Polyfunctional IL-21 IFNG T follicular helper cells contribute to checkpoint inhibitor diabetes mellitus and can be targeted by JAK inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, but their use is limited by the development of autoimmunity in healthy tissues as a side effect of treatment. Such immune-related adverse events (IrAE) contribute to hospitalizations, cancer treatment interruption and even premature death. ICI-induced autoimmune diabetes mellitus (ICI-T1DM) is a life-threatening IrAE that presents with rapid pancreatic beta-islet cell destruction leading to hyperglycemia and life-long insulin dependence.

Computational investigation of the social function of domestic cat facial signals.

There is growing interest in the facial signals of domestic cats. Domestication may have shifted feline social dynamics towards a greater emphasis on facial signals that promote affiliative bonding. Most studies have focused on cat facial signals during human interactions or in response to pain.

Occupational therapy's role in promoting the "Learn the Signs. Act Early." developmental monitoring program to public health employees.

Background: Occupational therapists can play a key role in early identification of delay at the population health level by providing education to public health employees on how to implement developmental monitoring with caregivers of children birth to age 5.

Methods: A pretest posttest design was utilized to assess the online education and training that was provided to Department of Public Health employees ( = 339), including Head Start, Special Supplemental Nutrition Program for Women, Infants and Children, Home Visiting, and Early Intervention.

Results: Analysis of pretest-posttest survey data showed significant results for all 12 key learning outcomes.

Further development and validation of the Multimorbidity Treatment Burden Questionnaire (MTBQ).

Objectives: To undertake further psychometric testing of the Multimorbidity Treatment Burden Questionnaire (MTBQ) and examine whether reversing the scale reduced floor effects.

Design: Survey.

Setting: UK primary care.

Feline faces: Unraveling the social function of domestic cat facial signals.

Lately, there has been a growing interest in studying domestic cat facial signals, but most of this research has centered on signals produced during human-cat interactions or pain. The available research on intraspecific facial signaling with domesticated cats has largely focused on non-affiliative social interactions. However, the transition to intraspecific sociality through domestication could have resulted in a greater reliance on affiliative facial signals that aid with social bonding.

Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome: proteomic and network analysis.

Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes.

Antigen presentation by clonally diverse CXCR5+ B cells to CD4 and CD8 T cells is associated with durable response to immune checkpoint inhibitors.

Introduction: Increased T cell infiltration and interferon gamma (IFNγ) pathway activation are seen in tumors of melanoma patients who respond to ICI (immune checkpoint inhibitor) or MAPK pathway inhibitor (MAPKi) therapies. Yet, the rate of durable tumor control after ICI is almost twice that of MAPKi, suggesting that additional mechanisms may be present in patients responding to ICI therapy that are beneficial for anti-tumor immunity.

Methods: We used transcriptional analysis and clinical outcomes from patients treated with ICI or MAPKi therapies to delineate immune mechanisms driving tumor response.

Advertisement of unhealthy commodities in Bristol and South Gloucestershire and rationale for a new advertisement policy.

Background: Bristol City Council introduced a new advertisement policy in 2021/2022 which included prohibiting the advertising of unhealthy food and drink (HFSS), alcohol, gambling and payday loans across council-owned advertising spaces. This mixed methods study is part of the BEAR study, and aimed to explore the rationale and the barriers and facilitators to implementing the policy, and describe the perceived advertising environment prior to implementation.

Methods: Semi-structured interviews were carried out with seven stakeholders involved in the design and implementation of the advertising policy.

Clonally expanded, thyrotoxic effector CD8 T cells driven by IL-21 contribute to checkpoint inhibitor thyroiditis.

Autoimmune toxicity occurs in up to 60% of patients treated with immune checkpoint inhibitor (ICI) therapy for cancer and represents an increasing clinical challenge for expanding the use of these treatments. To date, human immunopathogenic studies of immune-related adverse events (IRAEs) have relied on sampling of circulating peripheral blood cells rather than affected tissues. Here, we directly obtained thyroid specimens from individuals with ICI-thyroiditis, one of the most common IRAEs, and compared immune infiltrates with those from individuals with spontaneous autoimmune Hashimoto's thyroiditis (HT) or no thyroid disease.

Assessing exposure to outdoor advertisement for products high in fat, salt and sugar (HFSS); is self-reported exposure a useful exposure metric?

Background: Exposure to advertising of unhealthy commodities such as fast-food and gambling is recognised as a risk factor for developing non-communicable diseases. Assessment of the impact of such advertisement and the evaluation of the impact of any policies to restrict such advertisements on public health are reliant on the quality of the exposure assessment. A straightforward method for assessing exposure is to ask people whether they noticed any such advertisements in their neighbourhoods.

