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Brooke Benner,1,* Logan Good,1,* Dionisia Quiroga,2 Thomas E Schultz,3 Mahmoud Kassem,2 William E Carson,1 Mathew A Cherian,2 Sagar Sardesai,2 Robert Wesolowski2 1Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 2Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 3Department of Pharmacy, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA*These authors contributed equally to this workCorrespondence: Robert WesolowskiDivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, 1800 Cannon Drive, 1250 Lincoln Tower, Columbus, OH 43210 Tel +1 614 366 5125Fax +1 614 293 7264Email Robert.Wesolowski@osumc.eduAbstract: Tenosynovial giant cell tumor (TGCT) is a rare benign tumor that involves the synovium, bursa, and tendon sheath, resulting in reduced mobility of the affected joint or limb. The current standard of care for TGCT is surgical resection. However, some patients have tumor recurrence, present with unresectable tumors, or have tumors that are in locations where resection could result in amputations or significant debility. Therefore, the development of systemic agents with activity against TGCT to expand treatment options is a highly unmet medical need. Pathologically, TGCT is characterized by the overexpression of colony-stimulating factor 1 (CSF-1), which leads to the recruitment of colony-stimulating factor-1 receptor (CSF-1R) expressing macrophages that make up the primary cell type within these giant cell tumors. The binding of CSF-1 and CSF-1R controls cell survival and proliferation of monocytes and the switch from a monocytic to macrophage phenotype contributing to the growth and inflammation within these tumors. Therefore, molecules that target CSF-1/CSF-1R have emerged as potential systemic agents for the treatment of TGCT. Given the role of macrophages in regulating tumorigenesis, CSF1/CSF1R-targeting agents have emerged as attractive therapeutic targets for solid tumors. Pexidartinib is an orally bioavailable and potent inhibitor of CSF-1R which is one of the most clinically used agents. In this review, we discuss the biology of TGCT and review the pre-clinical and clinical development of pexidartinib which ultimately led to the FDA approval of this agent for the treatment of TGCT as well as ongoing clinical studies utilizing pexidartinib in the setting of cancer.Keywords: pexidartinib, colony-stimulating factor 1 receptor, tenosynovial giant cell tumors, pigmented villonodular synovitis

Multi-shell diffusion MRI and Diffusion Spectrum Imaging are modern neuroimaging modalities that acquire diffusion weighted images at a high angular resolution, while also probing varying levels of diffusion weighting (b values). This yields large and intricate data for which very few interactive visualization techniques are currently available. We designed and implemented the first system that permits an interactive, iteratively refined classification of such data, which can serve as a foundation for isosurface visualizations and direct volume rendering. Our system leverages features learned by a Convolutional Neural Network. CNNs are state of the art for representation learning, but training them is too slow for interactive use. Therefore, we combine a computationally efficient random forest classifier with autoencoder based features that can be pre-computed by the CNN. Since features from existing CNN architectures are not suitable for this purpose, we design a specific dual-branch CNN architecture, and carefully evaluate our design decisions. We demonstrate that our approach produces more accurate classifications compared to learning with raw data, established domain-specific features, or PCA dimensionality reduction., Eurographics Workshop on Visual Computing for Biology and Medicine, Feature Analysis, 1, 11, Agajan Torayev and Thomas Schultz

Investigative ophthalmology & visual science 61(3), 55 (2020). doi:10.1167/iovs.61.3.55, Published by ARVO, Rockville, Md.