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809 results on '"Mitchell, Duane A."'

5. A Study of Generative Large Language Model for Medical Research and Healthcare

Author

Peng, Cheng, Yang, Xi, Chen, Aokun, Smith, Kaleb E, PourNejatian, Nima, Costa, Anthony B, Martin, Cheryl, Flores, Mona G, Zhang, Ying, Magoc, Tanja, Lipori, Gloria, Mitchell, Duane A, Ospina, Naykky S, Ahmed, Mustafa M, Hogan, William R, Shenkman, Elizabeth A, Guo, Yi, Bian, Jiang, and Wu, Yonghui

Subjects
Computer Science - Computation and Language
Abstract

There is enormous enthusiasm and concerns in using large language models (LLMs) in healthcare, yet current assumptions are all based on general-purpose LLMs such as ChatGPT. This study develops a clinical generative LLM, GatorTronGPT, using 277 billion words of mixed clinical and English text with a GPT-3 architecture of 20 billion parameters. GatorTronGPT improves biomedical natural language processing for medical research. Synthetic NLP models trained using GatorTronGPT generated text outperform NLP models trained using real-world clinical text. Physicians Turing test using 1 (worst) to 9 (best) scale shows that there is no significant difference in linguistic readability (p = 0.22; 6.57 of GatorTronGPT compared with 6.93 of human) and clinical relevance (p = 0.91; 7.0 of GatorTronGPT compared with 6.97 of human) and that physicians cannot differentiate them (p < 0.001). This study provides insights on the opportunities and challenges of LLMs for medical research and healthcare.

Published
2023
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6. GatorTron: A Large Clinical Language Model to Unlock Patient Information from Unstructured Electronic Health Records

Author

Yang, Xi, Chen, Aokun, PourNejatian, Nima, Shin, Hoo Chang, Smith, Kaleb E, Parisien, Christopher, Compas, Colin, Martin, Cheryl, Flores, Mona G, Zhang, Ying, Magoc, Tanja, Harle, Christopher A, Lipori, Gloria, Mitchell, Duane A, Hogan, William R, Shenkman, Elizabeth A, Bian, Jiang, and Wu, Yonghui

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computer Science - Machine Learning
Abstract

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model - GatorTron - using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on 5 clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve 5 clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og., Comment: 24 pages, 2 figures, 3 tables

Published
2022

8. RNA aggregates harness the danger response for potent cancer immunotherapy

Author

Mendez-Gomez, Hector R., DeVries, Anna, Castillo, Paul, von Roemeling, Christina, Qdaisat, Sadeem, Stover, Brian D., Xie, Chao, Weidert, Frances, Zhao, Chong, Moor, Rachel, Liu, Ruixuan, Soni, Dhruvkumar, Ogando-Rivas, Elizabeth, Chardon-Robles, Jonathan, McGuiness, James, Zhang, Dingpeng, Chung, Michael C., Marconi, Christiano, Michel, Stephen, Barpujari, Arnav, Jobin, Gabriel W., Thomas, Nagheme, Ma, Xiaojie, Campaneria, Yodarlynis, Grippin, Adam, Karachi, Aida, Li, Derek, Sahay, Bikash, Elliott, Leighton, Foster, Timothy P., Coleman, Kirsten E., Milner, Rowan J., Sawyer, W. Gregory, Ligon, John A., Simon, Eugenio, Cleaver, Brian, Wynne, Kristine, Hodik, Marcia, Molinaro, Annette M., Guan, Juan, Kellish, Patrick, Doty, Andria, Lee, Ji-Hyun, Massini, Tara, Kresak, Jesse L., Huang, Jianping, Hwang, Eugene I., Kline, Cassie, Carrera-Justiz, Sheila, Rahman, Maryam, Gatica, Sebastian, Mueller, Sabine, Prados, Michael, Ghiaseddin, Ashley P., Silver, Natalie L., Mitchell, Duane A., and Sayour, Elias J.

