A modern view on potential biomarkers of Parkinson’s disease (review)
DOI:
https://doi.org/10.14739/2310-1237.2020.2.212810Keywords:
Parkinson disease, biomarkers, synuclein, glutathione, glutatione peroxidase, melatonin, nitrotyrosineAbstract
Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases. In spite of the large number of researches, the problem of earlier diagnosis and targeted pathogenetic therapy remains relevant. For more than 20 years, scientists have been continuing to study potential diagnostic and prognostic PD biomarkers. An accurate diagnostic biomarker can help identify PD before motor symptoms occur, or when motor and non-motor symptoms are insufficient to diagnose, and also can be used to differentiate between idiopathic PD and other forms of parkinsonism.
The aim of the research is to analyze the last studies of potential PD biomarkers in human biological fluids.
Conclusions. Most studies of recent years indicate that the level of total α-synuclein, its oligomers in blood plasma and its formed elements is elevated in patients at the early stages of PD, and it can be a valuable prognostic biomarker for disease progression, in particular its motor symptoms. Studies of the level of this potential biomarker not only in blood plasma and its formed elements, but also in neuronal exosomes, are promising. The negative impact of oxidative stress in PD is a significant trigger for irreversible pathogenetic processes that affect the development of neurodegenerative changes. Perspectives of further researches may lay not only in identifying the concentrations of nitrotyrosine and oxidative stress components and antioxidants in the blood of PD patients, but also in determining of the effect of antiparkinsonian and neuroprotective drugs on the antioxidant system in order to pathogenetically justify their use for reducing of oxidative stress. It is promising to study the activity of melatonin in the context of its relationship with the components of oxidative stress and antioxidants by determining their concentrations in blood of PD patients.
References
Jagmag, S. A., Tripathi, N., Shukla, S. D., Maiti, S., & Khurana, S. (2016). Evaluation of Models of Parkinson's Disease. Frontiers in neuroscience, 9, 503. https://doi.org/10.3389/fnins.2015.00503
Li, T., & Le, W. (2020). Biomarkers for Parkinson's Disease: How Good Are They?. Neuroscience bulletin, 36(2), 183-194. https://doi.org/10.1007/s12264-019-00433-1
Li, S., & Le, W. (2017). Milestones of Parkinson's Disease Research: 200 Years of History and Beyond. Neuroscience bulletin, 33(5), 598-602. https://doi.org/10.1007/s12264-017-0178-2
Kalia, L. V., & Lang, A. E. (2015). Parkinson's disease. Lancet, 386(9996), 896-912. https://doi.org/10.1016/S0140-6736(14)61393-3
Holden, S. K., Finseth, T., Sillau, S. H., & Berman, B. D. (2018). Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort. Movement disorders clinical practice, 5(1), 47-53. https://doi.org/10.1002/mdc3.12553
Schapira, A., Chaudhuri, K. R., & Jenner, P. (2017). Non-motor features of Parkinson disease. Nature reviews. Neuroscience, 18(7), 435-450. https://doi.org/10.1038/nrn.2017.62
Pfeiffer, R. F. (2016). Non-motor symptoms in Parkinson's disease. Parkinsonism & related disorders, 22 Suppl 1, S119-S122. https://doi.org/10.1016/j.parkreldis.2015.09.004
