Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response.

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like).

Immune checkpoint expression on tumor-infiltrating lymphocytes (TIL) is dependent on HPV status in oropharyngeal carcinoma (OPSCC) - A single-cell RNA sequencing analysis.

Introduction: A substantial proportion of head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is associated with human papillomavirus (HPV), resulting in distinct molecular phenotypes. In this study, we investigated differential immune checkpoint molecule (ICM) expression by HPV status using RNA sequencing data to identify additional ICM targets that may complement anti-PD1 antibodies.

Material And Methods: RNA sequencing was performed on 51 OPSCC cases and validated using the TCGA HNSCC dataset.

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).

Health visiting in the UK in light of the COVID-19 pandemic experience: (RReHOPE) findings from a realist review.

Background: Child health programmes in the United Kingdom offer every child and their family an evidence-based programme to support child health and development. During the COVID-19 pandemic, health visiting services in many areas were reduced to a partial service, with significant variability between and within the four United Kingdom countries. This study investigated the impact of the pandemic on health visiting services and developed recommendations for policy and practice.

A decision methodology for site-level ecosystem accounting.

The United Nations System of Environmental-Economic Accounting Ecosystem Accounting (SEEA EA) framework is the international standard for ecosystem accounting. To date, application of SEEA EA has been predominantly at large scales, usually at landscape and national levels. However, many environmental management decisions are taken locally, in site-specific contexts.

Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

Background: Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients.

Methods: A modified Delphi approach was used.

The Neo-Open Reading Frame Peptides That Comprise the Tumor Framome Are a Rich Source of Neoantigens for Cancer Immunotherapy.

Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate the whole-genome and long-read transcript sequencing of cancers to identify the collection of neo-open reading frame peptides (NOP) expressed in tumors. We termed this collection of NOPs the tumor framome.

Short-stay urgent hospital admissions of children with convulsions: A mixed methods exploratory study to inform out of hospital care pathways.

Objective: To inform interventions focused on safely reducing urgent paediatric short stay admissions (SSAs) for convulsions.

Methods: Routinely acquired administrative data from hospital admissions in Scotland between 2015-2017 investigated characteristics of unscheduled SSAs (an urgent admission where admission and discharge occur on the same day) for a diagnosis of febrile and/or afebrile convulsions. Semi-structured interviews to explore perspectives of health professionals (n = 19) making referral or admission decisions about convulsions were undertaken.

Differentiation signals induce expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study and expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas is expressed in keratinocytes entering mitosis, we show that expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3).

Evaluation of a mobile COVID-19 vaccination van outreach service in an outer South London borough.

Background: This study aimed to explore differences in users of a COVID-19 mobile vaccine van service and users of a COVID-19 static vaccination hub, and the impact of changes in national COVID-19 vaccine policy on vaccine uptake.

Methods: The age distribution of male and female service users in each service was compared. The average number of vaccines administered per hour per week was analysed.

Real-World Evaluation of the Feasibility, Acceptability and Safety of a Remote, Self-Management Parkinson's Disease Care Pathway: A Healthcare Improvement Initiative.

Background: There is significant unmet need for effective and efficiently delivered care for people with Parkinson's disease (PwP). We undertook a service improvement initiative to co-develop and implement a new care pathway, Home Based Care (HBC), based on supported self-management, remote monitoring and the ability to trigger a healthcare contact when needed.

Objective: To evaluate feasibility, acceptability and safety of Home Based Care.

Improving the mental health of farmers: what types of remote support are acceptable, feasible, and improve outcomes? A feasibility RCT.

Background: The farming community have high rates of poor mental health, and are relatively 'hard to reach' with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based 'Living Life to the Full for Farming Communities' (LLTTF-F; www.

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury.

Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury.

Investigating trial design variability in trials of disease-modifying therapies in Parkinson's disease: a scoping review protocol.

Introduction: Parkinson's disease (PD) is a debilitating neurological disorder for which the identification of disease-modifying interventions represents a major unmet need. Diverse trial designs have attempted to mitigate challenges of population heterogeneity, efficacious symptomatic therapy and lack of outcome measures that are objective and sensitive to change in a disease modification setting. It is not clear whether consensus is emerging regarding trial design choices.

Identifying and prioritising future interventions with stakeholders to improve paediatric urgent care pathways in Scotland, UK: a mixed-methods study.

Objectives: To identify and prioritise interventions, from the perspectives of parents and health professionals, which may be alternatives to current unscheduled paediatric urgent care pathways.

Design: FLAMINGO (FLow of AdMissions in chIldren and youNG peOple) is a sequential mixed-methods study, with public and patient involvement (PPI) throughout. Data linkage for urgent admissions and three referral sources: emergency department, out of hours service and general practice, was followed by qualitative interviews with parents and professionals.

NEAL: an open-source tool for audio annotation.

Passive acoustic monitoring is used widely in ecology, biodiversity, and conservation studies. Data sets collected via acoustic monitoring are often extremely large and built to be processed automatically using artificial intelligence and machine learning models, which aim to replicate the work of domain experts. These models, being supervised learning algorithms, need to be trained on high quality annotations produced by experts.

Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

Introduction: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC.

Virtual medical research mentoring.

Background: Medical research is important for professional advancement, and mentoring is a key means by which students and early-career doctors can engage in research. Contrasting international research collaborations, research mentoring programmes are often geographically limited. As the COVID-19 pandemic has led to increased use of online technology for classes and conferences, a virtual, international approach to medical research mentoring may be valuable.

The Role of Robotic Surgery in Laryngeal Cancer.

Transoral robotic surgery (TORS) is a growing field in the treatment of head and neck cancers. Its benefits have been proven in the treatment of oropharynx HPV-positive squamous cell carcinoma, replacing chemoradiation as primary treatment of early-stage cancers or reducing the required radiation dosage, leading to improved functional outcomes without compromising oncological outcomes. There is also interest in the application of TORS for larynx cancer with the hope of achieving similar outcomes to replace open surgery or radiation treatments.

Health visiting in the UK in light of the COVID-19 pandemic experience (RReHOPE): a realist review protocol.

Introduction: Health visiting services, providing support to under 5s and their families, are organised and delivered in very different ways in different parts of the UK. While there has been attention to the key components of health visiting practice and what works well and how, there is little research on how health visiting services are organised and delivered and how that affects their ability to meet their objectives. The COVID-19 pandemic rapidly disrupted service delivery from March 2020.

Universal Cooling Dynamics toward a Quantum Critical Point.

We investigate the loss of adiabaticity when cooling a many-body quantum system from an initial thermal state toward a quantum critical point. The excitation density, which quantifies the degree of adiabaticity of the dynamics, is found to obey scaling laws in the cooling velocity as well as in the initial and final temperatures of the cooling protocol. The scaling laws are universal, governed by the critical exponents of the quantum phase transition.