13384-Yan, Cong
Faculty

Cong Yan, PhD

Professor of Pathology & Laboratory Medicine

Phone 317-278-6005
Address
Indiana University School of Medicine, Dept of Pathology and Laboratory Medicine
975 W Walnut St, Room IB 424G

Indianapolis, IN 46202

Bio

1982 CUSBEA (China-United States Biochemistry Examination and Application) Program Graduate Student Scholarship

1987-90 Postdoctoral Fellow, Laboratory of Cell Physiology and Virology, The Rockefeller University, New York, NY

1990-92 Research Associate, Laboratory of Cell Physiology and Virology, The Rockefeller University, New York, NY

1992-94 Assistant Professor, Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, OH

1994-2005  Instructor-Associate Professor, Division of Pulmonary Biology, Children’s Hospital Medical Center, Cincinnati, OH

2005- Professor, the Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN

2005- Member, the Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN

2006- Member, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, IN

Key Publications

1) Yuan Li, Hong Du, Yulin Qin, Jennifer Roberts, Oscar W. Cummings and Cong Yan (corresponding author): Activation of the Stat3 Pathway in Alveolar Epithelial Cells Induces Inflammation and Adenocarcinomas in Mouse Lung (2007). Cancer Research, 67(18):8494-8503. PMID: 17875688.

2) Peng Qu, Jennifer Roberts, Yuan Li, Marjorie Albrecht, Oscar W. Cummings,John N. Eble, Hong Du and Cong Yan (corresponding author): Stat3 Downstream Genes Serve as Biomarkers in Human Lung Carcinomas and Chronic Obstructive Pulmonary Disease (2009). Lung Cancer, 63(3):341-7. PMID: 18614255.

3) Peng Qu, Hong Du, Yuan Li and Cong Yan (co-corresponding author). Myeloid-Specific Expression of Api6/AIM/Sp{alpha} Induces Systemic Inflammation and Adenocarcinoma in the Lung (2009). The Journal of Immunology 182, 1648-1659. PMID: 19155514.

4) Peng Qu, Hong Du, Yuan Li, David S. Wilkes, and Cong Yan (co-corresponding author): Critical Roles of Lysosomal Acid Lipase in T Cell Development and Function (2009). The American Journal of Pathology, 174:944-956. PMID: 19179613.

5) Peng Qu, Hong Du, Xi Wang and Cong Yan (corresponding author): Matrix-metalloproteinase 12 Overexpression in Lung Epithelial Cells Plays a Key Role in Emphysema to Lung Bronchioalveolar Adenocarcinoma Transition (2009). Cancer Research, 69(18):7252-61. PMID: 19706765.

6) Peng Qu, William C. Shelley, Mervin C. Yoder, Lingyan Wu, Hong Du and Cong Yan (corresponding author): Critical Roles of Lysosomal Acid Lipase in Myelopoiesis (2010). The American Journal of Pathology, 176:2394-2404. PMID: 20348241.

7) Lingyan Wu, Guixue Wang, Peng Qu, Cong Yan (corresponding author), and Hong Du: Overexpression of Dominant Negative Peroxisome Proliferator-Activated Receptor-? in Alveolar Type II Epithelial Cells Causes Inflammation and T Cell Suppression in the Lung (2011). The American Journal of Pathology, 178:2191-2204. PMID: 21514433.

8) Peng Qu, Cong Yan (co-corresponding author), and Hong Du: Matrix Metalloproteinase 12 Over-expression in Myeloid Lineage Cells Plays a Key Role in Modulating Myelopoiesis, Immune Suppression and Lung Tumorigenesis (2011). Blood, 117(17):4476-4489. PMID: 21378275.

9) Yuan Li, Peng Qu, Lingyan Wu, Beilin Li, Hong Du and Cong Yan (co-corresponding author): Api6/AIM/Spa/CD5L Overexpression in Alveolar Type II Epithelial Cells Induces Spontaneous Lung Adenocarcinoma (2011). Cancer Research, 71(16):5488-99, PMID: 21697282.

11) Lingyan Wu, Hong Du, Yuan Li, Peng Qu and Cong Yan (corresponding author): Signal Transducers and Activators of the Transcription 3 Promotes Myeloid-derived Suppressor Cell Expansion and Immune Suppression during Lung Tumorigenesis (2011). The American Journal of Pathology, 179(4):2131-41. PMID: 21864492.

