Consensus molecular subtyping of colorectal carcinoma brain metastases reveals a metabolic signature associated with poor patient survival.

The transcriptomic classification of primary colorectal cancer (CRC) into distinct consensus molecular subtypes (CMSs) is a well-described strategy for patient stratification. However, the molecular nature of CRC metastases remains poorly investigated. To this end, this study aimed to identify and compare organotropic CMS frequencies in CRC liver and brain metastases.

[Multimorbidity as a predictor for inpatient admission in clinical emergency and acute medicine : Single-center cluster analysis].

Background: Parallel to demographic trends, an increase of multimorbid patients in emergency and acute medicine is prominent. To define easily applicable criteria for the necessity of inpatient admission, a hierarchical cluster analysis was performed.

Methods: In a retrospective, single-center study data of n = 35,249 emergency cases (01/2016-05/2018) were statistically analyzed.

Spatial Cellular Networks from omics data with SpaCeNet.

Advances in omics technologies have allowed spatially resolved molecular profiling of single cells, providing a window not only into the diversity and distribution of cell types within a tissue, but also into the effects of interactions between cells in shaping the transcriptional landscape. Cells send chemical and mechanical signals which are received by other cells, where they can subsequently initiate context-specific gene regulatory responses. These interactions and their responses shape the individual molecular phenotype of a cell in a given microenvironment.

Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy.

Unlabelled: Treatment of patients with locally advanced rectal cancer (RC) is based on neoadjuvant chemoradiotherapy followed by surgery. In order to reduce the development of therapy resistance, it is necessary to further improve previous treatment approaches. Recent in vivo experimental studies suggested that the reduction of tumor hypoxia by tumor vessel normalization (TVN), through the inhibition of the glycolytic activator PFKFB3, could significantly improve tumor response to therapy.

Patients with paradoxical low-flow, low-gradient aortic stenosis gain the least benefit from TAVI among all hemodynamic subtypes.

Background: Substantial controversy exists regarding the clinical benefit of patients with severe paradoxical low-flow, low-gradient aortic stenosis (PLF-LG AS) from TAVI. Therefore, we compared post-TAVI benefit by long-term mortality (all-cause, CV and SCD), clinical improvement of heart failure symptoms, and cardiac reverse remodelling in guideline-defined AS subtypes.

Methods: We prospectively included 250 consecutive TAVI patients.

Adaptive digital tissue deconvolution.

Motivation: The inference of cellular compositions from bulk and spatial transcriptomics data increasingly complements data analyses. Multiple computational approaches were suggested and recently, machine learning techniques were developed to systematically improve estimates. Such approaches allow to infer additional, less abundant cell types.

CODEX: COunterfactual Deep learning for the in silico EXploration of cancer cell line perturbations.

Motivation: High-throughput screens (HTS) provide a powerful tool to decipher the causal effects of chemical and genetic perturbations on cancer cell lines. Their ability to evaluate a wide spectrum of interventions, from single drugs to intricate drug combinations and CRISPR-interference, has established them as an invaluable resource for the development of novel therapeutic approaches. Nevertheless, the combinatorial complexity of potential interventions makes a comprehensive exploration intractable.

The importance of DNA sequence for nucleosome positioning in transcriptional regulation.

Nucleosome positioning is a key factor for transcriptional regulation. Nucleosomes regulate the dynamic accessibility of chromatin and interact with the transcription machinery at every stage. Influences to steer nucleosome positioning are diverse, and the according importance of the DNA sequence in contrast to active chromatin remodeling has been the subject of long discussion.

Stable feature selection utilizing Graph Convolutional Neural Network and Layer-wise Relevance Propagation for biomarker discovery in breast cancer.

High-throughput technologies are becoming increasingly important in discovering prognostic biomarkers and in identifying novel drug targets. With Mammaprint, Oncotype DX, and many other prognostic molecular signatures breast cancer is one of the paradigmatic examples of the utility of high-throughput data to deliver prognostic biomarkers, that can be represented in a form of a rather short gene list. Such gene lists can be obtained as a set of features (genes) that are important for the decisions of a Machine Learning (ML) method applied to high-dimensional gene expression data.

A novel method to efficiently differentiate human osteoclasts from blood-derived monocytes.

Background: Osteoclasts are the tissue-specific macrophage population of the bone and unique in their bone-resorbing activity. Hence, they are fundamental for bone physiology in health and disease. However, efficient protocols for the isolation and study of primary human osteoclasts are scarce.

Histological assessment of cardiac amyloidosis in patients undergoing transcatheter aortic valve replacement.

