Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways.

Methods: This post-hoc, exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies.

A proof-of-mechanism trial in asthma with lunsekimig, a bispecific nanobody® molecule.

Background: Monovalent biologics blocking thymic stromal lymphopoietin or interleukin-13 have been shown to elicit pharmacodynamic responses in asthma following a single dose. Therefore, dual blockade of these cytokines may result in an enhanced response compared to single targeting and has the potential to break efficacy ceilings in asthma. This study assessed the safety and tolerability of lunsekimig, a bispecific NANOBODY molecule that blocks thymic stromal lymphopoietin and interleukin-13, and its effect on Type 2 inflammatory biomarkers and lung function in asthma.

Impact of porcelain aorta on outcomes in transfemoral aortic valve implantation (TAVI) with balloon-expandable valves.

Background: Current guidelines recommend transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis and porcelain aorta (PA). Neurological outcomes of patients with PA undergoing TAVI with modern valves require clarification as most trials examined balloon-expandable valves (BEV) and self-expandable valves in intermediate or high-risk patients, but not specifically in patients with PA. Our aim was to compare outcomes, including stroke and mortality, in well-matched patients with and without PA who received BEV during transfemoral TAVI procedures.

Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study.

Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.

Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol.

Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans.

Managing conflicts of interest (COIs) in scientific decision-making is important for minimizing bias and fostering public trust in science. Proper management of COIs has added significance when scientists are making decisions that impact public policy, such as assessing substances for carcinogenicity. The International Agency for Research on Cancer (IARC) organizes expert working groups to identify putative carcinogens and determine whether or not the hazard is likely to present significant potential harm to humans.

Prenatal Per- and Polyfluoroalkyl Substances in Relation to Antibody Titers and Infections in Childhood.

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals posing environmental and health risks. Impact on the human immune system is of particular concern, especially during fetal immune development. Alterations to fetal immune development can impact immunity later in life, e.

The big, the small and the weird: A phylogenomic analysis of extant Priapulida.

Priapulida is a small phylum of 22 described species that are divided into two size classes (microscopic and macroscopic), distinguished by adult and larval morphology. Most priapulidans are rare or live in inaccessible habitats, and freshly collected material for molecular studies is difficult to obtain. With this study, we for the first time aim to resolve the phylogeny of extant Priapulida using transcriptomic, genomic, and morphological data.

Historical biogeography of the Mugil cephalus species complex and its rapid global colonization.

Our understanding of speciation processes in marine environments remains very limited and the role of different reproductive barriers are still debated. While physical barriers were considered important drivers causing reproductive isolation, recent studies highlight the importance of climatic and hydrological changes creating unsuitable habitat conditions as factors promoting population isolation. Although speciation in marine fish has been investigated from different perspectives, these studies often have a limited geographical extant.

Comprehensive Extractables and Leachables Sensitization Analysis and Practical Application of a Risk-Based Approach to Sensitization Assessment for Parenteral Drug Products.

The Extractables and Leachables Safety Information Exchange (ELSIE) Consortium added to the sensitization potency analysis of Parris et al. (2023) by including the Product Quality Research Institute (PQRI) extractable and leachable dataset (Johnson et al., 2024; Product Quality Research Institute, 2021).

Volumetric assessment of the soft tissue envelope in unilateral closed ankle fractures using a portable 3D scanner.

Management of ankle fractures necessitating surgery is impacted by soft tissue swelling, often delaying open reduction and internal fixation (ORIF). Subjective evaluations are inconsistent, and traditional measurement methods are often inaccurate or impractical. This prospective observational study included 17 adults with unilateral closed ankle fractures requiring surgical fixation.

The importance of thiamine availability in the thermogenic competency of human adipocytes.

Brown and beige adipocytes express uncoupling protein-1 (UCP1), which is located in the inner mitochondrial membrane and facilitates the dissipation of excess energy as heat. The activation of thermogenic adipocytes is a potential therapeutic target for treating type 2 diabetes mellitus, obesity, and related co-morbidities. Therefore, identifying novel approaches to stimulate the function of these adipocytes is crucial for advancing therapeutic strategies.

Does transcutaneous auricular vagus nerve stimulation alter pupil dilation? A living Bayesian meta-analysis.

Background: Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising technique to modulate autonomic functions, and pupil dilation has been recognized as a promising biomarker for tVNS-induced monoaminergic release. Nevertheless, studies on the effectiveness of various tVNS protocols have produced heterogeneous results on pupil dilation to date.

Methods: Here, we synthesize the existing evidence and compare conventional ("continuous") and pulsed stimulation protocols using a Bayesian meta-analysis.

Radiation exposure in neurosurgical intensive care unit patients: Balancing diagnostic benefits and long-term risks.

Background: X-ray, computed tomography (CT), and digital subtraction angiography (DSA) techniques are indispensable in managing critically ill neurosurgical patients. However, repeated diagnostic imaging leads to cumulative radiation exposure, raising concerns about long-term risks such as malignancies. This study evaluates the frequency, dosage, and implications of radiation exposure in a neurosurgical intensive care unit (NICU) patient cohort.