Sui, X., Zhou, C., Li, J., Chen, L., Yang, X., & Li, F. (2019). Hyposmia as a Predictive Marker of Parkinson's Disease: A Systematic Review and Meta-Analysis. BioMed research international, 2019, 3753786. https://doi.org/10.1155/2019/3753786
Albers, J. A., Chand, P., & Anch, A. M. (2017). Multifactorial sleep disturbance in Parkinson's disease. Sleep medicine, 35, 41-48. https://doi.org/10.1016/j.sleep.2017.03.026
Savitt, D., & Jankovic, J. (2019). Targeting α-Synuclein in Parkinson's Disease: Progress Towards the Development of Disease-Modifying Therapeutics. Drugs, 79(8), 797-810. https://doi.org/10.1007/s40265-019-01104-1
Shao, Y. P., & Le, W. D. (2019). Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease. Molecular Neurodegeneration, 14, Article 3. https://doi.org/10.1186/s13024-018-0304-2
Chen-Plotkin, A. S., Albin, R., Alcalay, R., Babcock, D., Bajaj, V., Bowman, D., Buko, A., Cedarbaum, J., Chelsky, D., Cookson, M. R., Dawson, T. M., Dewey, R., Foroud, T., Frasier, M., German, D., Gwinn, K., Huang, X., Kopil, C., Kremer, T., Lasch, S., … Zhang, J. (2018). Finding useful biomarkers for Parkinson's disease. Science translational medicine, 10(454), eaam6003. https://doi.org/10.1126/scitranslmed.aam6003
Alafuzoff, I., & Hartikainen, P. (2017). Alpha-synucleinopathies. Handbook of clinical neurology, 145, 339-353. https://doi.org/10.1016/B978-0-12-802395-2.00024-9
Rocha, E. M., De Miranda, B., & Sanders, L. H. (2018). Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease. Neurobiology of disease, 109(Pt B), 249-257. https://doi.org/10.1016/j.nbd.2017.04.004
Liddle, R. A. (2018). Parkinson's disease from the gut. Brain research, 1693(Pt B), 201-206. https://doi.org/10.1016/j.brainres.2018.01.010
Parnetti, L., Gaetani, L., Eusebi, P., Paciotti, S., Hansson, O., El-Agnaf, O., Mollenhauer, B., Blennow, K., & Calabresi, P. (2019). CSF and blood biomarkers for Parkinson's disease. The Lancet. Neurology, 18(6), 573-586. https://doi.org/10.1016/S1474-4422(19)30024-9
Vicente Miranda, H., Cássio, R., Correia-Guedes, L., Gomes, M. A., Chegão, A., Miranda, E., Soares, T., Coelho, M., Rosa, M. M., Ferreira, J. J., & Outeiro, T. F. (2017). Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease. Scientific reports, 7(1), 13713. https://doi.org/10.1038/s41598-017-14175-5
Ding, J., Zhang, J., Wang, X., Zhang, L., Jiang, S., Yuan, Y., Li, J., Zhu, L., & Zhang, K. (2017). Relationship between the plasma levels of neurodegenerative proteins and motor subtypes of Parkinson's disease. Journal of neural transmission, 124(3), 353-360. https://doi.org/10.1007/s00702-016-1650-2
Lin, C. H., Yang, S. Y., Horng, H. E., Yang, C. C., Chieh, J. J., Chen, H. H., Liu, B. H., & Chiu, M. J. (2017). Plasma α-synuclein predicts cognitive decline in Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry, 88(10), 818-824. https://doi.org/10.1136/jnnp-2016-314857
Samat, N. A., Abdul Murad, N. A., Mohamad, K., Abdul Razak, M. R., & Mohamed Ibrahim, N. (2017). Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment. Frontiers in neuroscience, 11, 712. https://doi.org/10.3389/fnins.2017.00712
