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Division of Gynecologic Pathology


Email rkurman@jhmi.edu
Phone (410) 955-0471

Related Websites
Division of Gynecologic Pathology


Robert J. Kurman, M.D.

Director, Division of Gynecologic Pathology
Primary Appointment in Gynecology and Obstetrics; Secondary Appointment in Pathology


Our studies are aimed at elucidating the pathogenesis of a variety of neoplasms in the female genital tract; we are particularly interested in the morphologic and genetic alterations associated with the early events in carcinogenesis. We have proposed a dualistic model for the pathogenesis of endometrial cancer with distinctive precursor lesions and genetic alterations. Correlated morphologic and molecular studies are being conducted to determine whether or not this hypothesis is valid. In addition, the behavior and relationship of borderline tumors (low malignant potential tumors) of the ovary to invasive carcinoma are being investigated. Finally, the role of papillomaviruses in the development of cervical and vulvar carcinomas continues to be an area of interest.

Publications
Silverberg SG, Kurman RJ. Atlas of Tumor Pathology. Tumors of the Uterine Corpus and Gestational Trophoblastic Disease, Third Series, Fascicle 3, Armed Forces Institute of Pathology, Washington, D.C., 1992.

Kurman RJ, Norris HJ, Wilkinson E. Atlas of Tumor Pathology. Tumors of the Cervix, Vagina and Vulva, Third Series, Fascicle 4, Armed Forces Institute of Pathology, Washington, D.C., 1992.

Mazur MT, Kurman RJ. Diagnosis of Endometrial Biopsies and Curettings. Apractical Approach, Springer-Verlag, New York, 1995.

Kurman RJ (ed): Blaustein's Pathology of The Female Genital Tract. 5thed., Springer-Verlag, New York, 2002.




Email chung2@jhmi.edu
Phone (410) 614-4906
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Chien-Fu Hung, Ph.D.

Primary Appointment in Pathology


Cervical cancer and ovarian cancer represent two major issues in women’s health. Cervical cancer is the second most deadly form of cancer in women worldwide, while ovarian cancer is the most deadly gynecologic malignancy. My research centers primarily on developing immmunotherapeutic vaccination strategies for the prevention and treatment of cervical and ovarian cancers. Our lab has developed several strategies to enhance immunologic responses against cancers. Some of these strategies involve targeting an antigen into dendritic cells, targeting an antigen into MHC class I and II processing pathways, enhancing intercellular spreading of antigen, and combining antigen-specific immunotherapy and antiangiogenesis.

Recently, we have been focusing on developing innovative immunotherapeutic strategies against ovarian cancer. The efficacy of immunotherapies and vaccines against ovarian cancer are often compromised by pre-existing immune tolerance against endogenous antigens. To this end, we have been developing therapeutic agents that are capable of coating foreign antigenic peptides onto ovarian tumor cells, which render the tumor cells susceptible to killing by foreign antigen-specific CD8+ T cells. Our novel technologies have important implications in circumventing immune tolerance to enhance cancer immunotherapies.

Publications

Chang, C. L., Hsu, Y. T., Wu, C. C., Yang, Y. C., Wang, C., Wu, T. C., and Hung, C. F. (2012) Immune mechanism of the antitumor effects generated by bortezomib. J Immunol 189, 3209-3220.

Chang, C. L., Hsu, Y. T., Wu, C. C., Lai, Y. Z., Wang, C., Yang, Y. C., Wu, T. C., and Hung, C. F. (2013) Dose-dense chemotherapy improves mechanisms of antitumor immune response. Cancer Res 73, 119-127.

Kang, T. H., Ma, B., Wang, C., Wu, T. C., and Hung, C. F. (2013) Targeted coating with antigenic peptide renders tumor cells susceptible to CD8(+) T cell-mediated killing. Mol Ther 21, 542-553.

