Browsing by Author "Yang, Jing"
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Item A neurotechnological aid for semi-autonomous suction in robotic-assisted surgery(Springer, 2022-03-16) Barragan, Juan Antonio; Yang, Jing; Yu, Denny; Wachs, Juan P.; Surgery, School of MedicineAdoption of robotic-assisted surgery has steadily increased as it improves the surgeon’s dexterity and visualization. Despite these advantages, the success of a robotic procedure is highly dependent on the availability of a proficient surgical assistant that can collaborate with the surgeon. With the introduction of novel medical devices, the surgeon has taken over some of the surgical assistant’s tasks to increase their independence. This, however, has also resulted in surgeons experiencing higher levels of cognitive demands that can lead to reduced performance. In this work, we proposed a neurotechnology-based semi-autonomous assistant to release the main surgeon of the additional cognitive demands of a critical support task: blood suction. To create a more synergistic collaboration between the surgeon and the robotic assistant, a real-time cognitive workload assessment system based on EEG signals and eye-tracking was introduced. A computational experiment demonstrates that cognitive workload can be effectively detected with an 80% accuracy. Then, we show how the surgical performance can be improved by using the neurotechnological autonomous assistant as a close feedback loop to prevent states of high cognitive demands. Our findings highlight the potential of utilizing real-time cognitive workload assessments to improve the collaboration between an autonomous algorithm and the surgeon.Item An Adaptive Human-Robotic Interaction Architecture for Augmenting Surgery Performance Using Real-Time Workload Sensing—Demonstration of a Semi-autonomous Suction Tool(Sage, 2024) Yang, Jing; Barragan, Juan Antonio; Farrow, Jason Michael; Sundaram, Chandru P.; Wachs, Juan P.; Yu, Denny; Urology, School of MedicineObjective: This study developed and evaluated a mental workload-based adaptive automation (MWL-AA) that monitors surgeon cognitive load and assist during cognitively demanding tasks and assists surgeons in robotic-assisted surgery (RAS). Background: The introduction of RAS makes operators overwhelmed. The need for precise, continuous assessment of human mental workload (MWL) states is important to identify when the interventions should be delivered to moderate operators' MWL. Method: The MWL-AA presented in this study was a semi-autonomous suction tool. The first experiment recruited ten participants to perform surgical tasks under different MWL levels. The physiological responses were captured and used to develop a real-time multi-sensing model for MWL detection. The second experiment evaluated the effectiveness of the MWL-AA, where nine brand-new surgical trainees performed the surgical task with and without the MWL-AA. Mixed effect models were used to compare task performance, objective- and subjective-measured MWL. Results: The proposed system predicted high MWL hemorrhage conditions with an accuracy of 77.9%. For the MWL-AA evaluation, the surgeons' gaze behaviors and brain activities suggested lower perceived MWL with MWL-AA than without. This was further supported by lower self-reported MWL and better task performance in the task condition with MWL-AA. Conclusion: A MWL-AA systems can reduce surgeons' workload and improve performance in a high-stress hemorrhaging scenario. Findings highlight the potential of utilizing MWL-AA to enhance the collaboration between the autonomous system and surgeons. Developing a robust and personalized MWL-AA is the first step that can be used do develop additional use cases in future studies. Application: The proposed framework can be expanded and applied to more complex environments to improve human-robot collaboration.Item BATF sustains homeostasis and functionality of bone marrow Treg cells to preserve homeostatic regulation of hematopoiesis and development of B cells(Frontiers Media, 