The synthesis of β-enamino esters from the thermal, catalyst-free ring opening of aminocyclopropenones.

In an attempt to react aminocyclopropenones with cyclic imines in order to synthesise amido-substituted pyrrolizidine natural products, we found that aminocyclopropenones undergo a previously unreported stereospecific and regiospecific catalyst-free, thermal ring-opening reaction with alcohols to yield β-enamino esters (also known as vinylogous carbamates or aminoacrylates). We report 21 examples in 45 to 97% isolated yield. The reaction occurs nucleophilic attack at the cyclopropenone carbonyl followed by regiospecific ring opening of the cyclopropenone with retention of alkene geometry.

Beyond disenfranchized grief: Survey and interview accounts of animal loss through and beyond COVID-19 in the United Kingdom.

Although there was a rapidly growing body of literature on human-animal relationships during the COVID-19 pandemic, little attention was given to accounts of animal death through and beyond COVID-19. This paper reports on two connected studies undertaken after the end of COVID-19 restrictions in the United Kingdom, here focusing specifically on animal companion loss. From an online survey of 667 participants, 354 responded to an open-ended question about the loss of an animal.

Pre-diagnostic plasma proteomics profile uncovers new biomarkers and mechanistic insights for incident kidney cancer.

Background: The pathophysiological changes driving incident kidney cancer remain unclear. This study aimed to identify protein biomarkers and underlying mechanisms using pre-diagnostic plasma proteomics.

Materials And Methods: Among 48,851 UK Biobank participants, 165 were diagnosed with kidney cancer, and 2,911 plasma proteins were analyzed.

Water hardness and digestive diseases: a large-scale population-based prospective cohort study.

Background: Water hardness, which refers to the level of dissolved calcium and magnesium salts, is of significant public health concern due to its potential impact on health. The association between water hardness and digestive diseases remains underexplored, with limited evidence from small-scale clinical studies. Given the rising prevalence of digestive disorders worldwide, large-scale cohort studies are needed to address this gap in the literature.

Timing of Death in Children Referred for Intensive Care With Sepsis: Comparison of Two Cohorts in the United Kingdom, 2005-2011 vs. 2018-2023.

Objective: To review the timing of death in children with sepsis referred for intensive care, 2018-2023, and compare with our previous 2005-2011 practice. We hypothesized that most deaths occur within 24 hours of referral to the PICU, with many before PICU admission.

Design, Setting, And Patients: We reviewed referrals to the Children's Acute Transport Service (CATS), North Thames regional pediatric intensive care transport service in the United Kingdom, between January 2018 and March 2023.

Na-Cl Cotransporter (SLC12A3) Inhibition Exacerbates Age-Related Macular Degeneration Via the Nrf2/HO-1 Ferroptosis Pathway.

Purpose: To explore the causal links between antihypertension drugs usage and age-related macular degeneration (AMD).

Methods: Multiple genetic analyses, including summary data-based Mendelian randomization (SMR), traditional MR, and colocalization analysis, were used to explore the causal associations between antihypertension drugs and AMD. Clinical data from the UK Biobank and the National Health and Nutrition Examination Survey (NHANES) was applied to refined risk assessment of specific antihypertensive medications in the context of AMD development.

Barriers and Facilitators of Psychological Help-Seeking of People With Depression, Anxiety, and Stress Symptoms Among ASEAN Countries: A Systematic Review.

Background: Despite growing rates of common mental health disorders among country members of the Association of Southeast Asia Nations (ASEAN), there continue to be treatment gaps in these countries.

Aim: To systematically identify and synthesise barriers and facilitators to accessing formal psychological help for common mental health disorders in the existing literature.

Methods: APA PsycINFO, Web of Science, Scopus, and the Indonesian Portal Garuda were searched for studies reporting barriers or facilitators to individuals' engaging in formal psychological help-seeking for common mental health disorders in country members of ASEAN.

A New Family of Ternary Intermetallic Compounds with Dualistic Atomic Ordering - The ZIP Phases.

A new family of nanostructured ternary intermetallic compounds - named the ZIP phases - is introduced in this work. The ZIP phases exhibit dualistic atomic ordering, i.e.

Boosting POM-Ionosolv Biorefining of Lignocellulosic Biomass by Using Redox-Balanced Polyoxometalate Catalysts in Methanolic Ionic Liquid Reaction Media.

