Safety and immunogenicity of the ChAdOx1-MVA-vectored conserved mosaic HIVconsvX candidate T-cell vaccines in HIV-CORE 005.2, an open-label, dose-escalation, first-in-human, phase 1 trial in adults living without HIV-1 in the UK.

Background: An HIV-1 vaccine is long overdue. Although vaccine research focuses on the induction of broadly neutralising antibodies, challenging infections such as HIV-1 could require parallel induction of protective T cells. It is important to recognise that not all T cells contribute to protection equally.

Politics, policy and action: lessons from rural GP advocacy in Ireland.

Context: Ireland has one of the most rural populations in Europe. Rurality presents challenges when accessing health services but should not be perceived as problematic and in need of a structural fix. Structural urbanism where health care is viewed as a commodity for individuals, rather than an infrastructure for populations, innately favours larger urban populations and has detrimental outcomes for rural health.

Supporting General Practitioners and people with hypertension to maximise medication use to control blood pressure: the contribution of Collective Intelligence to the development of the 'Maximising Adherence, Minimising Inertia' (MIAMI) intervention.

Background: Hypertension remains one of the most important modifiable risk factors for stroke and heart disease. Anti-hypertensive medications are effective, but are often not used to maximum benefit. Sub-optimal dosing by prescribers and challenges with medication-taking for patients remain barriers to effective blood pressure control.

Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

Background: Infections have a poor prognosis in inpatients with cirrhosis. We aimed to determine regional variations in infections and their association with clinical outcomes in a global cohort of inpatients with cirrhosis.

Methods: In this prospective cohort study initiated by the CLEARED Consortium, we enrolled adults (aged >18 years) with cirrhosis who were non-electively admitted to 98 hospitals from 26 countries or regions across six continents between Nov 5, 2021, and Dec 10, 2022.

Semaglutide and blood pressure: an individual patient data meta-analysis.

Background And Aims: Randomized clinical trials (RCTs) assessing semaglutide reported reductions of systolic blood pressure (SBP) in trial populations with baseline blood pressure in the normotensive range. This study aimed to determine whether this SBP reduction is greater in hypertensive groups.

Methods: Individual patient data (IPD) from three RCTs examining the effect of semaglutide 2.

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), characterised by hepatic lipid accumulation, causes inflammation and oxidative stress accompanied by cell damage and fibrosis. Liver injury (LI) is also frequently reported in patients hospitalised with coronavirus disease 2019 (COVID-19), while pre-existing MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy. Mechanisms of injury at the cellular level remain unclear, but it may be significant that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19, uses angiotensin-converting expression enzyme 2 (ACE2), a key regulator of the 'anti-inflammatory' arm of the renin-angiotensin system, for viral attachment and host cell invasion.

Guideline-based exercise management for hip and knee osteoarthritis: a cross-sectional comparison of healthcare professional and patient beliefs in Ireland.

Objectives: To identify within-stakeholder agreement and between-stakeholder differences in beliefs regarding exercise for osteoarthritis among general practitioners (GPs), physiotherapists (PTs) and people with hip and knee osteoarthritis (PwOA). A secondary objective was to explore the association between referral patterns and beliefs of PwOA.

Design: Cross-sectional.

Supporting GPs and people with hypertension to maximise medication use to control blood pressure: Protocol for a pilot cluster RCT of the MIAMI intervention.

Hypertension is one of the most important risk factors for stroke and heart disease. Recent international guidelines have stated that The MaxImising Adherence, Minimising Inertia (MIAMI) intervention, which has been developed using a systematic, theoretical, user-centred approach, aims to support general practitioners (GPs) and people with hypertension to maximise medication use, through the facilitation of adequate information exchange within consultations about long-term antihypertensive medication use and adherence skill development. The aim of the MIAMI pilot cluster randomised controlled trial (RCT) is to gather and analyse feasibility data to allow us to (1) refine the intervention, and (2) determine the feasibility of a definitive RCT.

Study protocol for a Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in Acute Variceal Bleeding (REACT-AVB trial).

Introduction: In liver cirrhosis, acute variceal bleeding (AVB) is associated with a 1-year mortality rate of up to 40%. Data on early or pre-emptive transjugular intrahepatic portosystemic stent-shunt (TIPSS) in AVB is inconclusive and may not reflect current management strategies. Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent-shunt in AVB (REACT-AVB) aims to investigate the clinical and cost-effectiveness of early TIPSS in patients with cirrhosis and AVB after initial bleeding control.