12) Peng Qu, Cong Yan (corresponding author), Janice S. Blum, Reuben Kapur and Hong Du: Myeloid-Specific Expression of Human Lysosomal Acid Lipase Corrects Malformation and Malfunction of Myeloid-derived Suppressive Cells in lal-/- Mice (2011). The Journal of Immunology, 187(7):3854-66. PMID: 21900179.

13) Lingyan Wu, Cong Yan (co-corresponding author), Magdalena Czader, Oded Foreman, Janice S. Blum, Reuben Kapur and Hong Du: Inhibition of Peroxisome Proliferator-Activated Receptor-gamma in Myeloid Lineage Cells Induces Systemic Inflammation, Immunosuppression and Tumorigenesis (2012). Blood, 119(1):115-126. PMID:  22053106.

14) Xinchun Ding, Hong Du, Mervin C. Yoder, and Cong Yan (corresponding author): Critical Role of the mTOR Pathway in Development and Function of Myeloid-derived Suppressor Cells in lal-/- Mice (2014). The American Journal of Pathology,184(2):397-408. PMID: 24287405.

 

15) Ting Zhao, Xinchun Ding, Hong Du, and Cong Yan (co-corresponding author): Myeloid-derived Suppressor Cells Are Involved in Lysosomal Acid Lipase Deficiency-Induced Endothelial Cell Dysfunction (2014).  The Journal of Immunology, 193(4):1942-53.

 

16) Stanley Ching-Cheng Huang, Bart Everts, Yulia Ivanova, David O’Sullivan, Marcia Nascimento, Amber M. Smith, Wandy Beatty, Lastisha Love-Gregory, Wing Y. Lam, Christina M. O’Neill, Cong Yan, Hong Du, Nada A. Abumrad, Joseph F. Urban, Jr., Maxim N. Artyomov, Erika L. Pearce, and Edward J. Pearce: Cell-intrinsic lysosomal lipolysis is essential for macrophage alternative activation (2014). Nature Immunology, 15(9):846-55. PMID: 25086775.

 

17) Xinchun Ding, Wu, L., Cong Yan, (co-corresponding author), and Du, H. (2015). Establishment of lal-/- Myeloid Lineage Cell Line That Resembles Myeloid-Derived Suppressive Cells. PLoS One 10, e0121001. PMID: 25807535.

 

18) Cong Yan, Ting Zhao, Hong Du: Lysosomal Acid Lipase in Cancer – Editorial (2015). Oncoscience, 2(9):727-28.

 

19) Ting Zhao, Hong Du, Xinchun Ding, Katlin Walls, and Cong Yan (corresponding author): Activation of mTOR Pathway in Myeloid-derived Suppressor Cells Stimulates Cancer Cell Proliferation and Metastasis in lal-/- Mice (2015). Oncogene, 2015 Apr 9;34 (15):1938-48. Epub 2014 Jun 2. PMID: 24882582.  Highlighted by Immune Regulation News 6.20.

 

20) Hong Du, Ting Zhao, Xinchun Ding, Cong Yan: Hepatocyte-specific expression of human lysosome acid lipase corrects liver inflammation and tumor metastasis in lal-/- mice (2015). The American Journal of Pathology, 185(9):2379-89. PMID 26212911.

 

21) Ting Zhao, Hong Du, Janice Blum, Cong Yan: Critical Role of PPARγ in Myeloid-Derived Suppressor Cell-Stimulated Cancer Cell Proliferation and Metastasis (2016). Oncotarget, 12;7(2):1529-43.

 

22) Vinit Kumar, Pingyan Cheng, Thomas Condamine, Sridevi Mony, Lucia R. Languino, Judith C. McCaffrey, Neil Hockstein, Michael Guarino, Gregory Masters, Emily Penman, Fred Denstman, George Xu, Dario C. Altieri, Hong Du, Cong Yan, Dmitry I. Gabrilovich: CD45 phosphatase regulates the fate of myeloid cells in tumor microenvironment by inhibiting STAT3 activity (2016). Immunity, 44, 303–315.

