A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.

Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses and cellular reprogramming, although the full extent of its physiological roles is unexplored. Despite detailed molecular knowledge of PADI4 activation in vitro, we lack understanding of its regulation within cells, largely due to a lack of appropriate systems and tools.

Protocol for a national, multicentre study of post-endoscopy colorectal and upper gastrointestinal cancers: The POET study.

Aim: The primary aim of the study is to define the post-colonoscopy colorectal cancer (PCCRC) three-year rate and the post-endoscopy upper gastrointestinal cancer (PEUGIC) three-year rate across public hospitals in Aotearoa New Zealand.

Method: This retrospective cohort study will be conducted via the trainee-led STRATA Collaborative network. All public hospitals in Aotearoa New Zealand will be eligible to participate.

Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts.

Self-Supervised Machine Learning to Characterize Step Counts from Wrist-Worn Accelerometers in the UK Biobank.

Purpose: Step count is an intuitive measure of physical activity frequently quantified in health-related studies; however, accurate step counting is difficult in the free-living environment, with error routinely above 20% in wrist-worn devices against camera-annotated ground truth. This study aimed to describe the development and validation of step count derived from a wrist-worn accelerometer and assess its association with cardiovascular and all-cause mortality in a large prospective cohort.

Methods: We developed and externally validated a self-supervised machine learning step detection model, trained on an open-source and step-annotated free-living dataset.

Sunitinib malate induces cell death in adult human cardiac progenitor cells.

Sunitinib malate is known to cause cardiotoxicity in a sub-population of patients, with heart failure seen in more severe cases. Cardiac progenitor cells (CPCs) have been identified in adult human myocardium and contribute to overall tissue maintenance, with previous work identifying negative impacts of sunitinib on these cells. This study aimed to characterise the toxic effects of sunitinib in human CPCs, applying sunitinib concentrations equivalent to clinical plasma levels to these cells .

Influx of zwitterionic buffer after intracytoplasmic sperm injection (ICSI) membrane piercing alters the transcriptome of human oocytes.

Purpose/study Question: Does piercing oocyte membranes during ICSI allow the influx of surrounding zwitterionic buffer into human oocytes and result in altered developmental competence?

Methods: Human oocytes directed to IRB-approved research were used to determine the unrestricted influx of surrounding buffer into the oocyte after piercing of membranes via confocal fluorescence microscopy (n = 80 human MII oocytes) and the influence of the select buffer influx of HEPES, MOPS, and bicarbonate buffer on the oocyte transcriptome using ultra-low input RNA sequencing (n = 40 human MII oocytes).

Results: Piercing membranes of human MII oocytes during sham-ICSI resulted in the unrestricted influx of surrounding culture buffer into the oocyte that was beyond technician control. Transcriptome analysis revealed statistically significant decreased cytoskeletal transcripts in the pierced buffer cohorts, higher levels of embryo competency transcripts (IGF2 and G6PD) in the bicarbonate buffer cohort, higher levels of stress-induced transcriptional repressor transcripts (MAF1) in the HEPES and MOPS cohorts, and decreased levels of numerous chromosomal maintenance transcripts (SMC3) in the HEPES buffer cohort.

The effect of bariatric surgery on the expression of gastrointestinal taste receptors: A systematic review.

Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery.

Amount and intensity of physical activity and risk of incident cancer in the UK Biobank.

Importance: The influence of total daily and light intensity activity on cancer risk remains unclear, as most existing knowledge is drawn from studies relying on self-reported leisure-time activities of moderate-vigorous intensity.

Objective: To investigate associations between total daily activity, including step counts, and activity intensity on incident cancer risk.

Design Setting And Participants: Prospective analysis of cancer-free UK Biobank participants who wore accelerometers for 7-days (between 2013-2015), followed for cancer incidence through national registries (mean follow-up 5.

Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Background: Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts.

Development and Validation of a Machine Learning Wrist-worn Step Detection Algorithm with Deployment in the UK Biobank.

Background: Step count is an intuitive measure of physical activity frequently quantified in a range of health-related studies; however, accurate quantification of step count can be difficult in the free-living environment, with step counting error routinely above 20% in both consumer and research-grade wrist-worn devices. This study aims to describe the development and validation of step count derived from a wrist-worn accelerometer and to assess its association with cardiovascular and all-cause mortality in a large prospective cohort study.

