BDNF levels in serum and CSF are associated with clinicoradiological characteristics of aggressive disease in MS patients.

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial.

Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser.

Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response.

Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy.

HSPG-binding peptide Pep19-2.5 is a potent inhibitor of HPV16 infection.

Peptide-based therapeutics are gaining attention for their potential to target various viral and host cell factors. One notable example is Pep19-2.5 (Aspidasept), a synthetic anti-lipopolysaccharide peptide that binds to heparan sulfate proteoglycans (HSPGs) and has demonstrated inhibitory effects against certain bacteria and enveloped viruses.

Changes in life satisfaction over six years in the general population: A longitudinal study with the Satisfaction With Life Scale (SWLS).

Background: Satisfaction with life is a key concept for most individuals. The Satisfaction With Life Scale (SWLS) for measuring general life satisfaction has been widely analyzed in terms of cross-sectional associations. However, the knowledge about long-term changes in life satisfaction and the associations between such changes and changes in other variables of physical and mental health is limited.

Feasibility, trueness and precision of intraoral scanners in digitizing maxillectomy defects with exposed zygomatic implants in situ: An in vitro 3D comparative study.

Objectives: To in-vitro evaluate the feasibility and accuracy (trueness and precision) of various intraoral scanners (IOS) to digitize maxillectomy defect models with exposed zygomatic implants in situ.

Material And Methods: Six partially edentulous and edentulous maxillectomy defect models with 2 zygomatic implants each were obtained. References scans were obatined by using a laboratory scanner (inEos X5; Dentsply Sirona).

The α- and β-Subunits of Nitric Oxide-Sensitive Guanylyl Cyclase in Pericytes of Healthy Human Dental Pulp.

Nitric oxide-sensitive guanylyl cyclase (NO-GC) is a heterodimeric enzyme with an α- and a β-subunit. In its active form as an αβ-heterodimer, NO-GC produces cyclic guanosine-3',5'-monophophate (cGMP) to regulate vasodilation and proliferation of vascular smooth muscle cells (VSMCs). In contrast to VSMCs, only a few studies reported on the expression of the NO-GC αβ-heterodimer in human pericytes.

Assessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.

Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.

The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization.

Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development.

Activity and safety of avelumab in high-grade neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas progressive after chemotherapy (AveNEC trial).

Background: Neuroendocrine neoplasias grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear.

Methods: The phase II AVENEC study evaluated the effect of avelumab (AVE, 10 mg/kg IV Q2W) in 60 patients with well-differentiated high-grade neuroendocrine tumors (NET G3, N=22) or poorly differentiated neuroendocrine carcinomas (NEC, N=38) progressing after ≥ one prior chemotherapy (excluding Merkel cell and small-cell lung cancer).

Understanding GABAergic synapse diversity and its implications for GABAergic pharmacotherapy.

Despite the substantial contribution of disruptions in GABAergic inhibitory neurotransmission to the etiology of psychiatric, neurodevelopmental, and neurodegenerative disorders, surprisingly few drugs targeting the GABAergic system are currently available, partly due to insufficient understanding of circuit-specific GABAergic synapse biology. In addition to GABA receptors, GABAergic synapses contain an elaborate organizational protein machinery that regulates the properties of synaptic transmission. Until recently, this machinery remained largely unexplored, but key methodological advances have now led to the identification of a wealth of new GABAergic organizer proteins.

Hospital Costs of Intracranial Haemorrhage in Patients with Acute Pulmonary Embolism: Possible Implications for Emerging Therapies.

N/A.

Registries on transcatheter edge-to-edge repair in heart failure: Current evidence and future perspectives.

Aims: Secondary mitral regurgitation (SMR) and tricuspid regurgitation (TR) are the most common valvular heart diseases in patients with heart failure (HF). Transcatheter edge-to-edge repair (TEER) devices designed for treating MR and TR have been successfully tested in randomized controlled trials, but methodological issues have often challenged their interpretation. This manuscript aimed to provide an overview of TEER registries on SMR and TR in HF, highlighting their key features, describing clinical characteristics and outcomes of patients receiving these devices, and exploring the available data limitations.