This article presents an advanced iteration of the polyoxometalate (POM)-Ionosolv concept to generate biobased methyl formate in high yield and a bleached cellulose pulp from lignocellulosic biomass in a single-step operation by using redox-balanced POM catalysts and molecular oxygen in alcoholic ionic liquid (IL) mixtures. The performance of the three Ionosolv-ILs triethylammonium hydrogen sulfate ([TEA][HSO]), N,N-dimethylbutylammonium hydrogen sulfate ([DMBA][HSO4]), and tributylmethylphosphonium methyl sulfate ([TBMP][MeSO]), mixed with methanol (MeOH) (30/70 wt%), is evaluated by methyl formate yield from extracted hemicellulose and lignin as well as purity of the bleached cellulose pulp in the presence of various Keggin-type POMs. The redox-balanced HPVMnMoO POM catalyst in [TBMP][MeSO]/MeOH emerge as the most effective combination, achieving 20% methyl formate yield from commercial beech wood.

Interpretation of plasma pharmacokinetics and urinary excretion of phenolic metabolites and catabolites derived from (poly)phenols following ingestion of mango by ileostomists and subjects with a full gastrointestinal tract: complications associated with endogenous and ingested phenylalanine and tyrosine.

Consumption of mango has been associated with a number of beneficial effects on health which have been attributed to phenolic catabolites originating from (poly)phenols following ingestion. To investigate the origins of potentially bioactive phenolic catabolites, ileostomists and subjects with a full gastrointestinal tract on a low(poly)phenol diet ingested a mango pulp purée containing 426 μmol of (poly)phenols consisting mainly of gallotannins and cinnamic acids, along with 231 μmol of the aromatic amino acids phenylalanine and tyrosine. Over a 24 h period post-mango intake plasma and urine were collected and analysed by UHPLC-HRMS.

Spatial Difference-in-Differences with Bayesian Disease Mapping Models.

Bayesian disease-mapping models are widely used in small-area epidemiology to account for spatial correlation and stabilize estimates through spatial smoothing. In contrast, difference-in-differences (DID) methods-commonly used to estimate treatment effects from observational panel data-typically ignore spatial dependence. This paper integrates disease mapping models into an imputation-based DID framework to address spatially structured residual variation and improve precision in small-area evaluations.

Developing representations of a 'new' illness using the Common Sense Model: evolving COVID-19 illness representations and their associations with protective behaviours in the Scottish population.

Objective: There is a lack of research on how illness representations as represented in the Common Sense Self-Regulation Model (CS-SRM) emerge and develop. We aimed to describe the evolution of COVID-19 illness representations over time, and to explore associations with sociodemographic characteristics and protective behaviours.

Methods And Measures: This study (June 2020 release from lockdown to February 2021 after vaccine roll-out) used 17 independently recruited cross-sectional cohorts.

Patterns and Processes of Genomic Evolution Inferred From the Ten Smallest Vertebrate Genomes.

Pufferfish exhibit the smallest vertebrate genomes, making them ideal models for investigating evolutionary patterns and processes that affect genome size. While the Takifugu rubripes genome was fully sequenced two decades ago, key evolutionary drivers remain elusive. We sequenced 10 pufferfish genomes and generated 35 transcriptomes and 13 methylomes to understand genomic evolutionary mechanisms.

Composite endpoints in health technology assessment: part 2 - expanding the evidence base with a framework for best modeling practice.

The first paper of this two-part series critically examined the role of composite endpoints in health technology assessments (HTAs) and outlined strategies for determining whether to employ the composite estimate of treatment effect or disaggregate into the component endpoints of the composite and apply separate treatment effects within a modeling framework. In this second paper, we expand the discussion beyond a pivotal trial and consider the way in which additional evidence from the same indication for different drugs in the same class, or the same drug for different indications, could be employed within HTAs. We offer a continuation of the case study of dapagliflozin for the treatment of heart failure with preserved or mildly reduced ejection fraction, where the evidence base was expanded to consider empagliflozin for the same indication, as well as both dapagliflozin and empagliflozin for heart failure with reduced ejection fraction.

Composite endpoints in health technology assessment: Part 1 - an illustration of best modeling practice.

Composite endpoints amalgamate multiple clinical outcomes into a single measure, offering efficiency gains in clinical trials through increased event rates and reduced sample sizes, thus accelerating clinical development and regulatory approval. However, employing composite endpoints introduces complexities into health technology assessments (HTAs), particularly in economic modeling, due to the varying clinical significance and cost implications of the components. In this paper, we explore best modeling practice for HTAs that are based on clinical trials that employ composite endpoints.

Modeling and Simulation Identifies Endocytosis Uptake Rate and Fraction Unbound as Important Predictors of Oligonucleotide Pharmacokinetics.

