CDK5 interacts with MST2 and modulates the Hippo signalling pathway.

MST2 (STK3) is a major upstream kinase in the Hippo signalling pathway, an evolutionary conserved pathway in regulation of organ size, self-renewal and tissue homeostasis. Its downstream effectors are the transcriptional regulators YAP and TAZ. This pathway is regulated by a variety of factors, such as substrate stiffness or cell-cell contacts.

RICTOR variants are associated with neurodevelopmental disorders.

RICTOR is a key component of the mTORC2 signaling complex which is involved in the regulation of cell growth, proliferation and survival. RICTOR is highly expressed in neurons and is necessary for brain development. Here, we report eight unrelated patients presenting with intellectual disability and/or development delay and carrying variants in the RICTOR gene.

Orthotopic meningioma rat model exhibits morphological and immunohistochemical congruency and epigenetic concordance with benign primary patient-derived tumors.

Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation.

Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.

Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.

Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.

Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS).

Hyperreactive B cells instruct their elimination by T cells to curb autoinflammation and lymphomagenesis.

B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.

Addressing the role of surgery in brain tumour trials: A report from the neurosurgery committee of the EORTC brain tumour group.

The Brain Tumor Group (BTG) of the European Organization for Research and Treatment of Cancer (EORTC) conducts academic clinical trials and translational research to improve clinical management of patients with primary and secondary brain tumors. The EORTC BTG has traditionally played an important role in providing evidence and thus advancing the field, albeit with a main focus on radiotherapy and pharmacotherapy in gliomas. Although examples of well-designed neuro-oncological surgical trials can be found, evidence in surgical neuro-oncology predominantly includes data from uncontrolled prospective series or retrospective cohorts.

Establishment of Stable Knockdown of MACC1 Oncogene in Patient-Derived Ovarian Cancer Organoids.

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecological malignancy, and there is still an unmet medical need to deepen basic research on its origins and mechanisms of progression. Patient-derived organoids of high-grade serous ovarian cancer (HGSOC-PDO) are a powerful model to study the complexity of ovarian cancer as they maintain, in vitro, the mutational profile and cellular architecture of the cancer tissue. Genetic modifications by lentiviral transduction allow novel insights into signaling pathways and the potential identification of biomarkers regarding the evolution of drug resistance.

Why are we still in need for novel anti-obesity medications?

From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonists, and GLP-1R/GIPR/glucagon receptor (GcgR) triple agonists, have led to profound body weight-lowering capacities, with benefits that extend past obesity and towards obesity-associated diseases. The GLP-1R/GIPR dual-agonist tirzepatide has demonstrated a remarkable 23% body weight reduction in individuals with obesity over 72 weeks, eclipsing the average result achieved by certain types of bariatric surgery.

Contrastive Learning Approach for Assessment of Phonological Precision in Patients with Tongue Cancer Using MRI Data.

Magnetic Resonance Imaging (MRI) allows analyzing speech production by capturing high-resolution images of the dynamic processes in the vocal tract. In clinical applications, combining MRI with synchronized speech recordings leads to improved patient outcomes, especially if a phonological-based approach is used for assessment. However, when audio signals are unavailable, the recognition accuracy of sounds is decreased when using only MRI data.

Targeting T cell exhaustion: emerging strategies in non-small cell lung cancer.

Lung cancer continues to be a major contributor to cancer-related deaths globally. Recent advances in immunotherapy have introduced promising treatments targeting T cell functionality. Central to the efficacy of these therapies is the role of T cells, which are often rendered dysfunctional due to continuous antigenic stimulation in the tumor microenvironment-a condition referred to as T cell exhaustion.

Long-term patient-reported outcomes following congenital heart surgery in adults.

Objective: To investigate the long-term impact of cardiac surgery on the quality of life in adults with congenital heart disease (ACHDs).

Methods: Patients who had undergone cardiac surgery for congenital heart disease (CHD) at the age of 18 years or more were recruited in a single-center, cross-sectional study. The enrolled subjects completed online questionnaires to assess patient-reported outcomes: perceived health status and life satisfaction, psychological functioning, health behaviors, and illness perception.

Sophisticated perspective-takers are distinctive: Neural idiosyncrasy of functional connectivity in the mentalizing network.

Naive perspective-takers often perceive the social world in a simplistic and uniform way, whereas sophisticated ones recognize the diversity and complexity of others' minds. This commonly accepted distinction points to a possibility of greater inter-individual variability in mentalizing for sophisticated than naive perspective-takers, a difference previously overlooked in research. In the current study, participants were asked to watch a mentalizing-related movie and their neural responses, interpretations of the characters' mental states, and eye-gaze trajectories were recorded.

