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Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) in vitro . We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resistant LN229 cell line. This combination also showed robust tumor suppression and enhanced survival of mice bearing human xenografts of both solid and invasive GBMs. These findings elucidate a novel combination regimen and suggest that the combination of these clinically relevant agents may represent a new therapeutic option with increased efficacy for patients with GBM., Competing Interests: S.D.H. has ownership interest as the CSO of Falcon Therapeutics., (© 2024 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Objectives: Burnout is common among junior faculty. Professional development has been proposed as a method to improve engagement and reduce burnout among academic physicians. The Penn State College of Medicine Junior Faculty Development Program (JFDP) is a well-established, interdisciplinary program. However, an increase in burnout was noted among participants during the program. The authors sought to quantify the change in burnout seen among JFDP participants across 3 cohorts, and to explore sources of well-being and burnout among participants., Methods: Through a sequential explanatory mixed methods approach, participants in the 2018/19, 2019/20, and 2020/21 cohorts took a survey assessing burnout (Copenhagen Burnout Inventory), quality of life (QoL), job satisfaction, and work-home conflict at the start and end of the course. Descriptive statistics were generated as well as Pearson χ 2 test/Fisher exact test for categorical variables and Wilcoxon rank sum tests for continuous variables for group comparisons. To better understand the outcome, past participants were invited to interviews regarding their experience of burnout during the course. Inductive thematic analysis (kappa = 0.86) was used to derive themes., Results: Start- and end-of-course surveys were completed by 84 and 75 participants, respectively (response rates: 95.5% and 85.2%). Burnout associated with patient/learner/client/colleague increased ( P  = .005) and QoL decreased ( P  = .02) at the end compared with the start. Nonsignificant trends toward worsening in other burnout categories, work-home conflict, and job satisfaction were also observed. Nineteen interviews yielded themes related to risks and protective factors for burnout including competing demands, benefits of networking, professional growth, and challenges related to diverse faculty roles., Conclusion: Junior Faculty Development Program participants demonstrated worsening of burnout and QoL during the program while benefiting from opportunities including skill building and networking. The impact of Junior Faculty Development Programs on the well-being of participants should be considered as an element of their design, evaluation, and refinement over time., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)