 

23) Ting Zhao, Xinchun Ding, Hong Du, Cong Yan: Lung Epithelial Cell-Specific Expression of Human Lysosomal Acid Lipase Corrects Lung Inflammation and Tumor Metastasis in lal−/− Mice. The American Journal of Pathology, 186(8):2183-92.

 

24) Ting Zhao, Hong Du, Cong Yan: Lysosomal Acid Lipase in Mesenchymal Stem Cell Stimulation of Tumor Growth and Metastasis (2016). Oncotarget, 20;7(38):61121-61135.

 

25) Lukas Grumet, Thomas O. Eichmann, Ulrike Taschler, Kathrin A. Zierler, Christina Leopold, TarekMoustafa, Branislav Radovic, Matthias Romauch, Cong Yan, Hong Du, Guenter Haemmerle, Rudolf Zechner, Peter Fickert, Dagmar Kratky, Robert Zimmermann, and Achim Lass: Lysosomal acid lipase hydrolyzes retinyl ester and affects retinoid turnover (2016). Journal of Biological Chemistry, 19;291(34):17977-87.

 

26) Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du: Rab7 GTPase controls lipid metabolic signaling in myeloid-derived suppressor cells (2017). Oncotarget, 8(18): 30123–30137.

 

27) Hong Du, Xinchun Ding, and Cong Yan: Metabolic reprogramming of myeloid-derived suppressive cells (2017). Oncoscience. 4(3-4): 29–30.

 

28) Maidina Tuohetahuntila, Martijn R. Molenaar, Bart Spee, Jos F. Brouwers, Richard Wubbolts, Martin Houweling, Cong Yan, Hong Du, Brian C VanderVen, Arie B. Vaandrager and J. Bernd Helms: Lysosome-mediated Degradation of a Distinct Pool of Lipid Droplets during Hepatic Stellate Cell Activation (2017). Journal of Biological Chemistry. 2017 Jun 14. pii: jbc.M117.778472.

 

29) Ting Zhao, Cong Yan, Hong Du: Endothelial Rab7 GTPase in Tumor Growth and Metastasis (2017). Journal of Biological Chemistry, 24;292(47):19198-19208. PMID:28924047, PMCID:PMC5702662, doi: 10.1074/jbc.M116.773093.

30) Chih-Chun Lee, Xinchun Ding, Ting Zhao, Lingyan Wu, Susan Perkins, Hong Du, and Cong Yan: Transthyretin Stimulates Tumor Growth through Regulation of Tumor, Immune, and Endothelial Cells (2019), The Journal of Immunology, 202(3):991-1002. PMID:30567728. DOI:10.4049/jimmunol.1800736.

31)
Hung D. Nguyen, Taylor Ticer, David Bastian, Sandeepkumar Kuril, Hong Li, Hong Du, Cong Yan, Xue-Zhong Yu: Lysosomal Acid Lipase is required for Donor T Cells to Induce Graft-versus-Host Disease (2020), Cell Reports, 2020 Oct 27;33(4):108316. doi: 10.1016/j.celrep.2020.108316.

32) Xinchun Ding, Ting Zhao, Chih-Chun Lee, Cong Yan and Hong Du: Lysosomal Acid Lipase Deficiency Controls T- and B-Regulatory Cell Homeostasis in the Lymph Nodes of Mice with Human Cancer Xenotransplants (2021), The American Journal of Pathology, 191: 353-367; https://doi.org/10.1016/j.ajpath.2020.10.007).

 

Titles & Appointments

  • Professor of Pathology & Laboratory Medicine
  • Education
    1987 PhD City University of New York
    1985 MSC City University of New York
    1982 BSC Wuhan University
  • Research

    1) Interferon inducible gene regulation: I was trained at the Rockefeller University as a postdoctoral fellow with eminent Dr. Igor Tamm to study the interferon signaling pathway.  During this time, I identified and cloned several interferon inducible transcription factors, known as Stats now.  We are one of laboratories involved in early elucidation of Stats signaling pathways.  This has been my major research focus throughout my scientific career.

     

    a)  Yan, C., Sehgal, P.B. And Tamm, I.: Signal transduction pathways in the induction of 2’,5’ oligoadenylate synthetase gene expression by interferon-a/b (1989). Proc. Natl. Acad. Sci. USA 86: 2243-2247.

