Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: An international multicentre study.

Background And Purpose: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies.

Materials And Methods: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy.

Modi-2 a vaccine stimulating CD4 responses to homocitrullinated self epitopes as therapy for solid cancers.

Stresses within the tumour microenvironment can mediate post-translational modifications of self-proteins. Homocitrullination is the conversion of lysine to homocitrulline which generates neoepitopes and bypasses self-tolerance. In this study a vaccine targeting homocitrullinated antigens was assessed for stimulation of anti-tumour immunity.

Systemic inequalities in heat risk for greater London.

The temperature rise and increases in extreme heat events related to global climate change is a growing public health threat. Populations in temperate climates, including the UK, must urgently adapt to increased hot weather as current infrastructure primarily focusses on resilience to cold. As we adapt, care should be taken to ensure existing health inequalities are reduced.

Housing Characteristics and Hospital Admissions due to Falls on Stairs: A National Birth Cohort Study.

Objective: To assess associations between housing characteristics and risk of hospital admissions related to falls on/from stairs in children, to help inform prevention measures.

Study Design: An existing dataset of birth records linked to hospital admissions up to age 5 for a cohort of 3 925 737 children born in England between 2008 and 2014, was linked to postcode-level housing data from Energy Performance Certificates. Association between housing construction age, tenure (eg, owner occupied), and built form and risk of stair fall-related hospital admissions was estimated using Poisson regression.

Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine.

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection.

Vaccination with post-translational modified, homocitrullinated peptides induces CD8 T-cell responses that mediate antitumor immunity.

Background: Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. One such modification is carbamylation (homocitrullination) that results in the formation of homocitrulline (Hcit) residues in a non-enzymatic reaction of cyanate with the lysine residues in the polypeptide chain. Homocitrullination occurs in the tumor microenvironment and CD4-mediated immune responses to Hcit epitopes can target stressed tumor cells and provide a potent antitumor response in mouse models.

Analysis of inequalities in personal exposure to PM: A modelling study for the Greater London school-aged population.

Exposure to air pollution can lead to negative health impacts, with children highly susceptible due to their immature immune and lung systems. Childhood exposure may vary by socio-economic status (SES) due to differences in both outdoor and indoor air pollution levels, the latter of which depends on, for example, building quality, overcrowding and occupant behaviours; however, exposure estimates typically rely on the outdoor component only. Quantifying population exposure across SES requires accounting for variations in time-activity patterns, outdoor air pollution concentrations, and concentrations in indoor microenvironments that account for pollution-generating occupant behaviours and building characteristics.

Maternal outcomes of pregnant patients after trauma: a retrospective study of the Trauma Registry of England and Wales.

Introduction: Trauma accounts for 20% of deaths in pregnant women. Injury characterisation and outcome in pregnant women following trauma is poorly described. To understand and inform optimum care of this key injury population, a study was conducted using the Trauma Audit Research Network (TARN) database.

Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.

Citrullination and homocitrullination are stress induced post-translational modifications (siPTMs) which can be recognized by T cells. Peripheral blood mononuclear cells isolated from healthy donors and rheumatoid arthritis (RA) patients were stimulated with nine siPTM-peptides. CD45RA/CD45RO depletion was employed to determine if peptide-specific responses are naïve or memory.

Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy.

Introduction: Post translational modification of proteins plays a significant role in immune recognition. In particular the modification of arginine to citrulline which is mediated by PAD enzymes is increased during cellular stress (autophagy) which permits the presentation of modified epitopes upon MHC class II molecules for recognition by CD4 T cells. Citrullination also occurs in tumour cells as a result of continuous environmental stresses and increased autophagy.

High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer.

Introduction: We hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT).

Methods: The study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index.

The correlation between pre-treatment symptoms, acute and late toxicity and patient-reported health-related quality of life in non-small cell lung cancer patients: Results of the REQUITE study.

Background And Purpose: To investigate the association between clinician-scored toxicities and patient-reported health-related quality of life (HRQoL), in early-stage (ES-) and locally-advanced (LA-) non-small cell lung cancer (NSCLC) patients receiving loco-regional radiotherapy, included in the international real-world REQUITE study.

Materials And Methods: Clinicians scored eleven radiotherapy-related toxicities (and baseline symptoms) with the Common Terminology Criteria for Adverse Events version 4. HRQoL was assessed with the European Organization for Research and Treatment of Cancer core HRQoL questionnaire (EORTC-QLQ-C30).