2023-02-22) Tikka, Chiranjeevi; Beasley, Lindsay; Xu, Chengxian; Yang, Jing; Cooper, Scott; Lechner, Joseph; Gutch, Sarah; Kaplan, Mark H.; Capitano, Maegan; Yang, Kai; Pediatrics, School of MedicineBone marrow Treg cells (BM Tregs) orchestrate stem cell niches crucial for hematopoiesis. Yet little is known about the molecular mechanisms governing BM Treg homeostasis and function. Here we report that the transcription factor BATF maintains homeostasis and functionality of BM Tregs to facilitate homeostatic regulation of hematopoiesis and B cell development. Treg-specific ablation of BATF profoundly compromised proportions of BM Tregs associated with reduced expression of Treg effector molecules, including CD44, ICOS, KLRG1, and TIGIT. Moreover, BATF deficiency in Tregs led to increased numbers of hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), and granulocyte-macrophage progenitors (GMPs), while reducing the functionality of myeloid progenitors and the generation of common lymphoid progenitors. Furthermore, Tregs lacking BATF failed to support the development of B cells in the BM. Mechanistically, BATF mediated IL-7 signaling to promote expression of effector molecules on BM Tregs and their homeostasis. Our studies reveal a previously unappreciated role for BATF in sustaining BM Treg homeostasis and function to ensure hematopoiesis.Item Blood Biomarkers of Intestinal Epithelium Damage Regenerating Islet-derived Protein 3α and Trefoil Factor 3 Are Persistently Elevated in Patients with Alcoholic Hepatitis(Wiley, 2021) Yang, Jing; Syed, Fahim; Xia, Ying; Sanyal, Arun; Shah, Vijay; Chalasani, Naga; Zheng, Xiaoqun; Yu, Qigui; Lou, Yongliang; Li, Wei; Microbiology and Immunology, School of MedicineBackground: Heavy alcohol consumption disrupts gut epithelial integrity, leading to increased permeability of the gastrointestinal tract and subsequent translocation of microbes. Regenerating islet-derived protein 3α (REG3α) and Trefoil factor 3 (TFF3) are mainly secreted to the gut lumen by Paneth and Goblet cells, respectively, and are functionally linked to gut barrier integrity. Circulating levels of REG3α and TFF3 have been identified as biomarkers for gut damage in several human diseases. We examined whether plasma levels of REG3α and TFF3 were dysregulated and correlated with conventional markers of microbial translocation (MT) and pro-inflammatory mediators in heavy drinkers with and without alcoholic hepatitis (AH). Methods: Cross-sectional and longitudinal studies were performed to monitor plasma levels of REG3α and TFF3 in 79 AH patients, 66 heavy drinkers without liver disease (HDC), and 46 healthy controls (HC) at enrollment and at 6- and 12-month follow-ups. Spearman correlation was used to measure the relationships of REG3α and TFF3 levels with MT, disease severity, inflammation, and effects of abstinence from alcohol. Results: At enrollment, AH patients had significantly higher levels of REG3α and TFF3 than HDC and HC. The elevated REG3α levels were positively correlated with the 30-day fatality rate. Plasma levels of REG3α and TFF3 in AH patients differentially correlated with conventional MT markers (sCD14, sCD163, and LBP) and several highly up-regulated inflammatory cytokines/chemokines/growth factors. At follow-ups, although REG3α and TFF3 levels were decreased in AH patients with alcohol abstinence, they did not fully return to baseline levels. Conclusions: Circulating levels of REG3α and TFF3 were highly elevated in AH patients and differentially correlated with AH disease severity, MT, and inflammation, thereby serving as potential biomarkers of MT and gut epithelial damage in AH patients.Item Comment on “Evidence that the ProPerDP method is inadequate for protein persulfidation detection due to lack of specificity”(American Association for the Advancement of Science, 2021-04-21) Dóka, Éva; Arnér, Elias S.J.; Schmidt, Edward E.; Dick, Tobias P.; van der Vliet, Albert; Yang, Jing; Szatmári, Réka; Ditrói, Tamás; Wallace, John L.; Cirino, Giuseppe; Olson, Kenneth; Motohashi, Hozumi; Fukuto, Jon