{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T08:27:00Z","timestamp":1723796820266},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T00:00:00Z","timestamp":1453420800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T00:00:00Z","timestamp":1453420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Generative models are a popular instrument for illuminating the relationships between the hidden variables driving the growth of a complex network and its final topological characteristics, a process known as the \u201cgenotype to phenotype problem\u201d. However, the definition of a complete methodology encompassing all stages of the analysis and in particular the validation of the final model, is still an open problem. We here discuss a framework that allows to quantitatively optimise and validate each step of the model creation process. It is based on the execution of a classification task and on estimating the additional precision provided by the modelled genotype. This encompasses the three main steps of the model creation, namely the selection of topological features, the optimisation of the parameters of the generative model and the validation of the obtained results. We provide a minimum requirement for a generative model to be useful, prescribing the function mapping genotype to phenotype to be non-monotonic; and we further show how a previously published model does not fulfil such condition, casting doubts on its fitness for the study of neurological disorders. The generality of such framework guarantees its applicability beyond neuroscience, like the emergence of social or technological networks.<\/jats:p>","DOI":"10.1038\/srep19790","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T09:43:26Z","timestamp":1453455806000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["From phenotype to genotype in complex brain networks"],"prefix":"10.1038","volume":"6","author":[{"given":"Massimiliano","family":"Zanin","sequence":"first","affiliation":[]},{"given":"Marco","family":"Correia","sequence":"additional","affiliation":[]},{"given":"Pedro A. C.","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Cruz","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,1,22]]},"reference":[{"key":"BFsrep19790_CR1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1126\/science.1070534","volume":"296","author":"R Strohman","year":"2002","unstructured":"Strohman, R. Maneuvering in the complex path from genotype to phenotype. Science 296, 701\u2013703 (2002).","journal-title":"Science"},{"key":"BFsrep19790_CR2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1103\/RevModPhys.74.47","volume":"74","author":"R Albert","year":"2002","unstructured":"Albert, R. & Barab\u00e1si, A. L. Statistical mechanics of complex networks. Rev. Mod. Phys. 74, 47 (2002).","journal-title":"Rev. Mod. Phys."},{"key":"BFsrep19790_CR3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1137\/S003614450342480","volume":"45","author":"ME Newman","year":"2003","unstructured":"Newman, M. E. The structure and function of complex networks. SIAM Rev. 45, 167\u2013256 (2003).","journal-title":"SIAM Rev."},{"key":"BFsrep19790_CR4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.physrep.2005.10.009","volume":"424","author":"S Boccaletti","year":"2006","unstructured":"Boccaletti, S., Latora, V., Moreno, Y., Chavez, M. & Hwang, D. U. Complex networks: Structure and dynamics. Phys. Rep. 424, 175\u2013308 (2006).","journal-title":"Phys. Rep."},{"key":"BFsrep19790_CR5","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.physrep.2008.09.002","volume":"469","author":"A Arenas","year":"2008","unstructured":"Arenas, A., D\u00edaz-Guilera, A., Kurths, J., Moreno, Y. & Zhou, C. Synchronization in complex networks. Phys. Rep. 469, 93\u2013153 (2008).","journal-title":"Phys. Rep."