Peripheral artery disease recognition, diagnosis, and management in general practice in the Republic of Ireland and England: an online survey.

Background: Peripheral artery disease (PAD) is common and associated with future cardiovascular events. PAD is underdiagnosed, which limits opportunities to address secondary prevention of cardiovascular disease. It is unknown how closely guidelines for detection of PAD are followed in primary care.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

Background & Aims: Non-selective β-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis.

Enhancing early career professionals' representation and engagement at international conferences: WONCA "Rural Early Career Ambassador Integration" project.

Introduction: International conferences offer an excellent opportunity for career development and are global academic opportunities with the potential to foster educational and professional growth. However, equitable access to participation and meaningful involvement in such events remains an issue. In this article we describe the novel Rural Early Career Ambassador Integration project and its implications for the 2022 World Rural Health Conference, held at the University of Limerick, Ireland.

Mosaic HIV-1 vaccination induces anti-viral CD8 T cell functionality in the phase 1/2a clinical trial APPROACH.

The functionality of CD8+ T cells against human immunodeficiency virus-1 (HIV-1) antigens is indicative of HIV-progression in both animal models and people living with HIV. It is, therefore, of interest to assess CD8+ T cell responses in a prophylactic vaccination setting, as this may be an important component of the immune system that inhibits HIV-1 replication. T cell responses induced by the adenovirus serotype 26 (Ad26) mosaic vaccine regimen were assessed previously by IFN-γ ELISpot and flow cytometric assays, yet these assays only measure cytokine production but not the capacity of CD8+ T cells to inhibit replication of HIV-1.

Pre-emptive TIPS in high-risk acute variceal bleeding. An updated and revised individual patient data meta-analysis.

Background And Aims: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues.

A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: Self-controlled case-series analysis of national data.

Background And Aims: Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs.

Design: This was a self-controlled case-series study.

The evolution of ScotRIGHT: The first pan-Scotland physician trainee research network.

Scotland has a distinguished track record in foundational clinical research. From the completion of the first clinical trial undertaken in scurvy to cloning the world's first whole mammal, Scottish basic and clinical research is world leading. More recently, challenges in access to research skills, funding and programmes by clinical trainees led to the development of alternatives to these typical avenues of accessing research opportunities.

Neural network models for influenza forecasting with associated uncertainty using Web search activity trends.

Influenza affects millions of people every year. It causes a considerable amount of medical visits and hospitalisations as well as hundreds of thousands of deaths. Forecasting influenza prevalence with good accuracy can significantly help public health agencies to timely react to seasonal or novel strain epidemics.

Guidance document: risk assessment of patients with cirrhosis prior to elective non-hepatic surgery.

As a result of the increasing incidence of cirrhosis in the UK, more patients with chronic liver disease are being considered for elective non-hepatic surgery. A historical reluctance to offer surgery to such patients stems from general perceptions of poor postoperative outcomes. While this is true for those with decompensated cirrhosis, selected patients with compensated early-stage cirrhosis can have good outcomes after careful risk assessment.

Synthetic Cell Armor Made of DNA Origami.

The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment. Improved cellular robustness thus motivates investigations into cell encapsulation, which provides essential protection. Here we target the cell-surface glycocalyx and cross-link two layers of DNA nanorods on the cellular plasma membrane to form a modular and programmable nanoshell.

Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro.

The gut-liver axis is defined by dietary and environmental communication between the gut, microbiome and the liver with its redox and immune systems, the overactivation of which can lead to hepatic injury. We used media preconditioning to mimic some aspects of the enterohepatic circulation by treating the human Caco-2 intestinal epithelial cell line with 5, 10 and 20 mM paracetamol (N-acetyl-para-aminophenol; APAP) for 24 h, after which cell culture supernatants were transferred to differentiated human hepatic HepaRG cells for a further 24 h. Cell viability was assessed by mitochondrial function and ATP production, while membrane integrity was monitored by cellular-based impedance.

Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial.

Background And Aims: Beta-blockers have been studied for the prevention of variceal bleeding and, more recently, for the prevention of all-cause decompensation. Some uncertainties regarding the benefit of beta-blockers for the prevention of decompensation remain. Bayesian analyses enhance the interpretation of trials.