Pchelina, S., Emelyanov, A., Baydakova, G., Andoskin, P., Senkevich, K., Nikolaev, M., Miliukhina, I., Yakimovskii, A., Timofeeva, A., Fedotova, E., Abramycheva, N., Usenko, T., Kulabukhova, D., Lavrinova, A., Kopytova, A., Garaeva, L., Nuzhnyi, E., Illarioshkin, S., & Zakharova, E. (2017). Oligomeric α-synuclein and glucocerebrosidase activity levels in GBA-associated Parkinson's disease. Neuroscience letters, 636, 70-76. https://doi.org/10.1016/j.neulet.2016.10.039
Matsumoto, J., Stewart, T., Sheng, L., Li, N., Bullock, K., Song, N., Shi, M., Banks, W. A., & Zhang, J. (2017). Transmission of α-synuclein-containing erythrocyte-derived extracellular vesicles across the blood-brain barrier via adsorptive mediated transcytosis: another mechanism for initiation and progression of Parkinson's disease?. Acta neuropathologica communications, 5(1), 71. https://doi.org/10.1186/s40478-017-0470-4
Wang, H., Atik, A., Stewart, T., Ginghina, C., Aro, P., Kerr, K. F., Seibyl, J., Jennings, D., PARS Investigators, Jensen, P. H., Marek, K., Shi, M., & Zhang, J. (2018). Plasma α-synuclein and cognitive impairment in the Parkinson's Associated Risk Syndrome: A pilot study. Neurobiology of disease, 116, 53-59. https://doi.org/10.1016/j.nbd.2018.04.015
Papagiannakis, N., Koros, C., Stamelou, M., Simitsi, A. M., Maniati, M., Antonelou, R., Papadimitriou, D., Dermentzaki, G., Moraitou, M., Michelakakis, H., & Stefanis, L. (2018). Alpha-synuclein dimerization in erythrocytes of patients with genetic and non-genetic forms of Parkinson's Disease. Neuroscience letters, 672, 145-149. https://doi.org/10.1016/j.neulet.2017.11.012
Daniele, S., Frosini, D., Pietrobono, D., Petrozzi, L., Lo Gerfo, A., Baldacci, F., Fusi, J., Giacomelli, C., Siciliano, G., Trincavelli, M. L., Franzoni, F., Ceravolo, R., Martini, C., & Bonuccelli, U. (2018). α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson's Disease Patients and Correlate with Disease Severity. Frontiers in molecular neuroscience, 11, 53. https://doi.org/10.3389/fnmol.2018.00053
Singh, A. P., Bajaj, T., Gupta, D., Singh, S. B., Chakrawarty, A., Goyal, V., Dey, A. B., & Dey, S. (2018). Serum Mortalin Correlated with α-Synuclein as Serum Markers in Parkinson's Disease: A Pilot Study. Neuromolecular medicine, 20(1), 83-89. https://doi.org/10.1007/s12017-017-8475-5
Malec-Litwinowicz, M., Plewka, A., Plewka, D., Bogunia, E., Morek, M., Szczudlik, A., Szubiga, M., & Rudzińska-Bar, M. (2018). The relation between plasma α-synuclein level and clinical symptoms or signs of Parkinson's disease. Neurologia i neurochirurgia polska, 52(2), 243-251. https://doi.org/10.1016/j.pjnns.2017.11.009
Goldman, J. G., Andrews, H., Amara, A., Naito, A., Alcalay, R. N., Shaw, L. M., Taylor, P., Xie, T., Tuite, P., Henchcliffe, C., Hogarth, P., Frank, S., Saint-Hilaire, M. H., Frasier, M., Arnedo, V., Reimer, A. N., Sutherland, M., Swanson-Fischer, C., Gwinn, K., Fox Investigation of New Biomarker Discovery, … Kang, U. J. (2018). Cerebrospinal fluid, plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson's disease Features. Movement disorders, 33(2), 282-288. https://doi.org/10.1002/mds.27232