M.; Pluth, Michael D.; Feelisch, Martin; Akaike, Takaaki; Wink, David A.; Ignarro, Louis J.; Nagy, Péter; Medicine, School of MedicineThe recent report by Fan et al. alleged that the ProPerDP method is inadequate for the detection of protein persulfidation. Upon careful evaluation of their work, we conclude that the claim made by Fan et al. is not supported by their data, rather founded in methodological shortcomings. It is understood that the ProPerDP method generates a mixture of cysteine-containing and non–cysteine-containing peptides. Instead, Fan et al. suggested that the detection of non–cysteine-containing peptides indicates nonspecific alkylation at noncysteine residues. However, if true, then such peptides would not be released by reduction and therefore not appear as products in the reported workflow. Moreover, the authors’ biological assessment of ProPerDP using Escherichia coli mutants was based on assumptions that have not been confirmed by other methods. We conclude that Fan et al. did not rigorously assess the method and that ProPerDP remains a reliable approach for analyses of protein per/polysulfidation.Item Corrigendum: Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi(Frontiers Media, 2021-03-31) Liu, Qiang; Xu, Haijun; Zhang, Yan; Yang, Jing; Du, Jimei; Zhou, Yan; Yang, X. Frank; Lou, Yongliang; Microbiology and Immunology, School of MedicineItem ICOSL+ plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist(American Association for the Advancement of Science, 2020-10-07) Adom, Djamilatou; Dillon, Stacey R.; Yang, Jinfeng; Liu, Hao; Ramadan, Abdulraouf; Kushekhar, Kushi; Hund, Samantha; Albright, Amanda; Kirksey, Maykala; Adeniyan, Titilayo; Lewis, Katherine E.; Evans, Lawrence; Wu, Rebecca; Levin, Steven D.; Mudri, Sherri; Yang, Jing; Rickel, Erika; Seaberg, Michelle; Henderson, Katherine; Gudgeon, Chelsea J.; Wolfson, Martin F.; Swanson, Ryan M.; Swiderek, Kristine M.; Peng, Stanford L.; Hippen, Keli L.; Blazar, Bruce R.; Paczesny, Sophie; Pediatrics, School of MedicineAcute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs). We performed multiparametric flow cytometry in a cohort of 156 HCT recipients and conducted experiments with aGVHD murine models to understand the role of ICOSL+ DCs. We observed an increased frequency of ICOSL+ plasmacytoid DCs, correlating with CD146+CCR5+ T cell frequencies, in the 64 HCT recipients with gastrointestinal aGVHD. In murine models, donor bone marrow cells from ICOSL-deficient mice compared to those from wild-type mice reduced aGVHD-related mortality. Reduced aGVHD resulted from lower intestinal infiltration of pDCs and pathogenic Th17 cells. We transplanted activated human ICOSL+ pDCs along with human peripheral blood mononuclear cells into immunocompromised mice and observed infiltration of intestinal CD146+CCR5+ T cells. We found that prophylactic administration of a dual human ICOS/CD28 antagonist (ALPN-101) prevented aGVHD in this model better than did the clinically approved belatacept (CTLA-4-Fc), which binds CD80 (B7-1) and CD86 (B7-2) and interferes with the CD28 T cell costimulatory pathway. When started at onset of aGVHD signs, ALPN-101 treatment alleviated symptoms of ongoing aGVHD and improved survival while preserving antitumoral cytotoxicity. Our data identified ICOSL+-pDCs as an aGVHD biomarker and suggest that coinhibition of the ICOSL/ICOS and B7/CD28 axes with one biologic drug may represent a therapeutic opportunity to prevent or treat aGVHD.Item Immune Checkpoint Axes Are Dysregulated in Patients With Alcoholic Hepatitis(Wiley Open Access:, 2020-01-12) Li, Wei; Xia, Ying; Yang, Jing; Guo, Haitao; Sun, Guoqing; Sanyal, Arun J.; Shah, Vijay H.; Lou, Yongliang; Zheng, Xiaoqun; Chalasani, Naga; Yu, Qigui; Microbiology and Immunology, School of MedicineAlcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. The immune system in patients with AH is hyperactive and yet dysfunctional. Here, we investigated whether this immune‐dysregulated state is related to the alcoholic impact on immune checkpoints (ICPs). We used multiplex immunoassays and enzyme‐linked immunosorbent assay to quantify plasma levels of 18 soluble ICPs (sICPs) from 81 patients with AH, 65 heavy drinkers without liver diseases (HDCs), and 39 healthy controls (HCs) at baseline, 33 patients with AH and 32 HDCs at 6‐month follow‐up, and 18 patients with AH and 29 HDCs at 12‐month follow‐up. We demonstrated that baseline levels of 6 sICPs (soluble T‐cell immunoglobulin and mucin domain 3 [sTIM‐3], soluble cluster of differentiation [sCD]27, sCD40, soluble Toll‐like receptor‐2 [sTLR‐2], soluble herpesvirus entry mediator [sHVEM], and soluble lymphotoxin‐like inducible protein that competes with glycoprotein D for herpes virus entry on T cells [sLIGHT]) were up‐regulated, while 11 sICPs (soluble B‐ and T‐lymphocyte attenuator [sBTLA], sCD160, soluble cytotoxic T‐lymphocyte‐associated protein 4 [sCTLA‐4], soluble lymphocyte‐activation gene 3 [sLAG‐3], soluble programmed death 1 [sPD‐1], sPD ligand 1 [sPD‐L1], sCD28, soluble glucocorticoid‐induced tumor necrosis factor receptor‐related protein [sGITR], sGITR ligand [sGITRL], sCD80, and inducible T‐cell costimulator [sICOS]) were down‐regulated in patients with AH compared to HDCs. The up‐regulated sICPs except sLIGHT and down‐regulated sCD80, sCD160, sCTLA‐4, and sLAG‐3 correlated positively or negatively with AH disease severity, bacterial translocation, and inflammatory factors. At follow‐up, abstinent patients with AH still had higher levels of several sICPs compared to HDCs. We also compared expression of 10 membrane‐bound ICPs (mICPs) on peripheral blood mononuclear cells (PBMCs) from patients with AH and HCs by flow cytometry and found that several mICPs were dysregulated on blood cells from patients with AH. The function and regulation of sICPs and mICPs were studied using PBMCs from patients with AH and HCs. Recombinant sHVEM affected tumor necrosis factor (TNF)‐α and interferon‐γ production by T cells from patients with AH and HCs. Conclusion: Both sICPs and mICPs were dysregulated in patients with AH, and alcohol abstinence did not fully reverse these abnormalities. The HVEM axis plays a role in regulating T‐cell function in patients with AH.Item In vivo tumor growth of high-grade serous ovarian cancer cell lines(Elsevier, 2015-08) Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cardenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth; Yang, Jing; Stack, M. Sharon; Emerson, Robert E.; Dahl, Karen D. Cowden; Barbolina, Maria; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.; Department of Medicine, IU School of MedicineOBJECTIVE: Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. METHODS: To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119 and UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. RESULTS: Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. CONCLUSIONS: Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community.Item Insights from Engineering a Community-Family Partnership Project(ASEE, 2021) Simpson, Amber; Maltese, Adam V.; Yang, Jing; Kim, Jungsun; Knox, Peter N.; Kim, Soo Hyeon; D’Souza, Nikeetha F.; Library and Information Science, School of Informatics and ComputingThe objective of this three-year National Science Foundation’s Innovative Technology Experiences for Students and Teachers (NSF-ITEST) project is to develop, implement, and refine a program for integrating engineering design practices with an emphasis on emerging technologies (i.e., making, DIY electronics) into home environments of families with a child in grade 3-6 from under-resourced communities. This project has two components. Each family (1) defines a home- or community-based problem and creates a prototype to improve the lives of self or others; and (2) engages in low-cost engineering design kits in their home environments. This paper presents findings from two years of interview data, as well video data collected in project sessions and home environments from 21 families. Results are presented as highlights of finding from on-going analyses to address three research aims.