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6 "Hyunwoo Lee"
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Original Articles
Long-Term Prognostic Value and Analytical Parameters of the Next-Generation Sequencing-Based Multigene Assay in Hormone Receptor-Positive, HER2-Negative Breast Cancer
Hyunji Kim, Jiwon Koh, Hyunwoo Lee, Gyungyub Gong, Sujin Oh, Jiyoung Lee, Ho Eun Chang, Yunhee Choi, Eunhye Kang, Jai Min Ryu, Dong Seung Shin, Sae Byul Lee, Hee Jin Lee, Hong-Kyu Kim, Hee-Chul Shin, Wonshik Han, Han-Byoel Lee, Kyoung Un Park
Received July 7, 2025  Accepted August 29, 2025  Published online September 1, 2025  
DOI: https://doi.org/10.4143/crt.2025.701    [Accepted]
AbstractAbstract PDF
Purpose
In hormone receptor (HR)-positive, HER2-negative early breast cancer, gene expression testing facilitates treatment decisions. A next-generation sequencing (NGS)-based assay was developed to address test decentralization and underrepresentation of younger/premenopausal patients. We aimed to validate the long-term prognostic value of the NGS-based assay and analyze its quality control (QC) parameters.
Materials and Methods
We analyzed samples from 265 patients with breast cancer with at least 10 years of follow-up. We evaluated the long-term prognostic ability of the NGS-based assay according to the risk groups for distant recurrence, as determined by the Decision Index (DI), and the performance of the QC parameters used for the experimental process.
Results
Among 265 participants, 60.4% were ≤50 years old, and 39 (14.7%) experienced distant recurrence within 10 years. In the DI-stratified low- and high-risk groups (n=186; 70.2% and n=79; 29.8%), 10-year distant metastasis-free survival rates were 96.1% (95% CI 92.1-98.1) and 79.3% (95% CI 68.4-86.8), respectively. In patients aged ≤50 years, the high-risk group had a hazard ratio of 5.89 (95% CI 2.84-12.20). Analyses including 106 samples that failed the stringent QC criteria showed inferior prognostic value, wherein DV200 and cDNA concentrations were the most crucial parameters.
Conclusion
We validated the prognostic ability of an NGS-based assay to stratify HR-positive/HER2-negative breast cancers and predict the risk of distant recurrence, and confirmed the requirement for stringent QC criteria to ensure its prognostic ability.
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Breast cancer
Prognostic Performance of the Next-Generation Sequencing-Based Multigene Assay in Early Breast Cancer Patients Treated According to the 21-Gene Assay Results
Eunhye Kang, Jong-Ho Cheun, Jeeyeon Lee, Jiwon Koh, Hyunwoo Lee, Ji-Young Park, Hee Jin Lee, Byeongju Kang, Woong Ki Park, Jeongeun Son, Bumjoon Kim, Woosung Chung, Wonshik Han, Han-Byoel Lee, Sae Byul Lee, Jai Min Ryu
Cancer Res Treat. 2025;57(3):749-759.   Published online December 23, 2024
DOI: https://doi.org/10.4143/crt.2024.1035
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Multigene assays guide treatment decisions in early-stage hormone receptor-positive breast cancer. OncoFREE, a next-generation sequencing assay using 179 genes, was developed for this purpose. This study aimed to evaluate the concordance between the Oncotype DX (ODX) recurrence score (RS) and the OncoFREE Decision Index (DI) and to compare their performance.
Materials and Methods
We retrospectively collected tumor blocks from patients who underwent ODX and treatment between 2012 and 2022 at four tertiary hospitals and performed OncoFREE on these samples. Distant metastasis-free survival (DMFS) was compared using RS and DI, with score cut-offs of 25 and 20, respectively.
Results
Among 838 patients, a strong correlation was observed between RS and DI (Pearson correlation coefficient 0.83). At a median follow-up of 54 months, patients with high DI had significantly worse DMFS compared to those with low-DI (log-rank p < 0.001; hazard ratio [HR], 5.73; 95% confidence interval [CI], 1.87 to 17.57; multivariable p=0.048; HR, 3.45; 95% CI, 1.01 to 11.76). In 513 patients aged ≤ 50 years, DMFS was significantly different as a function of DI (p=0.035; HR, 3.98; 95% CI, 1.00 to 15.89) but not RS (p=0.792). Among 376 patients aged ≤ 50 years who avoided chemotherapy based on low-RS, 64 with high DI had worse DMFS (p=0.015; HR, 5.91; 95% CI, 1.17 to 29.78).
Conclusion
OncoFREE showed strong concordance with ODX and effectively identified high-risk patients, particularly in younger individuals. It could be an affordable alternative to ODX for guiding treatment in hormone receptor-positive early breast cancer.
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Next-Generation Sequencing in Breast Cancer Patients: Real-World Data for Precision Medicine
Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho
Cancer Res Treat. 2024;56(1):149-161.   Published online August 11, 2023
DOI: https://doi.org/10.4143/crt.2023.800
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer.
Materials and Methods
We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500.
Results
The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation.
Conclusion
NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

