Migraine in men.

Background: Migraine is a common primary headache disorder, less frequently affecting men than women, and often regarded as predominantly a "women's disease." Despite this, migraine in men presents with unique characteristics in terms of symptoms, treatment responses, comorbidities, and pain perception. Historically, research has focused more on migraine in women, overlooking critical male-specific aspects.

Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases.

Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases.

Moderate and Vigorous Physical Activity Intensity Cut-Points for Hip-, Wrist-, Thigh-, and Lower Back Worn Accelerometer in Very Old Adults.

Physical activity (PA) reduces the risk of negative mental and physical health outcomes in older adults. Traditionally, PA intensity is classified using METs, with 1 MET equal to 3.5 mL O·min·kg.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Single immunization with genetically attenuated Pf∆mei2 (GA2) parasites by mosquito bite in controlled human malaria infection: a placebo-controlled randomized trial.

Malaria vaccines consisting of metabolically active Plasmodium falciparum (Pf) sporozoites can offer improved protection compared with currently deployed subunit vaccines. In a previous study, we demonstrated the superior protective efficacy of a three-dose regimen of late-arresting genetically attenuated parasites administered by mosquito bite (GA2-MB) compared with early-arresting counterparts (GA1-MB) against a homologous controlled human malaria infection. Encouraged by these results, we explored the potency of a single GA2-MB immunization in a placebo-controlled randomized trial.

Flow-Based Coronary Artery Bypass Graft Patency Metrics: Uncertainty Quantification Simulations to Guide Development.

Purpose: Over time, transit time flow measurement (TTFM) has proven itself as a simple and effective tool for intra-operative evaluation of coronary artery bypass grafts (CABGs). However, metrics used to screen for possible technical error show considerable spread, preventing the definition of sharp cut-off values to distinguish between patent, questionable, and failed grafts. The simulation study presented in this paper aims to quantify this uncertainty for commonly used patency metrics, and to identify the most important physiological parameters influencing it.

Establishing bio-logging data collections as dynamic archives of animal life on Earth.

Rapid growth in bio-logging-the use of animal-borne electronic tags to document the movements, behaviour, physiology and environments of wildlife-offers opportunities to mitigate biodiversity threats and expand digital natural history archives. Here we present a vision to achieve such benefits by accounting for the heterogeneity inherent to bio-logging data and the concerns of those who collect and use them. First, we can enable data integration through standard vocabularies, transfer protocols and aggregation protocols, and drive their wide adoption.

Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.

Machine learning based prediction model for bile leak following hepatectomy for liver cancer.

Objective: We sought to develop a machine learning (ML) preoperative model to predict bile leak following hepatectomy for primary and secondary liver cancer.

Methods: An eXtreme Gradient Boosting (XGBoost) model was developed to predict post-hepatectomy bile leak using data from the ACS-NSQIP database. The model was externally validated using data from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) multi-institutional databases.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers' services play in ensuring diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs.

Behind the scenes of EQA - characteristics, capabilities, benefits and assets of external quality assessment (EQA).

External quality assessment (EQA) enhances patient safety through the evaluation of the quality of laboratory-based and point of care testing. Regulatory agencies and accreditation organizations utilize the results and the laboratory's response to them as part of assessing the laboratory's fitness to practice. In addition, where EQA samples are commutable and the assigned value has been determined using reference measurement procedures (RMPs), EQA data contributes to the verification of metrological traceability of assays as part of the post-market surveillance of diagnostic (IVD) medical devices (IVD-MDs).

Using Active and Passive Smartphone Data to Enhance Adolescents' Emotional Awareness in Forensic Outpatient Setting: A Qualitative Feasibility and Usability Study.

Background: Delinquent behavior in adolescence is a prevalent issue, often associated with difficulties across multiple life domains, which in turn perpetuates negative life outcomes. While current treatment programs show partial success in improving behavioral changes and reducing recidivism, comprehensive conclusions regarding the overall efficacy of these interventions have yet to be established. In forensic outpatient settings, the discrepancy between adolescents' limited emotional awareness and the predominant emphasis on cognitive reflection, combined with low treatment adherence, may be factors that undermine treatment efficacy.

Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.

Complement factor H (CFH) common genetic variants have been associated with age-related macular degeneration (AMD). While most previous in vitro RPE studies focused on the common p.His402Tyr CFH variant, we characterized rare CFH variants that are highly penetrant for AMD using induced pluripotent stem-cell-derived retinal pigment epithelium (iPSC-RPE).

Fluorescent Nanobodies for enhanced guidance in digestive tumors and liver metastasis surgery.

Background: Fluorescence molecular imaging, a potent and non-invasive technique, has become indispensable in medicine for visualizing molecular processes. In surgical oncology, it aids treatment by allowing visualization of tumor cells during fluorescence-guided surgery (FGS). Targeting the urokinase plasminogen activator receptor (uPAR), overexpressed during tissue remodeling and inflammation, holds promise for advancing FGS by specifically highlighting tumors.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Midwives' experience of managing emergencies during labour and birth in a community setting: a mixed-methods systematic review.

Background: For women at low risk of complications during labour and birth, in the United Kingdom, planned birth in a 'community' setting (at home or a freestanding midwifery unit) is generally safe, and intrapartum emergencies are uncommon. Limited exposure may affect midwives' experience of managing an emergency.

Aim: Identify and synthesise available evidence about midwives' experiences of managing intrapartum emergencies during labour in a community setting.

Psychometric properties of the Iranian version of the dissociative experiences measure, Oxford (DEMO).

Backgrounds: Dissociative experiences are described as crucial psychological mechanisms involving the organism's responses to severe psychological traumas and unpleasant past experiences. This research was conducted to examine the psychometric properties of the Dissociative Experiences Measure, Oxford (DEMO) in the Iranian general population.

Methods: This study used cross-sectional correlation, and the statistical population consisted of Iranians over 15 years old.

Antifungal Resistance Patterns of Microsporum canis: A 27-Year MIC Study in Mainland China.

Background: Microsporum canis, a dermatophyte commonly associated with pets, is a leading cause of severe tinea capitis. The increasing prevalence of antifungal resistance among dermatophytes poses a significant global health challenge.

Objectives: This study aims to define the updated antifungal susceptibility profile of M.

Cytoskeleton-functionalized synthetic cells with life-like mechanical features and regulated membrane dynamicity.

The cytoskeleton is a crucial determinant of mammalian cell structure and function, providing mechanical resilience, supporting the cell membrane and orchestrating essential processes such as cell division and motility. Because of its fundamental role in living cells, developing a reconstituted or artificial cytoskeleton is of major interest. Here we present an approach to construct an artificial cytoskeleton that imparts mechanical support and regulates membrane dynamics.

Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.

Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.

The effects of diazepam on sleep depend on the photoperiod.

Daylength (i.e., photoperiod) provides essential information for seasonal adaptations of organisms.