Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Hepatitis B Patients' Adherence to Treatment in Relation to Knowledge, Attitudes, and Practices (KAP) in the West Bank, Palestine, 2022-2023.

Hepatitis B is an infectious disease that inflicts high health and economic costs on the healthcare system. Poor adherence to treatment increases that cost. We aimed to assess the levels of knowledge, attitudes and practices (KAP) among patients in the West Bank, Palestine, and identify factors associated with good adherence.

A position and wave spectra dataset of Marginal Ice Zone dynamics collected around Svalbard in 2022 and 2023.

Sea ice is a key element of the global Earth system, with a major impact on global climate and regional weather. Unfortunately, accurate sea ice modeling is challenging due to the diversity and complexity of underlying physics happening there, and a relative lack of ground truth observations. This is especially true for the Marginal Ice Zone (MIZ), which is the area where sea ice is affected by incoming ocean waves.

Protein profile in urinary extracellular vesicles is a marker of malignancy and correlates with muscle invasiveness in urinary bladder cancer.

Urinary Bladder Cancer (UBC) ranks among the most prevalent cancers worldwide, has a high recurrence rate and unpredictable treatment responses. Thus, biomarkers are urgently needed. Extracellular vesicles (EVs) are released from both cancer- and immune cells and provide a snapshot of the originating cell.

Microresonator photonic wire bond integration for Kerr-microcomb generation.

Extremely high-Q microresonators provide an attractive platform for a plethora of photonic applications including optical frequency combs, high-precision metrology, telecommunication, microwave generation, narrow linewidth lasers, and stable frequency references. Moreover, the desire for compactness and a low power threshold for nonlinear phenomena have spurred investigation into integrated and scalable solutions. Historically, crystalline microresonators with Q ∼ 10 were one of the first material platforms providing unprecedented optical performance in a small form factor.

Device-Measured 24-Hour Movement Behaviors and Blood Pressure: A 6-Part Compositional Individual Participant Data Analysis in the ProPASS Consortium.

Background: Blood pressure (BP)-lowering effects of structured exercise are well-established. Effects of 24-hour movement behaviors captured in free-living settings have received less attention. This cross-sectional study investigated associations between a 24-hour behavior composition comprising 6 parts (sleeping, sedentary behavior, standing, slow walking, fast walking, and combined exercise-like activity [eg, running and cycling]) and systolic BP (SBP) and diastolic BP (DBP).

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Flow Cytometric Immunophenotyping: Minimal Differences in Fresh and Cryopreserved Peripheral Blood Mononuclear Cells versus Whole Blood.

: Flow cytometry is a convenient tool in immunophenotyping for monitoring the status of immunological conditions and diseases. The aim of this study was to investigate the effect of isolation and cryopreservation by flow cytometric analysis on subpopulations of CD4 T helper (Th), T regulatory (Treg), CD8 T cytotoxic (Tc), CD56 NK, CD19 B and monocytes. Freshly isolated and cryopreserved peripheral blood mononuclear cells (PBMCs) were compared to fresh whole blood.

Glucose-sensitive insulin with attenuation of hypoglycaemia.

The risk of inducing hypoglycaemia (low blood glucose) constitutes the main challenge associated with insulin therapy for diabetes. Insulin doses must be adjusted to ensure that blood glucose values are within the normal range, but matching insulin doses to fluctuating glucose levels is difficult because even a slightly higher insulin dose than needed can lead to a hypoglycaemic incidence, which can be anything from uncomfortable to life-threatening. It has therefore been a long-standing goal to engineer a glucose-sensitive insulin that can auto-adjust its bioactivity in a reversible manner according to ambient glucose levels to ultimately achieve better glycaemic control while lowering the risk of hypoglycaemia.

Successful use of point-of-care ultrasound for an elderly patient with heart failure in a primary care setting: a case report.

Background: Appropriate assessment of fluid status of patients with heart failure (HF) is challenging in outpatient settings, e.g. primary care, especially among elderly HF patients with multiple comorbidities.

Long-term real-world data of ustekinumab in ulcerative colitis: the Stockholm Ustekinumab Study (STOCUSTE).

Background: Ustekinumab (UST) is an anti-interleukin-12/23 antibody used in the treatment of inflammatory bowel disease. This study includes patients treated at four hospitals in Stockholm to provide long-term real-world data.

Methods: Retrospective study including patients diagnosed with ulcerative colitis and treated with UST between the years 2019 and 2021.

A short natural history of mental time travels: a journey still travelled?

Tulving's introduction of episodic memory and the metaphor of mental time travel has immensely enriched our understanding of human cognition. However, his focus on human psychology, with limited consideration of evolutionary perspectives, led to the entrenched notion that mental time travel is uniquely human. We contend that adopting a phylogenetic perspective offers a deeper insight into cognition, revealing it as a continuous evolutionary process.

Bivalent chromatin accommodates survivin and BRG1/SWI complex to activate DNA damage response in CD4 cells.

Background: Bivalent regions of chromatin (BvCR) are characterized by trimethylated lysine 4 (H3K4me3) and lysine 27 on histone H3 (H3K27me3) deposition which aid gene expression control during cell differentiation. The role of BvCR in post-transcriptional DNA damage response remains unidentified. Oncoprotein survivin binds chromatin and mediates IFNγ effects in CD4 cells.

The genetic landscape of neuro-related proteins in human plasma.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL.

The Role of Small-Bowel Capsule Endoscopy in the Diagnostic Algorithm of Complicated Perianal Disease.

Introduction: Complicated perianal disease (cPD) may be the sole presentation of Crohn's disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD.

Markers of imminent myocardial infarction.

Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case-cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw.

A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders.

Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets.

Enhancing Maturation and Translatability of Human Pluripotent Stem Cell-Derived Cardiomyocytes through a Novel Medium Containing Acetyl-CoA Carboxylase 2 Inhibitor.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) constitute an appealing tool for drug discovery, disease modeling, and cardiotoxicity screening. However, their physiological immaturity, resembling CMs in the late fetal stage, limits their utility. Herein, we have developed a novel, scalable cell culture medium designed to enhance the maturation of hPSC-CMs.

Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial.

ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB).

Sarcopenia definitions and their association with injurious falls in older Swedish women from the Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone fractures (SUPERB) study.

Unlabelled: Associations between different sarcopenia definitions and the risk of injurious falls were investigated in 75-80-year-old women in the Swedish SUPERB cohort. Only sarcopenia according to the Sarcopenia Definitions and Outcomes Consortium (SDOC) definition was associated with incident injurious falls with and without fractures in older women.

Purpose: To investigate the association between three commonly used sarcopenia definitions and the risk of injurious falls in a population of older Swedish women.