Cancer Research and Treatment

Original Articles

Hematologic malignancy

Clinical Impact of Microbiome Characteristics in Treatment-Naïve Extranodal NK/T-Cell Lymphoma Patients: Sang Eun Yoon, Woorim Kang, Junhun Cho, Mauricio Chalita, Je Hee Lee, Dong-Wook Hyun, Hyun Kim, Seok Jin Kim, Won Seog Kim; Cancer Res Treat. 2025;57(2):597-611. Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.675

Abstract PDF Supplementary Material PubReader ePub: Purpose
Extranodal natural killer/T-cell lymphoma (ENKTL) predominantly manifests in East Asia and Latin America. Despite shared intrinsic factors, such as ethnic and genetic backgrounds, the progression of ENKTL can be influenced by extrinsic factors related to changing lifestyle patterns.
Materials and Methods
This study collected stool samples from newly diagnosed (ND)–ENKTL patients (n=40) and conducted whole genome shotgun sequencing.
Results
ND-ENKTL revealed reduced alpha diversity in ND-ENKTL compared to healthy controls (HCs) (p=0.008), with Enterobacteriaceae abundance significantly contributing to the beta diversity difference between ENKTL and HCs (p < 0.001). Functional analysis indicated upregulated aerobic metabolism and degradation of aromatic compounds in ND-ENKTL. Enterobacteriaceae were associated not only with clinical data explaining disease status (serum C-reactive protein, stage, prognosis index of natural killer cell lymphoma [PINK], and PINK-E) but also with clinical outcomes (early relapse and short progression-free survival). The relative abundance of Enterobacteriaceae at the family level was similar between ENKTL and diffuse large B-cell lymphoma (DLBCL) (p=0.140). However, the ENKTL exhibited a higher abundance of Escherichia, in contrast to the prevalence of Enterobacter and Citrobacter in DLBCL. Linear regression analysis demonstrated a significant association between Escherichia abundance and programmed cell death-ligand-1 (PD-L1) levels in tissue samples (p=0.025), whereas no correlation with PD-L1 was observed for Enterobacteriaceae at the family level (p=0.571).
Conclusion
ND-ENKTL exhibited an abundance of Enterobacteriaceae and a dominant presence of Escherichia. These microbial characteristics correlated with disease status, treatment outcomes, and PD-L1 expression, suggesting the potential of the ENKTL microbiome as a biomarker and cause of lymphomagenesis, which warrants further exploration.

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Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma: Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2024;56(3):920-935. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.869

Abstract PDF Supplementary Material PubReader ePub

Purpose
The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear.
Materials and Methods
We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes.
Results
Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression.
Conclusion
Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.

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Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review
Marie Hairing Enemark, Jonas Klejs Hemmingsen, Maja Lund Jensen, Robert Kridel, Maja Ludvigsen
International Journal of Molecular Sciences.2024; 25(20): 11179. CrossRef

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Case Report

Case Report of Erdheim-Chester Disease Successfully Treated with Pegylated Interferon: A Single-Center Experience: Yujin Lim, Sang Eun Yoon, Junhun Cho, Darae Kim, Chul Won Jung; Cancer Res Treat. 2023;55(3):1053-1057. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.1535

Abstract PDF PubReader ePub

Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.

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An Autopsied Case of Erdheim-Chester Disease with Severe Cardiovascular Involvement
Atsushi Matsunashi, Wang Zhipeng, Akihiko Sugimoto, Masakazu Fujimoto, Akihiko Yoshizawa, Ryo Sakamoto, Michihiro Uyama, Kohei Ikezoe, Kiminobu Tanizawa, Tomohiro Handa, Toyohiro Hirai
Internal Medicine.2025;[Epub] CrossRef
Recent advances in therapeutic strategies of Erdheim-Chester disease
Rohit Doke, Rahul Lokhande, Kalyani Chande, Kuldeep Vinchurkar, Bhupendra G. Prajapati
Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub] CrossRef
Erdheim–Chester disease: Comprehensive insights from genetic mutations to clinical manifestations and therapeutic advances
Rishabh Chaudhary, Anand Kumar, Alpana Singh, Vipul Agarwal, Mujeeba Rehman, Arjun Singh Kaushik, Siddhi Srivastava, Sukriti Srivastava, Vikas Mishra
Disease-a-Month.2025; 71(2): 101845. CrossRef
Advances in Understanding and Management of Erdheim-Chester Disease
Aniruddha Murahar Kulkarni, Prasanna Kumar Reddy Gayam, Jesil Mathew Aranjani
Life Sciences.2024; 348: 122692. CrossRef