Overview of health-related quality of life and toxicity of non-small cell lung cancer patients receiving curative-intent radiotherapy in a real-life setting (the REQUITE study).

Objectives: Radiotherapy-induced toxicity may negatively impact health-related quality of life (HRQoL). This report investigates the impact of curative-intent radiotherapy on HRQoL and toxicity in early stage and locally-advanced non-small cell lung cancer patients treated with radiotherapy or chemo-radiotherapy enrolled in the observational prospective REQUITE study.

Materials And Methods: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire up to 2 years post radiotherapy.

PAD-2-mediated citrullination of nucleophosmin provides an effective target for tumor immunotherapy.

Background: The enzymatic conversion of arginine to citrulline is involved in gene and protein regulation and in alerting the immune system to stressed cells, including tumor cells. Nucleophosmin (NPM) is a nuclear protein that plays key roles in cellular metabolism including ribosome biogenesis, mRNA processing and chromatin remodeling and is regulated by citrullination. In this study, we explored if the same citrullinated arginines within NPM are involved in gene regulation and immune activation.

The CUSSH programme: supporting cities' transformational change towards health and sustainability.

This paper describes a global research programme on the complex systemic connections between urban development and health. Through transdisciplinary methods the (CUSSH) project will develop critical evidence on how to achieve the far-reaching transformation of cities needed to address vital environmental imperatives for planetary health in the 21st Century. CUSSH's core components include: (i) a review of evidence on the effects of climate actions (both mitigation and adaptation) and factors influencing their implementation in urban settings; (ii) the development and application of methods for tracking the progress of cities towards sustainability and health goals; (iii) the development and application of models to assess the impact on population health, health inequalities, socio-economic development and environmental parameters of urban development strategies, in order to support policy decisions; (iv) iterative in-depth engagements with stakeholders in partner cities in low-, middle- and high-income settings, using systems-based participatory methods, to test and support the implementation of the transformative changes needed to meet local and global health and sustainability objectives; (v) a programme of public engagement and capacity building.

Citrullinated Epitopes Identified on Tumour MHC Class II by Peptide Elution Stimulate Both Regulatory and Th1 Responses and Require Careful Selection for Optimal Anti-Tumour Responses.

Background: Somatic mutations or post-translational modifications of proteins result in changes that enable immune recognition. One such post-translational modification is citrullination, the conversion of arginine residues to citrulline. Citrullinated peptides are presented on MHC class II (MHCII) autophagy which is upregulated by cellular stresses such as tumourigenesis.

Relationship-building around a policy decision-support tool for urban health.

Contemporary challenges linked to public health and climate change demand more effective decision-making and urban planning practices, in particular by taking greater account of evidence. In order to do this, trust-building relationships between scientists and urban practitioners through collaborative research programmes is required. Based on a policy-relevant research project, Complex Urban Systems for Sustainability and Health (CUSSH), this project aims to support the transformation of cities to meet environmental imperatives and to improve health with a quantitative health impact assessment.

Homocitrullination of lysine residues mediated by myeloid-derived suppressor cells in the tumor environment is a target for cancer immunotherapy.

Background: Homocitrullination is the post-translational modification of lysine that is recognized by T cells.

Methods: This study identified homocitrullinated peptides from aldolase, enolase, cytokeratin and binding immunoglobulin protein and used human leukocyte antigen (HLA) transgenic mice to assess immunogenicity by enzyme-linked immunosorbent spot assay. Vaccine efficacy was assessed in tumor therapy studies using HLA-matched B16 melanoma expressing constitutive or interferon γ (IFNγ)-inducible major histocompatibility complex class II (MHC-II) as represented by most human tumors.

A tool for assessing the climate change mitigation and health impacts of environmental policies: the Cities Rapid Assessment Framework for Transformation (CRAFT).

A growing number of cities, including Greater London, have set ambitious targets, including detailed policies and implementation plans, to reach global goals on sustainability, health, and climate change. Here we present a tool for a rapid assessment of the magnitude of impact of specific policy initiatives to reach these targets. The decision-support tool simultaneously quantifies the environmental and health impacts of specified selected policies.

Systemic inequalities in indoor air pollution exposure in London, UK.

Unlabelled: Deprived communities in many cities are exposed to higher levels of outdoor air pollution, and there is increasing evidence of similar disparities for indoor air pollution exposure. There is a need to understand the drivers for this exposure disparity in order to develop effective interventions aimed at improving population health and reducing health inequities. With a focus on London, UK, this paper assembles evidence to examine why indoor exposure to PM, NO and CO may disproportionately impact low-income groups.