Complexity of brain-like signals in self-organised nanoscale networks.

The biological brain is comprised of a complex, interconnected, self-assembled network of neurons and synapses. This network enables efficient and accurate information processing, unsurpassed by any other known computational system. Percolating networks of nanoparticles (PNNs) are complex, interconnected, self-assembled systems that exhibit many emergent brain-like characteristics.

Use of Large Language Models for Rapid Quantitative Feedback in Case-Based Learning: A Pilot Study.

Unlabelled: Large language models (LLMs) may be able to deliver interactive case-based content and score student interactions with such cases. In this study, GPT-4o demonstrated a high correlation with expert scorers in the evaluation of medical students' interactions with cases. A difference between LLM scores and expert scorers was corrected through calibration.

The Learning-Teaching Nexus: Medical Students' Motivations to Engage in Peer-Assisted Learning.

Aims: This study describes the factors that motivate final-year medical students to undertake a structured experience of peer-assisted learning (PAL) as student tutors and explores their perceptions of the relevance of teaching to their future careers.

Methods: This exploratory qualitative study involved semistructured interviews with nine final-year medical students undertaking PAL within a formal medical education elective as part of their studies. Interviews were transcribed and analysed thematically.

Optimal risk assessment intervals for primary prevention of cardiovascular disease: a population-based two-stage landmarking study.

Introduction: The recommended assessment intervals for primary prevention of cardiovascular disease (CVD) differ in major international guidelines. We aimed to provide empirical evidence on the optimal frequency of CVD risk assessment to inform future guidelines.

Methods: We estimated the expected time to cross the 10-year CVD risk treatment threshold of 10% using extended two-stage landmarking for more than 2 million people using UK primary care electronic health records between April 2004 and May 2019 from the Clinical Practice Research Datalink GOLD Database (CPRD GOLD), which was linked to hospital admissions data from the Hospital Episodes Statistics (HES) dataset and national mortality records from the Office for National Statistics (ONS).

Large language model-supported interactive case-based learning: a pilot study.

Large language models (LLMs) have been proposed as a means to augment case-based learning but are prone to generating factually incorrect content. In this study, an LLM-based tool was developed, and its performance evaluated. In response to student-generated questions, the LLM adhered to the provided screenplay in 832/857 (97.

Janus-kinase inhibitor use in immune-mediated inflammatory diseases beyond licensed indications: A scoping review.

Introduction: The use of Janus kinase inhibitors (JAKis) in immune-mediated inflammatory diseases (IMIDs) beyond licence is expanding rapidly. The aim of this scoping review was to identify and present the available evidence on the efficacy of JAKis in all conditions without marketing authorisation.

Methods: Through a systematic literature search we identified studies including 5 or more patients that assessed the use of any JAKi for any efficacy outcome.

Evidence-Based Crossword Puzzles for Health Professions Education: A Systematic Review.

Unlabelled: Crossword puzzles have been utilised as a means of health professions education (HPE) gamification. A systematic review conducted in accordance with PRISMA guidelines was performed to evaluate the educational impact and describe the characteristics of crosswords in HPE contexts. Twenty-nine studies fulfilled inclusion criteria.

Age and sex specific thresholds for risk stratification of cardiovascular disease and clinical decision making: prospective open cohort study.

Objective: To quantify the potential advantages of using 10 year risk prediction models for cardiovascular disease, in combination with risk thresholds specific to both age and sex, to identify individuals at high risk of cardiovascular disease for allocation of statin treatment.

Design: Prospective open cohort study.

Setting: Primary care data from the UK Clinical Practice Research Datalink GOLD, linked with hospital admissions from Hospital Episode Statistics and national mortality records from the Office for National Statistics in England, 1 January 2006 to 31 May 2019.

Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD.

Background: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited.

Aim: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known.

Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

Introduction: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992).

Methods: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision.

Mesoporous Metal Sponges Produced by Explosive Decomposition.

The formation of mesoporous gold sponges by explosive decomposition of 'knallgold' (also known as 'fulminating' gold) is studied. Proof-of-principle experiments are conducted and then the phenomena are further investigated using 'toy physics' molecular dynamics simulations. The simulations invoked various ratios of a volatile Lennard-Jones element G and a noble metal element N.

