Advantages and challenges of using arterial spin labelling MRI to monitor cerebral blood flow in multi-centre clinical trials of neurodegenerative disease: Experience from the RADAR study.

Arterial spin labelling (ASL) enables non-invasive quantification of regional brain perfusion using MRI. ASL was used in the Reducing Pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR) multi-centre trial to pilot the assessment of the effects of the anti-hypertension drug losartan on cerebral blood flow (CBF). In the multi-centre setting, disparities in ASL implementation on scanners from different manufacturers lead to inherent differences in measured CBF and its associated parameters (e.

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.

Vascularised Composite Allotransplantation - A guide to optimal dissemination of scientific outputs.

Purpose: The impact of academic research is not just important within the clinical domain but within society as a whole. Altmetric Attention Score (AAS) offers a means of assessing how scholarly outputs are interacted with online. Vascularised Composite Allotransplantation (VCA) is a modern but rapidly evolving topic which encompasses a broad range of complex and clinically significant surgical interventions.

Assessing and Managing Primary Hyperparathyroidism and Fracture Risk in England: A Survey of Medical Professionals.

Purpose: To describe diagnostic approaches and management strategies for patients with primary hyperparathyroidism (PHPT) and recent fracture in England.

Methods: We developed a survey based on a patient at high fracture risk and a new diagnosis of probable PHPT. The survey was circulated among 50 secondary care professionals identified by the Society for Endocrinology Calcium and Bone special interest group.

Building Localized NADP(H) Recycling Circuits to Advance Enzyme Cascadetronics.

The catalytic action of enzymes of a cascade trapped within a mesoporous electrode material is simultaneously energized, controlled and observed through the efficient, reversible electrochemical NAD(P)(H) recycling catalyzed by one of the enzymes. In their nanoconfined state, nicotinamide cofactors are tightly channeled current carriers, mediating multi-step reactions in either direction (oxidation or reduction) with a rapid response time. By incorporating a hydrogen‑borrowing enzyme pair, the internal action of which opposes the external voltage bias driving oxidation or reduction, a reduction process can be performed under overall oxidizing conditions, and vice versa.

Estimation of end-of-outbreak probabilities in the presence of delayed and incomplete case reporting.

Towards the end of an infectious disease outbreak, when a period has elapsed without new case notifications, a key question for public health policymakers is whether the outbreak can be declared over. This requires the benefits of a declaration (e.g.

Geographic differences in the phenology of gonadal development and moult, but not of egg laying, are genetically based in a small songbird.

To forecast how fast populations can adapt to climate change, it is essential to determine the evolutionary potential of different life-cycle stages under selection. In birds, timing of gonadal development and moult are primarily regulated by photoperiod, while laying date is highly phenotypically plastic to temperature. We tested whether geographic variation in phenology of these life-cycle events between populations of great tits () has a genetic basis, indicating that contemporary genetic adaptation is possible.

The promise of community-driven preprints in ecology and evolution.

Publishing preprints is quickly becoming commonplace in ecology and evolutionary biology. Preprints can facilitate the rapid sharing of scientific knowledge establishing precedence and enabling feedback from the research community before peer review. Yet, significant barriers to preprint use exist, including language barriers, a lack of understanding about the benefits of preprints and a lack of diversity in the types of research outputs accepted (e.

Proximal humerus fracture dislocations: outcomes of management.

Purpose: Proximal humerus fracture dislocations are amongst the most severe proximal humerus injuries, presenting a challenging management problem. The aim of this study was to report on long-term outcomes of management of proximal humerus fracture dislocations.

Methods: Patients with a proximal humerus fracture dislocation managed at a Level 1 trauma centre from January 2010 to December 2018 were included.

Experiences, perceptions and ethical considerations of the malaria infection study in Thailand.

Background: Thailand has made significant progress in malaria control efforts in the past decade, with a decline in the number of reported cases. However, due to cross-border movements over the past 5 years, reported malaria cases in Thailand have risen. The Malaria Infection Study in Thailand (MIST) involves deliberate infection of healthy volunteers with Plasmodium vivax malaria parasites, and the assessment of the efficacy of potential vaccine and drug candidates in order to understand acquired protection against malaria parasites.

Barriers and facilitators to engagement with between-session work for low-intensity Cognitive Behavioural Therapy (CBT)-based interventions: a qualitative exploration of practitioner perceptions.

Background: To address the growing demand for psychological treatment, healthcare providers are increasingly utilising low-intensity interventions, characterised by reduced practitioner contact and emphasis on independent patient engagement with therapeutic materials through between-session work (BSW). While BSW is critical for maximising treatment outcomes, patients and practitioners report challenges with its completion. Research identifying factors influencing between-session engagement in Cognitive Behavioural Therapy (CBT) has largely focused on high-intensity CBT, limiting understanding within low-intensity contexts.