Soong, R. S., Song, L., Trieu, J., Knoff, J., He, L., Tsai, Y. C., Huh, W., Chang, Y. N., Cheng, W. F., Roden, R. B., Wu, T. C., Trimble, C. L., and Hung, C. F. (2014) Toll-like receptor agonist imiquimod facilitates antigen-specific CD8+ T-cell accumulation in the genital tract leading to tumor control through IFNgamma. Clin Cancer Res 20, 5456-5467.

Lee, S. J., Song, L., Yang, M. C., Mao, C. P., Yang, B., Yang, A., Jeang, J., Peng, S., Wu, T. C., and Hung, C. F. (2015) Local administration of granulocyte macrophage colony-stimulating factor induces local accumulation of dendritic cells and antigen-specific CD8+ T cells and enhances dendritic cell cross-presentation. Vaccine 33, 1549-1555.




Email roden@jhmi.edu
Phone (410) 502-5161

Related Websites
Ovarian Cancer

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Richard B.S. Roden, Ph.D.

Primary Appointment in Pathology; Secondary Appointments in Gynecology and Obstetrics, and Oncology
Member, Graduate Program in Pathobiology


The oncogenic genotypes of human papillomavirus (HPV), typified by HPV16, are the primary etiologic agent of cervical cancer. Papillomavirus has only two capsid (late) proteins, L1 and L2. Both capsid proteins represent targets for prophylactic intervention, but not therapy of established infections. Our primary research goal is to prevent cervical cancer through the development of an L2-based preventative vaccine that is active against all oncogenic types of HPV and combining this with a therapeutic component targeting early viral antigens to treat existing infection.

Little is known about the pathogenesis of ovarian cancer and there is currently no screening test for its detection while still confined to the ovary. Our goal is to identify novel tumor antigens of significance in the biology of ovarian cancer and applicable as biomarkers for early detection or targets for immunotherapy.

Publications

Click here for the full list of Dr. Roden's publications.



Email bronnett@jhmi.edu
Phone (410) 614-2971

Related Websites
Gynecologic Pathology Consultation

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Brigitte M. Ronnett, M.D.

Primary Appointment in Pathology; Secondary Appointment in Gynecology and Obstetrics


Brigitte M. Ronnett, M.D. is Professor of Pathology and Gynecology & Obstetrics at The Johns Hopkins Hospital, Baltimore, MD. Dr. Ronnett graduated from Northwestern University, Evanston, IL (B.A. chemistry, 1982). She received her medical degree from the University of Chicago Pritzker School of Medicine, Chicago, IL (M.D., 1986). She completed residency training in anatomic and clinical pathology at The Johns Hopkins Hospital, Baltimore, MD, (anatomic: 7/1986-6/1989; clinical: 7/1991-6/1993). She also completed a 1-year surgical pathology fellowship at Memorial Sloan-Kettering Cancer Center, New York, NY (7/1989-6/1990) and a 1-year surgical pathology fellowship/chief residency at The Johns Hopkins Hospital, Baltimore, MD (7/1990-6/1991). She then completed a 2-year subspecialty fellowship in gynecologic pathology at The Johns Hopkins Hospital, Baltimore, MD (7/1993-6/1995). She joined the faculty of the Department of Pathology at The Johns Hopkins Hospital in 1995 and achieved the rank of Full Professor in 2007. Her clinical efforts are focused on a large gynecologic pathology consultation practice at The Johns Hopkins Hospital. Her research efforts have focused on the following topics:
1. ovarian mucinous tumors (distinction of primary and metastatic mucinous tumors in the ovaries, the origin of pseudomyxoma peritonei in women),
2. uterine cervical and endometrial pathology (HPV-related cervical lesions, ancillary techniques for distinction of endocervical and endometrial adenocarcinomas and subtyping of endometrial adenocarcinomas), and
3. hydatidiform moles (ancillary techniques for refined diagnosis).

Publications

Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis: a clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to pseudomyxoma peritonei. Am J Surg Pathol 1995;19(12):1390-1408.