Published
2024
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10. Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions

Author

Nguyen, Duy T., Liu, Ruixuan, Ogando-Rivas, Elizabeth, Pepe, Alfonso, Pedro, Diego, Qdaisat, Sadeem, Nguyen, Nhi Tran Yen, Lavrador, Julia M., Golde, Griffin R., Smolchek, Ryan A., Ligon, John, Jin, Linchun, Tao, Haipeng, Webber, Alex, Phillpot, Simon, Mitchell, Duane A., Sayour, Elias J., Huang, Jianping, Castillo, Paul, and Gregory Sawyer, W.

Published
2023
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11. Unique challenges for glioblastoma immunotherapy—discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank

Author

Chuntova, Pavlina, Chow, Frances, Watchmaker, Payal B, Galvez, Mildred, Heimberger, Amy B, Newell, Evan W, Diaz, Aaron, DePinho, Ronald A, Li, Ming O, Wherry, E John, Mitchell, Duane, Terabe, Masaki, Wainwright, Derek A, Berzofsky, Jay A, Herold-Mende, Christel, Heath, James R, Lim, Michael, Margolin, Kim A, Chiocca, E Antonio, Kasahara, Noriyuki, Ellingson, Benjamin M, Brown, Christine E, Chen, Yvonne, Fecci, Peter E, Reardon, David A, Dunn, Gavin P, Liau, Linda M, Costello, Joseph F, Wick, Wolfgang, Cloughesy, Timothy, Timmer, William C, Wen, Patrick Y, Prins, Robert M, Platten, Michael, and Okada, Hideho

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Vaccine Related, Immunization, Rare Diseases, Biotechnology, Orphan Drug, Brain Cancer, Cancer, Neurosciences, Brain Disorders, Immunotherapy, 5.1 Pharmaceuticals, Good Health and Well Being, Brain Neoplasms, Glioblastoma, Humans, Medical Oncology, Neoplasms, Tumor Microenvironment, clinical trial, conference report, glioblastoma, immunosuppression, immunotherapy, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Cancer immunotherapy has made remarkable advances with over 50 separate Food and Drug Administration (FDA) approvals as first- or second-line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T cells, and bispecific T-cell-engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights into the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells, T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner.

Published
2021

17. A large language model for electronic health records

Author

Yang, Xi, Chen, Aokun, PourNejatian, Nima, Shin, Hoo Chang, Smith, Kaleb E., Parisien, Christopher, Compas, Colin, Martin, Cheryl, Costa, Anthony B., Flores, Mona G., Zhang, Ying, Magoc, Tanja, Harle, Christopher A., Lipori, Gloria, Mitchell, Duane A., Hogan, William R., Shenkman, Elizabeth A., Bian, Jiang, and Wu, Yonghui

Published
2022
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19. The current landscape of immunotherapy for pediatric brain tumors

Author

Hwang, Eugene I., Sayour, Elias J., Flores, Catherine T., Grant, Gerald, Wechsler-Reya, Robert, Hoang-Minh, Lan B., Kieran, Mark W., Salcido, Joanne, Prins, Robert M., Figg, John W., Platten, Michael, Candelario, Kate M., Hale, Paul G., Blatt, Jason E., Governale, Lance S., Okada, Hideho, Mitchell, Duane A., and Pollack, Ian F.

Published
2022
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22. Contributors

Author

Bell, April, primary, Bloch, Orin, additional, Bollu, Lakshmi, additional, Chiocca, E. Antonio, additional, Chuntova, Pavlina, additional, Coxon, Andrew T., additional, Dunn, Gavin P., additional, Ellsworth, Susannah G., additional, Fecci, Peter E., additional, Gilbert, Ryan, additional, Grossman, Stuart A., additional, Haskell-Mendoza, Aden P., additional, Hoang-Minh, Lan B., additional, Jin, Michael, additional, Kim, Miri, additional, Ladomersky, Erik, additional, Lauing, Kristen L., additional, Li, Gordon, additional, Liu, Connor J., additional, Lorrey, Selena, additional, Mitchell, Duane A., additional, Okada, Hideho, additional, Polania, Jessica Waibl, additional, Rabin, Erik, additional, Solomon, Isaac H., additional, Wainwright, Derek A., additional, Watchmaker, Payal B., additional, Wilkinson, Daniel, additional, Wu, Adela, additional, and Zhai, Lijie, additional

