Early blast clearance during sequential conditioning prior to allogeneic stem cell transplantation in patients with acute myeloid leukaemia.

For patients with relapsed or refractory AML, sequential conditioning prior to allogeneic stem cell transplantation (alloSCT) is an established and potentially curative treatment option. Early response to treatment during conditioning indicates chemotherapy-responsive disease and may have prognostic value. We retrospectively evaluated blast clearance on day 5 after melphalan, administered 11 days prior to alloSCT as part of a sequential conditioning in 176 patients with active AML.

Systematic analysis of ChatGPT, Google search and Llama 2 for clinical decision support tasks.

It is likely that individuals are turning to Large Language Models (LLMs) to seek health advice, much like searching for diagnoses on Google. We evaluate clinical accuracy of GPT-3·5 and GPT-4 for suggesting initial diagnosis, examination steps and treatment of 110 medical cases across diverse clinical disciplines. Moreover, two model configurations of the Llama 2 open source LLMs are assessed in a sub-study.

GEFAAR: a generic framework for the analysis of antimicrobial resistance providing statistics and cluster analyses.

Easy access to antimicrobial resistance data and meaningful visualization is essential to guide the empirical antimicrobial treatment and to promote the rational use of antimicrobial agents. Currently available solutions are commonly externally hosted, centralized systems. However, there is a need for close monitoring by local analysis tools.

Knockout of the Cardiac Transcription Factor NKX2-5 Results in Stem Cell-Derived Cardiac Cells with Typical Purkinje Cell-like Signal Transduction and Extracellular Matrix Formation.

The human heart controls blood flow, and therewith enables the adequate supply of oxygen and nutrients to the body. The correct function of the heart is coordinated by the interplay of different cardiac cell types. Thereby, one can distinguish between cells of the working myocardium, the pace-making cells in the sinoatrial node (SAN) and the conduction system cells in the AV-node, the His-bundle or the Purkinje fibres.

Mitochondrial DNA mutations in Medulloblastoma.

To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups-WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups.

Immune gene co-expression signatures implicated in occurence and persistence of cognitive dysfunction in depression.

Cognitive dysfunction contributes significantly to the burden caused by Major Depressive Disorder (MDD). Yet, while compelling evidence suggests that different biological processes play a part in both MDD aetiology and the development of cognitive decline more generally, we only begin to understand the molecular underpinnings of depression-related cognitive impairment. Developments in psychometric assessments, molecular high-throughput methods and systems biology derived analysis strategies advance this endeavour.

Pharyngeal Communities and Antimicrobial Resistance in Pangolins in Gabon.

Wildlife can be a reservoir and source of zoonotic pathogens for humans. For instance, pangolins were considered one of the potential animal reservoirs of SARS-CoV-2. The aim of this study was to assess the prevalence of antimicrobial-resistant species (e.

Group-specific cellular metabolism in Medulloblastoma.

Background: Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients' outcomes.

Research article network analysis of polymicrobial chronic wound infections in Masanga, Sierra Leone.

Background: Chronic wounds are frequently colonized or infected with multiple bacterial or fungal species, which can both promote or inhibit each other. Network analyses are helpful to understand the interplay of these species in polymicrobial infections. Our aim was to analyse the network of bacterial and fungal species in chronic wounds.

Reconstructing Clonal Evolution-A Systematic Evaluation of Current Bioinformatics Approaches.

The accurate reconstruction of clonal evolution, including the identification of newly developing, highly aggressive subclones, is essential for the application of precision medicine in cancer treatment. Reconstruction, aiming for correct variant clustering and clonal evolution tree reconstruction, is commonly performed by tedious manual work. While there is a plethora of tools to automatically generate reconstruction, their reliability, especially reasons for unreliability, are not systematically assessed.

The Role of Clonal Evolution on Progression, Blood Parameters, and Response to Therapy in Multiple Myeloma.

Introduction: A variety of biomarkers are considered for diagnosis (e.g., β2-microgobulin, albumin, or LDH) and prognosis [e.

Clonal Evolution at First Sight: A Combined Visualization of Diverse Diagnostic Methods Improves Understanding of Leukemic Progression.

Patients with myeloid neoplasia are classified by the WHO classification systems. Besides clinical and hematological criteria, cytogenetic and molecular genetic alterations highly impact treatment stratification. In routine diagnostics, a combination of methods is used to decipher different types of genetic variants.

Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age.

While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults.

Pharmacokinetics and mass balance of vericiguat in rats and dogs and distribution in rats.

Vericiguat is a soluble guanylate cyclase stimulator. The pharmacokinetics, absorption, metabolism, and excretion properties of vericiguat in rats and dogs and the distribution in rats are reported. [C]-labelled vericiguat was studied in intact and bile duct-cannulated rats (oral and intravenous administration), and dogs (oral administration).

Machine learning in the detection and management of atrial fibrillation.

Machine learning has immense novel but also disruptive potential for medicine. Numerous applications have already been suggested and evaluated concerning cardiovascular diseases. One important aspect is the detection and management of potentially thrombogenic arrhythmias such as atrial fibrillation.

Design of a targeted next-generation DNA sequencing panel for pediatric T-cell lymphoblastic lymphoma to unravel biology and optimize treatment.

Low incidence and molecular heterogeneity of pediatric T-cell lymphoblastic lymphoma (T-LBL) require an international, large-scale effort to identify novel clinical biomarkers. The ongoing international clinical trial LBL2018 (NCT04043494) represents an ideal opportunity to implement a common analytic approach. Targeted next-generation sequencing is well-suited for this purpose; however, selection of relevant target genes for T-LBL remains subject of ongoing debates.

Exploring Current Challenges and Perspectives for Automatic Reconstruction of Clonal Evolution.

Background/aim: In the field of cancer research, reconstructing clonal evolution is of major interest. The technique provides new insights for analysis and prediction of tumor development. However, reconstruction based on mutational data is characterized by several challenges.

Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas.

T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood.

Calcitonin receptor-like (CALCRL) is a marker of stemness and an independent predictor of outcome in pediatric AML.

We have recently identified the G protein-coupled neuropeptide receptor calcitonin receptor-like (CALCRL) as an independent prognostic biomarker and a therapeutic target in more than 1500 adult patients with acute myeloid leukemia (AML). Here, we confirmed CALCRL expression as a prognostic factor in a cohort of 284 pediatric patients with AML. High CALCRL expression was independently associated with event-free survival (hazard ratio [HR], 1.