5-HT Receptors in the BNST Modulate Contextual Fear Conditioning Without Affecting Acute Early Life Stress-Enhanced Fear Learning in Adult Rats.

Background/objectives: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with post-traumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with individuals exposed to early adverse experiences and women having increased vulnerability for diagnoses; however, the mechanisms of this increased vulnerability remain unknown.

Rising Prevalence of Low-Frequency Gene Mutations after Second HDCT in Multiple Myeloma.

Multiple myeloma (MM) first-line treatment algorithms include immuno-chemotherapy (ICT) induction, high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) consolidation, followed by lenalidomide maintenance. After these initial therapies, most patients suffer a disease relapse and require subsequent treatment lines including ICT, additional HDCT and ASCT, or novel immunotherapies. The presence of somatic mutations in peripheral blood cells has been associated with adverse outcomes in a variety of hematological malignancies.

Gemtuzumab Ozogamicin and Stem Cell Mobilization for Autologous Stem Cell Transplantation in Favorable Risk Acute Myeloid Leukemia.

Gemtuzumab ozogamicin (GO), a CD33-targeting antibody drug conjugate, previously showed longer relapse-free survival when combined with induction chemotherapy in patients with favorable-risk acute myeloid leukemia (AML). In this patient population, characterized by lower relapse risk as compared to other ELN risk groups, autologous stem cell transplantation (ASCT) can be used as consolidation strategy. However, there are limited data on the impact of GO on the peripheral blood stem cell (PBSC) mobilization potential.

FLT3 and IRAK4 Inhibitor Emavusertib in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia.

Targeting the FLT3 receptor and the IL-1R associated kinase 4 as well as the anti-apoptotic proteins MCL1 and BCL2 may be a promising novel approach in the treatment of acute myeloid leukemia (AML). The FLT3 and IRAK4 inhibitor emavusertib (CA4948), the MCL1 inhibitor S63845, the BCL2 inhibitor venetoclax, and the HSP90 inhibitor PU-H71 were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells in vitro. AML cells represented all major morphologic and molecular subtypes, including and mutant AML cell lines and a variety of patient-derived AML cells.