Faculty Bibliography

Targeted therapies and immunotherapy have improved treatment outcomes for many melanoma patients. However, patients whose melanomas harbor driver mutations in the neurofibromin 1 (NF1) tumor suppressor gene often lack effective targeted treatment options when their tumors do not respond to immunotherapy. In this study, we utilized patient-derived short-term cultures (STCs) and multiomics approaches to identify molecular features that could inform the development of therapies for patients with NF1 mutant melanoma. Differential gene expression analysis revealed that the epidermal growth factor receptor (EGFR) is highly expressed and active in NF1 mutant melanoma cells, where it hyper-activates ERK and AKT, leading to increased tumor cell proliferation, survival, and growth. In contrast, genetic or pharmacological inhibition of EGFR hindered cell proliferation and survival and suppressed tumor growth in patient-derived NF1 mutant melanoma models but not in NF1 wild-type models. These results reveal a connection between NF1 loss and increased EGFR expression that is critical for the survival and growth of NF1 mutant melanoma cells in patient-derived culture and xenograft models, irrespective of their BRAF and NRAS mutation status.

PURPOSE/OBJECTIVE:Artificial intelligence (AI) promises to significantly impact medical education, yet its implementation raises important questions about educational effectiveness, ethical use, and equity. In the second part of a 2-part innovation report, which was commissioned by the Josiah Macy Jr. Foundation to inform discussions at a conference on AI in medical education, the authors explore the perspectives of innovators actively integrating AI into medical education, examining their perceptions regarding the impacts, opportunities, challenges, and strategies for successful AI adoption and risk mitigation. METHOD/METHODS:Semi-structured interviews were conducted with 25 medical education AI innovators-including learners, educators, institutional leaders, and industry representatives-from June to August 2024. Interviews explored participants' perceptions of AI's influence on medical education, challenges to integration, and strategies for mitigating challenges. Transcripts were analyzed using thematic analysis to identify themes and synthesize participants' recommendations for AI integration. RESULTS:Innovators' responses were synthesized into 2 main thematic areas: (1) AI's impact on teaching, learning, and assessment, and (2) perceived threats and strategies for mitigating them. Participants identified AI's potential to enact precision education through virtual tutors and standardized patients, support active learning formats, enable centralized teaching, and facilitate cognitive offloading. AI-enhanced assessments could automate grading, predict learner trajectories, and integrate performance data from clinical interactions. Yet, innovators expressed concerns over threats to transparency and validity, potential propagation of biases, risks of over-reliance and deskilling, and institutional disparities. Proposed mitigation strategies emphasized validating AI outputs, establishing foundational competencies, fostering collaboration and open-source sharing, enhancing AI literacy, and maintaining robust ethical standards. CONCLUSIONS:AI innovators in medical education envision transformative opportunities for individualized learning and precision education, balanced against critical threats. Realizing these benefits requires proactive, collaborative efforts to establish rigorous validation frameworks; uphold foundational medical competencies; and prioritize ethical, equitable AI integration.

In healthy cells, cyclin D1 is expressed during the G1 phase of the cell cycle, where it activates CDK4 and CDK6. Its dysregulation is a well-established oncogenic driver in numerous human cancers. The cancer-related function of cyclin D1 has been primarily studied by focusing on the phosphorylation of the retinoblastoma (RB) gene product. Here, using an integrative approach combining bioinformatic analyses and biochemical experiments, we show that GTSE1 (G-Two and S phases expressed protein 1), a protein positively regulating cell cycle progression, is a previously unrecognized substrate of cyclin D1-CDK4/6 in tumor cells overexpressing cyclin D1 during G1 and subsequent phases. The phosphorylation of GTSE1 mediated by cyclin D1-CDK4/6 inhibits GTSE1 degradation, leading to high levels of GTSE1 across all cell cycle phases. Functionally, the phosphorylation of GTSE1 promotes cellular proliferation and is associated with poor prognosis within a pan-cancer cohort. Our findings provide insights into cyclin D1's role in cell cycle control and oncogenesis beyond RB phosphorylation.

BACKGROUND:Objective measures and large datasets are needed to determine aspects of the Clinical Learning Environment (CLE) impacting the essential skill of clinical reasoning documentation. Artificial Intelligence (AI) offers a solution. Here, the authors sought to determine what aspects of the CLE might be impacting resident clinical reasoning documentation quality assessed by AI. METHODS:In this observational, retrospective cross-sectional analysis of hospital admission notes from the Electronic Health Record (EHR), all categorical internal medicine (IM) residents who wrote at least one admission note during the study period July 1, 2018- June 30, 2023 at two sites of NYU Grossman School of Medicine's IM residency program were included. Clinical reasoning documentation quality of admission notes was determined to be low or high-quality using a supervised machine learning model. From note-level data, the shift (day or night) and note index within shift (if a note was first, second, etc. within shift) were calculated. These aspects of the CLE were included as potential markers of workload, which have been shown to have a strong relationship with resident performance. Patient data was also captured, including age, sex, Charlson Comorbidity Index, and primary diagnosis. The relationship between these variables and clinical reasoning documentation quality was analyzed using generalized estimating equations accounting for resident-level clustering. RESULTS:Across 37,750 notes authored by 474 residents, patients who were older, had more pre-existing comorbidities, and presented with certain primary diagnoses (e.g., infectious and pulmonary conditions) were associated with higher clinical reasoning documentation quality. When controlling for these and other patient factors, variables associated with clinical reasoning documentation quality included academic year (adjusted odds ratio, aOR, for high-quality: 1.10; 95% CI 1.06-1.15; P <.001), night shift (aOR 1.21; 95% CI 1.13-1.30; P <.001), and note index (aOR 0.93; 95% CI 0.90-0.95; P <.001). CONCLUSIONS:AI can be used to assess complex skills such as clinical reasoning in authentic clinical notes that can help elucidate the potential impact of the CLE on resident clinical reasoning documentation quality. Future work should explore residency program and systems interventions to optimize the CLE.