Published
2022
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24. Blocking Immune Checkpoint—LAIR1: Disrupting the LAIR1—FXIII-A—Collagen Immunosuppressive Circuit for Enhanced Antitumor Therapeutics

Author

Huang, Jianping, primary, Tao, Haipeng, additional, Chen, Dongjiang, additional, Yang, Changlin, additional, Nguyen, Duy, additional, Liu, Ruixuan, additional, Liu, Tianyi, additional, Chakraborty, Avirup, additional, Hou, Alicia, additional, Petit, Nicole, additional, Abbas, Muhammad, additional, Roemeling, Christina, additional, Gbadamosi, Mohammed, additional, Jin, Linchun, additional, Gu, Tongjun, additional, Lin, Tuo, additional, Pepe, Alfonso, additional, Pedro, Diego, additional, Yu, Shengkun, additional, Abboud, Georges, additional, Mendez-Gomez, Hector, additional, Karachi, Aida, additional, Weidert, Frances, additional, Jin, Dan, additional, Long-James, Kaytora, additional, Molchan, Elizabeth, additional, Castillo, Paul, additional, Ligon, John, additional, Ghiaseddin, Ashley, additional, Sayour, Elias, additional, Rahman, Maryam, additional, Deleyrolle, Loic, additional, Kim, Betty, additional, Mitchell, Duane, additional, and Sawyer, W. Gregory, additional

Published
2024
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25. Figure S4 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

Author

Von Roemeling, Christina A., primary, Doonan, Bently P., primary, Klippel, Kelena, primary, Schultz, Daniel, primary, Hoang-Minh, Lan, primary, Trivedi, Vrunda, primary, Li, Chenglong, primary, Russell, Rylynn A., primary, Kanumuri, Raju S., primary, Sharma, Abhisheak, primary, Tun, Han W., primary, and Mitchell, Duane A., primary

Published
2024
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26. Data from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases

Author

Von Roemeling, Christina A., primary, Doonan, Bently P., primary, Klippel, Kelena, primary, Schultz, Daniel, primary, Hoang-Minh, Lan, primary, Trivedi, Vrunda, primary, Li, Chenglong, primary, Russell, Rylynn A., primary, Kanumuri, Raju S., primary, Sharma, Abhisheak, primary, Tun, Han W., primary, and Mitchell, Duane A., primary

Published
2024
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29. Prioritization schema for immunotherapy clinical trials in glioblastoma

Author

Hodges, Tiffany R, Ferguson, Sherise D, Caruso, Hillary G, Kohanbash, Gary, Zhou, Shouhao, Cloughesy, Timothy F, Berger, Mitchel S, Poste, George H, Khasraw, Mustafa, Ba, Sujuan, Jiang, Tao, Mikkelson, Tom, Yung, WK Alfred, de Groot, John F, Fine, Howard, Cantley, Lewis C, Mellinghoff, Ingo K, Mitchell, Duane A, Okada, Hideho, and Heimberger, Amy B

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Vaccine Related, Immunization, Cancer, Rare Diseases, Brain Cancer, Neurosciences, Brain Disorders, Good Health and Well Being, Clinical trial, glioblastoma, immunotherapy, prioritization, score card, Oncology and carcinogenesis
Abstract

BackgroundEmerging immunotherapeutic strategies for the treatment of glioblastoma (GBM) such as dendritic cell (DC) vaccines, heat shock proteins, peptide vaccines, and adoptive T-cell therapeutics, to name a few, have transitioned from the bench to clinical trials. With upcoming strategies and developing therapeutics, it is challenging to critically evaluate the practical, clinical potential of individual approaches and to advise patients on the most promising clinical trials.MethodsThe authors propose a system to prioritize such therapies in an organized and data-driven fashion. This schema is based on four categories of factors: antigenic target robustness, immune-activation and -effector responses, preclinical vetting, and early evidence of clinical response. Each of these categories is subdivided to focus on the most salient elements for developing a successful immunotherapeutic approach for GBM, and a numerical score is generated.ResultsThe Score Card reveals therapeutics that have the most robust data to support their use, provides a reference prioritization score, and can be applied in a reiterative fashion with emerging data.ConclusionsThe authors hope that this schema will give physicians an evidence-based and rational framework to make the best referral decisions to better guide and serve this patient population.