     

    b)  Yan, C. and Tamm, I.: Transacting factors binding to 2’,5’ oligoadenylate synthetase (2’,5’ OAS) gene regulatory regions (1990). J. Biol. Chem. 265:20188-20194.

     

    c)  Yan, C. and Tamm, I.: Molecular cloning and characterization of IFN-a/b responsive element binding factors of the murine 2’,5’ oligoadenylate synthetase ME-12 gene (1991), Proc. Natl. Acad. Sci. USA 88:144-148.

     

    d)  Yan, C. and Tamm, I.: Molecular cloning and characterization of additional IFN-a/b responsive element binding factors of the murine 2’,5’ oligoadenylate synthetase ME-12 gene (1992). Proc. Natl. Acad. Sci. USA 89:8859-8863.

     

    2) Establishment of lung cancer animal models: The lung has two major functions, gas exchange and host defense through inflammatory responses. However, exuberant inflammation can cause severe consequences and lead to carcinogenesis in the lung.  My laboratory has generated multiple animal models to study the relationship between inflammation and lung cancer.  These inflammation-induced animal models greatly accelerate the understanding of mechanisms by which inflammation induce lung cancer initiation and progression. They also facilitate identification of biomarkers for lung cancer diagnosis and prognosis. Four representative papers listed below.

     

    a) Peng Qu, Hong Du, Xi Wang and Cong Yan (corresponding author): Matrix-metalloproteinase 12 Overexpression in Lung Epithelial Cells Plays a Key Role in Emphysema to Lung Bronchioalveolar Adenocarcinoma Transition (2009). Cancer Research, 69(18):7252-61. PMID: 19706765.

     

    b) Peng Qu, Hong Du, Yuan Li and Cong Yan (co-corresponding author). Myeloid-Specific Expression of Api6/AIM/Sp{alpha} Induces Systemic Inflammation and Adenocarcinoma in the Lung (2009). The Journal of Immunology 182, 1648-1659. PMID: 19155514.

     

    c) Peng Qu, Cong Yan (co-corresponding author), and Hong Du: Matrix Metalloproteinase 12 Over-expression in Myeloid Lineage Cells Plays a Key Role in Modulating Myelopoiesis, Immune Suppression and Lung Tumorigenesis (2011). Blood, 117(17):4476-4489.

     

    d) Yuan Li, Peng Qu, Lingyan Wu, Beilin Li, Hong Du and Cong Yan (co-corresponding author): Api6/AIM/Spa/CD5L Overexpression in Alveolar Type II Epithelial Cells Induces Spontaneous Lung Adenocarcinoma (2011). Cancer Research, 71(16):5488-99, PMID: 21697282.

     

    3) Lung cancer biomarker identification: Lung cancer is one of the biggest public health challenges facing the United States and many other countries. Lung cancer is a difficult disease to detect in its early stages.  It is essential to find biomarkers for lung cancer detection. We have demonstrated that both lung epithelial cell-initiated regional inflammation and myeloid cell-initiated systemic inflammation induce spontaneous lung adenocarcinoma in multiple lung tumor mouse models, indicating that inflammation is a major contributing factor to induce lung tumor formation.  We generated the first Stat3 spontaneous lung tumor model (CCSP-rtTA/(tetO)7Stat3C), which showed that Stat3 plays a critical role in inflammation-induced lung adenocarcinoma. This was further supported by our human studies, in which the Stat3 expression level was up-regulated in human lung cancers.  Affymetrix GeneChip microarray analysis in the preclinical Stat3C mouse lung tumor model successfully identified multiple Stat3 downstream secretory proteins as biomarkers in the human sera.  If these biomarkers are used in combination with low-dose computed tomography (LDCT), the false-positive rate will be significantly dropped.

    a)   Yuan Li, Hong Du, Yulin Qin, Jennifer Roberts, Oscar W. Cummings and Cong Yan (corresponding author): Activation of the Stat3 Pathway in Alveolar Epithelial Cells Induces Inflammation and Adenocarcinomas in Mouse Lung (2007). Cancer Research, 67(18):8494-8503. PMID: 17875688.