Methods: We developed and externally validated a hybrid step detection model that involves self-supervised machine learning, trained on a new ground truth annotated, free-living step count dataset (OxWalk, n=39, aged 19-81) and tested against other open-source step counting algorithms.

Biomarkers in the early prediction of rescue therapy in acute severe colitis-a single-centre retrospective study.

Nil.

The Challenges of Visualisation During Delivery and Assessment of Clinical Teaching Under COVID-19: A Reflective Account of Problem Solving.

Whilst the in-person clinical immersion of students in their final years of medical programmes was relatively protected from the impact of COVID-19, the ability to deliver in-person clinical teaching was restricted or heavily altered for early-year students. Our challenge as a 3-year BSc (Hons) in Medicine programme at the University of St Andrew's School of Medicine was to continue to immerse and engage students in their clinical training when in-person access to the authentic environment was impossible, restricted, or completely altered from the original image held by students.In this chapter, we aim to discuss the problems faced, the solutions considered within the contextual restraints and then reflect on the successes and failures of the approaches we took in aiding students to visualise themselves in the clinical environment, or when using altered delivery modes that introduced radically different optics on the learning experience.

Imatinib Mesylate Induces Necroptotic Cell Death and Impairs Autophagic Flux in Human Cardiac Progenitor Cells.

The receptor tyrosine kinase inhibitor imatinib improves patient cancer survival but is linked to cardiotoxicity. This study investigated imatinib's effects on cell viability, apoptosis, autophagy, and necroptosis in human cardiac progenitor cells in vitro. Imatinib reduced cell viability (75.

Your best day: An interactive app to translate how time reallocations within a 24-hour day are associated with health measures.

Reallocations of time between daily activities such as sleep, sedentary behavior and physical activity are differentially associated with markers of physical, mental and social health. An individual's most desirable allocation of time may differ depending on which outcomes they value most, with these outcomes potentially competing with each other for reallocations. We aimed to develop an interactive app that translates how self-selected time reallocations are associated with multiple health measures.

Artificial intelligence improves adenoma detection rate during colonoscopy.

Background: Artificial intelligence-assisted colonoscopy (AIAC) has gained attention as a tool to assist with polyp detection during colonoscopy. Uncertainty remains as to the clinical benefit, given limited publications using different modules.

Method: A single-centre retrospective study was performed at Waitematā Endoscopy, a private endoscopy centre in Auckland, New Zealand.

Inlet hydrogenation gas chromatography to predict mass % linear paraffin content.

The light condensate fraction obtained from the low temperature Fischer-Tropsch (LT-FT) process is very complex and it is processed further by hydrotreating to produce hydrocarbon products that can be sold as final products. The mass% linear paraffins in some of the final paraffin products is listed as a required specification. Usually gas chromatography equipped with a flame ionisation detector (GC-FID) is used for the analysis of the condensate feeds to estimate the mass% linear paraffins that can be expected in the final products after commercial hydrogenation.

Perspectives on strategies for improving ultra-deep desulfurization of liquid fuels through hydrotreatment: Catalyst improvement and feedstock pre-treatment.

Reliance on crude oil remains high while the transition to green and renewable sources of fuel is still slow. Developing and strengthening strategies for reducing sulfur emissions from crude oil is therefore imperative and makes it possible to sustainably meet stringent regulatory sulfur level legislations in end-user liquid fuels (mostly less than 10 ppm). The burden of achieving these ultra-low sulfur levels has been passed to fuel refiners who are battling to achieve ultra-deep desulfurization through conventional hydroprocessing technologies.

Receptor tyrosine kinase inhibitors negatively impact on pro-reparative characteristics of human cardiac progenitor cells.

Receptor tyrosine kinase inhibitors improve cancer survival but their cardiotoxicity requires investigation. We investigated these inhibitors' effects on human cardiac progenitor cells in vitro and rat heart in vivo. We applied imatinib, sunitinib or sorafenib to human cardiac progenitor cells, assessing cell viability, proliferation, stemness, differentiation, growth factor production and second messengers.

The Latest Treatment Interventions Improving Mental Health Outcomes for Women, Following Gender-Based Violence in Low-and-Middle-Income Countries: A Mini Review.

Gender-based violence (GBV), specifically violence against women, is a worldwide pandemic. Prevalence is further escalated in low-and-middle-income countries and in humanitarian crises. Survivors are left with a combination of post-traumatic stress disorder, depression and anxiety.

Correction: Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.

Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.

Objective: To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.

Methods: Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours.