The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction.

Cells are continuously subjected to physical and chemical cues from the extracellular environment, and sense and respond to mechanical cues via mechanosensation and mechanotransduction. Although the role of the cytoskeleton in these processes is well known, the contribution of intracellular membranes has been long neglected. Recently, it has become evident that various organelles play active roles in both mechanosensing and mechanotransduction.

Sexual health and healthy relationships for Further Education (SaFE) in Wales and England: results from a pilot cluster randomised controlled trial.

Objectives: To examine the acceptability of implementing, trialling and estimating the cost of the Sexual health and healthy relationships for Further Education (SaFE) intervention.

Design: Two-arm repeated cross-sectional pilot cluster randomised controlled trial (cRCT) of SaFE compared with usual practice, including a process evaluation and an economic assessment.

Setting: Eight further education (FE) settings in South Wales and the West of England, UK.

Association of volatile substance, nitrous oxide and alkyl nitrate use with mental health in UK adolescents.

Background: 'Inhalants' have been associated with poorer mental health in adolescence, but little is known of associations with specific types of inhalants.

Aims: We aimed to investigate associations of using volatile substances, nitrous oxide and alkyl nitrates with mental health problems in adolescence.

Method: We conducted a cross-sectional analysis using data from 13- to 14-year-old adolescents across England and Wales collected between September 2019 and March 2020.

Development of a Preclinical Double Model of Mandibular Irradiated Bone and Osteoradionecrosis in New Zealand Rabbits.

Purpose: Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical study with assessment of translationally relevant aspects.

Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model.

Association between cannabis potency and mental health in adolescence.

Introduction: In legal and illegal markets, high-potency cannabis (>10 % delta-9-tetrahydrocannabinol (THC)) is increasingly available. In adult samples higher-potency cannabis has been associated with mental health disorder but no studies have considered associations in adolescence.

Methods: A population-wide study compared no, low and high potency cannabis using adolescents (aged 13-14 years) self-reported symptoms of probable depression, anxiety, and auditory hallucinations.

Predicting type 1 diabetes in children using electronic health records in primary care in the UK: development and validation of a machine-learning algorithm.

Background: Children presenting to primary care with suspected type 1 diabetes should be referred immediately to secondary care to avoid life-threatening diabetic ketoacidosis. However, early recognition of children with type 1 diabetes is challenging. Children might not present with classic symptoms, or symptoms might be attributed to more common conditions.

Integrating qualitative research within a clinical trials unit: developing strategies and understanding their implementation in contexts.

Background/aims: The value of using qualitative methods within clinical trials is widely recognised. How qualitative research is integrated within trials units to achieve this is less clear. This paper describes the process through which qualitative research has been integrated within Cardiff University's Centre for Trials Research (CTR) in Wales, UK.

Dynamic modes of Notch transcription hubs conferring memory and stochastic activation revealed by live imaging the co-activator Mastermind.

Developmental programming involves the accurate conversion of signalling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the co-activator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote the formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module.

Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models.

Unlabelled: Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer-containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT.

Satisfaction with remote consultations in primary care during COVID-19: a population survey of UK adults.

Background: Mode of access to primary care changed during the COVID-19 pandemic; remote consultations became more widespread. With remote consultations likely to continue in UK primary care, it is important to understand people's perceptions of remote consultations and identify potential resulting inequalities.

Aim: To assess satisfaction with remote GP consultations in the UK during the COVID-19 pandemic and identify demographic variation in satisfaction levels.

OptIC-Notch reveals mechanism that regulates receptor interactions with CSL.

Active Notch signalling is elicited through receptor-ligand interactions that result in release of the Notch intracellular domain (NICD), which translocates into the nucleus. NICD activates transcription at target genes, forming a complex with the DNA-binding transcription factor CSL [CBF1/Su(H)/LAG-1] and co-activator Mastermind. However, CSL lacks its own nuclear localisation sequence, and it remains unclear where the tripartite complex is formed.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

Introduction: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.

Methods: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies.

Protocol for a feasibility study of a cancer symptom awareness campaign to support the rapid diagnostic centre referral pathway in a socioeconomically deprived area: Targeted Intensive Community-based campaign To Optimise Cancer awareness (TIC-TOC).

Introduction: Rapid diagnostic centres (RDCs) are being implemented across the UK to accelerate the assessment of vague suspected cancer symptoms. Targeted behavioural interventions are needed to augment RDCs that serve socioeconomically deprived populations who are disproportionately affected by cancer, have lower cancer symptom awareness and are less likely to seek help for cancer symptoms. The aim of this study is to assess the feasibility and acceptability of delivering and evaluating a community-based vague cancer symptom awareness intervention in an area of high socioeconomic deprivation.

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study.

Objective: To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection.

Methods: Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant.

Health behaviour change among UK adults during the pandemic: findings from the COVID-19 cancer attitudes and behaviours study.

Background: COVID-19 related lockdowns may have affected engagement in health behaviours among the UK adult population. This prospective observational study assessed socio-demographic patterning in attempts to change and maintain a range of health behaviours and changes between two time points during the pandemic.

Methods: Adults aged 18 years and over (n = 4,978) were recruited using Dynata (an online market research platform) and the HealthWise Wales platform, supplemented through social media advertising.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines.

Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration.

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area.

The UK stand together trial: protocol for a multicentre cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of KiVa to reduce bullying in primary schools.

Background: Reducing bullying is a public health priority. KiVa, a school-based anti-bullying programme, is effective in reducing bullying in Finland and requires rigorous testing in other countries, including the UK. This trial aims to test the effectiveness and cost-effectiveness of KiVa in reducing child reported bullying in UK schools compared to usual practice.

Identifying researcher learning needs to develop online training for UK researchers working with administrative data: CENTRIC training.

Background: The use of administrative data in health and social science research continues to expand, with increased availability of data and interest from funders. Researchers, however, continue to experience delays in access, storage and sharing of administrative data. Training opportunities are limited and typically specific to individual data providers or focussed on the analytical aspects of working with administrative data.