Aims: Studies have reported a strongly varying co-prevalence of aortic stenosis (AS) and cardiac amyloidosis (CA). We sought to histologically determine the co-prevalence of AS and CA in patients undergoing transcatheter aortic valve replacement (TAVR). Consequently, we aimed to derive an algorithm to identify cases in which to suspect the co-prevalence of AS and CA.

Impact of Portal Vein Resection (PVR) in Patients Who Underwent Curative Intended Pancreatic Head Resection.

The oncological impact of portal vein resection (PVR) in pancreatic cancer surgery remains contradictory. Different variables might have an impact on the outcome. The aim of the present study is the retrospective assessment of the frequency of PVR, histological confirmation of tumor infiltration, and comparison of oncological outcomes in PVR patients.

Ensemble-GNN: federated ensemble learning with graph neural networks for disease module discovery and classification.

Summary: Federated learning enables collaboration in medicine, where data is scattered across multiple centers without the need to aggregate the data in a central cloud. While, in general, machine learning models can be applied to a wide range of data types, graph neural networks (GNNs) are particularly developed for graphs, which are very common in the biomedical domain. For instance, a patient can be represented by a protein-protein interaction (PPI) network where the nodes contain the patient-specific omics features.

Onkopipe: A Snakemake Based DNA-Sequencing Pipeline for Clinical Variant Analysis in Precision Medicine.

NGS is increasingly used in precision medicine, but an automated sequencing pipeline that can detect different types of variants (single nucleotide - SNV, copy number - CNV, structural - SV) and does not rely on normal samples as germline comparison is needed. To address this, we developed Onkopipe, a Snakemake-based pipeline that integrates quality control, read alignments, BAM pre-processing, and variant calling tools to detect SNV, CNV, and SV in a unified VCF format without matched normal samples. Onkopipe is containerized and provides features such as reproducibility, parallelization, and easy customization, enabling the analysis of genomic data in precision medicine.

Influence of Sociodemographic, Premorbid, and Injury-Related Factors on Post-Traumatic Stress, Anxiety, and Depression after Traumatic Brain Injury.

Psychopathological symptoms are common sequelae after traumatic brain injury (TBI), leading to increased personal and societal burden. Previous studies on factors influencing Post-traumatic Stress Disorder (PTSD), Generalized Anxiety Disorder (GAD), and Major Depressive Disorder (MDD) after TBI have produced inconclusive results, partly due to methodological limitations. The current study investigated the influence of commonly proposed factors on the clinical impairment, occurrence, frequency, and intensity of symptoms of PTSD, GAD, and MDD after TBI.

An overview and a roadmap for artificial intelligence in hematology and oncology.

Background: Artificial intelligence (AI) is influencing our society on many levels and has broad implications for the future practice of hematology and oncology. However, for many medical professionals and researchers, it often remains unclear what AI can and cannot do, and what are promising areas for a sensible application of AI in hematology and oncology. Finally, the limits and perils of using AI in oncology are not obvious to many healthcare professionals.

Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution.

Background: Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO).

Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain.

Brain metastasis in breast cancer remains difficult to treat and its incidence is increasing. Therefore, the development of new therapies is of utmost clinical relevance. Recently, toll-like receptor (TLR) 4 was correlated with IL6 expression and poor prognosis in 1 215 breast cancer primaries.

Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury.

Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in individuals after TBI with differential severity. Data for six language groups (n ≥ 200; Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database.

Identifying Actionable Variants in Cancer - The Dual Web and Batch Processing Tool MTB-Report.

Next-generation sequencing methods continuously provide clinicians and researchers in precision oncology with growing numbers of genomic variants found in cancer. However, manually interpreting the list of variants to identify reliable targets is an inefficient and cumbersome process that does not scale with the increasing number of cases. Support by computer systems is needed for the analysis of large scale experiments and clinical studies to identify new targets and therapies, and user-friendly applications are needed in molecular tumor boards to support clinicians in their decision-making processes.

BITES: balanced individual treatment effect for survival data.

Motivation: Estimating the effects of interventions on patient outcome is one of the key aspects of personalized medicine. Their inference is often challenged by the fact that the training data comprises only the outcome for the administered treatment, and not for alternative treatments (the so-called counterfactual outcomes). Several methods were suggested for this scenario based on observational data, i.

Gene-expression profiles of pretreatment biopsies predict complete response of rectal cancer patients to preoperative chemoradiotherapy.

Purpose: Preoperative (neoadjuvant) chemoradiotherapy (CRT) and total mesorectal excision is the standard treatment for rectal cancer patients (UICC stage II/III). Up to one-third of patients treated with CRT achieve a pathological complete response (pCR). These patients could be spared from surgery and its associated morbidity and mortality, and assigned to a "watch and wait" strategy.