Association of Specific Antiphospholipid Antibodies to Platelet Count and Thrombocytopenia.

Thrombocytopenia is one of the most common manifestations of the antiphospholipid syndrome (APS). However, its causes are still poorly defined. We have shown recently that antiphospholipid antibodies (aPL) directed against β2-glycoprotein I (β2GPI) of the IgG isotype induced platelet activation and aggregation while aPL directed against cardiolipin and anti-β2GPI IgM had no effect.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Tumor burden with AFP improves survival prediction for TACE-treated patients with HCC: An international observational study.

Background & Aims: Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification.

Methods: Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets.

Toward structured abdominal examination training using augmented reality.

Purpose: Structured abdominal examination is an essential part of the medical curriculum and surgical training, requiring a blend of theory and practice from trainees. Current training methods, however, often do not provide adequate engagement, fail to address individual learning needs or do not cover rare diseases.

Methods: In this work, an application for structured Abdominal Examination Training using Augmented Reality (AETAR) is presented.

Simulator training in focus assessed transthoracic echocardiography (FATE) for undergraduate medical students: results from the FateSim randomized controlled trial.

Introduction: Ultrasound is important in heart diagnostics, yet implementing effective cardiac ultrasound requires training. While current strategies incorporate digital learning and ultrasound simulators, the effectiveness of these simulators for learning remains uncertain. This study evaluates the effectiveness of simulator-based versus human-based training in Focused Assessed with Transthoracic Echocardiography (FATE).

A subcellular sampling instrument allows spatial resolution of amyloid deposit-derived organelle-specific effects in microglia.

Methodological developments in biomedical research are currently moving towards single-cell approaches. This allows for a much better spatial and functional characterization of, for example, the deterioration of cells within a tissue in response to noxae. However, subcellular resolution is also essential to elucidate whether observed impairments are driven by an explicit organelle.

Outcomes and Impact of Device Iterations in Mitral Valve Transcatheter Edge-to-Edge Repair: The REPAIR Study.

Background: The PASCAL P10 system for mitral valve transcatheter edge-to-edge repair has undergone iterations, including introduction of the narrower Ace implant and the Precision delivery system.

Objectives: The study sought to evaluate outcomes and the impact of PASCAL mitral valve transcatheter edge-to-edge repair device iterations.

Methods: The REPAIR (REgistry of PAscal for mltral Regurgitation) study is an investigator-initiated, multicenter registry including consecutive patients with mitral regurgitation (MR) treated from 2019 to 2024.

Outpatient group therapy for post-COVID patients - a naturalistic feasibility study of a face-to-face and online group concept.

Background: A significant number of individuals diagnosed with SARS-CoV-2 continue to suffer from persistent symptoms, a condition commonly referred to as Post-COVID syndrome (PCS). The most common manifestations are fatigue, post-exertional malaise, respiratory problems and cognitive deficits due to the lack of a causal treatment, therapeutic options remain symptom oriented. The aim of this study was to develop a low-threshold group therapy concept for patients with PCS and to test its feasibility in face-to-face and online format.

Patient Support in Obstructive Sleep Apnoea by a Large Language Model - ChatGPT 4o on Answering Frequently Asked Questions on First Line Positive Airway Pressure and Second Line Hypoglossal Nerve Stimulation Therapy: A Pilot Study.

Purpose: Obstructive sleep apnoea (OSA) is a common disease that benefits from early treatment and patient support in order to prevent secondary illnesses. This study assesses the capability of the large language model (LLM) ChatGPT-4o to offer patient support regarding first line positive airway pressure (PAP) and second line hypoglossal nerve stimulation (HGNS) therapy.

Methods: Seventeen questions, each regarding PAP and HGNS therapy, were posed to ChatGPT-4o.

Somatic symptom disorder and the role of epistemic trust, personality functioning and child abuse: Results from a population-based representative German sample.

Background: A growing body of evidence explored symptom burden of somatic symptom disorder (SSD) and its complex etiology involving psychosocial aspects. Child abuse has been linked to numerous psychopathologies including somatic symptoms as well as impaired personality functioning and disruptions in epistemic trust. This work aims to investigate personality functioning and epistemic trust in the association between child abuse and somatic symptom burden.