How to optimize and evaluate diversity in gynecologic cancer clinical trials: statements from the GCIG Barcelona Meeting.

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups.

Multiplatform metabolomic interlaboratory study of a whole human stool candidate reference material from omnivore and vegan donors.

Introduction: Human metabolomics has made significant strides in understanding metabolic changes and their implications for human health, with promising applications in diagnostics and treatment, particularly regarding the gut microbiome. However, progress is hampered by issues with data comparability and reproducibility across studies, limiting the translation of these discoveries into practical applications.

Objectives: This study aims to evaluate the fit-for-purpose of a suite of human stool samples as potential candidate reference materials (RMs) and assess the state of the field regarding harmonizing gut metabolomics measurements.

Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis.

Background: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined.

Methods: A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD).

Phospholipase A2 group IVD mediates the transacylation of glycerophospholipids and acylglycerols.

In mammalian cells, glycerolipids are mainly synthesized using acyl-CoA-dependent mechanisms. The acyl-CoA-independent transfer of fatty acids between lipids, designated as transacylation reaction, represents an additional mechanism for lipid remodeling and synthesis pathways. Here, we demonstrate that human and mouse phospholipase A2 group IVD (PLA2G4D) catalyzes transacylase reactions using both phospholipids and acylglycerols as substrates.

Development and evolution of Drosophila chromatin landscape in a 3D genome context.

Little is known about how the epigenomic states change during development and evolution in a 3D genome context. Here we use Drosophila pseudoobscura with complex turnover of sex chromosomes as a model to address this, by collecting massive epigenomic and Hi-C data from five developmental stages and three adult tissues. We reveal that over 60% of the genes and transposable elements (TE) exhibit at least one developmental transition of chromatin state.

Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

Background: Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised.

Methods: In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital.

Symptom Severity and Glucocorticoid Dosing in Patients With Polymyalgia Rheumatica and Obesity.

Objective: Polymyalgia rheumatica (PMR) is an inflammatory disorder of the elderly characterized by girdle pain and stiffness. Obesity has an influence on disease activity and outcome in rheumatic diseases like osteoarthritis and rheumatoid arthritis. We aimed to investigate the relationship between high BMI and the severity and outcome of PMR, which is incompletely understood.

Road network disruptions during extreme flooding events and their impact on the access to emergency medical services: A spatiotemporal vulnerability analysis.

The impact of extreme floods can be significant, affecting humans, the environment and any type of human-built infrastructure. A further consequence of flooding is restricted access to medical facilities, including constraints to access more dedicated emergency medical services (EMS). To date, there has been a lack of investigation into EMS accessibility dynamics during extreme floods.

Artificial Intelligence for Response Assessment in Neuro Oncology (AI-RANO), part 1: review of current advancements.

The development, application, and benchmarking of artificial intelligence (AI) tools to improve diagnosis, prognostication, and therapy in neuro-oncology are increasing at a rapid pace. This Policy Review provides an overview and critical assessment of the work to date in this field, focusing on diagnostic AI models of key genomic markers, predictive AI models of response before and after therapy, and differentiation of true disease progression from treatment-related changes, which is a considerable challenge based on current clinical care in neuro-oncology. Furthermore, promising future directions, including the use of AI for automated response assessment in neuro-oncology, are discussed.

Effect of therapeutic plasma exchange on tissue factor and tissue factor pathway inhibitor in septic shock.

Background: Coagulopathy is part of the pathological host response to infection in sepsis. Higher plasma concentrations of both tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are associated with occurrence of disseminated intravascular coagulation (DIC), multi-organ dysfunction and increased mortality in patients with sepsis. Currently no treatment approaches specifically targeting this axis are available.

Barriers and facilitators to conducting randomised controlled trials within routine care of neurorehabilitation centres: a qualitative study.

Background: Randomised controlled trials (RCTs) are considered the gold standard for generating clinical evidence. The focus on high internal validity in RCTs challenges the external validity and generalisability of findings, potentially hindering their application in routine care. In neurorehabilitation, limited literature addresses conducting RCTs feasibly and efficiently.

Cerebrospinal fluid red blood cells and total protein are associated with clinical outcome in spontaneous subarachnoid hemorrhage.

Background And Purpose: Prognostication in patients with spontaneous subarachnoid hemorrhage (SAH) can be challenging. The aim of this study was to assess whether cerebrospinal fluid (CSF) red blood cell (RBC) count and total protein (TP) concentration are associated with SAH prognosis.

Methods: Patients with SAH treated at the neurological intensive care unit (ICU) in Innsbruck were included in this real-world, observational study.

Fibrolytic vaccination against ADAM12 reduces desmoplasia in preclinical pancreatic adenocarcinomas.

A hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.

Sex dimorphism in kidney health and disease: mechanistic insights and clinical implication.

Sex is a key variable in the regulation of human physiology and pathology. Many diseases disproportionately affect one sex: autoimmune diseases, such as systemic lupus erythematosus, are more common in women but more severe in men, whereas the incidence of other disorders such as gouty arthritis and malignant cancers is higher in men. Besides the pathophysiology, sex may also influence the efficacy of therapeutics; participants in clinical trials are still predominately men, and the side effects of drugs are more common in women than in men.

A genetically encoded actuator boosts L-type calcium channel function in diverse physiological settings.

L-type Ca channels (Ca1.2/1.3) convey influx of calcium ions that orchestrate a bevy of biological responses including muscle contraction, neuronal function, and gene transcription.

Caspase-2 kills cells with extra centrosomes.

Centrosomes are membrane-less organelles that orchestrate a wide array of biological functions by acting as microtubule organizing centers. Here, we report that caspase-2-driven apoptosis is elicited in blood cells failing cytokinesis and that extra centrosomes are necessary to trigger this cell death. Activation of caspase-2 depends on the PIDDosome multi-protein complex, and priming of PIDD1 at extra centrosomes is necessary for pathway activation.

The Cancer-Specific Health Economic Measure QLU-C10D is Valid and Responsive for Assessing Health Utility in Patients with Thyroid Cancer.

Health economic appraisals often rely on the assessment of health utilities using preference-based measures (PBM). The cancer-specific PBM, European Organisation for Research and Treatment of Cancer Quality of Life Utility - Core 10 Dimensions (EORTC QLU-C10D), was developed recently, and now needs to be validated in various clinical populations. In a multicenter, multinational prospective cohort study, we longitudinally collected EORTC QLQ-C30 and EQ-5D-5L data from patients with thyroid cancer.

Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications.

Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under "" and therefore could be considered a prohibited method if used as a non-diagnostic tool.

PERCC1 -Related Congenital Enteropathy.

A total of 14 patients are known with the nonsyndromic enteropathy caused by biallelic deletions (∆L and ∆S) or truncating mutations affecting PERCC1 or its adjacent regulatory region. PERCC1 is so far in gnomAD only annotated in the GRCh38 reference sequence. Parenteral nutrition is required throughout childhood and often in adolescence.

PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the brain including the hypothalamic paraventricular nucleus (PVN) implying a regulatory role in stress function. Recent evidence indicates that one of the main targets of PACAP within the PVN are corticotropin-releasing factor (CRF) neurons, which are key regulators of the hypothalamic-pituitary-adrenal (HPA) axis. However, the neural correlates that mediate PACAP effects on stress function are not fully understood.