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R package version 0.1.2 (The R Foundation). https:\/\/cran.r-project.org\/web\/packages\/drLumi\/index.html."},{"key":"10.1016\/j.ymthe.2018.06.021_bib72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0361-9230(99)00012-X","article-title":"Stereotaxic atlas of the pig brain","volume":"49","author":"F\u00e9lix","year":"1999","journal-title":"Brain Res. 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