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High-dimensional, outcome-dependent missing data problems: Models for the human loci.
Stat Methods Med Res
January 2025
Biomedical Data Sciences, LUMC, Leiden, The Netherlands.
Missing data problems are common in biological, high-dimensional data, where data can be partially or completely missing. Algorithms have been developed to reconstruct the missing values by means of imputation or expectation-maximization algorithms. For missing data problems, it has been suggested that the regression model of interest should be incorporated into the imputation procedure to reduce bias of the regression coefficients.
View Article and Find Full Text PDFSteroid-resistant nephrotic syndrome due to renal-limited thrombotic microangiopathy and membranous nephropathy after allogeneic hematopoietic stem cell transplantation successfully treated with calcineurin inhibitors.
Int J Hematol
January 2025
Department of Hematology, Kobe City Medical Center General Hospital, 2-1-1, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Transplantation-associated thrombotic microangiopathy (TMA) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with high mortality. As calcineurin inhibitors (CNIs) reportedly contribute to TMA via drug-induced endothelial injury, treatment of TMA often involves CNI discontinuation or dose reduction. However, renal-limited TMA, defined as biopsy-proven renal TMA without the classical triad (hemolytic anemia, thrombocytopenia, and organ damage), has rarely been reported after allo-HSCT, and its optimal management remains unknown.
View Article and Find Full Text PDFEngineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.
Nat Commun
January 2025
Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components.
View Article and Find Full Text PDFMulticentre adaptive randomised trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin versus calcineurin inhibitor-based or sirolimus-based post-transplant cyclophosphamide (Methods of T cell Depletion, MoTD trial).
BMJ Open
January 2025
Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
Introduction: Graft-versus-host disease (GvHD) remains a major complication of allogeneic stem cell transplantation (allo-SCT), affecting 30-70% of patients (representing 800 new patients per year in the UK). The risk is higher in patients undergoing unrelated allo-SCT. About 1 in 10 patients die as a result of GvHD or through complications of its treatment.
View Article and Find Full Text PDFOrgan-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.
Sci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
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