Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments.

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of identical-by-descent DNA segments (IBD) yield the most precise relatedness estimates.

Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State.

Transgenic mice and organoid models, such as three-dimensional tumoroid cultures, have emerged as powerful tools for investigating cancer development and targeted therapies. Yet, the extent to which these preclinical models recapitulate the cellular identity of heterogeneous malignancies, like neuroblastoma (NB), remains to be validated. Here, we characterized the transcriptional landscape of TH-MYCN tumors by single-cell RNA sequencing (scRNA-seq) and developed ex vivo tumoroids.

Benchmarking the Efficacy of Salvage Systemic Therapies for Recurrent Meningioma: A RANO Group Systematic Review and Meta-analysis to Guide Clinical Trial Design.

Background: Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a "rate of probable interest" to inform future clinical trial design and development on behalf of the RANO meningioma group.

Methods: PubMed, ClinicalTrials.

Lateralization of Neural Speech Discrimination at Birth Is a Predictor for Later Language Development.

Newborns are able to neurally discriminate between speech and nonspeech right after birth. To date it remains unknown whether this early speech discrimination and the underlying neural language network is associated with later language development. Preterm-born children are an interesting cohort to investigate this relationship, as previous studies have shown that preterm-born neonates exhibit alterations of speech processing and have a greater risk of later language deficits.

Do national cancer control plans address care and research for children, adolescents, and young adults? A review of status, priorities, and recommendations across 41 European countries.

Paediatric cancers, although rare, are the leading cause of disease-related mortality in European children above one year. A key pillar of the European Health Union, Europe's Beating Cancer Plan (EBCP) puts a spotlight on childhood cancer. National Cancer Control Plans (NCCPs) have a key role but did not address childhood cancers sufficiently previously.

Elevated Hepatic Copper Content in Porto-Sinusoidal Vascular Disorder (PSVD): Leading Down a Wrong Track.

Background And Aims: Porto-sinusoidal vascular disorder (PSVD) is a rare vascular liver disorder characterised by specific histological findings in the absence of cirrhosis, which is poorly understood in terms of pathophysiology. While elevated hepatic copper content serves as diagnostic hallmark in Wilson disease (WD), hepatic copper content has not yet been investigated in PSVD.

Methods: Patients with a verified diagnosis of PSVD at the Medical University of Vienna and available hepatic copper content at the time of diagnosis of PSVD were retrospectively included.

The Optimal Dosage and Duration of Omega-3 Polyunsaturated Fatty Acid Supplementation in Heart Failure Management: Evidence from a Network Meta-Analysis.

Heart failure is a progressive condition associated with a high mortality rate. Despite advancements in treatment, many patients continue to experience less-than-ideal outcomes. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been studied as a potential supplementary therapy for heart failure, but the optimal dosage and duration of supplementation remain unclear.

Improvement in Serum Eosinophilia is Observed in Clinical Responders to Ustekinumab but not Adalimumab in Inflammatory Bowel Disease.

Introduction: In inflammatory bowel disease (IBD), the number of eosinophils increases in the lamina propria of the intestinal tract, but their specific patho-mechanistic role remains unclear. Elevated blood eosinophil counts in active IBD suggest their potential as biomarkers for predicting response to biologic therapies. This study evaluates blood eosinophil count trends and their predictive value for clinical response and endoscopic improvement in patients with IBD receiving ustekinumab or adalimumab induction therapy.

Managing depression in the elderly: real-world clinical considerations and perspectives.

This study aims to elucidate current trends in clinical practice for managing depression in elderly patients, focusing on the utilization of pharmacotherapeutics and integrated care models to improve patient outcomes. A comprehensive survey was conducted among physicians from various European countries to gather insights into prescribing habits, treatment patterns, and the impact of comorbidities on therapeutic choices, with a focus on trazodone. The participants included psychiatrists, general practitioners, and neurologists actively involved in elderly depression care.

Usability, efficacy, and safety of candidate tocilizumab biosimilar CT-P47 self-administration via auto-injector and pre-filled syringe in patients with rheumatoid arthritis: a single-arm, open-label, phase 3 study.

Background: CT-P47 is a candidate tocilizumab biosimilar that is currently in clinical development. We assessed the usability of CT-P47 self-administration via auto-injector (AI) in patients with rheumatoid arthritis (RA).

Research Design And Methods: This was a 12-week, single-arm, open-label, multiple-dose, Phase 3 study.