Ronnett BM, Kajdacsy-Balla A, Gilks CB, Merino MJ, Silva E, Werness BA, Young RH. Mucinous borderline ovarian tumors: points of general agreement and persistent controversies regarding nomenclature, diagnostic criteria, and behavior. Hum Pathol 2004;35(8):949-960.

Vang R, Ronnett BM. Distinction of primary ovarian mucinous tumors and mucinous tumors metastatic to the ovary: a practical approach with guidelines for prediction of primary site for metastases of uncertain origin. Pathol Case Rev 2006;11(1):18-30.

Ronnett BM, Yemelyanova AV, Vang R, Gilks CB, Miller D, Gravitt PE, Kurman RJ. Endocervical adenocarcinomas with ovarian metastases: analysis of 29 cases, with emphasis on minimally invasive cervical tumors and the ability of the metastases to simulate primary ovarian neoplasms. Am J Surg Pathol 2008;32(12):1835-1853.

Ronnett BM, DeScipio C, Murphy KM. Hydatidiform moles: ancillary techniques to refine diagnosis. Int J Gynecol Pathol 2011;30(2):101-116.

Darragh TM, Colgan TJ, J. Cox T, Heller DS, Henry MR, Luff RD, McCalmont T, Nayar R, Palefsky JM, Stoler MH, Wilkinson EJ, Zaino RJ, Wilbur DC and members of the LAST Project Work Groups. The lower anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med 2012;136(10):1266-1297; J Low Genit Tract Dis 2012;16(3):205-242; Int J Gynecol Pathol 2013;32(1):76-115. (Ronnett BM, member of the LAST Project Work Groups)

Banet N, DeScipio C, Murphy KM, Beierl K, Adams E, Vang R, Ronnett BM. Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping. Mod Pathol 2014;27(2):238-254.




Email ishih@jhmi.edu
Phone (410) 502-7774

Related Websites
Lab Research Website

Richard TeLinde Distinguished Professorship of Gynecologic Pathology

GYN/OB Research Website

Ovarian Cancer Prevention

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Ie-Ming Shih, M.D., Ph.D.

Primary Appointment in Pathology;
Secondary Appointment in Pathology;
Member, Gradutate Program in Pathobiology


Dr. Ie-Ming Shih is the Richard TeLinde Distinguished Professor of Gynecologic Pathology at the Johns Hopkins University School of Medicine. Dr. Shih directs the Molecular Genetics Laboratory of Female Reproductive Cancer in the Department of Pathology and co-directs the Breast and Ovarian Cancer Program at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Institutions. Dr. Shih received his M.D. from Taipei Medical University and earned his Ph.D. in pathology from the University of Pennsylvania. Dr. Shih went on to do a clinical fellowship in gynecologic pathology and a research fellowship in cancer genetics at Johns Hopkins before joining the faculty in 2001.

Dr. Shih’s research focuses on molecular and translational studies on various gynecological neoplasms, especially ovarian cancer. His research team helps to elucidate the genomic landscape in ovarian clear cell carcinoma, ovarian low-grade serous carcinoma and uterine serous carcinoma. Dr. Shih has published extensive basic and translational research on gynecologic pathology and oncology, with more than 300 original publications and book chapters. Dr. Shih’s research team has contributed to the discovery and functional characterization of cancer-associated genes and the pathways they control, including ARID1A and Syk in ovarian cancer. Based on molecular genetic analysis in ovarian cancer, his team is exploring new molecular targets and pathways for experimental therapeutics and is initiating new clinical trials based on new findings.

Dr. Shih sits on several advisory boards, such as the NCI Ovarian Task Force of Gynecologic Cancer Steering Committee (for clinical trials on gynecologic cancer), the Ovarian Cancer Research Foundation, and the International Society of Gynecologic Pathology/World Health Organization (WHO) Nomenclature Committee for Gynecologic Neoplasms. In addition to his clinical, research and teaching obligations, Dr. Shih is a passionate photographer (www.shih-photography.com).

Publications

Yu Y, Gaillard S, Jude MP, Huang TC, Pinto SM, Tessarollo NG, Zhang Z, Pandey A, Wirtz D, Ayhan A, Davidson B, Wang TL, Shih IM. Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules. Cancer Cell, 28:82-96, 2015. PMID: 26096845

Guan B, Suryo Rahmanto Y, Wu RC, Wang Y, Wang Z, Wang TL, Shih IeM. Roles of deletion of arid1a, a tumor suppressor, in mouse ovarian tumorigenesis. J Natl Cancer Inst. 2014;106(7). PMID: 24899687

Gao M, Uw RC, Herlinger AL, Yap K, Kim JW, Wang TL, Shih IM. Identification of NAC1-regulated genes in ovarian cancer. Am J Pathol, 184:133-140, 2014. PMID:24200849

Ardighieri L, Zeppernick F, Hannibal CG, Vang R, Cope L, Junge J, Kjaer SK, Kurman RJ, Shih IM. Mutational analysis of BRAF and KRAS in ovarian atypical proliferative serous (borderline) tumors and associated peritoneal implants. J Pathol, 232:16-22, 2014. PMID:24307542

Zeppernick F. Ardigheri L, Hannibal CG, Vang R, Junge J, Kjaer SK, Zhang R, Kurman RJ, Shih IM. BRAF mutation is associated with a specific cell-type with features suggestive of senescence in ovarian serous borderline tumors. Am J Surg Pathol, 38:1603-1611, 2014. PMID: 25188864




Email rvang1@jhmi.edu
Phone (410) 502-0532

Related Websites
NCI Ovarian Borderline Tumor Workshop Web Atlas

Division of GYN Pathology

Division of Gynecologic Oncology

More information on Dr. Vang

Additional Publications

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Russell S. Vang, M.D.

Primary Appointment in Pathology; Secondary Appointment in Gynecology & Obstetrics


My research interests have involved clinicopathologic and immunohistochemical studies of epithelial and non-epithelial tumors of the ovary and fallopian tube, including metastatic mucinous tumors in the ovary, ovarian sex cord-stromal tumors, and serous tubal intraepithelial carcinoma (STIC). Currently, I am in the process of investigating serous borderline tumors of the ovary (atypical proliferative serous tumor and non-invasive low-grade serous carcinoma) using a large population-based cohort from Denmark. Multiple studies from this project will focus to clinicopathologic and molecular aspects of these tumors, including long-term behavior of the subtypes of serous borderline tumor, criteria for implants, potential application of mutational analysis of KRAS/BRAF for determining prognosis, and molecular comparison of serous borderline tumors and their subsequent serous carcinomas.

Publications
VandenBussche CJ, Ali SZ, Rosenthal DL, Vang R. Atlas of Gynecologic Cytopathology with Histopathologic Correlations. New York, NY: Demos Medical Publishing. (In Press)

Vang R, Levine DA, Soslow RA, Zaloudek C, Shih IM, Kurman RJ. Molecular alterations of TP53 are a defining feature of ovarian high-grade serous carcinoma: a re-review of cases lacking TP53 mutations in The Cancer Genome Atlas Ovarian study. Int J Gynecol Pathol (In Press)

Banet N, Gown AM, Shih IeM, Kay Li Q, Roden RB, Nucci MR, Cheng L, Przybycin CG, Nasseri-Nik N, Wu LS, Netto GJ, Ronnett BM, Vang R. GATA-3 expression in trophoblastic tissues: an immunohistochemical study of 445 cases, including diagnostic utility. Am J Surg Pathol 2015;39:101-8.

Vang R, Cheung ANY, Kommoss F, Matias-Guiu X, Ronnett BM, Young RH. Tumours of the ovary: Secondary tumours. In: Kurman RJ, Carcangiu ML, Herrington CS, Young RH, eds. WHO Classification of Tumours of Female Reproductive Organs, 4th Edition. Lyon, France: IARC Press, 2014:83-86.