Population-based, first-tier genomic newborn screening in the maternity ward.

The rapid development of therapies for severe and rare genetic conditions underlines the need to incorporate first-tier genetic testing into newborn screening (NBS) programs. A workflow was developed to screen newborns for 165 treatable pediatric disorders by deep sequencing of regions of interest in 405 genes. The prospective observational BabyDetect pilot project was launched in September 2022 in a maternity ward of a public hospital in the Liege area, Belgium.

Hearing loss and risk of major osteoporotic fracture: a population-based cohort study in the United Kingdom.

Unlabelled: Using the UK Clinical Practice Research Datalink, our cohort study matched 237,297 individuals with hearing loss (HL) to 829,431 without HL. The study found an 8-10% higher risk of major osteoporotic fracture in individuals with HL compared to those without. Additionally, within the HL cohort, we identified risk factors for potential inclusion in fracture risk models.

Enhancing immunity during ageing by targeting interactions within the tissue environment.

Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as 'inflammageing'.

Investigating time-independent and time-dependent diffusion phenomena using steady-state diffusion MRI.

Diffusion MRI is a leading method to non-invasively characterise brain tissue microstructure across multiple domains and scales. Diffusion-weighted steady-state free precession (DW-SSFP) is an established imaging sequence for post-mortem MRI, addressing the challenging imaging environment of fixed tissue with short T and low diffusivities. However, a current limitation of DW-SSFP is signal interpretation: it is not clear what diffusion 'regime' the sequence probes and therefore its potential to characterise tissue microstructure.

A phenotype-based AI pipeline outperforms human experts in differentially diagnosing rare diseases using EHRs.

Rare diseases, affecting ~350 million people worldwide, pose significant challenges in clinical diagnosis due to the lack of experienced physicians and the complexity of differentiating between numerous rare diseases. To address these challenges, we introduce PhenoBrain, a fully automated artificial intelligence pipeline. PhenoBrain utilizes a BERT-based natural language processing model to extract phenotypes from clinical texts in EHRs and employs five new diagnostic models for differential diagnoses of rare diseases.

The number of central nervous system-driven symptoms predicts subsequent chronic primary pain: evidence from UK Biobank.

Background: Chronic primary pain describes conditions where pain is the principal problem rather than a consequence of another disease. Primary pain is thought to be primarily owing to nociplastic pain (i.e.

The spectrum and outcome of metastatic hepatocellular carcinoma in a South African patient cohort.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally, particularly in developing countries in Southeast Asia and sub-Saharan Africa (SSA), where chronic hepatitis B virus (HBV) dominates as a major aetiological factor.

Methods: We conducted a retrospective cohort study to quantify the metastatic profile of HCC in a South African patient population managed at a tertiary centre. Demographic, clinical and treatment data were extracted from an institutional registry.

Destined for destruction: The role of methionine aminopeptidases and plant cysteine oxidases in N-degron formation.

The cysteine/arginine (Cys/Arg) branch of the N-degron pathway controls the stability of certain proteins with methionine (Met)-Cys N-termini, initiated by Met cleavage and Cys oxidation. In seeding plants, target proteins include the Group VII Ethylene Response Factors, which initiate adaptive responses to low oxygen (hypoxic) stress, as well as Vernalization 2 (VRN2) and Little Zipper 2 (ZPR2), which are involved in responses to endogenous developmental hypoxia. It is essential that these target proteins are only degraded by the N-degron pathway under the appropriate physiological conditions.

Unravelling phylogenetic relationships within the genus Lispe (Diptera: Muscidae) through genome-assisted and de novo analyses of RAD-seq data.

Lispe represents a species-rich genus within the family Muscidae. The current subdivision of Lispe species into species groups is based mainly on adult morphology and ecology, with the only available phylogenetic study based on three molecular markers. Nonetheless, certain species groups remain unclear and the relationships and composition of these groups are still unresolved.

Inequity of access to contrast-enhanced cardiovascular magnetic resonance in patients with chronic kidney disease: A survey from the British Society of Cardiovascular Magnetic Resonance.

Objectives: To examine the provision of cardiovascular magnetic resonance (CMR) using gadolinium-based contrast agents (GBCA) in patients with chronic kidney disease (CKD).

Methods: An electronic survey was sent to the service leads of all CMR units in the UK in October 2022 requesting information on current departmental protocols and practice.

Results: A response rate of 55% was achieved from the 82 UK CMR units surveyed.

Minimally invasive treatment strategies for submucosal tumors of the upper gastrointestinal tract: Advances in innovative endoscopy-based therapies.

The increasing detection of submucosal tumors (SMTs) in the upper gastrointestinal tract (UGI) is due to the increased clinical use of endoscopy and imaging technology. Some of these SMTs have malignant potential and may cause clinical symptoms. Thus, it is recommended in clinical guidelines to consider resection of these SMTs.