Emelyanov, A., Kulabukhova, D., Garaeva, L., Senkevich, K., Verbitskaya, E., Nikolaev, M., Andoskin, P., Kopytova, A., Milyukhina, I., Yakimovskii, A., Timofeeva, A., Prakhova, L., Ilves, A., Vlasova, I., & Pchelina, S. (2018). SNCA variants and alpha-synuclein level in CD45+ blood cells in Parkinson's disease. Journal of the neurological sciences, 395, 135-140. https://doi.org/10.1016/j.jns.2018.10.002
Si, X., Tian, J., Chen, Y., Yan, Y., Pu, J., & Zhang, B. (2019). Central Nervous System-Derived Exosomal Alpha-Synuclein in Serum May Be a Biomarker in Parkinson's Disease. Neuroscience, 413, 308-316. https://doi.org/10.1016/j.neuroscience.2019.05.015
Tian, C., Liu, G., Gao, L., Soltys, D., Pan, C., Stewart, T., Shi, M., Xie, Z., Liu, N., Feng, T., & Zhang, J. (2019). Erythrocytic α-Synuclein as a potential biomarker for Parkinson’s disease. Translational neurodegeneration, 8, 15. https://doi.org/10.1186/s40035-019-0155-y
Ng, A., Tan, Y. J., Lu, Z., Ng, E., Ng, S., Chia, N., Setiawan, F., Xu, Z., Tay, K. Y., Prakash, K. M., Au, W. L., Tan, E. K., & Tan, L. (2019). Plasma alpha-synuclein detected by single molecule array is increased in PD. Annals of clinical and translational neurology, 6(3), 615-619. https://doi.org/10.1002/acn3.729
Bougea, A., Stefanis, L., Paraskevas, G. P., Emmanouilidou, E., Vekrelis, K., & Kapaki, E. (2019). Plasma alpha-synuclein levels in patients with Parkinson's disease: a systematic review and meta-analysis. Neurological sciences, 40(5), 929-938. https://doi.org/10.1007/s10072-019-03738-1
Chang, C. W., Yang, S. Y., Yang, C. C., Chang, C. W., & Wu, Y. R. (2020). Plasma and Serum Alpha-Synuclein as a Biomarker of Diagnosis in Patients With Parkinson's Disease. Frontiers in neurology, 10, 1388. https://doi.org/10.3389/fneur.2019.01388
Fan, Z., Pan, Y. T., Zhang, Z. Y., Yang, H., Yu, S. Y., Zheng, Y., Ma, J. H., & Wang, X. M. (2020). Systemic activation of NLRP3 inflammasome and plasma α-synuclein levels are correlated with motor severity and progression in Parkinson's disease. Journal of neuroinflammation, 17(1), 11. https://doi.org/10.1186/s12974-019-1670-6
Shi, M., Sheng, L., Stewart, T., Zabetian, C. P., & Zhang, J. (2019). New windows into the brain: Central nervous system-derived extracellular vesicles in blood. Progress in neurobiology, 175, 96-106. https://doi.org/10.1016/j.pneurobio.2019.01.005
Niu, M., Li, Y., Li, G., Zhou, L., Luo, N., Yao, M., Kang, W., & Liu, J. (2020). A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression. European journal of neurology, 27(6), 967-974. https://doi.org/10.1111/ene.14208
Jiang, C., Hopfner, F., Katsikoudi, A., Hein, R., Catli, C., Evetts, S., Huang, Y., Wang, H., Ryder, J. W., Kuhlenbaeumer, G., Deuschl, G., Padovani, A., Berg, D., Borroni, B., Hu, M. T., Davis, J. J., & Tofaris, G. K. (2020). Serum neuronal exosomes predict and differentiate Parkinson's disease from atypical parkinsonism. Journal of neurology, neurosurgery, and psychiatry, 91(7), 720-729. https://doi.org/10.1136/jnnp-2019-322588
Blesa, J., Trigo-Damas, I., Quiroga-Varela, A., & Jackson-Lewis, V. R. (2015). Oxidative stress and Parkinson's disease. Frontiers in neuroanatomy, 9, 91. https://doi.org/10.3389/fnana.2015.00091
Khan, Z., & Ali, S. A. (2018). Oxidative stress-related biomarkers in Parkinson's disease: A systematic review and meta-analysis. Iranian journal of neurology, 17(3), 137-144.