Factors related to adverse long-term outcomes after mild traumatic brain injury in children: a scoping review.

Objective: To identify demographic, premorbid and injury-related factors, or biomarkers associated with long-term (≥3 months) adverse outcomes in children after mild traumatic brain injury (mTBI).

Design: Scoping review of literature.

Patients: Children and adolescents with mTBI.

Evaluating a pre-surgical health optimisation programme: a feasibility study.

Background: Health optimisation programmes are increasingly popular and aim to support patients to lose weight or stop smoking ahead of surgery, yet there is little published evidence about their impact. This study aimed to assess the feasibility of evaluating a programme introduced by a National Health Service (NHS) clinical commissioning group offering support to smokers/obese patients in an extra 3 months prior to the elective hip/knee surgery pathway.

Methods: Feasibility study mapping routinely collected data sources, availability and completeness for 502 patients referred to the hip/knee pathway in February-July 2018.

Prognostic value of National Early Warning Scores (NEWS2) and component physiology in hospitalised patients with COVID-19: a multicentre study.

Background: National Early Warning Scores (NEWS2) are used to detect all-cause deterioration. While studies have looked at NEWS2, the use of virtual consultation and remote monitoring of patients with COVID-19 mean there is a need to know which physiological observations are important.

Aim: To investigate the relationship between outcome and NEWS2, change in NEWS2 and component physiology in COVID-19 inpatients.

Automated Machine Learning Pipeline Framework for Classification of Pediatric Functional Nausea Using High-Resolution Electrogastrogram.

Objective: Pediatric functional nausea is challenging for patients to manage and for clinicians to treat since it lacks objective diagnosis and assessment. A data-driven non-invasive diagnostic screening tool that distinguishes the electro-pathophysiology of pediatric functional nausea from healthy controls would be an invaluable aid to support clinical decision-making in diagnosis and management of patient treatment methodology. The purpose of this paper is to present an innovative approach for objectively classifying pediatric functional nausea using cutaneous high-resolution electrogastrogram data.

Regression discontinuity analysis for pharmacovigilance: statin example reflected trial findings showing little evidence of harm.

Objectives: The study aims to explore the use of regression discontinuity analysis (RDA) to examine effects of prescription of statins on total cholesterol and adverse outcomes (type 2 diabetes, rhabdomyolysis and myopathy, myalgia and myositis, liver disease, CVD, and mortality).

Study Design And Setting: We conducted a prospective cohort study using the Clinical Practice Research Datalink including patients with QRISK scores of 10 to 30 in 2010 to 2013 who were last followed-up in October 2016. Comparing patients with QRISK≥20 and QRISK<20, we explored RDA assumptions, provided proof of concept analyses (total cholesterol as outcome), and investigated the effect of statins prescription on adverse outcomes.

Maintaining face-to-face contact during the COVID-19 pandemic: a longitudinal qualitative investigation in UK primary care.

Background: In March 2020, the COVID-19 pandemic required a rapid reconfiguration of UK general practice to minimise face-to-face contact with patients to reduce infection risk. However, some face-to-face contact remained necessary and practices needed to ensure such contact could continue safely.

Aim: To examine how practices determined when face-to-face contact was necessary and how face-to-face consultations were reconfigured to reduce COVID-19 infection risk.

Cost-effectiveness of the i-gel supraglottic airway device compared to tracheal intubation during out-of-hospital cardiac arrest: Findings from the AIRWAYS-2 randomised controlled trial.

Aim: Optimal airway management during out-of-hospital cardiac arrest (OHCA) is uncertain. Complications from tracheal intubation (TI) may be avoided with supraglottic airway (SGA) devices. The AIRWAYS-2 cluster randomised controlled trial (ISRCTN08256118) compared the i-gel SGA with TI as the initial advanced airway management (AAM) strategy by paramedics treating adults with non-traumatic OHCA.

Changes in presentations with features potentially indicating cancer in primary care during the COVID-19 pandemic: a retrospective cohort study.

Objectives: To investigate how the COVID-19 pandemic affected the number of people aged 50+ years presenting to primary care with features that could potentially indicate cancer, and to explore how reporting differed by patient characteristics and in face-to-face vs remote consultations.

Design, Setting And Participants: A retrospective cohort study of general practitioner (GP), nurse and paramedic primary care consultations in 21 practices in South-West England covering 123 947 patients. The models compared potential cancer indicators reported in April-July 2019 with April-July 2020.

Quantifying interfacial substrate interactions via surface energy analyses.

Determination of a substrate's surface energy profile is a facile and inexpensive method to indicate the substrate's interfacial thermodynamics with another substance (e.g., microorganisms, biomacromolecules, medical devices, etc).