Published
2016

31. Disruption of KIF3A in patient-derived glioblastoma cells: effects on ciliogenesis, hedgehog sensitivity, and tumorigenesis

Author

Hoang-Minh, Lan B, Deleyrolle, Loic P, Siebzehnrubl, Dorit, Ugartemendia, George, Futch, Hunter, Griffith, Benjamin, Breunig, Joshua J, De Leon, Gabriel, Mitchell, Duane A, Semple-Rowland, Susan, Reynolds, Brent A, and Sarkisian, Matthew R

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Brain Cancer, Biotechnology, Rare Diseases, Brain Disorders, Neurosciences, Cancer, Adult, Aged, Animals, Apoptosis, Blotting, Western, Carcinogenesis, Cell Proliferation, Cilia, Genes, Dominant, Glioblastoma, Hedgehog Proteins, Humans, Immunoenzyme Techniques, Kinesins, Male, Mice, Mice, Inbred NOD, Mice, SCID, Middle Aged, Signal Transduction, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, kinesin-2, brain tumor, cilium, intraflagellar transport, sonic hedgehog, Oncology and carcinogenesis
Abstract

KIF3A, a component of the kinesin-2 motor, is necessary for the progression of diverse tumor types. This is partly due to its role in regulating ciliogenesis and cell responsiveness to sonic hedgehog (SHH). Notably, primary cilia have been detected in human glioblastoma multiforme (GBM) tumor biopsies and derived cell lines. Here, we asked whether disrupting KIF3A in GBM cells affected ciliogenesis, in vitro growth and responsiveness to SHH, or tumorigenic behavior in vivo. We used a lentiviral vector to create three patient-derived GBM cell lines expressing a dominant negative, motorless form of Kif3a (dnKif3a). In all unmodified lines, we found that most GBM cells were capable of producing ciliated progeny and that dnKif3a expression in these cells ablated ciliogenesis. Interestingly, unmodified and dnKif3a-expressing cell lines displayed differential sensitivities and pathway activation to SHH and variable tumor-associated survival following mouse xenografts. In one cell line, SHH-induced cell proliferation was prevented in vitro by either expressing dnKif3a or inhibiting SMO signaling using cyclopamine, and the survival times of mice implanted with dnKif3a-expressing cells were increased. In a second line, expression of dnKif3a increased the cells' baseline proliferation while, surprisingly, sensitizing them to SHH-induced cell death. The survival times of mice implanted with these dnKif3a-expressing cells were decreased. Finally, expression of dnKif3a in a third cell line had no effect on cell proliferation, SHH sensitivity, or mouse survival times. These findings indicate that KIF3A is essential for GBM cell ciliogenesis, but its role in modulating GBM cell behavior is highly variable.

Published
2016

35. CD70 CXCR2-Modified CAR T-Cells Against Acute Myeloid Leukemia

Author

Ligon, John A, primary, Castillo, Paul, additional, Ma, Xiaojie, additional, Jin, Linchun, additional, Tao, Haipeng, additional, Nguyen, Duy, additional, Jobin, Gabriel, additional, Guryanova, Olga, additional, Lamba, Jatinder K, additional, Sawyer, W Greg, additional, Mitchell, Duane, additional, Mendez-Gomez, Hector, additional, Sayour, Elias, additional, and Huang, Jianping, additional

Published
2024
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36. KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system

Author

Chakraborty, Avirup, primary, Yang, Changlin, additional, Kresak, Jesse L., additional, Silver, Aryeh, additional, Feier, Diana, additional, Tian, Guimei, additional, Andrews, Michael, additional, Sobanjo, Olusegun O., additional, Hodge, Ethan D., additional, Engelbart, Mia K., additional, Huang, Jianping, additional, Harrison, Jeffrey K., additional, Sarkisian, Matthew R., additional, Mitchell, Duane A., additional, and Deleyrolle, Loic P., additional

Published
2024
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38. KR158 Spheres Harboring Slow-Cycling Cells Recapitulate High-Grade Glioma Features in an Immunocompetent System.