Citations

Citations to this article as recorded by  
  • Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience
    Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim,
    Cancer Research and Treatment.2025; 57(2): 443.     CrossRef
  • Comprehensive genomic profiling of Taiwanese triple-negative breast cancer with a large targeted sequencing panel
    Chi-Cheng Huang, Yi-Chen Yeh, Han-Fang Cheng, Bo-Fang Chen, Chun-Yu Liu, Yi-Fang Tsai, Hsiang-Ling Ho, Ling-Ming Tseng
    Journal of the Chinese Medical Association.2025; 88(8): 641.     CrossRef
  • Perceived Barriers to NGS-Based Molecular Profiling Among US Metastatic Breast Cancer Patients
    Nicholas Cadirov, Moumita Chaki, Olivia Foroughi, Omar Perez, Stella Redpath, Gary Gustavsen
    Diagnostics.2025; 15(20): 2626.     CrossRef
  • Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
    Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
    Pathology.2024; 56(5): 653.     CrossRef
  • Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer
    Elena Guerini-Rocco, Konstantinos Venetis, Giulia Cursano, Eltjona Mane, Chiara Frascarelli, Francesco Pepe, Mariachiara Negrelli, Edoardo Olmeda, Davide Vacirca, Alberto Ranghiero, Dario Trapani, Carmen Criscitiello, Giuseppe Curigliano, Christian Rolfo,
    Critical Reviews in Oncology/Hematology.2024; 201: 104427.     CrossRef
  • An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer
    Yi Bi, Xiao Lv, Ke Wang, Jinyu Wu, Xiang Shi, Xiaodong Zheng, Xiaogang Lin
    Frontiers in Bioengineering and Biotechnology.2024;[Epub]     CrossRef
  • NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
    Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
    Romanian Journal of Morphology and Embryology.2024; 65(2): 195.     CrossRef
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Lung and Thoracic cancer
Selection Strategies and Practical Application of BRAF V600E-Mutated Non–Small Cell Lung Carcinoma
Inwoo Hwang, Yoon-La Choi, Hyunwoo Lee, Soohyun Hwang, Boram Lee, Hobin Yang, Chaithanya Chelakkot, Joungho Han
Cancer Res Treat. 2022;54(3):782-792.   Published online November 23, 2021
DOI: https://doi.org/10.4143/crt.2021.843
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The incidence of BRAF V600E mutation in non-small cell lung carcinoma (NSCLC) is lower than 2%, which poses difficulties in finding legitimate patients for targeted therapy. We investigated the predictive factors pertaining to BRAF V600E and the effectiveness of the VE1 antibody as a screening method for patient selection.
Materials and Methods
The study was designed into two steps. In a first group, BRAF-mutated NSCLCs were identified from sequencing data to determine the features of BRAF V600E mutation. The results of the first group helped the collection of adenocarcinomas with a papillary or micropapillary pattern but without EGFR or ALK alterations as a second group so that the frequency of BRAF V600E mutation could be calculated. The sensitivity and specificity of the VE1 were compared with BRAF V600E status.
Results
Among 39 BRAF-mutated NSCLCs in the first group, 20 (51%) were V600E. BRAF V600E mutation was more common in female patients and showed no significant correlation with smoking status. Nineteen cases were adenocarcinomas without EGFR and ALK alterations. The most common patterns of invasion were papillary and micropapillary along with central fibrosis. The sensitivity and specificity of the VE1 were 90.0% and 92.3%, respectively. In the second group, 6.7% of cases were VE1-positive, indicating that the prevalence was significantly higher than that reported in previous studies (0.3-1.8%).
Conclusion
BRAF V600E-mutated NSCLCs could be enriched with the application of clinicopathologic parameters, which are not perfect. Therefore, additional VE1 immunohistochemistry may be useful as a screening method.

