Diagnosis of Unruptured Intracranial Aneurysm by High-Performance Serum Metabolic Fingerprints
Jiabin Su
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorJing Cao
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorHeng Yang
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorWei Xu
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorWanshan Liu
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorRuimin Wang
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorYida Huang
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorJiao Wu
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorXinjie Gao
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorRuiyuan Weng
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorJun Pu
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
Search for more papers by this authorNing Liu
School of Electronics Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorCorresponding Author
Yuxiang Gu
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Kun Qian
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Wei Ni
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorJiabin Su
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorJing Cao
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorHeng Yang
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorWei Xu
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorWanshan Liu
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorRuimin Wang
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorYida Huang
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorJiao Wu
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorXinjie Gao
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorRuiyuan Weng
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
Search for more papers by this authorJun Pu
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
Search for more papers by this authorNing Liu
School of Electronics Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
Search for more papers by this authorCorresponding Author
Yuxiang Gu
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Kun Qian
State Key Laboratory for Oncogenes and Related Genes, Division of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, 160 Pujian Road, Shanghai, 200127 P. R. China
School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030 P. R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Wei Ni
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040 P. R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorAbstract
Unruptured intracranial aneurysm (UIA) is a high-risk cerebrovascular saccular dilatation, the effective medical management of which depends on high-performance diagnosis. However, most UIAs are diagnosed incidentally during neurovascular imaging modalities, which are time-consuming and harmful (e.g., radiation). Serum metabolic fingerprints is a promising alternative for early diagnosis of UIA. Here, nanoparticle enhanced laser desorption/ionization mass spectrometry is applied to obtain high-performance UIA-specific serum metabolic fingerprints. Diagnostic performance with an area-under-the-curve (AUC) of 0.842 (95% confidence interval (CI): 0.783-0.891) is achieved by the constructed machine learning (ML) model, including ML algorithm selection and feature selection. Lactate, glutamine, homoarginine, and 3-methylglutaconic acid are identified as the metabolic biomarker panel, which showed satisfactory diagnosis (AUC of 0.812, 95% CI: 0.727-0.897) and effective growth risk assessment (p<0.05, two-tailed t-test) of UIAs. This work aims to promote the diagnostics of UIAs and metabolic biomarker screening for medical management.
Conflict of Interest
The authors declare competing financial interest. The authors have filed patents for both the technology and the use of the technology to detect biosamples.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
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| smtd202201486-sup-0001-SuppMat.pdf425.9 KB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1a) M. H. M. Vlak, A. Algra, R. Brandenburg, G. J. E. Rinkel, Lancet Neurol. 2011, 10, 626; b) M. Li, S. Chen, Y. Li, Y. Chen, Y. Cheng, D. Hu, H. Tan, Q. Wu, W. Wang, Z. Sun, X. Wei, J. Zhang, R. Qiao, W. Zong, Y. Zhang, W. Lou, Z. Chen, Y. Zhu, D. Peng, S. Ding, X. Xu, X. Hou, W. Jia, Ann. Intern. Med. 2013, 159, 514.
- 2K. A. M. Hackenberg, D. Hanggi, N. Etminan, Stroke 2018, 49, 2268.
- 3Z. Shi, C. Miao, U. J. Schoepf, R. H. Savage, D. M. Dargis, C. Pan, X. Chai, X. L. Li, S. Xia, X. Zhang, Y. Gu, Y. Zhang, B. Hu, W. Xu, C. Zhou, S. Luo, H. Wang, L. Mao, K. Liang, L. Wen, L. Zhou, Y. Yu, G. M. Lu, L. J. Zhang, Nat. Commun. 2020, 11, 6090.
- 4A. Malhotra, X. Wu, A. Chugh, A. Mustafa, C. C. Matouk, D. Gandhi, P. Sanelli, Stroke 2019, 50, 76.
- 5H. Lusic, M. W. Grinstaff, Chem. Rev. 2013, 113, 1641.
- 6a) H. Zhang, L. Zhao, J. Jiang, J. Zheng, L. Yang, Y. Li, J. Zhou, T. Liu, J. Xu, W. Lou, W. Yang, L. Tan, W. Liu, Y. Yu, M. Ji, Y. Xu, Y. Lu, X. Li, Z. Liu, R. Tian, C. Hu, S. Zhang, Q. Hu, Y. Deng, H. Ying, S. Zhong, X. Zhang, Y. Wang, H. Wang, J. Bai, et al, Nat. Commun. 2022, 13, 617; b) Y. Huang, S. Du, J. Liu, W. Huang, W. Liu, M. Zhang, N. Li, R. Wang, J. Wu, W. Chen, M. Jiang, T. Zhou, J. Cao, J. Yang, L. Huang, A. Gu, J. Niu, Y. Cao, W. X. Zong, X. Wang, J. Liu, K. Qian, H. Wang, Proc. Natl. Acad. Sci. USA 2022, 119, e2122245119; c) V. Vedarethinam, L. Huang, M. C. Zhang, H. Y. Su, H. Q. Hu, H. P. Xia, Y. Liu, B. R. Wu, X. Wan, J. Shen, L. Xu, W. Liu, J. Ma, K. Qian, Adv. Funct. Mater. 2020, 30, 2002791; d) R. Zhang, C. Rejeeth, W. Xu, C. Y. Zhu, X. Y. Liu, J. J. Wan, M. W. Jiang, K. Qian, Anal. Chem. 2019, 91, 7078; e) L. Huang, D. D. Gurav, S. Wu, W. Xu, V. Vedarethinam, J. Yang, H. Y. Su, X. Z. Wan, Y. Fang, B. Y. Shen, C. A. H. Price, E. Velliou, J. Liu, K. Qian, Matter 2019, 1, 1669; f) Y. Y. Broza, H. Haick, View 2022, 3, 20200164.
