Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients.

Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of and -family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications.

Copy Number Variant Does Not Influence Stroke Severity in 2 C57BL/6J Mouse Models nor in Humans: An Exploratory Study.

Background: Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory.

An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development.

Transcriptional activation of the embryonic genome (EGA) is a major developmental landmark enabling the embryo to become independent from maternal control. The magnitude and control of transcriptional reprogramming during this event across mammals remains poorly understood. Here, we developed Smart-seq+5' for high sensitivity, full-length transcript coverage and simultaneous capture of 5' transcript information from single cells and single embryos.

A non-interventional biomarker study in patients with adenocarcinoma of the lung treated with nintedanib plus docetaxel following progression on chemotherapy and/or immunotherapy: LUME-BioNIS.

Background: Anti-angiogenic agents, such as nintedanib and ramucirumab, when combined with docetaxel, are subsequent treatment options in patients with non-small cell lung cancer (NSCLC) who have failed on first-line chemotherapy or immunochemotherapy. However, to date, there are no validated predictive biomarkers for efficacy of anti-angiogenic therapies in this setting. The aim of this study was to explore whether genetic or genomic markers, alone or combined with clinical covariates, could be used to predict overall survival (OS) in patients with NSCLC who are eligible for treatment with nintedanib plus docetaxel.

Disentangling the neural underpinnings of response inhibition in disruptive behavior and co-occurring ADHD.

While impaired response inhibition has been reported in attention-deficit/hyperactivity disorder (ADHD), findings in disruptive behavior disorders (DBDs) have been inconsistent, probably due to unaccounted effects of co-occurring ADHD in DBD. This study investigated the associations of behavioral and neural correlates of response inhibition with DBD and ADHD symptom severity, covarying for each other in a dimensional approach. Functional magnetic resonance imaging data were available for 35 children and adolescents with DBDs (8-18 years old, 19 males), and 31 age-matched unaffected controls (18 males) while performing a performance-adjusted stop-signal task.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Artificial intelligence-based biomarkers for treatment decisions in oncology.

The development of new therapeutic strategies such as immune checkpoint inhibitors (ICIs) and targeted therapies has increased the complexity of the treatment landscape for solid tumors. At the current rate of annual FDA approvals, the potential treatment options could increase by tenfold over the next 5 years. The cost of personalized medicine technologies limits its accessibility, thus increasing socioeconomic disparities in the treated population.

Treatment Quality of Rectal Cancer Patients in Certified Colorectal Cancer Centers Versus Non-Certified Hospitals: A Comparative Analysis.

: The certification of hospitals as colorectal cancer centers aims to improve treatment quality, but evidence supporting its effectiveness remains limited. This study evaluated the impact of certification on treatment outcomes for rectal cancer patients in Germany. : We conducted a retrospective analysis of 14,905 patients with primary rectal cancer (UICC Stages I-III) treated at 271 hospitals.

Longitudinal association between nailfold capillaroscopy and incident interstitial lung disease: A EUSTAR database analysis.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e.

Longitudinal Study of SARS-CoV-2 Vaccinations and Infections in Patients with Gastrointestinal Cancer: Stabilizing Immune Responses and Neutralizing Emerging Variants with Variant-Adapted Antigen Exposures.

This longitudinal study examined how active gastrointestinal (GI) cancer types affect immune responses to SARS-CoV-2, focusing on the ability to neutralize the Omicron variants. Patients with GI cancer ( = 168) were categorized into those with hepatocellular carcinoma, hepatic metastatic GI cancer, non-hepatic metastatic GI cancer, and two control groups of patients with and without underlying liver diseases. Humoral and cellular immune responses were evaluated before and after Omicron antigen exposures.

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.

AI allows pre-screening of FGFR3 mutational status using routine histology slides of muscle-invasive bladder cancer.

Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10-15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.

High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH.

Optimization of a Mobile Transdiagnostic Emotion Regulation Intervention for University Students: A Micro-Randomized Trial.

Increasing mental health problems among university students highlight the need for scalable, effective solutions. We have developed a transdiagnostic mobile intervention called ROOM, promoting adaptive emotion regulation (ER) skills among university students. Understanding how the intervention works and optimising content and delivery is essential for creating an effective and adaptive system.

Analysis of systemic serum vancomycin levels following intraarticular application in primary total joint arthroplasty.

Introduction: Periprosthetic joint infection (PJI) is a serious complication following primary total joint arthroplasty (TJA). PJI accounts for 15-25% of revision surgeries, therefore it is associated with PJI is associated with substantial patient morbidity and mortality as well as increased healthcare expenditures due to complex treatment strategies. Recently, intraoperative local application of vancomycin powder is increasingly being used in primary total hip and knee arthroplasty (THA, TKA) as an additive strategy for PJI prevention.

Large Language Model Ability to Translate CT and MRI Free-Text Radiology Reports Into Multiple Languages.

Background High-quality translations of radiology reports are essential for optimal patient care. Because of limited availability of human translators with medical expertise, large language models (LLMs) are a promising solution, but their ability to translate radiology reports remains largely unexplored. Purpose To evaluate the accuracy and quality of various LLMs in translating radiology reports across high-resource languages (English, Italian, French, German, and Chinese) and low-resource languages (Swedish, Turkish, Russian, Greek, and Thai).

T cell margination: investigating the detour of T cells following forimtamig treatment in humanized mice.

T cell bispecific antibodies (TCBs) are a promising new class of therapeutics for relapsed/refractory multiple myeloma. A frequently observed, yet incompletely understood effect of this treatment is the transient reduction of circulating T cell counts, also known as T cell margination (TCM). After administration of the GPRC5D-targeting TCB forimtamig (RG6234), TCM occurred in patients and correlated with cytokine release and soluble B cell maturation antigen decrease.

A Tumor Volume Segmentation Algorithm Based on Radiomics Features in FDG-PET in Lung Cancer Patients, Validated Using Surgical Specimens.

Background: Although the integration of positron emission tomography into radiation therapy treatment planning has become part of clinical routine, the best method for tumor delineation is still a matter of debate. In this study, therefore, we analyzed a novel, radiomics-feature-based algorithm in combination with histopathological workup for patients with non-small-cell lung cancer.

Methods: A total of 20 patients with biopsy-proven lung cancer who underwent [F]fluorodeoxyglucose positron emission/computed tomography (FDG-PET/CT) examination before tumor resection were included.

Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study.

Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry.

Band Visibility in High-Resolution Optical Coherence Tomography Assessed With a Custom Review Tool and Updated, Histology-Derived Nomenclature.

Purpose: For structure-function research at the transition of aging to age-related macular degeneration, we refined the current consensus optical coherence tomography (OCT) nomenclature and evaluated a novel review software for investigational high-resolution OCT imaging (HR-OCT; <3 µm axial resolution).

Method: Volume electron microscopy, immunolocalizations, histology, and investigational devices informed a refined OCT nomenclature for a custom ImageJ-based review tool to assess retinal band visibility. We examined effects on retinal band visibility of automated real-time averaging (ART) 9 and 100 (11 eyes of 10 healthy young adults), aging (10 young vs 22 healthy aged), and age-related macular degeneration (AMD; 22 healthy aged, 17 early (e)AMD, 15 intermediate (i)AMD).

Prescribing patterns in older people with advanced chronic kidney disease towards the end of life.

Background: Advancing age and chronic kidney disease (CKD) are risk factors for polypharmacy. Polypharmacy is associated with negative healthcare outcomes. Deprescribing, the systematic rationalization of potentially inappropriate medications, is a proposed way of addressing polypharmacy.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.