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Original Articles

Hematologic malignancy

Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas: Seok Jin Kim, Yeon Jeong Kim, Sang Eun Yoon, Kyung Ju Ryu, Bon Park, Donghyun Park, Duck Cho, Hyun-Young Kim, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Won Seog Kim; Cancer Res Treat. 2023;55(1):291-303. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2022.017

Abstract PDF Supplementary Material PubReader ePub

Purpose
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

Citations

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Clinical use of circulating tumor DNA analysis in patients with lymphoma
Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
Human Pathology.2025; 156: 105679. CrossRef
Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
Molecular Cancer.2024;[Epub] CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Minimal residual disease detection in lymphoma: methods, procedures and clinical significance
Sijun Zhang, Xiangyu Wang, Zhenzhen Yang, Mengjie Ding, Mingzhi Zhang, Ken H. Young, Xudong Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas
Laurence de Leval, Philippe Gaulard, Ahmet Dogan
Blood.2024; 144(18): 1855. CrossRef
In-depth circulating tumor DNA sequencing for prognostication and monitoring in natural killer/T-cell lymphomas
Jin Ju Kim, Hyun-Young Kim, Zisun Choi, So yoon Hwang, Hansol Jeong, Jong Rak Choi, Sang Eun Yoon, Won Seog Kim, Sun-Hee Kim, Hee-Jin Kim, Sang-Yong Shin, Seung-Tae Lee, Seok Jin Kim
Frontiers in Oncology.2023;[Epub] CrossRef
Circulating tumor DNA in NK/T and peripheral T cell lymphoma
Yu-Jia Huo, Wei-Li Zhao
Seminars in Hematology.2023; 60(3): 173. CrossRef
A genetic profiling guideline to support diagnosis and clinical management of lymphomas
Margarita Sánchez-Beato, Miriam Méndez, María Guirado, Lucía Pedrosa, Silvia Sequero, Natalia Yanguas-Casás, Luis de la Cruz-Merino, Laura Gálvez, Marta Llanos, Juan Fernando García, Mariano Provencio
Clinical and Translational Oncology.2023; 26(5): 1043. CrossRef

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Plasma Circulating Tumor DNA in Patients with Primary Central Nervous System Lymphoma: Sang Eun Yoon, Yeon Jeong Kim, Joon Ho Shim, Donghyun Park, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Yeung-Chul Mun, Kyoung Eun Lee, Duck Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2022;54(2):597-612. Published online July 23, 2021; DOI: https://doi.org/10.4143/crt.2021.752

Abstract PDF Supplementary Material PubReader ePub

Purpose
Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL.
Materials and Methods
Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.
Results
Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment.
Conclusion
The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

