Single-cell analysis of neoplastic plasma cells identifies myeloma pathobiology mediators and potential targets.

Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138 cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models.

Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

Multi-target gene therapy AUP1602-C to improve healing and quality of life for diabetic foot ulcer patients: a phase I, open-label, dose-finding study.

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU.

Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose.

Towards a unified approach in managing resistance to vaccines, drugs, and pesticides.

Everywhere, pests and pathogens evolve resistance to our control efforts, impairing human health and welfare. Developing sustainable solutions to this problem requires working with evolved immune and ecological systems, rather than against these evolutionary forces. We advocate a transdisciplinary approach to resistance based on an evolutionary foundation informed by the concepts of integrated pest management and One Health.