Maintained renin-angiotensin-aldosterone system inhibitor therapy with sodium zirconium cyclosilicate following a hyperkalaemia episode: a multicountry cohort study.

Background: This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K) binder.

Methods: Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K binder cohort on baseline characteristics.

ChatGPT-Based Learning: Generative Artificial Intelligence in Medical Education.

Unlabelled: Large language models like ChatGPT are a type of machine learning model that can offer a positive paradigm shift in case-based/problem-based learning (CBL/PBL). ChatGPT may be able to augment the existing paradigm to work in conjunction with the clinical-teacher in PBL/CBL case generation. It can develop realistic patient cases that could be revised by clinical teachers to ensure accuracy and relevance.

Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults.

Background: The impact of vaccination prior to infection on postacute sequelae of coronavirus disease 2019 (COVID-19, PASC), also known as long COVID, remains unclear. Here we assess the protective effect of vaccination on long COVID in a community-based setting.

Methods: The Immunity Associated with SARS-CoV-2 (IASO) study is an ongoing prospective cohort of working adults that began in October 2020.

Hyperkalaemia-related reduction of RAASi treatment associates with more subsequent inpatient care.

Background: Hyperkalaemia is a barrier to achieving optimal, guideline-directed treatment with renin-angiotensin-aldosterone system inhibitors (RAASis) in patients with chronic kidney disease (CKD) and/or heart failure (HF). This study describes the association between hyperkalaemia-related RAASi treatment reduction and the number of hospitalized days in patients with CKD and/or HF in Sweden and Japan.

Methods: Using data from health registers and hospital medical records, patients with CKD and/or HF currently receiving RAASis who experienced an index hyperkalaemia episode were identified and categorized as having maintained or reduced RAASi treatment post-index; propensity score matching (1:1) was applied to balance the groups in terms of baseline characteristics.

TIME-seq reduces time and cost of DNA methylation measurement for epigenetic clock construction.

Epigenetic 'clocks' based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types.

Computation via Neuron-like Spiking in Percolating Networks of Nanoparticles.

The biological brain is a highly efficient computational system in which information processing is performed via electrical spikes. Neuromorphic computing systems that work on similar principles could support the development of the next generation of artificial intelligence and, in particular, enable low-power edge computing. Percolating networks of nanoparticles (PNNs) have previously been shown to exhibit critical spiking behavior, with promise for highly efficient natural computation.

A community of practice to address system-based issues and promote clinical leadership among trainee medical officers in a large public health service: an evaluation of a trainee-led forum.

Clinical leadership is necessary to improve the performance of large public hospitals. Trainee medical officers (TMOs) are important stakeholders in organisation-wide initiatives that affect the medical workforce and support clinician engagement. This case study describes the development of a representative body known as the 'TMO Forum' within the Central Adelaide Local Health Network as a mechanism to promote engagement between medical trainees and the hospital executive to facilitate escalation and discussion of system-based issues.

Prioritising cardiovascular disease risk assessment to high risk individuals based on primary care records.

Objective: To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds.

Methods And Analysis: eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment.

Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.

Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models.

Chemically induced reprogramming to reverse cellular aging.

A hallmark of eukaryotic aging is a loss of epigenetic information, a process that can be reversed. We have previously shown that the ectopic induction of the Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals can restore youthful DNA methylation patterns, transcript profiles, and tissue function, without erasing cellular identity, a process that requires active DNA demethylation. To screen for molecules that reverse cellular aging and rejuvenate human cells without altering the genome, we developed high-throughput cell-based assays that distinguish young from old and senescent cells, including transcription-based aging clocks and a real-time nucleocytoplasmic compartmentalization (NCC) assay.

Surgical treatment of ankle instability in children with os subfibulare.

Introduction: Ankle instability in children due to soft tissue injury usually resolves after non-operative treatment. However, some children and adolescents with chronic instability require surgical treatment. A rarer cause of developing ankle instability is injury to the ligament complex in the presence of os subfibulare, an accessory bone inferior to the lateral malleolus.