Citations

Citations to this article as recorded by  
  • High-Quality Samples for Next-Generation Sequencing and PD-L1 Assessment in Non-Small Cell Lung Cancer: The Role of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
    Marta Rodríguez González, Juan Montero, José Sayagués, Tamara Sánchez, Jonnathan Ruiz, Miguel Iglesias Heras, María Rivas Marcos, Mar Abad, Rosa Cordovilla Pérez
    Diagnostics.2025; 15(9): 1064.     CrossRef
  • The rapidly changing field of predictive biomarkers of non-small cell lung cancer
    László József Tóth, Attila Mokánszki, Gábor Méhes
    Pathology and Oncology Research.2024;[Epub]     CrossRef
  • BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
    Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin, Ahrong Kim
    Medicina.2023; 59(6): 1085.     CrossRef
  • The Impact of Liquid Biopsies Positive for EGFR Mutations on Overall Survival in Non-Small Cell Lung Cancer Patients
    Jonnathan Roldan Ruiz, Marta Fuentes Gago, Luis Chinchilla Tabora, Idalia Gonzalez Morais, José Sayagués, Mar Abad Hernández, Maria Cordovilla Pérez, Maria Ludeña de la Cruz, Edel del Barco Morillo, Marta Rodriguez Gonzalez
    Diagnostics.2023; 13(14): 2347.     CrossRef
  • Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
    Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
    Journal of Pathology and Translational Medicine.2022; 56(6): 334.     CrossRef
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CNS cancer
Detection of TERT Promoter Mutations Using Targeted Next-Generation Sequencing: Overcoming GC Bias through Trial and Error
Hyunwoo Lee, Boram Lee, Deok Geun Kim, Yoon Ah Cho, Jung-Sun Kim, Yeon-Lim Suh
Cancer Res Treat. 2022;54(1):75-83.   Published online May 3, 2021
DOI: https://doi.org/10.4143/crt.2021.107
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Detection of telomerase reverse transcriptase (TERT) promoter mutations is a crucial process in the integrated diagnosis of glioblastomas. However, the TERT promoter region is difficult to amplify because of its high guanine-cytosine (GC) content (> 80%). This study aimed to analyze the capturing of TERT mutations by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tissues.
Materials and Methods
We compared the detection rate of TERT mutations between targeted NGS and Sanger sequencing in 25 cases of isocitrate dehydrgenase (IDH)-wildtype glioblastomas and 10 cases of non-neoplastic gastric tissues. Our customized panel consisted of 232 essential glioma-associated genes.
Results
Sanger sequencing detected TERT mutations in 17 out of 25 glioblastomas, but all TERT mutations were missed by targeted NGS. After the manual visualization of the NGS data using an integrative genomics viewer, 16 cases showed a TERT mutation with a very low read depth (mean, 21.59; median, 25), which revealed false-negative results using auto-filtering. We optimized our customized panel by extending the length of oligonucleotide baits and increasing the number of baits spanning the coverage of the TERT promoter, which did not amplify well due to the high GC content.
Conclusion
Our study confirmed that it is crucial to consider the recognition of molecular bias and to carefully interpret NGS data.