Unveiling the Distinctions: Computer Versus Sport-Specific Neurocognitive Tests.

Context: Traditional assessments of high-order neurocognitive functions are conducted using pen and paper or computer-based tests; this neglects the complex motor actions athletes have to make in team ball sports. Previous research has not explored the combination of neurocognitive functions and motor demands through complex tasks for team ball sport athletes. The primary aim of the present study was to determine the construct validity of agility-based neurocognitive tests of working memory (WM) and inhibition.

Identification, structure, and agonist design of an androgen membrane receptor.

Androgens, such as 5α-dihydrotestosterone (5α-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5α-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5α-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition.

Ion implantation of the electron-capture nuclide Fe for measurements by means of metallic microcalorimeters.

Precise measurements of fundamental decay data such as energies and transition probabilities of radioactive isotopes are important for the development of corresponding nuclear modelling, activity determination and various applications in science and technology. The EMPIR project PrimA-LTD -"Towards new Primary Activity standardisation methods based on Low-Temperature Detectors" - aims to measure the electron-capture decay of Fe very precisely using Metallic Microcalorimeters (MMCs) with outstandingly high energy resolution. Using a high-statistics measurement, electron-capture probabilities shall be precisely determined and higher-order effects such as electron shake-up and shake-off shall be examined with unprecedented precision.

Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical.

Plastic materials are ubiquitous, leading to constant human exposure to plastic additives such as plasticizers. There is growing evidence that plasticizers may contribute to obesity due to their disruptive effects on metabolism. Alternatives like diisononylcyclohexane-1,2-dicarboxylate (DINCH) are replacing traditional phthalates such as di-(2-ethylhexyl) phthalate (DEHP), which are now banned due to their proven harmful health effects.

Struggling over water, losing it through evaporation: The case of Afghanistan and Iran.

Prolonged droughts and rising water demand have worsened water disputes in the transboundary Helmand basin, shared by Afghanistan and Iran. While both countries have built water storage reservoirs to mitigate water shortages, evaporative losses from these reservoirs reduce their effectiveness. This issue intensifies challenges over water shortages in the region without reliable monitoring data.

Vaccines and AMR: An analysis of the funding landscape for human bacterial vaccines in low-and middle-income countries.

Background: Vaccines are critical tools to prevent the emergence and spread of antimicrobial resistance (AMR) through prevention of infection and reduction of subsequent antibiotic use. Since AMR is a critical issue disproportionately affecting Low- and Middle- Income Countries (LMICs), we examined investments in research and development for bacterial vaccines with a focus on LMIC-driven research.

Methods: Publicly available funding data on projects active from January 2007 to 15 January 2024 from the G-FINDER and Global AMR R&D Hub databases were analysed.

McDonald criteria application by German neurologists suggests a need for further training.

Background: McDonald criteria (MC) are a globally accepted standard for the diagnosis of multiple sclerosis (MS). Misdiagnosis of MS is a common problem that has significant clinical consequences for patients. Misapplication of MC is a potential source of MS misdiagnosis.

Trends and challenges in bispecific antibody production.

Bispecific antibodies (bsAbs) represent a rapidly growing field of therapeutic agents. More bsAbs are being approved worldwide and are in various stages of clinical trials. However, the discovery and production of novel bsAbs presents significant challenges due to their complex structure.

Separation of deaminated impurities from the desired oligonucleotides using supercritical fluid chromatography.

With recent advancements concerning the optimization of the analytical conditions, it is feasible to analyze polar molecules using supercritical fluid chromatography (SFC). In this study, the applicability of SFC is evaluated for analyzing 5-, 10-, 15-, and 18-mer oligonucleotides, and SFC is then applied to analyze deaminated products, which are side products generated during oligonucleotide synthesis. These side products are difficult to separate from the target oligonucleotide, with the difficulty varying depending on the deamination position and sequences, even when using ion-pair reversed-phase liquid chromatography (IP-RPLC), a common method for oligonucleotide analysis.

Reliability, validity and practicability of the Chelsea Critical Care Physical Assessment tool (CPAx) following an e-learning programme: A clinimetric study.

Objectives: To investigate inter- and intra-rater reliability, content and concurrent validity, and practicability of the Chelsea Critical Care Physical Assessment tool (CPAx) - a measurement instrument for physical function and activity for patients with a critical illness - from multidisciplinary, German-speaking healthcare professionals.

Methods: This was a prospective, longitudinal, clinimetric study. Participants who completed a novel German CPAx e-learning were invited to participate in a voluntary, web-based, piloted, two-round survey.

ExPDrug: Integration of an interpretable neural network and knowledge graph for pathway-based drug repurposing.

Precision medicine aims to provide personalized therapies by analyzing patient molecular profiles, often focusing on gene expression data. However, effectively linking these data to actionable drug discovery for clinical application remains challenging. In this paper, we introduce ExPDrug, a neural network (NN) model that integrates biological pathways from transcriptomic data with a biomedical knowledge graph to facilitate pathway-based drug repurposing.