Vang R, Shih IM, Kurman RJ. Fallopian tube precursors of ovarian low- and high-grade serous neoplasms. Histopathology 2013;62:44-58.




Email tlw@jhmi.edu
Phone (410) 502-0863

Related Websites
Lab Research Website

Ovarian Cancer Prevention

Sidney Kimmel Ovarian Cancer Center

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Tian-Li Wang, Ph.D.


Dr. Tian-Li Wang is a Professor in the Departments of Pathology, Oncology, and Gynecology & Obstetrics at the Johns Hopkins School of Medicine. She is also a faculty member of the Pathobiology Graduate Program. Dr. Wang co-directs the Biorepository Bank of Gynecologic Malignancies and co-leads the Molecular Genetics Laboratory of Female Reproductive Cancer at Johns Hopkins.

Dr. Wang earned her undergraduate degree at National Taiwan University. She completed a Ph.D. at the Johns Hopkins University School of Medicine. Then in 2004, she joined the faculty at the Johns Hopkins Departments of Gynecology/Obstetrics and Oncology and established her research team. She went on to join the Department of Pathology in 2014.

Dr. Wang's research interest is to elucidate the molecular pathogenesis of gynecologic malignancies, with a special focus on tumor recurrence, tumor evolution and the development of preventive and therapeutic strategies. She has applied functional genomic and proteomic technologies to identify genetic and protein markers in ovarian and uterine carcinomas. The novel cancer-associated genes identified by her team include NOTCH3, SYK, ARID1A, PPP2R1A, and PBX1. Her research is supported by several NCI/NIH and DoD grants, as well as private foundations, including the Ovarian Cancer Research Fund. Dr. Wang is also an investigator in the DoD-sponsored Ovarian Cancer Consortium, which aims at identifying and characterizing early molecular alterations in the genesis of ovarian cancer.

Publications

Stoeck A, Jung J, Guan B, Wu R-C, Zhu H, Blackshaw S, Shih Ie, Wang TL. Notch3 interactome analysis identified WWP2 as a negative regulator of Notch3 signaling in ovarian cancer. Plos Genetics . Oct 30;10(10):e1004751. PMID: 25356737

Yusuke Kobayashi, Hiroyasu Kashima, Ren-Chin Wu, Jin- Gyoung Jung, Jen-Chun Kuan, Jinghua Gu, Jianhua Xuan, Lori Sokoll, Kala Visvanathan, Ie-Ming Shih, Wang TL. Mevalonate Pathway Antagonist Inhibits Proliferation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models. Clinical Cancer Research, 2015 Jun 24 PMID: 26109099 [Epub ahead of print]. PMID: 26109099

Wu RC, Ayhan A, Maeda D, Kim KR, Clarke BA, Shaw P, Herman Chui M, Rosen B, Shih IM, Wang TL. Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynecologic malignancies. J Pathol. 2014 Mar; 232(4):473-81. PMID: 24338723

Yuyu Fun, et al, Wang TL* and Shih IeM. Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules. Cancer Cell, Jul 13;28(1):82-96. PMID: 26096845 *Corresponding author

Guan B, Suryo Rahmanto Y, Wu RC, Wang Y, Wang Z, Wang TL, Shih IeM. Roles of deletion of arid1a, a tumor suppressor, in mouse ovarian tumorigenesis. J Natl Cancer Inst. 2014 Jun 4;106(7). PMID: 24899687 * Co-corresponding author




Email tcwu@jhmi.edu
Phone (410) 614-3899

Related Websites
Cervical Cancer Research Lab

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Tzyy Choou (T-C) Wu, M.D., Ph.D.