Citations

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  • Modernizing Neuro-Oncology: The Impact of Imaging, Liquid Biopsies, and AI on Diagnosis and Treatment
    John Rafanan, Nabih Ghani, Sarah Kazemeini, Ahmed Nadeem-Tariq, Ryan Shih, Thomas A. Vida
    International Journal of Molecular Sciences.2025; 26(3): 917.     CrossRef
  • A Concordance Study among 26 NGS Laboratories Participating in the NCI Molecular Analysis for Therapy Choice Clinical Trial
    Linda K. Zane, Laura M. Yee, Ting-Chia Chang, Jeffrey Sklar, Guangxiao Yang, Jia Di Wen, Peining Li, Robin Harrington, David J. Sims, Kneshay Harper, Jeffrey M. Trent, Janine R. LoBello, Szabolcs Szelinger, Kasey Benson, Jia Zeng, Kelsey Poorman, Danbin X
    Clinical Cancer Research.2025; 31(16): 3512.     CrossRef
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    Subit Barua, Susan Hsiao, Emily Clancy, Christopher Freeman, Mahesh Mansukhani, Helen Fernandes
    Journal of Clinical Pathology.2024; 77(1): 46.     CrossRef
  • Diagnostic utility of genetic alterations in distinguishing IDH‐wildtype glioblastoma from lower‐grade gliomas: Insight from next‐generation sequencing analysis of 479 cases
    Boram Lee, Soohyun Hwang, Hyunsik Bae, Kyue‐Hee Choi, Yeon‐Lim Suh
    Brain Pathology.2024;[Epub]     CrossRef
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    Ákos Kovács, Farkas Sükösd, Levente Kuthi, Imre M. Boros, Balázs Vedelek
    Clinical and Experimental Medicine.2024;[Epub]     CrossRef
  • Changes in Mutations of Cell-Free DNA and Liver Tumor Tissue in Patients with Advanced Hepatocellular Carcinoma before and after Introduction of Lenvatinib
    Mio Tsuruoka, Masashi Ninomiya, Jun Inoue, Tomoaki Iwata, Akitoshi Sano, Kosuke Sato, Masazumi Onuki, Satoko Sawahashi, Atsushi Masamune
    Oncology.2024; 102(12): 1072.     CrossRef
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    Justyna Mirek, Wiesław Bal, Magdalena Olbryt
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
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    Jinhee Kim, Seokhwan Ko, Moonsik Kim, Nora Jee-Young Park, Hyungsoo Han, Junghwan Cho, Ji Young Park
    Medicina.2023; 59(3): 536.     CrossRef
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    Guodong Fu, Ronald S. Chazen, Eric Monteiro, Allan Vescan, Jeremy L. Freeman, Ian J. Witterick, Christina MacMillan
    JAMA Network Open.2023; 6(7): e2323500.     CrossRef
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    Yuanbin Wu, Xuning Wang, Meng Zhang, Dongdong Wu
    Molecules.2023; 28(15): 5660.     CrossRef
  • Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas
    Gábor Bedics, Péter Szőke, Bence Bátai, Tibor Nagy, Gergő Papp, Noémi Kránitz, Hajnalka Rajnai, Lilla Reiniger, Csaba Bödör, Bálint Scheich
    Scientific Reports.2023;[Epub]     CrossRef
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Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting
Jin Hyoung Kang, Jung Hye Kwon, Yun-Gyoo Lee, Keon Uk Park, Ho Jung An, Joohyuk Sohn, Young Mi Seol, Hyunwoo Lee, Hwan-Jung Yun, Jin Seok Ahn, Ji Hyun Yang, Hunho Song, Dong-Hoe Koo, Jin Young Kim, Gun Min Kim, Hwa Jung Kim
Cancer Res Treat. 2020;52(3):907-916.   Published online March 18, 2020
DOI: https://doi.org/10.4143/crt.2019.713
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting.
Materials and Methods
Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.
Results
A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.
Conclusion
In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Citations

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  • Impact of body weight-based dosing of palonosetron and ondansetron on postoperative nausea and vomiting following laparoscopic sleeve gastrectomy: a randomized, double-blind study
    Büşra Burcu, Nadir Adnan Hacım, Ozan Caliskan, Serdar Demirgan, Talar Vartanoglu Aktokmakyan, Serhat Meric, Tomris Duymaz, Onder Karabay, Ali Solmaz
    Acta Chirurgica Belgica.2024; 124(1): 41.     CrossRef
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    Jørn Herrstedt, L Celio, PJ Hesketh, L Zhang, R Navari, A Chan, M Saito, R Chow, M Aapro
    Supportive Care in Cancer.2024;[Epub]     CrossRef
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    ESMO Open.2024; 9(2): 102195.     CrossRef
  • Ramosetron 3.0 μg/mL Combining with Dexamethasone (0.05, 0.1, 0.2 mg/mL) in Infusion Solutions: A Physicochemical Stability Study
    Baoxia Fang, Lijun Zhao, Shirong Yu, Fuchao Chen
    Dose-Response.2024;[Epub]     CrossRef
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    Marco Filetti, Pasquale Lombardi, Raffaele Giusti, Rosa Falcone, Florian Scotte, Diana Giannarelli, Antonella Carcagnì, Valeria Altamura, Giovanni Scambia, Gennaro Daniele
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    Mei Qian, Yang Liu
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    Hyo Jin Kim, EunJin Ahn, Geun Joo Choi, Hyun Kang
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    Qi Meng, Pingping Bi, Guanglong Zhang, Yaqi Li, Siqi Chen, Ke Nie
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    Ajay Raghunath, Sahan D. Chandrasekara, Shane N. Anthony, Ben Markman
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