},{"key":"BFsrep19790_CR6","doi-asserted-by":"crossref","first-page":"258702","DOI":"10.1103\/PhysRevLett.89.258702","volume":"89","author":"G Caldarelli","year":"2002","unstructured":"Caldarelli, G., Capocci, A., De Los Rios, P. & Mu\u00f1oz, M. A. Scale-free networks from varying vertex intrinsic fitness. Phys. Rev. Lett. 89, 258702 (2002).","journal-title":"Phys. Rev. Lett."},{"key":"BFsrep19790_CR7","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1209\/epl\/i2002-00248-2","volume":"60","author":"S Valverde","year":"2002","unstructured":"Valverde, S., Cancho, R. F. & Sole, R. V. Scale-free networks from optimal design. Europhys. Lett. 60, 512 (2002).","journal-title":"Europhys. Lett."},{"key":"BFsrep19790_CR8","doi-asserted-by":"crossref","first-page":"036123","DOI":"10.1103\/PhysRevE.65.036123","volume":"65","author":"K Klemm","year":"2002","unstructured":"Klemm, K. & Eguiluz, V. M. Highly clustered scale-free networks. Phys Rev E 65, 036123 (2002).","journal-title":"Phys Rev E"},{"key":"BFsrep19790_CR9","first-page":"021016","volume":"3","author":"JP Bagrow","year":"2013","unstructured":"Bagrow, J. P. & Brockmann, D. Natural emergence of clusters and bursts in network evolution. Phys Rev X 3, 021016 (2013).","journal-title":"Phys Rev X"},{"key":"BFsrep19790_CR10","doi-asserted-by":"crossref","first-page":"228701","DOI":"10.1103\/PhysRevLett.99.228701","volume":"99","author":"JM Kumpula","year":"2007","unstructured":"Kumpula, J. M., Onnela, J. P., Saram\u00e4ki, J., Kaski, K. & Kert\u00e9sz, J. Emergence of communities in weighted networks. Phys. Rev. Lett. 99, 228701 (2007).","journal-title":"Phys. Rev. Lett."},{"key":"BFsrep19790_CR11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/srep00099","volume":"1","author":"S Assenza","year":"2011","unstructured":"Assenza, S., Guti\u00e9rrez, R., G\u00f3mez-Garde\u00f1es, J., Latora, V. & Boccaletti, S. Emergence of structural patterns out of synchronization in networks with competitive interactions. Sci. Rep. 1, 99 (2011).","journal-title":"Sci. Rep."},{"key":"BFsrep19790_CR12","doi-asserted-by":"crossref","first-page":"012116","DOI":"10.1103\/PhysRevE.89.012116","volume":"89","author":"C Schmeltzer","year":"2014","unstructured":"Schmeltzer, C., Soriano, J., Sokolov, I. M. & R\u00fcdiger, S. Percolation of spatially constrained Erds-Rnyi networks with degree correlations. Phys Rev E 89, 012116 (2014).","journal-title":"Phys Rev E"},{"key":"BFsrep19790_CR13","doi-asserted-by":"crossref","first-page":"228701","DOI":"10.1103\/PhysRevLett.108.228701","volume":"108","author":"AA Rad","year":"2012","unstructured":"Rad, A. A. et al. Topological measure locating the effective crossover between segregation and integration in a modular network. Phys. Rev. Lett. 108, 228701 (2012).","journal-title":"Phys. Rev. Lett."},{"key":"BFsrep19790_CR14","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.1073374","volume":"297","author":"E Ravasz","year":"2002","unstructured":"Ravasz, E., Somera, A. L., Mongru, D. A., Oltvai, Z. N. & Barab\u00e1si, A. L. Hierarchical organization of modularity in metabolic networks. Science 297, 1551\u20131555 (2002).","journal-title":"Science"},{"key":"BFsrep19790_CR15","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1023\/A:1022001117715","volume":"3","author":"D Yamins","year":"2003","unstructured":"Yamins, D., Rasmussen, S. & Fogel, D. Growing urban roads Netw Spat Econ 3, 69\u201385 (2003).","journal-title":"Netw Spat Econ"},{"key":"BFsrep19790_CR16","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00168-005-0230-4","volume":"39","author":"BM Yerra","year":"2005","unstructured":"Yerra, B. M. & Levinson, D. M. The emergence of hierarchy in transportation networks. Ann Reg Sci 39, 541\u2013553 (2005).","journal-title":"Ann Reg Sci"},{"key":"BFsrep19790_CR17","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1287\/trsc.1050.0132","volume":"40","author":"D Levinson","year":"2006","unstructured":"Levinson, D. & Yerra, B. Self-organization of surface transportation networks. Transportation Sci 40, 179\u2013188 (2006).","journal-title":"Transportation Sci"},{"key":"BFsrep19790_CR18","doi-asserted-by":"crossref","first-page":"128701","DOI":"10.1103\/PhysRevLett.88.128701","volume":"88","author":"J Davidsen","year":"2002","unstructured":"Davidsen, J., Ebel, H. & Bornholdt, S. Emergence of a small world from local interactions: Modeling acquaintance networks. Phys. Rev. Lett. 88, 128701 (2002).","journal-title":"Phys. Rev. Lett."