- 7a) M. K. Bakker, R. A. A. van der Spek, W. van Rheenen, S. Morel, R. Bourcier, I. C. Hostettler, V. S. Alg, K. R. van Eijk, M. Koido, M. Akiyama, C. Terao, K. Matsuda, R. G. Walters, K. Lin, L. Li, I. Y. Millwood, Z. Chen, G. A. Rouleau, S. Zhou, K. Rannikmae, C. L. M. Sudlow, H. Houlden, L. H. van den Berg, C. Dina, O. Naggara, J. C. Gentric, E. Shotar, F. Eugene, H. Desal, B. S. Winsvold, et al, Nat. Genet. 2020, 52, 1303; b) W. Xu, J. X. Lin, M. Gao, Y. H. Chen, J. Cao, J. Pu, L. Huang, J. Zhao, K. Qian, Adv. Sci. 2020, 7, 2002021; c) T. Gong, Z. Y. Hong, C. H. Chen, C. Y. Tsai, L. D. Liao, K. V. Kong, ACS Nano 2017, 11, 3365.
- 8a) K. E. Poppenberg, L. Li, M. Waqas, N. Paliwal, K. Jiang, J. N. Jarvis, Y. Sun, K. V. Snyder, E. I. Levy, A. H. Siddiqui, J. Kolega, H. Meng, V. M. Tutino, PLoS One 2020, 15, e0241838; b) Y. Xiong, J. Yao, Y. Zheng, F. Shen, H. Zhao, J. Hu, B. Leng, P. Yang, X. Liu, Talanta 2022, 240, 123159; c) K. J. Karczewski, M. P. Snyder, Nat. Rev. Genet. 2018, 19, 299; d) X. Zhang, D. Wei, Y. Yap, L. Li, S. Guo, F. Chen, Mass Spectrom Rev 2007, 26, 403; e) J. Cao, Y. Wang, Y. Zhang, K. Qian, Adv Intell Syst 2022, 4, 2100191.
- 9H. Y. Su, X. X. Li, L. Huang, J. Cao, M. J. Zhang, V. Vedarethinam, W. Di, Z. Q. Hu, K. Qian, Adv. Mater. 2021, 33, 2007978.
- 10S. S. S. J. Ahmed, Metabolomics 2013, 10, 52.
- 11a) A. Bauermeister, H. Mannochio-Russo, L. V. Costa-Lotufo, A. K. Jarmusch, P. C. Dorrestein, Nat. Rev. Microbiol. 2022, 20, 143; b) Z. Yang, B. Li, D. D. Stuart, Q. Cheng, View 2022, 20220041; c) L. Z. Samarah, A. Vertes, View 2020, 1, 20200063; d) Q. Shu, M. Rajagopal, J. Fan, L. Zhan, X. Kong, Y. He, S. Rotcheewaphan, C. J. Lyon, W. Sha, A. M. Zelazny, T. Hu, View 2022, 3, 20210019.
- 12a) E. J. Want, I. D. Wilson, H. Gika, G. Theodoridis, R. S. Plumb, J. Shockcor, E. Holmes, J. K. Nicholson, Nat. Protoc. 2010, 5, 1005;
b) W. B. Dunn, D. Broadhurst, P. Begley, E. Zelena, S. Francis-McIntyre, N. Anderson, M. Brown, J. D. Knowles, A. Halsall, J. N. Haselden, A. W. Nicholls, I. D. Wilson, D. B. Kell, R. Goodacre, C. H. S. Metabolome, Nat. Protoc. 2011, 6, 1060;
c) X. Liu, J. Liu, View 2020, 2, 20200102.