Citations

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Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR
Yujie Zhong, Geok Wee Tan, Johanna Bult, Nick Veltmaat, Wouter Plattel, Joost Kluiver, Roelien Enting, Arjan Diepstra, Anke van den Berg, Marcel Nijland
BMC Cancer.2024;[Epub] CrossRef
Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma
Jin-Hua Liang, Yi-Fan Wu, Hao-Rui Shen, Yue Li, Jun-Heng Liang, Rui Gao, Wei Hua, Chun-Yu Shang, Kai-Xin Du, Tong-Yao Xing, Xin-Yu Zhang, Chen-Xuan Wang, Liu-Qing Zhu, Yang W. Shao, Jian-Yong Li, Jia-Zhu Wu, Hua Yin, Li Wang, Wei Xu
Leukemia.2024; 38(7): 1541. CrossRef
Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review
Lakshmi Nayak, Chetan Bettegowda, Florian Scherer, Norbert Galldiks, Manmeet Ahluwalia, Alexander Baraniskin, Louisa von Baumgarten, Jacoline E C Bromberg, Andrés J M Ferreri, Christian Grommes, Khê Hoang-Xuan, Julia Kühn, James L Rubenstein, Roberta Rudà
Neuro-Oncology.2024; 26(6): 993. CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas
Jurik A. Mutter, Stefan K. Alig, Mohammad S. Esfahani, Eliza M. Lauer, Jan Mitschke, David M. Kurtz, Julia Kühn, Sabine Bleul, Mari Olsen, Chih Long Liu, Michael C. Jin, Charles W. Macaulay, Nicolas Neidert, Timo Volk, Michel Eisenblaetter, Sebastian Raue
Journal of Clinical Oncology.2023; 41(9): 1684. CrossRef
Clinical applications of circulating tumor DNA in central nervous system lymphoma
Anna Katharina Foerster, Eliza M. Lauer, Florian Scherer
Seminars in Hematology.2023; 60(3): 150. CrossRef
Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
Gloria Figaredo, Alejandro Martín-Muñoz, Santiago Barrio, Laura Parrilla, Yolanda Campos-Martín, María Poza, Laura Rufián, Patrocinio Algara, Marina De La Torre, Ana Jiménez Ubieto, Joaquín Martínez-López, Luis-Felipe Casado, Manuela Mollejo
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Yong-Pyo Lee, Seung-Myoung Son, Jihyun Kwon
World Journal of Clinical Cases.2023; 11(33): 8058. CrossRef
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Rafael Colmenares, Noemí Álvarez, Santiago Barrio, Joaquín Martínez-López, Rosa Ayala
Cancers.2022; 14(5): 1310. CrossRef

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Efficacy of Brentuximab Vedotin in Relapsed or Refractory High-CD30–Expressing Non-Hodgkin Lymphomas: Results of a Multicenter, Open-Labeled Phase II Trial: Seok Jin Kim, Dok Hyun Yoon, Jin Seok Kim, Hye Jin Kang, Hye Won Lee, Hyeon-Seok Eom, Jung Yong Hong, Junhun Cho, Young Hyeh Ko, Jooryung Huh, Woo-Ick Yang, Weon Seo Park, Seung-Sook Lee, Cheolwon Suh, Won Seog Kim; Cancer Res Treat. 2020;52(2):374-387. Published online August 13, 2019; DOI: https://doi.org/10.4143/crt.2019.198

Abstract PDF PubReader ePub

Purpose
The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma (NHL) patients most likely to benefit.
Materials and Methods
This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry.
Results
High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma. The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survival were not associated with CD30 expression levels. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis for the association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1- negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients (13.3%, 2/15).
Conclusion
BV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles, especially MUM1-negative patients.

Citations

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Mohammad Sadegh Fallahi, Nasibeh Zerangian, Atousa Ghorbani, Gisou Erabi, Melika Shirali, Elaheh Shabani, Foad Rommasi, Mahsa Mohammadi Najafabadi, Shima Karbasi, Samaneh Toutounchian, Ramin Ahangar-Sirous, Ava Motaghy, Mahsa Heidari, Niloofar Deravi
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Yoji Hirai, Jun Sakurai, Shiho Yoshida, Takashi Kikuchi, Toshiharu Mitsuhashi, Tomoko Miyake, Taku Fujimura, Riichiro Abe, Hiroki Fujikawa, Hikari Boki, Hiraku Suga, Sayaka Shibata, Tomomitsu Miyagaki, Takatoshi Shimauchi, Eiji Kiyohara, Yoshio Kawakami,
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Jiewen Tan, Jinman Zhong, Wanzhen Hu, Guobiao Wu, Chong Zeng, Dan Xiong
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Roxanne C. Jewell, Richard J. Mills, Colm Farrell, Sandra A. G. Visser
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Eric Tse, Christopher P. Fox, Alexander Glover, Sang Eun Yoon, Won Seog Kim, Yok-Lam Kwong
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Hua Wang, Bi-bo Fu, Robert Peter Gale, Yang Liang
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