},{"key":"BFsrep19790_CR19","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1073\/pnas.0305684101","volume":"101","author":"M Marsili","year":"2004","unstructured":"Marsili, M., Vega-Redondo, F. & Slanina, F. The rise and fall of a networked society: A formal model. Proc. Natl. Acad. Sci. USA 101, 1439\u20131442 (2004).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep19790_CR20","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.socnet.2009.06.004","volume":"31","author":"R Toivonen","year":"2009","unstructured":"Toivonen, R. et al. A comparative study of social network models: Network evolution models and nodal attribute models. Soc. Networks 31, 240\u2013254 (2009).","journal-title":"Soc. Networks"},{"key":"BFsrep19790_CR21","doi-asserted-by":"crossref","unstructured":"Stegen, J. C., Ferriere, R. & Enquist, B. J. Evolving ecological networks and the emergence of biodiversity patterns across temperature gradients. Proc. R. Soc. B rspb20111733 (2011).","DOI":"10.1098\/rspb.2011.1733"},{"key":"BFsrep19790_CR22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.neucom.2004.01.059","volume":"58","author":"M Kaiser","year":"2004","unstructured":"Kaiser, M. & Hilgetag, C. C. Modelling the development of cortical systems networks. Neurocomputing 58, 297\u2013302 (2004).","journal-title":"Neurocomputing"},{"key":"BFsrep19790_CR23","doi-asserted-by":"crossref","first-page":"e1002937","DOI":"10.1371\/journal.pcbi.1002937","volume":"9","author":"Y Chen","year":"2013","unstructured":"Chen, Y., Wang, S., Hilgetag, C. C. & Zhou, C. Trade-off between multiple constraints enables simultaneous formation of modules and hubs in neural systems. PLoS Comput. Biol. 9, e1002937 (2013).","journal-title":"PLoS Comput. Biol."},{"key":"BFsrep19790_CR24","doi-asserted-by":"crossref","first-page":"7880","DOI":"10.1073\/pnas.1300753110","volume":"110","author":"V Nicosia","year":"2013","unstructured":"Nicosia, V., V\u00e9rtes, P. E., Schafer, W. R., Latora, V. & Bullmore, E. T. Phase transition in the economically modeled growth of a cellular nervous system. Proc. Natl. Acad. Sci. USA 110, 7880\u20137885 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep19790_CR25","doi-asserted-by":"crossref","first-page":"e1003491","DOI":"10.1371\/journal.pcbi.1003491","volume":"10","author":"F Klimm","year":"2014","unstructured":"Klimm, F., Bassett, D. S., Carlson, J. M. & Mucha, P. J. Resolving structural variability in network models and the brain. PLoS Comput. Biol. 10, e1003491 (2014).","journal-title":"PLoS Comput. Biol."},{"key":"BFsrep19790_CR26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11571-006-9006-5","volume":"1","author":"HF Kwok","year":"2007","unstructured":"Kwok, H. F., Jurica, P., Raffone, A. & van Leeuwen, C. Robust emergence of small-world structure in networks of spiking neurons. Cogn. Neurodyn. 1, 39\u201351 (2007).","journal-title":"Cogn. Neurodyn."},{"key":"BFsrep19790_CR27","first-page":"133","volume":"4","author":"CJ Stam","year":"2010","unstructured":"Stam, C. J., Hillebrand, A., Wang, H. & Van Mieghem, P. Emergence of modular structure in a large-scale brain network with interactions between dynamics and connectivity. Front Comput Neurosci. 4, 133 (2010).","journal-title":"Front Comput Neurosci."