Accuracy of an artificial intelligence as a medical device as part of a UK-based skin cancer teledermatology service.

Introduction: An artificial intelligence as a medical device (AIaMD), built on convolutional neural networks, has demonstrated high sensitivity for melanoma. To be of clinical value, it needs to safely reduce referral rates. The primary objective of this study was to demonstrate that the AIaMD had a higher rate of correctly classifying lesions that did not need to be referred for biopsy or urgent face-to-face dermatologist review, compared to teledermatology standard of care (SoC), while achieving the same sensitivity to detect malignancy.

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial.

Introduction: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes.

Methods And Analysis: A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control).

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R.

The Intellectual Disability Risk Gene Regulates Long-Term Memory Consolidation in the Hippocampus.

The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders, and heterozygous, protein-truncating variants in are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a allele that lacks demethylase activity.

Getting Your First Publication in Medical Education-Why? What? Where? How?

The process of getting one's work published is a major milestone for many in their early academic and clinical careers. However, this process can be confusing and overwhelming for many who have yet to publish themselves. There are differing motivators for publishing work in our early career stages, alongside considerations, such as what we publish, where we decide to submit work, and how we logistically undertake the submission process.

Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder.

Sequence variants in the HERC2 gene are associated with a significant reduction in HERC2 protein levels and cause a neurodevelopmental disorder known as the HERC2-related disorder, which shares clinical features with Angelman syndrome, including global developmental delay, intellectual disability, autism, and movement disorders. Remarkably, the HERC2 gene is commonly deleted in individuals with Angelman syndrome, suggesting a potential contribution of HERC2 to the pathophysiology of this disease. Given the known critical role of autophagy in brain development and its implication in neurodevelopmental diseases, we undertook different experimental approaches to monitor autophagy in fibroblasts derived from individuals affected by the HERC2-related disorder.

Investigating harms of testing for ovarian cancer - psychological outcomes and cancer conversion rates in women with symptoms of ovarian cancer: A cohort study embedded in the multicentre ROCkeTS prospective diagnostic study.

Objective: To investigate psychological correlates in women referred with suspected ovarian cancer via the fast-track pathway, explore how anxiety and distress levels change at 12 months post-testing, and report cancer conversion rates by age and referral pathway.

Design: Single-arm prospective cohort study.

Setting: Multicentre.

Skin cancer referrals by nonmedical practitioners: a prospective observational study.

The aim of this study was to investigate the appropriateness of suspected skin cancer referrals made by nonmedical practitioners (NMPs) and compare this with referrals made by local general practitioners (GPs). Data were collected prospectively from patients referred from primary care to a UK hospital dermatology department. The profession of the referrer was ascertained from review of referral letters and direct questioning.

Aphantasia and hyperphantasia: exploring imagery vividness extremes.

The vividness of imagery varies between individuals. However, the existence of people in whom conscious, wakeful imagery is markedly reduced, or absent entirely, was neglected by psychology until the recent coinage of 'aphantasia' to describe this phenomenon. 'Hyperphantasia' denotes the converse - imagery whose vividness rivals perceptual experience.

Cellular Pre-Adaptation to the High O Concentration Used in Standard Cell Culture Confers Resistance to Subsequent HO-Induced Cell Death.

The addition of hydrogen peroxide (HO) to cultured cells is widely used as a method to modulate redox-regulated cellular pathways, including the induction of programmed cell death in cell culture experiments and the testing of pro- and antioxidant compounds. Here, we assessed the effect on the cellular response to HO of pre-adapting squamous cell carcinoma cells (A431) to the standard cell culture oxygenation of 18.6% O, compared to cells pre-adapted to a physiological skin O concentration (3.

Sustainable green extraction of anthocyanins and carotenoids using deep eutectic solvents (DES): A review of recent developments.

Recently, deep eutectic solvents (DES) have been extensively researched as a more biocompatible and efficient alternative to conventional solvents for extracting pigments from natural resources. The efficiency of DES extraction for the anthocyanin and carotenoid can be enhanced by microwave-assisted extraction (MAE) and/or ultrasound-assisted extraction (UAE) techniques. Apart from the extraction efficiency, the toxicity and recovery of the pigments and their bioavailability are crucial for potential applications.

The Role of Insulin-like Growth Factor (IGF) System in the Corneal Epithelium Homeostasis-From Limbal Epithelial Stem Cells to Therapeutic Applications.

The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of the lacrimal gland, tear film, and corneal nerves. Crucially, limbal epithelial stem cells located in the limbus (transitional zone between the cornea and the conjunctiva) are instrumental for the corneal epithelium integrity by replenishing and renewing cells.

Extent of investigation and management of cases of 'unexplained' mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus.

Background: Mismatch repair deficiency (dMMR) is a characteristic feature of cancers linked to Lynch syndrome. However, in most cases, it results from sporadic somatic events rather than hereditary factors. The term 'Lynch-like syndrome' (LLS) has been used to guide colorectal cancer surveillance for relatives of individuals with a dMMR tumour when somatic and germline genomic testing is uninformative.

Wider institutional research cultures and their influence on patient and public involvement and engagement in health research - An institutional ethnography.

Focus on patient and public involvement and engagement (PPIE) is increasing in health policy and research governance. PPIE is considered by some to be a democratic right, and by others to be a way to improve health care and research outcomes and implementation. Most recently, policy makers, funders and (clinical) research institutions are making PPIE a strategic requirement for health research urging researchers to invite patients and relatives into their research activities.

Emotion in public involvement: A conceptual review.

Background: Experiential knowledge can aid in designing research by highlighting what an idea looks like from a patient and carer perspective. Experiential knowledge can be emotional, and this can create challenges at formal research meetings.

Objective: The aim of this study was to consider the role of emotions in public involvement.

Sleep disturbance in people living with dementia or mild cognitive impairment: a realist review of general practice.

Background: Sleep disturbance is a prevalent condition among people living with dementia (PLwD) or mild cognitive impairment (MCI). Its assessment and management within primary care is complex because of the comorbidities, older age, and cognitive impairment typical of this patient group.

Aim: To explore how primary care clinicians assess, understand, and manage sleep disturbance for PLwD or MCI; if and why such initiatives work; and how people and their carers experience sleep disturbance and its treatment.

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

Background: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure.

Methods: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities.

Reliability, validity and acceptability of an online clinical reasoning simulator for medical students: An international pilot.

Introduction: Clinical reasoning skills are essential for decision-making. Current assessment methods are limited when testing clinical reasoning and management of uncertainty. This study evaluates the reliability, validity and acceptability of Practicum Script, an online simulation-based programme, for developing medical students' clinical reasoning skills using real-life cases.