Jiang, T., Sun, Q., & Chen, S. (2016). Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson's disease and Alzheimer's disease. Progress in neurobiology, 147, 1-19. https://doi.org/10.1016/j.pneurobio.2016.07.005
Islam, M. T. (2017). Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurological research, 39(1), 73-82. https://doi.org/10.1080/01616412.2016.1251711
Coles, L. D., Tuite, P. J., Öz, G., Mishra, U. R., Kartha, R. V., Sullivan, K. M., Cloyd, J. C., & Terpstra, M. (2018). Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress. Journal of clinical pharmacology, 58(2), 158-167. https://doi.org/10.1002/jcph.1008
Deas, E., Cremades, N., Angelova, P. R., Ludtmann, M. H., Yao, Z., Chen, S., Horrocks, M. H., Banushi, B., Little, D., Devine, M. J., Gissen, P., Klenerman, D., Dobson, C. M., Wood, N. W., Gandhi, S., & Abramov, A. Y. (2016). Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease. Antioxidants & redox signaling, 24(7), 376-391. https://doi.org/10.1089/ars.2015.6343
Vida, C., Kobayashi, H., Garrido, A., Martínez de Toda, I., Carro, E., Molina, J. A., & De la Fuente, M. (2019). Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson's Disease Patients. International journal of molecular sciences, 20(3), 771. https://doi.org/10.3390/ijms20030771
Gökçe Çokal, B., Yurtdaş, M., Keskin Güler, S., Güneş, H. N., Ataç Uçar, C., Aytaç, B., Durak, Z. E., Yoldaş, T. K., Durak, İ., & Çubukçu, H. C. (2017). Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehyde levels in patients with Parkinson's disease. Neurological sciences, 38(3), 425-431. https://doi.org/10.1007/s10072-016-2782-8
Wei, Z., Li, X., Li, X., Liu, Q., & Cheng, Y. (2018). Oxidative Stress in Parkinson's Disease: A Systematic Review and Meta-Analysis. Frontiers in molecular neuroscience, 11, 236. https://doi.org/10.3389/fnmol.2018.00236
Yuan, Y., Tong, Q., Zhang, L., Jiang, S., Zhou, H., Zhang, R., Zhang, S., Xu, Q., Li, D., Zhou, X., Ding, J., & Zhang, K. (2016). Plasma antioxidant status and motor features in de novo Chinese Parkinson's disease patients. The International journal of neuroscience, 126(7), 641-646. https://doi.org/10.3109/00207454.2015.1054031
Mischley, L. K., Standish, L. J., Weiss, N. S., Padowski, J. M., Kavanagh, T. J., White, C. C., & Rosenfeld, M. E. (2016). Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity. Oxidative medicine and cellular longevity, 2016, 9409363. https://doi.org/10.1155/2016/9409363
Colamartino, M., Duranti, G., Ceci, R., Sabatini, S., Testa, A., & Cozzi, R. (2018). A multi-biomarker analysis of the antioxidant efficacy of Parkinson's disease therapy. Toxicology in vitro, 47, 1-7. https://doi.org/10.1016/j.tiv.2017.10.020
Kumar, S., Dang, S., Nigam, K., Ali, J., & Baboota, S. (2018). Selegiline Nanoformulation in Attenuation of Oxidative Stress and Upregulation of Dopamine in the Brain for the Treatment of Parkinson's Disease. Rejuvenation research, 21(5), 464-476. https://doi.org/10.1089/rej.2017.2035
Mischley, L. K., Leverenz, J. B., Lau, R. C., Polissar, N. L., Neradilek, M. B., Samii, A., & Standish, L. J. (2015). A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson's disease. Movement disorders, 30(12), 1696-1701. https://doi.org/10.1002/mds.26351
Jakubczyk, K., Dec, K., Kałduńska, J., Kawczuga, D., Kochman, J., & Janda, K. (2020). Reactive oxygen species - sources, functions, oxidative damage. Polski merkuriusz lekarski, 48(284), 124-127.