},{"key":"BFsrep19790_CR28","doi-asserted-by":"crossref","first-page":"061922","DOI":"10.1103\/PhysRevE.79.061922","volume":"79","author":"D Fraiman","year":"2009","unstructured":"Fraiman, D., Balenzuela, P., Foss, J. & Chialvo, D. R. Ising-like dynamics in large-scale functional brain networks. Phys Rev E 79, 061922 (2009).","journal-title":"Phys Rev E"},{"key":"BFsrep19790_CR29","doi-asserted-by":"crossref","first-page":"e20039","DOI":"10.1371\/journal.pone.0020039","volume":"6","author":"SL Simpson","year":"2011","unstructured":"Simpson, S. L., Hayasaka, S. & Laurienti, P. J. Exponential Random Graph Modeling for Complex Brain Networks. PLoS ONE 6, e20039 (2011).","journal-title":"PLoS ONE"},{"key":"BFsrep19790_CR30","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.1073\/pnas.1111738109","volume":"109","author":"PE V\u00e9rtes","year":"2012","unstructured":"V\u00e9rtes, P. E. et al. Simple models of human brain functional networks. Proc. Natl. Acad. Sci. USA 109, 5868\u20135873 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep19790_CR31","doi-asserted-by":"crossref","first-page":"e73186","DOI":"10.1371\/journal.pone.0073186","volume":"8","author":"Y Li","year":"2013","unstructured":"Li, Y., Qin, Y., Chen, X. & Li, W. Exploring the functional brain network of Alzheimer\u00e2\u20ac\u2122s disease: based on the computational experiment. PloS ONE 8, e73186 (2013).","journal-title":"PloS ONE"},{"key":"BFsrep19790_CR32","doi-asserted-by":"crossref","first-page":"20130531","DOI":"10.1098\/rstb.2013.0531","volume":"369","author":"PE V\u00e9rtes","year":"2014","unstructured":"V\u00e9rtes, P. E., Alexander-Bloch, A. & Bullmore, E. T. Generative models of rich clubs in Hebbian neuronal networks and large-scale human brain networks. Phil. Trans. R. Soc. B 369, 20130531 (2014).","journal-title":"Phil. Trans. R. Soc. B"},{"key":"BFsrep19790_CR33","doi-asserted-by":"crossref","first-page":"e19584","DOI":"10.1371\/journal.pone.0019584","volume":"6","author":"JM Buld\u00fa","year":"2011","unstructured":"Buld\u00fa, J. M. et al. Reorganization of functional networks in mild cognitive impairment. PLoS ONE 6, e19584 (2011).","journal-title":"PLoS ONE"},{"key":"BFsrep19790_CR34","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/00018732.2011.572452","volume":"60","author":"LdF Costa","year":"2011","unstructured":"Costa, L. d. F. et al. Analyzing and modeling real-world phenomena with complex networks: a survey of applications. Adv. Phys. 60, 329\u2013412 (2011).","journal-title":"Adv. Phys."},{"key":"BFsrep19790_CR35","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/srep00630","volume":"2","author":"M Zanin","year":"2012","unstructured":"Zanin, M. et al. Optimizing functional network representation of multivariate time series. Sci. Rep. 2, 630 (2012).","journal-title":"Sci. Rep."},{"key":"BFsrep19790_CR36","unstructured":"Zanin, M., Correia, M., Sousa, P. A. & Cruz, J. Probabilistic Constraint Programming for Parameters Optimisation of Generative Models. arXiv preprint 1505.07744 (2012)."},{"key":"BFsrep19790_CR37","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1109\/TPAMI.2006.211","volume":"28","author":"JJ Rodriguez","year":"2006","unstructured":"Rodriguez, J. J., Kuncheva, L. I. & Alonso, C. J. Rotation forest: A new classifier ensemble method. IEEE Trans. Pattern Anal. Mach. Intell. 28, 1619\u20131630 (2006).","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"BFsrep19790_CR38","doi-asserted-by":"crossref","unstructured":"Hastie, T. et al. The elements of statistical learning. Springer (2009).","DOI":"10.1007\/978-0-387-84858-7"},{"key":"BFsrep19790_CR39","unstructured":"Bellman, R. E. Dynamic programming. Princeton University Press (1957)."