Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.

Objectives: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modelling the natural history, and uncovering genotype-phenotype associations.

Methods: A cross-sectional analysis of 90 published and one novel case was performed, employing a Human Phenotype Ontology-based approach.

Increased PD-1 Expression on Circulating T Cells Correlates with Inferior Outcome after Autologous Stem Cell Transplantation.

High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is a well-established treatment option for multiple myeloma and malignant lymphoma patients. It is able to induce long-term progression-free survival (PFS) in both patient groups and even provide a cure in patients with aggressive lymphoma. However, relapse is common and has been associated with the pace and quality of immunologic reconstitution after transplantation, as well as with immune cell exhaustion and immunometabolic defects.

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 metabolic profile of reconstituting T-cells, NK-cells, and monocytes following autologous stem cell transplantation and its impact on outcome.

Previous studies indicated a role of the reconstituting immune system for disease outcome upon high-dose chemotherapy (HDCT) and autologous stem cell transplantation (auto-SCT) in multiple myeloma (MM) and lymphoma patients. Since immune cell metabolism and function are closely interconnected, we used flow-cytometry techniques to analyze key components and functions of the metabolic machinery in reconstituting immune cells upon HDCT/auto-SCT. We observed increased proliferative activity and an upregulation of the glycolytic and fatty acid oxidation (FAO) machinery in immune cells during engraftment.

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.