Targeted therapy for rare BRAF-mutated melanoma: Updated multicenter analysis and launch of a publicly accessible online outcome database.

Introduction: While BRAF-/MEK-inhibitor therapy is well established in V600E/K-mutated melanoma, the efficacy in advanced melanoma with rare BRAF mutations remains uncertain. This is an updated analysis of an international data collection including 49 new patients, accompanied by development of a publicly accessible global database.

Patients And Methods: A retrospective analysis was conducted at 20 international cancer centers, evaluating 143 patients with rare BRAF V600 (V600-nonE/K; 48 %) and non-V600 (52 %) mutations.

Automated Testing to Improve Data Quality in Clinical Study Databases.

Reliable and interoperable clinical research data is important for medical research. We have developed ODM-AutoAssess, a web-app that automates the validation of CDISC ODM metadata. It parses ODM XML, detects structural and logical errors, generates test cases, and simulates user interactions in EDC systems.

ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.

Embryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations - RG-like, NProg-like and NB-like - positioned within a putative neurodevelopmental hierarchy.

Quality of Life Trajectories with EHR Integration.

Quality of life (QoL) is a key outcome in clinical research. New electronic tools enable high-frequent collection of QoL. To make QoL data available for the treatment process, integration into Electronic Health Record (EHR) systems is needed.

mdm2neo4j: Generating Graph Representations of Medical Data Models.

Medical sciences generate and collect large amounts of data. To advance patient care, it is necessary to analyse the data at hand. This however is only possible if data and metadata are findable.

FAIRifying in Intensive Care: From Raw Data to HDF5 with Semantic Annotation and Data Quality Checks.

The heterogeneity of formats and quality levels of intensive care data represents a significant challenge for both patient treatment and scientific research. The introduction of a data format that provides unified access and a rich structure of metadata could enhance data analysis in this area. Therefore, a data structure based on HDF5 is proposed, which divides data into smaller segments and extends the metadata with semantic annotation and data quality indicators.

Automated generation of discharge summaries: leveraging large language models with clinical data.

This study explores the use of open-source large language models (LLMs) to automate generation of German discharge summaries from structured clinical data. The structured data used to produce AI-generated summaries were manually extracted from electronic health records (EHRs) by a trained medical professional. By leveraging structured documentation collected for research and quality management, the goal is to assist physicians with editable draft summaries.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

Medical researchers' perception of sharing of metadata from case report forms.

Introduction: Publishing medical metadata stored in case report forms (CRFs) is a prerequisite for the development of a learning health system (LHS) by fostering reuse of metadata and standardization in health research. The aim of our study was to investigate medical researchers' (MRs) willingness to share CRFs, to identify reasons for and against CRF sharing, and to determine if and under which conditions MRs might consider sharing CRF metadata via a public registry.

Methods: We examined CRF data sharing commitments for 1842 interventional trials registered on the German Clinical Trials Registry (DRKS) from January 1, 2020, to December 31, 2021.

Single-cell transcriptomics link gene expression signatures to clinicopathological features of gonadotroph and lactotroph PitNET.

Background: Pituitary neuroendocrine tumors (PitNET) are among the most common intracranial tumors. Despite a frequent benign course, aggressive behavior can occur. Tumor behavior is known to be under the influence of the tumor microenvironment (TME).

Employment, work ability and sick leave in melanoma patients within the first year of diagnosis.

Background And Objectives: Malignant melanoma affects younger working individuals. This study investigated work ability and sick leave within one year after diagnosis, as well as the impact of rehabilitation and psycho-oncological measures on employment outcomes.

Patients And Methods: In this monocentric, prospective, observational cohort study, 221 patients (62.

Phenotyping peripheral neuropathies with and without pruritus: a cross-sectional multicenter study.

Pruritus often escapes physicians' attention in patients with peripheral neuropathy (PNP). Here we aimed to characterize neuropathic pruritus in a cohort of 191 patients with PNP (large, mixed, or small fiber) and 57 control subjects with deep phenotyping in a multicenter cross-sectional observational study at 3 German sites. All participants underwent thorough neurological examination, nerve conduction studies, quantitative sensory testing, and skin biopsies to assess intraepidermal nerve fiber density.

Europe's Largest Research Infrastructure for Curated Medical Data Models with Semantic Annotations.

Background: Structural metadata from the majority of clinical studies and routine health care systems is currently not yet available to the scientific community.

Objective: To provide an overview of available contents in the Portal of Medical Data Models (MDM Portal).

Methods: The MDM Portal is a registered European information infrastructure for research and health care, and its contents are curated and semantically annotated by medical experts.

Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia.

Epigenetic modulation of the cell-intrinsic immune response holds promise as a therapeutic approach for leukemia. However, current strategies designed for transcriptional activation of endogenous transposons and subsequent interferon type-I (IFN-I) response, show limited clinical efficacy. Histone lysine methylation is an epigenetic signature in IFN-I response associated with suppression of IFN-I and IFN-stimulated genes, suggesting histone demethylation as key mechanism of reactivation.

Integration of Patient-Reported Outcome Data Collected Via Web Applications and Mobile Apps Into a Nation-Wide COVID-19 Research Platform Using Fast Healthcare Interoperability Resources: Development Study.

Background: The Network University Medicine projects are an important part of the German COVID-19 research infrastructure. They comprise 2 subprojects: COVID-19 Data Exchange (CODEX) and Coordination on Mobile Pandemic Apps Best Practice and Solution Sharing (COMPASS). CODEX provides a centralized and secure data storage platform for research data, whereas in COMPASS, expert panels were gathered to develop a reference app framework for capturing patient-reported outcomes (PROs) that can be used by any researcher.

Next-generation study databases require FAIR, EHR-integrated, and scalable Electronic Data Capture for medical documentation and decision support.

Structured patient data play a key role in all types of clinical research. They are often collected in study databases for research purposes. In order to describe characteristics of a next-generation study database and assess the feasibility of its implementation a proof-of-concept study in a German university hospital was performed.

Narcissistic dimensions and depressive symptoms in patients across mental disorders in cognitive behavioural therapy and in psychoanalytic interactional therapy in Germany: a prospective cohort study.

Background: Narcissistic personality traits have been theorised to negatively affect depressive symptoms, therapeutic alliance, and treatment outcome, even in the absence of narcissistic personality disorder. We aimed to examine how the dimensional narcissistic facets of admiration and rivalry affect depressive symptoms across treatment modalities in two transdiagnostic samples.

Methods: We did a naturalistic, observational prospective cohort study in two independent adult samples in Germany: one sample pooled from an inpatient psychiatric clinic and an outpatient treatment service offering cognitive behavioural treatment (CBT), and one sample from an inpatient clinic providing psychoanalytic interactional therapy (PIT).

Active learning for extracting surgomic features in robot-assisted minimally invasive esophagectomy: a prospective annotation study.

Background: With Surgomics, we aim for personalized prediction of the patient's surgical outcome using machine-learning (ML) on multimodal intraoperative data to extract surgomic features as surgical process characteristics. As high-quality annotations by medical experts are crucial, but still a bottleneck, we prospectively investigate active learning (AL) to reduce annotation effort and present automatic recognition of surgomic features.

Methods: To establish a process for development of surgomic features, ten video-based features related to bleeding, as highly relevant intraoperative complication, were chosen.

Germ line variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy.

Growth factor independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of hematopoiesis. GFI1-36N is a germ line variant, causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10% to 15% among patients with acute myeloid leukemia (AML) and 5% to 7% among healthy Caucasians and promotes the development of this disease.

Dose-dependent expression of GFI1 alters metabolism in the haematopoietic progenitors and MLL::AF9-induced leukaemic cells.

Growth factor independence 1 (GFI1) is a transcriptional repressor protein that plays an essential role in the differentiation of myeloid and lymphoid progenitors. We and other groups have shown that GFI1 has a dose-dependent role in the initiation, progression, and prognosis of acute myeloid leukaemia (AML) patients by inducing epigenetic changes. We now demonstrate a novel role for dose-dependent GFI1 expression in regulating metabolism in haematopoietic progenitor and leukaemic cells.

A Carboxy-terminal Smarcb1 Point Mutation Induces Hydrocephalus Formation and Affects AP-1 and Neuronal Signalling Pathways in Mice.

The BAF (BRG1/BRM-associated factor) chromatin remodelling complex is essential for the regulation of DNA accessibility and gene expression during neuronal differentiation. Mutations of its core subunit SMARCB1 result in a broad spectrum of pathologies, including aggressive rhabdoid tumours or neurodevelopmental disorders. Other mouse models have addressed the influence of a homo- or heterozygous loss of Smarcb1, yet the impact of specific non-truncating mutations remains poorly understood.

Portal of Medical Data Models: Application in Federated Data Capture.

So far, the portal for medical data models allows its users to download medical forms in a standardized format. Importing data models into electronic data capture software involved a manual step of downloading and importing the files. Now, the portal was enhanced with a web services interface to allow electronic data capture systems to automatically download the forms.