    b)   Peng Qu, Jennifer Roberts, Yuan Li, Marjorie Albrecht, Oscar W. Cummings,John N. Eble, Hong Du and Cong Yan (corresponding author): Stat3 Downstream Genes Serve as Biomarkers in Human Lung Carcinomas and Chronic Obstructive Pulmonary Disease (2009). Lung Cancer, 63(3):341-7. PMID: 18614255.

    c) Lingyan Wu, Hong Du, Yuan Li, Peng Qu and Cong Yan (corresponding author): Signal Transducers and Activators of the Transcription 3 Promotes Myeloid-derived Suppressor Cell Expansion and Immune Suppression during Lung Tumorigenesis (2011). The American Journal of Pathology, 179(4):2131-41. PMID: 21864492.

    d) Cong Yan (corresponding author), Xinchun Ding, Lingyan Wu, Menggang Yu, Peng Qu, and Hong Du: Stat3 Downstream Gene Product Chitinase 3-Like 1 Is a Potential Biomarker of Inflammation-induced Lung Cancer in Multiple Mouse Lung Tumor Models and Humans (2013). PlosOne, 22;8(4):e61984. PMID:23613996.

    e) Chih-Chun Lee, Xinchun Ding, Ting Zhao, Lingyan Wu, Susan Perkins, Hong Du, and Cong Yan (corresponding author): Transthyretin Stimulates Tumor Growth through Regulation of Tumor, Immune, and Endothelial Cells (2019), The Journal of Immunology, 202(3):991-1002. PMID:30567728.

    4) Functional roles of myeloid-suppressive cells in tumor immunology:  Myeloid-derived suppressive cells (MDSCs) are actively involved in regulating inflammation-induced tumorigenesis.  We have demonstrated that MDSCs possess dual functions to facilitate cancer growth and invasion: i) suppress immune surveillance, and ii) directly stimulate cancer cell proliferation, progression and invasion.  We also identified that MDSCs expansion is arisen from abnormally increased primitive LSK, CMP, and GMP populations that skew toward CD11b+Ly6G+  MDSCs expansion in the bone marrow, peripheral blood, spleen and other distal organs. MDSCs trafficking and function are regulated by endothelial cells.  Our studies have identified that lysosomal acid lipase, PPARg, Stat3 and mTOR are critical signaling molecules controlling MDSCs pathogenesis and homeostasis.

    a) Cong Yan, Xinchun Ding, Nupur Dasgupta, Lingyan Wu, and Hong Du: Gene Profile of Myeloid-derived Suppressive Cells from the Bone Marrow of Lysosomal Acid Lipase Knock-out Mice (2012). PlosOne, 7(2):e30701.  PMID: 22383970.

    b) Lingyan Wu, Cong Yan (co-corresponding author), Magdalena Czader, Oded Foreman, Janice S. Blum, Reuben Kapur and Hong Du: Inhibition of Peroxisome Proliferator-Activated Receptor-g in Myeloid Lineage Cells Induces Systemic Inflammation, Immunosuppression and Tumorigenesis (2012). Blood, 119(1):115-126. PMID:  22053106.

    c) Xinchun Ding, Hong Du, Mervin C. Yoder, and Cong Yan (co-corresponding author): Critical Role of the mTOR Pathway in Development and Function of Myeloid-derived Suppressor Cells in lal-/- Mice (2014). The American Journal of Pathology, 184(2):397-408. PMID: 24287405.

    d) Ting Zhao, Xinchun Ding, Hong Du, and Cong Yan (co-corresponding author): Myeloid-derived Suppressor Cells Are Involved in Lysosomal Acid Lipase Deficiency-Induced Endothelial Cell Dysfunction (2014).  The Journal of Immunology, 193(4):1942-53. PMID: 25000979.

    e)  Ting Zhao, Hong Du, Xinchun Ding, Katlin Walls, and Cong Yan (co-corresponding author) (2015): Activation of mTOR Pathway in Myeloid-derived Suppressor Cells Stimulates Cancer Cell Proliferation and Metastasis in lal-/- Mice (2015). Oncogene, 34 (15):1938-48. PMID: 24882582.  Highlighted by Immune Regulation News 6.20.


