Developing Topics.

Background: Disease-modifying therapies for tauopathies like Alzheimer's disease have targeted Tau hyperphosphorylation and aggregation, as both pathological changes are implicated in Tau-mediated toxicity. However, the interplay between Tau hyperphosphorylation and aggregation, and their relative contribution towards overall Tau toxicity is not entirely understood.

Method: Leveraging the genetic tractability of Drosophila, we generated novel transgenic lines designed to manipulate Tau phosphorylation and aggregation to address these questions and unpick the relationship between these pathological changes.

Impact of Day 11 Methotrexate Dose Adjustments due to Mucositis on the Outcomes Following Allogeneic Stem Cell Transplant in the Setting of Anti Thymocyte Globulin (ATG) Based GVHD Prophylaxis.

Background: Dose adjustments of Day 11 Methotrexate (MTx) for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation (HCT) are common due to mucositis, renal injury, or other reasons. The impact of omitting or adjusting doses of MTx in the era of ATG-based GVHD prophylaxis remains unexplored.

Methods: We retrospectively analyzed the outcomes of all adult patients undergoing allogeneic HCT who received ATG-based GVHD prophylaxis at The Ottawa Hospital from January 2019 to December 2022.

Refractory myasthenia gravis treated with autologous hematopoietic stem cell transplantation.

Objectives: Patients with refractory myasthenia gravis (MG) have few treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has been used to treat immune diseases; however, its use in the treatment of MG is not broadly considered. Our objective is to report on the efficacy and safety of HSCT in refractory MG.

Obesity modulates NK-cell activity via LDL & DUSP1 signaling for Populations with Adverse Social Determinants.

African American (AA) women are disproportionally affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) contributing to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair Natural Killer cells (NKs). As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK dysfunction related to obesity and hyperlipidemia in AA women from under-resourced neighborhoods.

Efficacy of chimeric antigen receptor engineered natural killer cells in the treatment of hematologic malignancies: a systematic review and meta-analysis of preclinical studies.

Background: Chimeric antigen receptor (CAR) engineered NK cells (CAR-NK) are a novel approach to the immunotherapy of hematologic malignancies which seeks to overcome some of the challenges faced by CAR-T cells (CAR-T). With few published clinical studies, preclinical studies can identify strategies to accelerate clinical translation. We conducted a systematic review on the preclinical in vivo use of CAR-NK for the treatment of hematologic malignancies to assess these therapies in a holistic and unbiased manner.