New insights on the shell-crusher shark Agassiz, 1838 (Elasmobranchii, Ptychodontidae) based on the first known articulated dentition from the Upper Cretaceous of Croatia.

Unlabelled: A new lower tooth plate of from the Turonian (Upper Cretaceous) of the Dalmatian region (southern Croatia) is documented here for the first time. The specimen represents the first articulated dentition of a ptychodontid shark that has been discovered from the Balkan Peninsula and the most complete ever found for the un-cuspidate species up to now. The reconstruction of the entire lower dentition of based on this exceptionally well-preserved dentition shows a wider crushing plate than previously hypothesised with bulgy teeth limited to the central area.

Bilateral foot drop as presenting feature of facioscapulohumeral muscular dystrophy type 1.

•FSHD1 may present with bilateral foot drop in adulthood.•Clinical examination, EMG and muscle MRI may additionally guide genetic testing.•Targeted genetic testing is crucial in atypical cases, particularly in light of new therapies.

A new fluorescent oxaliplatin(iv) complex with EGFR-inhibiting properties for the treatment of drug-resistant cancer cells.

Platinum chemotherapy is part of every second anticancer treatment regimen. However, its application is limited by severe side effects and drug resistance. The combination of platinum-based chemotherapeutics with EGFR inhibitors has shown remarkable synergism in clinical treatment.

Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors.

Background: Patients with cancer treated with immune-checkpoint inhibitors (ICIs) have a substantial risk of venous thromboembolism (VTE). The association between ICI-induced inflammation and hypercoagulability is unclear, and no biomarkers currently exist to stratify VTE risk.

Objectives: The authors sought to determine the association between the early changes in C-reactive protein (CRP) after ICI initiation and the risk of VTE.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Impact of smoking on biological treatment response in patients from the German Severe Asthma (GAN) Registry.

Background: Clinical studies of biologics in severe asthma exclude smokers or ex-smokers (ExS) with over 10 pack-years (py). Thus, the effectiveness of this therapy in ex-smokers with severe asthma is not well understood.

Objectives: To assess the impact of smoking on clinical efficiency of biologics in patients with severe asthma from the German Asthma Net (GAN), a comprehensive international registry.

The UBR domain of plant Ubr1 homolog PRT6 accommodates basic and hydrophobic amino termini for substrate recognition.

N-degrons are amino-terminal degradation signals. Non-acetylated first residues with bulky side chains were the first discovered N-degrons. In yeast, their ability to destabilize a protein depends on ubiquitin ligase Ubr1, which has a binding site for basic first residues, the UBR box, and one for hydrophobic first residues, the N domain.

Enhanced Recovery After Surgery for patients undergoing radical cystectomy: Surgeons' perspectives and recommendations ten years after its implementation.

Background And Objectives: Enhanced Recovery After Surgery (ERAS) guidelines for Radical Cystectomy (RC) were published over ten years ago. Aim of this systematic review is to update ERAS recommendations for patients undergoing RC and to give an expert opinion on the relevance of each single ERAS item.

Methods: A systematic review was performed to identify the impact of each single ERAS item on RC outcomes.

Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion FVIII linked to the D'D3 domain of VWF and two XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab. We hypothesized that the chromogenic (CSA) FVIII assay, specifically calibrated for efanesoctocog using bovine coagulation factors, could provide an accurate assessment of efanesoctocog activity.

Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.

Introduction: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.

Objective: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.

Methods: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.

Poor Prognostic Factors and Unmet Needs in Rheumatoid Arthritis.

Prognostic factors in rheumatoid arthritis relate to several aspects, such as prediction of joint damage and loss of function or prediction of response to a particular therapy. Since many decades, it is well established that high disease activity, especially exemplified by swollen joint counts and acute phase reactants, is associated with progression of joint damage. In addition, rheumatoid factor (RF) positive patients, but not patients with anti-citrullinated peptide antibodies (ACPA) are particularly prone to high disease activity and joint destruction.

Postgraduate medical education in obstetrics and gynecology in Switzerland in comparison to Germany and Austria: the results of an international survey.

Background: There is frequent academic exchange between Switzerland, Germany and Austria, facilitated by the common language. Additionally, the postgraduate training curricula in obstetrics and gynecology show some similarities. We aimed to compare self-perceived level of ability, availability of simulation training and teaching and feedback culture among residents in obstetrics and gynecology in Switzerland, Germany, and Austria.