Greasing the wheels of inflammasome formation: regulation of NLRP3 function by S-linked fatty acids.

NLRP3 is an inflammasome seeding pattern recognition receptor that initiates a pro-inflammatory signalling cascade in response to changes in intracellular homeostasis that are indicative of bacterial infection or tissue damage. Several types of post-translational modification (PTM) have been identified that are added to NLRP3 to regulate its activity. Recent progress has revealed that NLRP3 is subject to a further type of PTM, S-acylation (or palmitoylation), which involves the reversible addition of long-chain fatty acids to target cysteine residues by opposing sets of enzymes.

Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank.

Aims: Glucagon-like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off-target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill-health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank.

Materials And Methods: All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes.

Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

The decision to tell or not to tell is associated with experiences of stigma and hearing aid use among adults with hearing loss.

Objectives: To explore the extent to which an international sample of adults with hearing loss experience and respond to stigma-induced identity threat; and the associations between experiences of hearing loss stigma, responses to hearing loss stigma (concealment of hearing loss), and hearing aid use.

Design: Cross-sectional online survey comprising published questionnaires and multiple response questions designed to capture five of seven constructs of the Major and O'Brien model of stigma-induced identity threat. Multivariate modelling examined factors associated with hearing aid use and concealment of hearing loss.

Study of High Performance Nanoscale Channel Length Vertical Transistors with a Self-Aligned Blocking Layer.

A transistor design employing all vertically stacked components has attracted considerable attention due to the simplicity of the fabrication process and the high conductivity easily realized by achieving nanolevel short channel lengths with two-dimensional current paths. However, fundamental issues, specifically the blocking of the gate electrical field to the semiconductive channel layer and high leakage current at the "off" state, have impeded this configuration in becoming a major transistor design. To address these issues, it has been proposed to introduce a blocking layer (BL) with embedded hole structures and source electrode with embedded hole structures, enhancing gate field penetration and carrier modulation.

Artificial intelligence assisted risk prediction in organ transplantation: a UK Live-Donor Kidney Transplant Outcome Prediction tool.

Predicting the outcome of a kidney transplant involving a living donor advances donor decision-making donors for clinicians and patients. However, the discriminative or calibration capacity of the currently employed models are limited. We set out to apply artificial intelligence (AI) algorithms to create a highly predictive risk stratification indicator, applicable to the UK's transplant selection process.

Developing generic clinical trial animated explainer videos in the UK: results of a survey and case study.

Background: Animated short videos used to explain a concept or project are often called animated explainer videos (AEVs). AEVs can supplement or provide an alternative to participant information sheets as a means of giving information about clinical research to potential participants. Current use of AEVs tends to focus on the specifics of a particular trial, yet there are many common aspects of clinical research regardless of the interventions being investigated that can be poorly covered in current trial materials.

What are the training and support needs for homelessness hostel staff supporting older residents with memory and cognitive problems? A qualitative study.

Background: An increasing number of older people are experiencing homelessness and memory problems, many of whom are supported in temporary hostel accommodation. This can be a challenge for hostel staff who may not have adequate training and support but who often support those with significant memory impairment in their day-to-day work. The study aimed to investigate the training and support that hostel staff require to meet the needs of older hostel residents experiencing memory and cognitive problems, and thus enhance hostel resident quality of life and well-being, considering what additional knowledge, skills, and support hostel staff need to achieve this.

Green sanctuaries: residential green and garden space and the natural environment mitigate mental disorders risk of diabetic patients.

Background: The co-occurrence of diabetes and mental disorders is an exceedingly common comorbidity with poor prognosis. We aim to investigate the impact of green space, garden space, and the natural environment on the risk of mental disorders among the population living with diabetes.

Methods: We performed a longitudinal analysis based on 39,397 participants with diabetes from the UK Biobank.

"If that would have lessened my symptoms, that would have been great...": a qualitative study about the acceptability of tecovirimat as treatment for mpox.

Background: Tecovirimat, an antiviral treatment for smallpox, was approved as a treatment for mpox by the European Medicines Agency in January 2022. Approval was granted under "exceptional circumstances" based on effectiveness found in pre-clinical challenge studies in animals and safety studies in humans showing minimal side effects. As clinical efficacy studies are still ongoing, there is currently limited information with regard to the acceptability of tecovirimat to treat mpox.

Translation of oral health research priorities into research topics in an equity-based priority setting exercise.

Background: In the context of research priority-setting, participants express their research priorities and ideas in various forms, ranging from narratives to explicit topics or questions. However, the transition from these expressions to well-structured research topics or questions is not always straightforward. Challenges intensify when research priorities pertain to interventions or diagnostic accuracy, requiring the conversion of narratives into the Participant, Intervention, Comparator, Outcome (PICO) format.

Qualitative evaluation of the implementation and national roll-out of the NHS App in England.

Background: The NHS App launched in 2019 as the 'digital front door' to the National Health Service in England with core features including General Practitioner (GP) appointment booking, repeat prescriptions, patient access to records and, later on, COVID-19 vaccination certification. Similar patient portals have been adopted in different formats and with variable levels of success. In this longitudinal study (2021-2023) we examined how the NHS App became implemented in the pandemic context and beyond.

Adding salt to foods and risk of incident depression and anxiety.

Background: Diet is a well-known determinant of mental health outcomes. However, epidemiologic evidence on salt consumption with the risk of developing depression and anxiety is still very limited. This study aimed to examine the association between adding salt to foods and incident depression and anxiety longitudinally.

A realist evaluation to explain and understand the role of paramedics in primary care.