Picón-Pagès, P., Garcia-Buendia, J., & Muñoz, F. J. (2019). Functions and dysfunctions of nitric oxide in brain. Biochimica et biophysica acta, 1865(8), 1949-1967. https://doi.org/10.1016/j.bbadis.2018.11.007
Tsikas, D. (2017). What we-authors, reviewers and editors of scientific work-can learn from the analytical history of biological 3-nitrotyrosine. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 1058, 68-72. https://doi.org/10.1016/j.jchromb.2017.05.012
Burai, R., Ait-Bouziad, N., Chiki, A., & Lashuel, H. A. (2015). Elucidating the Role of Site-Specific Nitration of α-Synuclein in the Pathogenesis of Parkinson's Disease via Protein Semisynthesis and Mutagenesis. Journal of the American Chemical Society, 137(15), 5041-5052. https://doi.org/10.1021/ja5131726
Feng, J., Chen, X., Guan, B., Li, C., Qiu, J., & Shen, J. (2018). Inhibition of Peroxynitrite-Induced Mitophagy Activation Attenuates Cerebral Ischemia-Reperfusion Injury. Molecular neurobiology, 55(8), 6369-6386. https://doi.org/10.1007/s12035-017-0859-x
Yuan, Y. Q., Wang, Y. L., Yuan, B. S., Yuan, X., Hou, X. O., Bian, J. S., Liu, C. F., & Hu, L. F. (2018). Impaired CBS-H2S signaling axis contributes to MPTP-induced neurodegeneration in a mouse model of Parkinson's disease. Brain, behavior, and immunity, 67, 77-90. https://doi.org/10.1016/j.bbi.2017.07.159
Campolo, M., Casili, G., Biundo, F., Crupi, R., Cordaro, M., Cuzzocrea, S., & Esposito, E. (2017). The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-κB/Nuclear Transcription Factor Related to NF-E2. Antioxidants & redox signaling, 27(8), 453-471. https://doi.org/10.1089/ars.2016.6800
Bandookwala, M., Sahu, A. K., Thakkar, D., Sharma, M., Khairnar, A., & Sengupta, P. (2019). Edaravone-caffeine combination for the effective management of rotenone induced Parkinson's disease in rats: An evidence based affirmative from a comparative analysis of behavior and biomarker expression. Neuroscience letters, 711, 134438. https://doi.org/10.1016/j.neulet.2019.134438
Cardinali, D. P. (2019). Melatonin: Clinical Perspectives in Neurodegeneration. Frontiers in endocrinology, 10, 480. https://doi.org/10.3389/fendo.2019.00480
Gallardo-Fernández, M., Hornedo-Ortega, R., Cerezo, A. B., Troncoso, A. M., & García-Parrilla, M. C. (2019). Melatonin, protocatechuic acid and hydroxytyrosol effects on vitagenes system against alpha-synuclein toxicity. Food and Chemical Toxicology, 134, 110817. https://doi.org/10.1016/j.fct.2019.110817
Wei, H. J., DU, M., & Bai, H. Y. (2019). Correlations of Melatonin and Glutathione Levels with Oxidative Stress Mechanism in Parkinson's Disease. Acta Academiae Medicinae Sinicae, 41(2), 183-187. https://doi.org/10.3881/j.issn.1000-503X.10775
Uysal, H. A., Tıftıkcıoğlu, B. I., Öcek, L., & Zorlu, Y. (2018). Serum Levels of Melatonin and Sleep Evaluation Scales in the Diagnosis of Sleep Disorders in Patients with Idiopathic Parkinson's Disease. Noro psikiyatri arsivi, 56(4), 264-268. https://doi.org/10.5152/npa.2017.19367
Ortiz, G. G., Moráles-Sánchez, E. W., Pacheco-Moisés, F. P., Jiménez-Gil, F. J., Macías-Islas, M. A., Mireles-Ramírez, M. A., & González-Usigli, H. (2017). Efecto de la administración de melatonina sobre la actividad de la ciclooxigenasa-2, la concentración sérica de metabolitos del óxido nítrico, los lipoperóxidos y la actividad de la glutatión peroxidasa en pacientes con enfermedad de Parkinson [Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson’s disease]. Gaceta medica de Mexico, 153(Supl. 2), S72-S81. https://doi.org/10.24875/GMM.M17000008
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