Browsing by Author "Neff, Jadee"
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Item Open Access A multiple instance learning approach for detecting COVID-19 in peripheral blood smears.(PLOS digital health, 2022-08) Cooke, Colin L; Kim, Kanghyun; Xu, Shiqi; Chaware, Amey; Yao, Xing; Yang, Xi; Neff, Jadee; Pittman, Patricia; McCall, Chad; Glass, Carolyn; Jiang, Xiaoyin Sara; Horstmeyer, RoarkeA wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understood. In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose disease at a per-patient level. We integrated image and diagnostic information from across 236 patients to demonstrate not only that there is a significant link between blood and a patient's COVID-19 infection status, but also that novel machine learning approaches offer a powerful and scalable means to analyze peripheral blood smears. Our results both backup and enhance hematological findings relating blood cell morphology to COVID-19, and offer a high diagnostic efficacy; with a 79% accuracy and a ROC-AUC of 0.90.Item Open Access Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma(Frontiers in Immunology) Yu, Tiantian; Xu-Monette, Zijun Y; Lagoo, Anand; Shuai, Wen; Wang, Bangchen; Neff, Jadee; Carrillo, Luis F; Carlsen, Eric D; Pina-Oviedo, Sergio; Young, Ken HIntroductionOur previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center.MethodsWe collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations.ResultsWe found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patients with low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response.SummaryTILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication.Item Open Access Histopathologic assessment of cultured human thymus.(PloS one, 2020-01) Hale, Laura P; Neff, Jadee; Cheatham, Lynn; Cardona, Diana; Markert, M Louise; Kurtzberg, JoanneThe maintenance and propagation of complex mixtures of cells in vitro in the form of native organs or engineered organoids has contributed to understanding mechanisms of cell and organ development and function which can be translated into therapeutic benefits. For example, allogeneic cultured postnatal human thymus tissue has been shown to support production of naïve recipient T cells when transplanted into patients with complete DiGeorge anomaly and other genetic defects that result in congenital lack of a thymus. Patients receiving such transplants typically exhibit reversal of their immunodeficiency and normalization of their peripheral blood T cell receptor V-beta repertoire, with long-term survival. This study was designed to assess the histopathologic changes that occur in postnatal human thymus slices when cultured according to protocols used for transplanted tissues. Results showed that as thymic organ cultures progressed from days 0 through 21, slices developed increasing amounts of necrosis, increasing condensation of thymic epithelium, and decreasing numbers of residual T cells. The architecture of the thymic epithelial network remained generally well-preserved throughout the 21 days of culture, with focal expression of cytokeratin 14, a putative biomarker of thymic epithelial cells with long-term organ-repopulating potential. All organ slices derived from the same donor thymus closely resembled one another, with minor differences in size, shape, and relative content of cortex versus medulla. Similarly, slices derived from different donors showed similar histopathologic characteristics when examined at the same culture time point. Taken together, these results demonstrate that diagnostic criteria based on structural features of the tissue identifiable via hematoxylin and eosin staining and cytokeratin immunohistochemistry can be used to evaluate the quality of slices transplanted into patients with congenital athymia.