10.1002/VIW.20200102 Google Scholar
- 13a) C. Y. Shi, C. H. Deng, Analyst 2016, 141, 2816; b) W. Liu, Y. Luo, J. Dai, L. Yang, L. Huang, R. Wang, W. Chen, Y. Huang, S. Sun, J. Cao, J. Wu, M. Han, J. Fan, M. He, K. Qian, X. Fan, R. Jia, Small Methods 2022, 6, 2101220; c) L. Huang, L. Wang, X. M. Hu, S. Chen, Y. W. Tao, H. Y. Su, J. Yang, W. Xu, V. Vedarethinam, S. Wu, B. Liu, X. Z. Wan, J. T. Lou, Q. Wang, K. Qian, Nat. Commun. 2020, 11, 3556; d) J. Cao, X. J. Shi, D. D. Gurav, L. Huang, H. Y. Su, K. K. Li, J. Y. Niu, M. J. Zhang, Q. Wang, M. W. Jiang, K. Qian, Adv. Mater. 2020, 32, 2000906.
- 14a) C. Liu, X. Xu, W. Cui, H. Zhang, Eng. Regen 2021, 2, 105;
10.1016/j.engreg.2021.09.001 Google Scholarb) M. Furtado, L. Chen, Z. Chen, A. Chen, W. Cui, Eng. Regen. 2022, 3, 217;10.1016/j.engreg.2022.05.002 Google Scholarc) C. Li, W. Cui, Eng. Regen. 2021, 2, 195.
- 15a) R. Wang, Z. Gu, Y. Wang, X. Yin, W. Liu, W. Chen, Y. Huang, J. Wu, S. Yang, L. Feng, L. Zhou, L. Li, W. Di, X. Pu, L. Huang, K. Qian, Adv. Funct. Mater. 2022, 32, 202206670; b) J. Wu, M. Xu, W. Liu, Y. Huang, R. Wang, W. Chen, L. Feng, N. Liu, X. Sun, M. Zhou, K. Qian, Small Methods 2022, 6, 2200264; c) S. Y. Sun, W. S. Liu, J. Yang, H. Wang, K. Qian, Angew. Chem.-Int. Edit. 2021, 60, 11310.
- 16H. Iida, K. Takayanagi, T. Nakanishi, T. Osaka, J. Colloid Interface Sci. 2007, 314, 274.
- 17a) J. Chong, D. S. Wishart, J. Xia, Curr. Protoc. Bioinformatics 2019, 68, e86; b) E. S. Rawson, H. R. Lieberman, T. M. Walsh, S. M. Zuber, J. M. Harhart, T. C. Matthews, Physiol. Behav. 2008, 95, 130; c) M. Perugini, M. Gallucci, G. Costantini, Int. Rev. Soc. Psychol. 2018, 31, 20.
- 18P. Bijlenga, R. Gondar, S. Schilling, S. Morel, S. Hirsch, J. Cuony, M. V. Corniola, F. Perren, D. Rufenacht, K. Schaller, Stroke 2017, 48, 2105.
- 19J. Chong, O. Soufan, C. Li, I. Caraus, S. Li, G. Bourque, D. S. Wishart, J. Xia, Nucleic Acids Res. 2018, 46, W486.
- 20a) I. Roberts, M. W. Muelas, J. M. Taylor, A. S. Davison, Y. Xu, J. M. Grixti, N. Gotts, A. Sorokin, R. Goodacre, D. B. Kell, Metabolomics 2021, 18, 6; b) H. U. Zacharias, M. Altenbuchinger, W. Gronwald, Metabolites 2018, 8, 47.
- 21a) J. Guo, L. Yang, R. Bie, J. Yu, Y. Gao, Y. Shen, A. Kos, Comput. Netw. 2019, 151, 166; b) J. Yang, R. Wang, L. Huang, M. J. Zhang, J. Y. Niu, C. D. Bao, N. Shen, M. Dai, Q. Guo, Q. Wang, Q. Wang, Q. Fu, K. Qian, Angew. Chem.-Int. Edit. 2020, 59, 1703.
- 22N. Bar, T. Korem, O. Weissbrod, D. Zeevi, D. Rothschild, S. Leviatan, N. Kosower, M. Lotan-Pompan, A. Weinberger, C. I. Le Roy, C. Menni, A. Visconti, M. Falchi, T. D. Spector, I. D. consortium, J. Adamski, P. W. Franks, O. Pedersen, E. Segal, Nature 2020, 588, 135.
- 23H. Liu, M. Zhou, Q. Liu, IEEE-CAA J. Automatica Sin. 2019, 6, 703.
- 24O. B. Bakker, R. Aguirre-Gamboa, S. Sanna, M. Oosting, S. P. Smeekens, M. Jaeger, M. Zorro, U. Vosa, S. Withoff, R. T. Netea-Maier, H. Koenen, I. Joosten, R. J. Xavier, L. Franke, L. A. B. Joosten, V. Kumar, C. Wijmenga, M. G. Netea, Y. Li, Nat. Immunol. 2018, 19, 776.
- 25H. Li, H. Xu, Y. Li, Y. Jiang, Y. Hu, T. Liu, X. Tian, X. Zhao, Y. Zhu, S. Wang, C. Zhang, J. Ge, X. Wang, H. Wen, C. Bai, Y. Sun, L. Song, Y. Zhang, R. Hui, J. Cai, J. Chen, Nat. Commun. 2020, 11, 3218.
