique versus oscillating positive expiratory pressure therapy: Effect on lung function in children with primary ciliary dyskinesia; A feasibility study.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder requiring airway clearance techniques for mucus removal. We aimed to evaluate the feasibility and the effect of the active cycle of breathing technique (ACBT) versus oscillating positive expiratory pressure therapy (OPEP) in improving lung function and functional exercise capacity among children with PCD in Palestine. 32 PCD children (6-18 years) were included in a 12-week home-based feasibility study.

Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.

Background: While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions.

Objective: This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality.

Methods: PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others.

Investigating eating architecture and the impact of the precision of recorded eating time: a cross-sectional study.

Background: The precision of recorded eating times directly affects the estimation of eating architecture i.e. size, timing, and frequency of eating.

Plasma metabolomic signature of a proinflammatory diet in relation to breast cancer risk: a prospective cohort study.

Background: A proinflammatory diet has been linked to an increased risk of breast cancer. However, the underlying metabolic roles remain to be elucidated.

Objective: To investigate the metabolic mechanism between proinflammatory diet and breast cancer risk.

Altered Neural Responses to Punishment Learning in Conduct Disorder.

Objective: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision-making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared to typically-developing controls (TDCs).

Methods: 75 youths with CD and 99 TDCs (9-18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies.

Mepolizumab real-world effectiveness in severe asthma with an eosinophilic phenotype and overlapping severe allergic asthma.

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics.

Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study.

Methods: The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL).

The Optimal Dosage and Duration of Omega-3 Polyunsaturated Fatty Acid Supplementation in Heart Failure Management: Evidence from a Network Meta-Analysis.

Heart failure is a progressive condition associated with a high mortality rate. Despite advancements in treatment, many patients continue to experience less-than-ideal outcomes. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been studied as a potential supplementary therapy for heart failure, but the optimal dosage and duration of supplementation remain unclear.

Relationship between severe hypoglycemia or impaired awareness of hypoglycemia and diabetes-related health status, global cognition and executive functions in adults with type 1 diabetes without severe anxiety or depression.

Aims: To explore the relationship between impaired awareness of hypoglycemia (IAH) or severe hypoglycemia (SH), and health status and cognition in adults with type 1 diabetes (T1D).

Methods: T1D adults attending a tertiary diabetes service were recruited into this cross-sectional study. People screening positive for severe anxiety or depression were not included.

Uromodulin and Risk of Upper Urinary Tract Infections: A Mendelian Randomization Study.

Rationale & Objective: Observational studies suggest that uromodulin, produced by the kidneys, is associated with a reduced the risk of upper urinary tract infections, but inferences are limited by potential confounding factors. This study sought to explore further the validity of this association using Mendelian randomization.

Study Design: Two-sample Mendelian randomization study.

Potential interactions between antimicrobials and direct oral anticoagulants: population-based cohort and case-crossover study.

Background: Although drug interactions between clarithromycin/erythromycin/fluconazole and direct oral anticoagulants (DOACs) are mechanistically plausible, it is uncertain whether they are clinically relevant.

Objective: To investigate the association between co-prescribed DOACs and antimicrobials and bleeding, cardiovascular disease and mortality.

Methods: We identified DOAC users in the Clinical Practice Research Datalink Aurum from 1/1/2011-29/3/2021.

Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT Trial embedded phase II population.

Background: The FOxTROT trial has reported advantages of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). Here we present results of the embedded randomized phase II trial testing the addition of panitumumab to neoadjuvant FOLFOX compared with FOLFOX alone in RAS and BRAF-wild-type patients and with biomarker hyperselction.

Patients And Methods: Patients had operable, CT-predicted stage T3-4, N0-2, M0 colon adenocarcinoma.

A constrained optimisation framework for parameter identification of the SIRD model.

We consider a numerical framework tailored to identifying optimal parameters in the context of modelling disease propagation. Our focus is on understanding the behaviour of optimisation algorithms for such problems, where the dynamics are described by a system of ordinary differential equations associated with the epidemiological SIRD model. Applying an optimise-then-discretise approach, we examine properties of the solution operator and determine existence of optimal parameters for the problem considered.

Clinical Guidelines for Canine Transmissible Venereal Tumour Treatment: Systematic Review and Meta-Analysis.

The treatment of canine transmissible venereal tumour (CTVT) has evolved since its initial description in 1810. Initially considered untreatable in the early 20th century, extensive research over time has significantly advanced our understanding of its aetiopathogenesis. This led to successful chemotherapy treatments, which have shown superior outcomes compared to surgical interventions.

Evaluation of a novel malaria anti-sporozoite vaccine candidate, R21 in Matrix-M adjuvant, in the UK and Burkina Faso: two phase 1, first-in-human trials.

Background: Malaria remains a substantial public health burden among young children in sub-Saharan Africa and a highly efficacious vaccine eliciting a durable immune response would be a useful tool for controlling malaria. R21 is a malaria vaccine comprising nanoparticles, formed from a circumsporozoite protein and hepatitis B surface antigen (HBsAg) fusion protein, without any unfused HBsAg, and is administered with the saponin-based Matrix-M adjuvant. This study aimed to assess the safety and immunogenicity of the malaria vaccine candidate, R21, administered with or without adjuvant Matrix-M in adults naïve to malaria infection and in healthy adults from malaria endemic areas.

R21 in Matrix-M adjuvant in UK malaria-naive adult men and non-pregnant women aged 18-45 years: an open-label, partially blinded, phase 1-2a controlled human malaria infection study.

Background: R21 is a novel malaria vaccine, composed of a fusion protein of the malaria circumsporozoite protein and hepatitis B surface antigen. Following favourable safety and immunogenicity in a phase 1 study, we aimed to assess the efficacy of R21 administered with Matrix-M (R21/MM) against clinical malaria in adults from the UK who were malaria naive in a controlled human malaria infection study.

Methods: In this open-label, partially blinded, phase 1-2A controlled human malaria infection study undertaken in Oxford, Southampton, and London, UK, we tested five novel vaccination regimens of R21/MM.

Frailism: a scoping review exploring discrimination against people living with frailty.

People living with frailty can experience discrimination, but unlike the characteristics of age and disability, frailty is not protected by law. Frailty is a clinical syndrome associated with ageing in which health deficits increase a person's vulnerability to illness, disability, and death. This scoping review, conducted by a team of methodologists, clinicians, lawyers, and patients, aimed to investigate the extent of discrimination against people living with frailty described in health-care literature.

Baseline characteristics of patients in the Chinese Bronchiectasis Registry (BE-China): a multicentre prospective cohort study.

Background: Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China.

Methods: The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China.

Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals.

Ramadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients' risk as low or moderate, high, or very high.