1924-2024: First centennial of EEG.

On July 6th of 1924 Hans Berger -a German psychiatrist- first recorded electric signals from the human brainvia scalp electrodes. This date marks the beginning of Electroencephalography. In this review a representative panel of past and present Officers of the International Federation of Clinical Neurophysiology (IFCN) and of its Official Journal briefly summarizes the past, present and future of Electroencephalographic and related neurophysiological techniques' impact and the role of the IFCN in global collaboration, education, standardization, research innovation, and clinical practice.

Crosstalk between periodontitis and cardiovascular risk.

Recent demographic developments resulted in an aged society with a rising disease burden of systemic and non-communicable diseases (NCDs). In cardiovascular disease (CVD), a NCD with high morbidity and mortality, recent preventive strategies include the investigation of comorbidities to reduce its significant economic burden. Periodontal disease, an oral bacterial-induced inflammatory disease of tooth-supporting tissue, is regulated in its prevalence and severity by the individual host response to a dysbiotic oral microbiota.

CD8 T cell exhaustion in the tumor microenvironment of breast cancer.

CD8+ T cells are crucial cytotoxic components of the tumor immune system. In chronic inflammation, they become low-responsive, a state known as T cell exhaustion (TEX). The aim of immune checkpoint blockade is to counteract TEX, yet its dynamics in breast cancer remain poorly understood.

BMIgap: a new tool to quantify transdiagnostic brain signatures of current and future weight.

Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. We used support-vector machines and whole-brain voxel-wise grey matter volume to generate and validate a BMI predictor in healthy individuals (N = 1504) and applied it to individuals with schizophrenia (SCZ,N = 146), clinical high-risk states for psychosis (CHR,N = 213) and recent-onset depression (ROD,N = 200). We computed BMIgap (BMI-BMI), interrogated its brain-level overlaps with SCZ and explored whether BMIgap predicted weight gain at 1- and 2-year follow-up.

Cobalt Chromium or Stainless Steel Balloon-Expandable Bare Metal Stents for Iliac Occlusive Disease?

Background: To compare the performance of a new-generation cobalt-chromium balloon-expandable bare metal stent with a stainless steel platform for the treatment of iliac occlusive disease.

Methods: Consecutive patients treated for symptomatic iliac occlusive disease between 2014 and 2021 with the cobalt-chromium Dynetic-35 or the stainless steel Dynamic platform were retrospectively evaluated. Outcome measures included technical success, device- or procedure-related death, clinically-driven target lesion revascularization (CD-TLR), primary patency, and major index limb amputation up to 12 months.

Effects of individually calibrated white and pink noise vestibular stimulation on standing balance of young healthy adults.

Imperceptible noisy galvanic vestibular stimulation (nGVS) improves standing balance due to the presence of stochastic resonance (SR). There is, however, a lack of consensus regarding the optimal levels and type of noise used to elicit SR like dynamics. We aimed to confirm the presence of SR behavior in the vestibular system of young healthy adults by examining postural responses to increasing amplitudes of white and pink noise stimulation scaled to individual cutaneous perceptual threshold.

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2024.

A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.

Plate tectonics, cold adaptation and long-distance range expansion to remote archipelagos and the high Andes as drivers of a circumantarctic freshwater arthropod radiation.

Disjunct distributions, characterised by spatially separated populations of related species, offer insights into historical biogeographic patterns and evolutionary processes. This study investigates the evolutionary history of the diving beetle subfamily Lancetinae through a phylogenomic approach incorporating ultraconserved elements (UCEs) and heritage genetic markers. Our findings support an early Miocene origin for Lancetinae, with subsequent diversification influenced by historical vicariance events and long-distance dispersal.

Recent range expansion and lineage idiosyncratic population structure of Liodessus diving beetles in the high Andes (Coleoptera: Dytiscidae, Bidessini).

Here, we review the taxonomy and population genetic structure of diving beetles in the genus Liodessus Guignot, 1939 from the high Andes of southern Colombia and Ecuador. Liodessus quillacinga ecuadoriensis ssp. nov.

Optimal Medical Therapy for Heart Failure and Integrated Care in Patients With Atrial Fibrillation: A Report From the ESC-EHRA EORP Atrial Fibrillation Long-Term General Registry.

Background: Heart failure (HF) often occurs in patients with atrial fibrillation (AF), with a major impact on prognosis. Few data are available on the effect of integrated treatment strategies to improve prognosis in patients with AF. We aimed to evaluate the association between HF (according to left ventricular ejection fraction [LVEF]), HF optimal medical therapy and adherence to the Atrial Fibrillation Better Care pathway, and major outcomes in patients with AF.