},{"key":"BFsrep19790_CR40","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1097\/00001756-200112210-00013","volume":"12","author":"F Maest\u00fa","year":"2001","unstructured":"Maest\u00fa, F. et al. Spatio-temporal patterns of brain magnetic activity during a memory task in Alzheimer\u2019s disease. Neuroreport 12, 3917\u20133922 (2001).","journal-title":"Neuroreport"},{"key":"BFsrep19790_CR41","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S0167-2789(01)00386-4","volume":"163","author":"CJ Stam","year":"2002","unstructured":"Stam, C. J. & Van Dijk, B. W. Synchronization likelihood: an unbiased measure of generalized synchronization in multivariate data sets. Physica D 163, 236\u2013251 (2002).","journal-title":"Physica D"},{"key":"BFsrep19790_CR42","doi-asserted-by":"crossref","first-page":"198701","DOI":"10.1103\/PhysRevLett.87.198701","volume":"87","author":"V Latora","year":"2001","unstructured":"Latora, V. & Marchiori, M. Efficient behavior of small-world networks. Phys. Rev. Lett. 87, 198701 (2001).","journal-title":"Phys. Rev. Lett."},{"key":"BFsrep19790_CR43","doi-asserted-by":"crossref","first-page":"016131","DOI":"10.1103\/PhysRevE.64.016131","volume":"64","author":"ME Newman","year":"2001","unstructured":"Newman, M. E. Scientific collaboration networks. I. Network construction and fundamental results. Phys Rev E 64, 016131 (2001).","journal-title":"Phys Rev E"},{"key":"BFsrep19790_CR44","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.physa.2004.07.011","volume":"346","author":"L Demetrius","year":"2005","unstructured":"Demetrius, L. & Manke, T. Robustness and network evolutionan entropic principle. Physica A 346, 682\u2013696 (2005).","journal-title":"Physica A"},{"key":"BFsrep19790_CR45","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1371\/journal.pcbi.0030017","volume":"3","author":"S Achard","year":"2007","unstructured":"Achard, S. & Bullmore, E. Efficiency and cost of economical brain functional networks. PLoS Comput. Biol. 3, e17 (2007).","journal-title":"PLoS Comput. Biol."},{"key":"BFsrep19790_CR46","unstructured":"Zanin, M. On alternative formulations of the small-world metric in complex networks. arXiv:1505.03689 (2015)."},{"key":"BFsrep19790_CR47","doi-asserted-by":"crossref","first-page":"30001","DOI":"10.1209\/0295-5075\/106\/30001","volume":"106","author":"M Zanin","year":"2014","unstructured":"Zanin, M., Sousa, P. A. & Menasalvas, E. Information content: Assessing meso-scale structures in complex networks. EPL (Europhys. Lett.) 106, 30001 (2014).","journal-title":"EPL (Europhys. Lett.)"},{"key":"BFsrep19790_CR48","first-page":"81","volume":"1","author":"JR Quinlan","year":"1986","unstructured":"Quinlan, J. R. Induction of decision trees. Machine learning 1, 81\u2013106 (1986).","journal-title":"Machine learning"},{"key":"BFsrep19790_CR49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1023\/A:1007607513941","volume":"40","author":"TG Dietterich","year":"2000","unstructured":"Dietterich, T. G. An experimental comparison of three methods for constructing ensembles of decision trees: Bagging, boosting and randomization. Machine learning 40, 139\u2013157 (2000).","journal-title":"Machine learning"},{"key":"BFsrep19790_CR50","doi-asserted-by":"crossref","unstructured":"Berthold, M. R. et al. KNIME: The Konstanz information miner. In Data analysis, machine learning and applications. 319\u2013326 Springer: Berlin Heidelberg, (2008).","DOI":"10.1007\/978-3-540-78246-9_38"},{"key":"BFsrep19790_CR51","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1080\/00401706.1979.10489751","volume":"21","author":"GH Golub","year":"1979","unstructured":"Golub, G. H., Heath, M. & Wahba, G. Generalized cross-validation as a method for choosing a good ridge parameter. Technometrics 21, 215\u2013223 (1979).","journal-title":"Technometrics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep19790.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep19790","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep19790.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T23:30:23Z","timestamp":1672875023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep19790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,22]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFsrep19790"],"URL":"https:\/\/doi.org\/10.1038\/srep19790","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,22]]},"assertion":[{"value":"24 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19790"}}