    5) T cell development and function:  We have done pioneer works to investigate development, differentiation, and functions of lysosomal acid lipase (LAL) in lymphocytes. LAL deficiency impairs T-cell development in the thymus at the DN3 (CD44CD25+) to DN4 (CD44CD25-) transition, reduces the peripheral T-cell populations (spleen, lung, liver etc.), and increases the ratio of CD4+CD25+FoxP3+ Tregs to CD4+ T cells through various molecular and cellular mechanisms. LAL is required for donor T cells to induce graft-versus-host disease. Human cancer xenotransplants are able to grow in lal-/- mice due to increased Tregs- and B-regs in the lymph nodes. LAL is also involved in the interplay between endothelial cells and T cells.

    a) Peng Qu, Hong Du, Yuan Li, David S. Wilkes, and Cong Yan (co-corresponding author): Critical Roles of Lysosomal Acid Lipase in T Cell Development and Function (2009). The American Journal of Pathology, 174:944-956. PMID: 19179613.

    b) Ting Zhao, Xinchun Ding, Hong Du, and Cong Yan (co-corresponding author): Myeloid-derived Suppressor Cells Are Involved in Lysosomal Acid Lipase Deficiency-Induced Endothelial Cell Dysfunction (2014).  The Journal of Immunology, 193(4):1942-53.

    c) Hung D. Nguyen, Taylor Ticer, David Bastian, Sandeepkumar Kuril, Hong Li, Hong Du, Cong Yan, Xue-Zhong Yu: Lysosomal Acid Lipase is required for Donor T Cells to Induce Graft-versus-Host Disease (2020), Cell Reports, 27;33(4):108316. doi: 10.1016/j.celrep.2020.108316.

    d) Xinchun Ding, Ting Zhao, Chih-Chun Lee, Cong Yan (co-corresponding author) and Hong Du: Lysosomal Acid Lipase Deficiency Controls T- and B-Regulatory Cell Homeostasis in the Lymph Nodes of Mice with Human Cancer Xenotransplants (2020 Nov 4), The American Journal of Pathology, doi.org/10.1016/j.ajpath.2020.10.007.

    6) Lung biology:  I have been working on various lung projects.  In addition to lung inflammation, my laboratory has made contributions to lung development, surfactant protein gene expression, emphysema/chronic obstructive pulmonary disease (COPD), oxygen injury, stem cells to lung epithelial cell trans-differentiation, etc.  

    a) Cong Yan (corresponding author), Angela Naltner, Michelle Martin, Michael Naltner, Jessica M. Fangman and Oky Gurel: Transcriptional Stimulation of the Surfactant Protein B Gene by STAT3 in Respiratory Epithelial Cells (2002). J. Biol. Chem. 277(13): 10967-10972.

    b) Li Yang, Xuemei Lian, Angelynn Cowen, Huan Xu, Hong Du and Cong Yan (corresponding author): Synergy between STAT3 and RARa in Regulation of the Surfactant Protein B Gene in the Lung (2004). Mol Endocrinol, 18(6):1520-32.

    c) Xuemei Lian, Yulin Qin, Shaikh Abu Hossain, Li Yang, Amanda Clarke, Huan Xu, J. Michael Shipley, Tingyu Li, Robert M. Senior, Hong Du and Cong Yan (corresponding author): Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury (2005). The Journal of Immunology, 174(11):7250-7256.

    d) Cong Yan (corresponding author), Peng Qu, and Hong Du: Myeloid-Specific Expression of Stat3C Results in Conversion of Bone Marrow Stem Cells into Alveolar Type II Epithelial Cells in the Lung (2012).  Science China Life Sciences. 55(7):576-590. PMID: 22864832.

     

  • Professional Organizations
    Member of American Association for Cancer Research
    Member of American Chemical Society
    Member of American Society for Biochemistry and Molecular Biology
    Member of American Thoracic Society
    Member of International Society for Interferon Research
    Member of the American Society for Cell Biology
  • Awards
    Org: City University of New York
    Desc: Graduate Student Award
    Scope: University
    Date:
    Org: University of Cincinnati, Research Council
    Desc: Research Award
    Scope: University
    Date:
    Org: American Lung Association
    Desc: American Lung Association Research Award
    Scope: National
    Date:

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