Background: In response to the unsustainable workload and workforce crises in primary care, paramedics (with their generalist clinical background acquired from ambulance service experience) are increasingly employed in primary care. However, the specific contribution paramedics can offer to the primary care workforce has not been distinctly outlined. We used realist approaches to understand the ways in which paramedics impact (or not) the primary care workforce.

Postpartum depression in relation to chronic diseases and multimorbidity in women's mid-late life: a prospective cohort study of UK Biobank.

Background: Maternal short-term outcomes of postpartum depression (PPD) were widely examined, but little is known about its long-term association with multiple chronic diseases (multimorbidity) in women's later life. This study aims to assess the association of PPD with chronic diseases and multimorbidity in women's mid-late life.

Methods: This prospective cohort study included female participants in UK Biobank who attended online follow-up assessment and reported their history of PPD.

The epidemiology and unmet need of migraine in five european countries: results from the national health and wellness survey.

Background: Despite the high global prevalence, burden, and direct and indicated costs, migraines are often under-diagnosed and undertreated. Understanding the prevalence of migraine and unmet needs is crucial for improving diagnosis and treatment across Europe (EU) countries; however, real-world studies are limited.

Methods: This retrospective cross-sectional survey utilized weighted patient-reported data from the 2020 National Health and Wellness Survey (NHWS) in five EU (5EU) countries (France, Germany, United Kingdom [UK], Italy, and Spain).

Identification of robust RT-qPCR reference genes for studying changes in gene expression in response to hypoxia in breast cancer cell lines.

Hypoxia is common in breast tumours and is linked to therapy resistance and advanced disease. To understand hypoxia-driven breast cancer progression, RT-qPCR is a widely used technique to quantify transcriptional changes that occur during malignant transformation. Reference genes (RGs) are endogenous RT-qPCR controls used to normalise mRNA levels, allowing accurate assessment of transcriptional changes.

Current applications and challenges in large language models for patient care: a systematic review.

Background: The introduction of large language models (LLMs) into clinical practice promises to improve patient education and empowerment, thereby personalizing medical care and broadening access to medical knowledge. Despite the popularity of LLMs, there is a significant gap in systematized information on their use in patient care. Therefore, this systematic review aims to synthesize current applications and limitations of LLMs in patient care.

"Comparative analysis of large language models against the NHS 111 online triaging for emergency ophthalmology".

Background: This study presents a comprehensive evaluation of the performance of various large language models in generating responses for ophthalmology emergencies and compares their accuracy with the established United Kingdom's National Health Service 111 online system.

Methods: We included 21 ophthalmology-related emergency scenario questions from the NHS 111 triaging algorithm. These questions were based on four different ophthalmology emergency themes as laid out in the NHS 111 algorithm.

Tumour growth rate and invasive interval cancer characteristics in a UK breast cancer screening population.

Objectives: To estimate tumour volume doubling time (TVDT) of interval cancers (ICs).

Methods: Two radiologists retrospectively reviewed prior screening and diagnostic mammograms and measured mean diameter on "visible" ICs. Univariate analyses of clinicopathological variables (ER, HER2, grade, age at diagnosis, and breast density) were undertaken, and those with p < 0.

Vital signs-based healthcare kiosks for screening chronic and infectious diseases: a systematic review.

Background: Increasing demands, such as the COVID-19 pandemic, have presented substantial challenges to global healthcare systems, resulting in staff shortages and overcrowded emergency rooms. Health kiosks have emerged as a promising solution to improve overall efficiency and healthcare accessibility. However, although kiosks are commonly used worldwide for access to information and financial services, the health kiosk industry, valued at $800 million, accounts for just 1.

The association of origin and environmental conditions with performance in professional IRONMAN triathletes.

We have (i) little knowledge about where the fastest professional IRONMAN triathletes originate from and where the fastest races take place and (ii) we have no knowledge of the optimal weather conditions for an IRONMAN triathlon. The aims of the present study were, therefore, (i) to investigate the origin and the fastest IRONMAN race courses for professional triathletes and (ii) to evaluate the best environmental conditions (i.e.

Developmental defects in ectodermal appendages caused by missense mutation in edaradd gene in the nfr mangrove killifish kryptolebias marmoratus.

The mangrove killifish, Kryptolebias marmoratus, can reproduce with self-fertilisation, offering a unique and useful genetic tool for generation of genetic mutants and quick identification of mutated genes. From an ENU-mutated mangrove killifish line R228, we have isolated a novel mutant line, no-fin-ray/nfr in which homozygous mutant of adult fish fin ray development is largely reduced. Illumina RNAseq with 3 embryos each from mutants, siblings and the parental WT strain Hon9 (only 9 embryos as total) identified a mutation in the edaradd in a highly conserved C-terminal death domain.

Ligand-Directed Actinide Oxo-Bond Manipulation in Actinyl Thiacalix[4]arene Complexes.

Understanding the chemistry of the inert actinide oxo bond in actinyl ions AnO22+ is important for controlling actinide behavior in the environment, during separations, and in nuclear waste (An = U, Np, Pu). The thioether calixarene TC4A (4-tert-butyltetrathiacalix[4]arene) binds equatorially to [AnO2]n+ (An = U, Np) forming a conical pocket that differentiates the two trans-oxo groups. The 'ate' complexes, [A]2[UO2(TC4A)] (A = [Li(DME)2], HNEt3) and [HNEt3]2[NpO2(TC4A)], enable selective oxo chemistry.

Creating codes of ethics for public health professionals and institutions.

Background: The World Health Organization and the Association of Schools of Public Health in the European Region called for the professionalization of the public health workforce, including the creation of codes of ethics. In this article, the Public Health Ethics and Law Network provides guidance on creating such codes, based on values and principles commonly identified for public health.

Methods: Our interest was in codes addressing public health broadly rather than disciplines within public health.