Author

Chakraborty, Avirup, Yang, Changlin, Kresak, Jesse L., Silver, Aryeh J., Feier, Diana, Tian, Guimei, Andrews, Michael, Sobanjo, Olusegun O., Hodge, Ethan D., Engelbart, Mia K., Huang, Jianping, Harrison, Jeffrey K., Sarkisian, Matthew R., Mitchell, Duane A., and Deleyrolle, Loic P.

Subjects
GLIOMAS, CANCER stem cells, GLIOBLASTOMA multiforme, TELECOMMUNICATION systems, TUMOR microenvironment, SPHERES
Abstract

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM pathology, and explore specifically the SCC–immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Developing a computable phenotype for glioblastoma

Author

Yan, Sandra, primary, Melnick, Kaitlyn, additional, He, Xing, additional, Lyu, Tianchen, additional, Moor, Rachel S F, additional, Still, Megan E H, additional, Mitchell, Duane A, additional, Shenkman, Elizabeth A, additional, Wang, Han, additional, Guo, Yi, additional, Bian, Jiang, additional, and Ghiaseddin, Ashley P, additional

Published
2023
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43. A study of generative large language model for medical research and healthcare

Author

Peng, Cheng, primary, Yang, Xi, additional, Chen, Aokun, additional, Smith, Kaleb E., additional, PourNejatian, Nima, additional, Costa, Anthony B., additional, Martin, Cheryl, additional, Flores, Mona G., additional, Zhang, Ying, additional, Magoc, Tanja, additional, Lipori, Gloria, additional, Mitchell, Duane A., additional, Ospina, Naykky S., additional, Ahmed, Mustafa M., additional, Hogan, William R., additional, Shenkman, Elizabeth A., additional, Guo, Yi, additional, Bian, Jiang, additional, and Wu, Yonghui, additional

Published
2023
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44. CXCL9 recombinant adeno-associated virus (AAV) virotherapy sensitizes glioblastoma (GBM) to anti-PD-1 immune checkpoint blockade

Author

von Roemeling, Christina, primary, Yegorov, Oleg, additional, Yang, Changlin, additional, Klippel, Kelena, additional, Russell, Rylynn, additional, Trivedi, Vrunda, additional, Bhatia, Alisha, additional, Doonan, Bently, additional, Carpenter, Savannah, additional, Ryu, Daniel, additional, Grippen, Adam, additional, Futch, Hunter, additional, Ran, Yong, additional, Hoang-Minh, Lan, additional, Weidert, Frances, additional, Golde, Todd, additional, and Mitchell, Duane, additional

Published
2023
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47. IMMU-33. PRECISION ANTIGEN-DIRECTED IMMUNOTHERAPY TREATMENT OF BRAIN TUMORS INCREASES TUMOR-INFILTRATING EFFECTOR LYMPHOCYTE RESPONSES

Author

Trivedi, Vrunda, primary, Yang, Changlin, additional, Yegorov, Oleg, additional, Klippel, Kelena, additional, Von Roemeling, Christina, additional, Hoang-Minh, Lan, additional, Fenton, Graeme, additional, Ogando-Rivas, Elizabeth, additional, Castillo, Paul, additional, Moore, Ginger, additional, Dyson, Kyle, additional, and Mitchell, Duane, additional

Published
2023
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50. EXTH-81. RE-EXPRESSION OF CXCL9 FOLLOWING ADENO-ASSOCIATED VIRUS (AAV) TRANSGENE DELIVERY TRANSFORMS THE IMMUNOLOGICAL LANDSCAPE OF GLIOBLASTOMA, SENSITIZING TUMORS TO PD-1 IMMUNE CHECKPOINT BLOCKADE (ICB)

Author

von Roemeling, Christina, primary, Yegorov, Oleg, additional, Yang, Changlin, additional, Russell, Rylynn, additional, Carpenter, Savannah, additional, Trivedi, Vrunda, additional, Bhatia, Alisha, additional, Doonan, Bently, additional, Golde, Todd, additional, and Mitchell, Duane, additional

Published
2023
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