The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia.

We retrospectively evaluated the treatment outcomes of 47 adult patients with TP53-mutated acute lymphoblastic leukaemia (ALL) treated with either blinatumomab, inotuzumab or/and CD19 CAR T-cell therapy. The complete remission with or without count recovery (CR/CRi) (negative minimal residual disease (MRD-) rate) following treatment with blinatumomab (n = 46), inotuzumab (n = 26) and CD19 CAR T cells (n = 6) was 58.7% (96.

Individual differences in prospective and retrospective memory offloading.

Prior research focused on the relationship between cognitive offloading and working memory ability in the prospective and retrospective memory domains have produced conflicting results. Specifically, past work in the prospective memory domain has found that individuals with lower working memory capacity (WMC) choose to offload more often and benefit more from offloading than those with higher WMC (Ball, Peper, et al., 2022) while work in the retrospective memory domain has not found a relationship between WMC and the use of or benefit from offloading (Morrison & Richmond, 2020).

Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 in advanced MDS and AML.

Background: BTX A51, a first-in-class oral small molecule inhibitor of casein kinase 1α (CK1α) and cyclin-dependent kinase (CDK) 7 and 9, induces apoptosis of leukemic cells by activating p53 and inhibiting expression of Mcl1. Here, we report on the results of the phase 1 clinical trial of BTX A51 in patients with relapsed or refractory AML and MDS.

Methods: Adult patients with R/R AML and high-risk MDS were enrolled into eight potential doses ranging from 1 to 42 mg dosed orally three days/week for 21 or 28 days out of a 28-day cycle.

An integrative framework linking molecular signatures and locomotory phenotypes in space-induced sarcopenia.

Age-related skeletal muscle deterioration, referred to as sarcopenia, poses significant risks to astronaut health and mission success during spaceflight, yet its multisystem drivers remain poorly understood. While terrestrial sarcopenia manifests gradually through aging, spaceflight induces analogous musculoskeletal decline within weeks, providing an accelerated model to study conserved atrophy mechanisms. Here, we introduced an integrative framework combining cross-species genetic analysis with physiological modeling to understand mechanistic pathways in space-induced sarcopenia.

Disruption of the ATP-dependent unfoldase ClpX reverses antifungal resistance in Cryptococcus neoformans.

Fungal diseases impact the lives of a millions of people across the globe, and with our current repertoire of therapeutic options dwindling, effective treatment strategies are urgently needed. Critically, the emergence of azole-resistant isolates in the clinic following prolonged treatment regimes, environmental fungicide exposure, and fungal evolution, threatens the outcome of current therapeutics, further endangering the survival of infected individuals. Here, we investigate the underpinnings of antifungal resistance using quantitative proteomics to discover protein-level signatures of fluconazole (FLC) resistance in the opportunistic human fungal pathogen, Cryptococcus neoformans.