Primary Appointment in Pathology; Secondary Appointments in Oncology, Obstetrics and Gynecology; Joint Appointment in Molecular Microbiology and Immunology (BSPH)
Member, Graduate Program in Immunology; Member, Graduate Program in Pathobiology; Member, Graduate Program in Molecular Microbiology and Immunology (BSPH)


Each year, approximately 500,000 women worldwide develop cervical cancer and 200,000 women die from this cancer. We are currently developing vaccines and immunotherapeutic strategies for human papillomavirus (HPV)-related cervicalcancer and are running a molecular diagnostic lab for the diagnosis of HPVinfection.

My research focus has been in the area of human papillomavirus (HPV) vaccine development. I have created a unique preclinical murine tumor model that expresses HPV-16 oncogenic proteins, E6 and E7, and simulates specific molecular events in the progression of HPV+ precancerous lesions(CIN 3) to invasive cancer. This preclinical tumor model has been widely used and tested by researchers worldwide for HPV vaccine development. I have focused on identifying vaccine and immunotherapeutic approaches to enhance antigen processing and presentation by dendritic cells, including intracellular targeting and intercellular spreading strategies, for the purpose of prevention and treatment of cervical lesions and cancers. Intracellular targeting directs antigen to different subcellular locations to enhance antigen processing and presentation. Meanwhile, intercellularspreading facilitates the distribution of antigen to neighboring cells by taking advantage of unique intercellular transport properties, allowing for an increase in the amount of antigen presented to effector cells. Recently, I have created an innovative approach that combines both antigen-specific immunotherapy and anti-angiogenesis to treat HPV E7-expressing tumors. The continued development of these strategies will facilitate the development of vaccines that generate a potent immune response and antitumor effect against cervical cancer. I am also actively involved with investigating mechanisms of immune evasion of tumors, identifying new tumor-specific antigens, and applying vaccine strategies to other cancer systems with tumor-specific antigens.

Publications

Lee SY, Kang TH, Knoff J, Huang Z, Soong RS, Alvarez RD, Hung CF, Wu TC. Intratumoral injection of therapeutic HPV vaccinia vaccine following cisplatin enhances HPV-specific antitumor effects. Cancer Immunol Immunother. 2013 Jul;62(7):1175-85. doi: 10.1007/s00262-013-1421-y. Epub 2013 Apr 25. PubMed PMID: 23615841; PubMed Central PMCID: PMC3690484.

Kang TH, Mao CP, Lee SY, Chen A, Lee JH, Kim TW, Alvarez RD, Roden RB, Pardoll D, Hung CF, Wu TC. Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity. Cancer Res. 2013 Apr 15;73(8):2493-504. doi: 10.1158/0008-5472.CAN-12-4241. Epub 2013 Feb 15. PubMed PMID: 23418322; PubMed Central PMCID: PMC3630272.

Lee SY, Huang Z, Kang TH, Soong RS, Knoff J, Axenfeld E, Wang C, Alvarez RD, Chen CS, Hung CF, Wu TC. Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination. J Mol Med (Berl). 2013 Oct;91(10):1221-31. doi: 10.1007/s00109-013-1054-9. Epub 2013 May 29. PubMed PMID: 23715898; PubMed Central PMCID: PMC3783646.

Sun Y, Peng S, Qiu J, Miao J, Yang B, Jeang J, Hung CF, Wu TC. Intravaginal HPV DNA vaccination with electroporation induces local CD8+ T-cell immune responses and antitumor effects against cervicovaginal tumors. Gene Ther. 2015 Jul;22(7):528-35. doi: 10.1038/gt.2015.17. Epub 2015 Mar 19. PubMed PMID: 25786869; PubMed Central PMCID: PMC4490060.

Wu CY, Yang LH, Yang HY, Knoff J, Peng S, Lin YH, Wang C, Alvarez RD, Pai SI, Roden RB, Hung CF, Wu TC. Enhanced cancer radiotherapy through immunosuppressive stromal cell destruction in tumors. Clin Cancer Res. 2014 Feb 1;20(3):644-57. doi: 10.1158/1078-0432.CCR-13-1334. Epub 2013 Dec 3. PubMed PMID: 24300786; PubMed Central PMCID: PMC3946442.



 


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