Therapeutic oligonucleotides (TOs) represent an emerging modality, which offers a promising alternative treatment option, particularly for intracellular targets. The two types of TOs, antisense oligonucleotides (ASO) and small interfering RNAs (siRNAs), distribute highly into tissues, especially into the liver and the kidneys. However, molecular processes at the cellular level such as the uptake into the cell, endosomal escape, binding to the target mRNA, and redistribution back to the systemic circulation are not well characterized because experimental data and assays are lacking.

Models of care for children and adolescents with type 1 diabetes in low- and middle-income countries: a scoping review.

Background: In order to improve the outcomes of children and adolescents with type 1 diabetes mellitus (T1DM), access to and quality of comprehensive acute and chronic care services in low- and middle-income countries (LMIC) must be improved.

Objectives: To identify and summarise the characteristics of models of care for T1DM in children and adolescents in LMIC.

Search Methods: We searched MEDLINE, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) Global Index Medicus from inception to 11 December 2023 without restrictions.

Use of the Capability, Opportunity, Motivation-Behaviour Model and Theoretical Domains Framework to Understand Barriers and Enablers of Research Capacity and Culture for Speech and Language Therapy Staff.

Background: Research Capacity and Culture (RCC) is important for research engagement. Little is known of what speech and language therapy staff perceives to be the barriers or enablers to this at individual, team and organisational levels.

Aims: To identify the barriers and enablers to RCC among speech and language therapy staff, using behaviour change theory as a framework, and to explore their self-reported level of research engagement.

Disentangling temporal trends of clade Ib monkeypox virus transmission in Burundi.

Utilising mpox case data from Burundi between August 2024 and April 2025, we calibrated a mathematical model to quantify the temporal trends of clade Ib monkeypox virus transmission. The model outputs indicated a declining overall transmission trend. Children aged 0-4 and 5-9 years were estimated to be at higher risk of infection compared to older age groups, while sexual contact was inferred to contribute up to 50% of the overall transmission.

The value of over-the-counter products/services in the management of mild-to-moderate menopausal symptoms.

For women with mild-to-moderate menopausal symptoms, lifestyle changes and over-the-counter products and services can be beneficial for symptom management, especially for those who are contraindicated or averse to using menopausal hormone therapy (MHT). Lifestyle changes, such as increased exercise and improvements in diet, enhance overall health and are suggested by some low-level evidence - largely from observational studies - to alleviate menopausal symptoms. Over-the-counter dietary and herbal supplements are a popular alternative to MHT.

Systematic analyses uncover plasma proteins linked to incident cardiovascular diseases.

Cardiovascular disease (CVD) research is hindered by limited comprehensive analyses of plasma proteome across disease subtypes. Here, we systematically investigated the associations between plasma proteins and cardiovascular outcomes in 53,026 UK Biobank participants over a 14-year follow-up. Association analyses identified 3,089 significant associations involving 892 unique protein analytes across 13 CVD outcomes.

Key locations of oxidative damage in human hair keratins after heat and ultraviolet light exposure.

Objective: This study investigated the locations of amino acid modifications within two major human hair keratins (Type I K31 and Type II K85) with probable implications for protein and hair structural component integrity. The particular focus was on cysteine modifications that disrupt intra-protein and inter-protein disulphide bonds.

Methods: Human hair was exposed to accelerated, sequential heat or UV treatments, simulating effects resulting from the use of heated styling tools and environmental exposure over a time frame approximating one year.

Medical treatment of fibroids: FIGO best practice guidance.

Even though uterine fibroids are a widespread condition, the range of approved medical treatment options remains limited. In fact, only a few drugs are officially approved for the therapy of fibroids. In both the USA and the European Medicines Agency region, selected gonadotropin-releasing hormone (GnRH) antagonists have been approved for this indication.

Multiyear Drought Strengthens Positive and Negative Functional Diversity Effects on Tree Growth Response.

Mixed-species forests are proposed to enhance tree resistance and resilience to drought. However, growing evidence shows that tree species richness does not consistently improve tree growth responses to drought. The underlying mechanisms remain uncertain, especially under unprecedented multiyear droughts.

Hydroclimatic Rebound Drives Extreme Fire in California's Non-Forested Ecosystems.

The catastrophic Los Angeles Fires of January 2025 underscore the urgent need to understand the complex interplay between hydroclimatic variability and wildfire behavior. This study investigates how sequential wet and dry periods, hydroclimatic rebound events, create compounding environmental conditions that culminate in extreme fire events. Our results show that a cascade of moisture anomalies, from the atmosphere to vegetation health, precedes these fires by around 6-27 months.