Phase I Clinical Trial of Systemically Administered TUSC2(FUS1)-Nanoparticles Mediating Functional Gene Transfer in Humans
- Publication Date
- April 25, 2012
- Journal
- PLOS ONE
- Authors
- Charles Lu, David J. Stewart, J. Jack Lee, Lin Ji, et al
- Volume
- 7
- Issue
- 4
- Pages
- e34833
- DOI
- https://dx.plos.org/10.1371/journal.pone.0034833
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0034833
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/22558101
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338819
- Europe PMC
- http://europepmc.org/abstract/MED/22558101
- Web of Science
- 000305345200014
- Scopus
- 84865850008
- Mendeley
- http://www.mendeley.com/research/phase-i-clinical-trial-systemically-administered-tusc2fus1nanoparticles-mediating-functional-gene-tr
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Mendeley | Further Information
{"title"=>"Phase I Clinical Trial of Systemically Administered TUSC2(FUS1)-Nanoparticles Mediating Functional Gene Transfer in Humans", "type"=>"journal", "authors"=>[{"first_name"=>"Charles", "last_name"=>"Lu"}, {"first_name"=>"David J.", "last_name"=>"Stewart"}, {"first_name"=>"J. Jack", "last_name"=>"Lee"}, {"first_name"=>"Lin", "last_name"=>"Ji"}, {"first_name"=>"Rajagopal", "last_name"=>"Ramesh"}, {"first_name"=>"Gitanjali", "last_name"=>"Jayachandran"}, {"first_name"=>"Maria I.", "last_name"=>"Nunez"}, {"first_name"=>"Ignacio I.", "last_name"=>"Wistuba"}, {"first_name"=>"Jeremy J.", "last_name"=>"Erasmus"}, {"first_name"=>"Marshall E.", "last_name"=>"Hicks"}, {"first_name"=>"Elizabeth A.", "last_name"=>"Grimm"}, {"first_name"=>"James M.", "last_name"=>"Reuben"}, {"first_name"=>"Veerabhadran", "last_name"=>"Baladandayuthapani"}, {"first_name"=>"Nancy S.", "last_name"=>"Templeton"}, {"first_name"=>"John D.", "last_name"=>"McMannis"}, {"first_name"=>"Jack A.", "last_name"=>"Roth"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"1932-6203", "scopus"=>"2-s2.0-84865850008", "pui"=>"365585967", "doi"=>"10.1371/journal.pone.0034833", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84865850008", "pmid"=>"22558101"}, "id"=>"a6c18331-6e5c-3904-a54f-0c32a5bc5c2f", "abstract"=>"BACKGROUND: Tumor suppressor gene TUSC2/FUS1 (TUSC2) is frequently inactivated early in lung cancer development. TUSC2 mediates apoptosis in cancer cells but not normal cells by upregulation of the intrinsic apoptotic pathway. No drug strategies currently exist targeting loss-of-function genetic abnormalities. We report the first in-human systemic gene therapy clinical trial of tumor suppressor gene TUSC2. METHODS: Patients with recurrent and/or metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP):cholesterol nanoparticles encapsulating a TUSC2 expression plasmid (DOTAP:chol-TUSC2) every 3 weeks. RESULTS: Thirty-one patients were treated at 6 dose levels (range 0.01 to 0.09 milligrams per kilogram). The MTD was determined to be 0.06 mg/kg. Five patients achieved stable disease (2.6-10.8 months, including 2 minor responses). One patient had a metabolic response on positron emission tomography (PET) imaging. RT-PCR analysis detected TUSC2 plasmid expression in 7 of 8 post-treatment tumor specimens but not in pretreatment specimens and peripheral blood lymphocyte controls. Proximity ligation assay, performed on paired biopsies from 3 patients, demonstrated low background TUSC2 protein staining in pretreatment tissues compared with intense (10-25 fold increase) TUSC2 protein staining in post-treatment tissues. RT-PCR gene expression profiling analysis of apoptotic pathway genes in two patients with high post-treatment levels of TUSC2 mRNA and protein showed significant post-treatment changes in the intrinsic apoptotic pathway. Twenty-nine genes of the 82 tested in the apoptosis array were identified by Igenuity Pathway Analysis to be significantly altered post-treatment in both patients (Pearson correlation coefficient 0.519; p<0.01). CONCLUSIONS: DOTAP:chol-TUSC2 can be safely administered intravenously in lung cancer patients and results in uptake of the gene by human primary and metastatic tumors, transgene and gene product expression, specific alterations in TUSC2-regulated pathways, and anti-tumor effects (to our knowledge for the first time for systemic DOTAP:cholesterol nanoparticle gene therapy). TRIAL REGISTRATION: ClinicalTrials.gov NCT00059605.", "link"=>"http://www.mendeley.com/research/phase-i-clinical-trial-systemically-administered-tusc2fus1nanoparticles-mediating-functional-gene-tr", "reader_count"=>46, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>2, "Student > Bachelor"=>6}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>2, "Student > Bachelor"=>6}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Materials Science"=>2, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>7, "Chemistry"=>2, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Chemistry"=>{"Chemistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>7}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "India"=>1}, "group_count"=>1}CrossRef
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Scopus | Further Information
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- {"month"=>"7", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"52"}
- {"month"=>"8", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"34"}
- {"month"=>"9", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"3", "html_views"=>"44"}
- {"month"=>"10", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"33"}
- {"month"=>"11", "year"=>"2019", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"58"}
- {"month"=>"12", "year"=>"2019", "pdf_views"=>"16", "xml_views"=>"3", "html_views"=>"61"}
- {"month"=>"1", "year"=>"2020", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"283"}
- {"month"=>"2", "year"=>"2020", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"373"}
- {"month"=>"3", "year"=>"2020", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"157"}
- {"month"=>"4", "year"=>"2020", "pdf_views"=>"26", "xml_views"=>"3", "html_views"=>"99"}
- {"month"=>"5", "year"=>"2020", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"179"}
- {"month"=>"6", "year"=>"2020", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"80"}
- {"month"=>"7", "year"=>"2020", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"24"}
- {"month"=>"8", "year"=>"2020", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"14"}
- {"month"=>"9", "year"=>"2020", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"20"}
- {"month"=>"10", "year"=>"2020", "pdf_views"=>"30", "xml_views"=>"0", "html_views"=>"26"}
- {"month"=>"11", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"11"}
- {"month"=>"12", "year"=>"2020", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"19"}
- {"month"=>"1", "year"=>"2021", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"27"}
- {"month"=>"2", "year"=>"2021", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"33"}
PMC Usage Stats | Further Information
- {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"88", "unique-ip"=>"81", "pdf"=>"43", "year"=>"2012", "figure"=>"9", "scanned-summary"=>"0", "supp-data"=>"0"}
- {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"50", "year"=>"2012", "pdf"=>"28", "unique-ip"=>"47", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"12"}
- {"unique-ip"=>"47", "full-text"=>"50", "pdf"=>"24", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2012", "month"=>"7"}
- {"unique-ip"=>"28", "full-text"=>"29", "pdf"=>"24", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2012", "month"=>"8"}
- {"unique-ip"=>"25", "full-text"=>"28", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
- {"unique-ip"=>"37", "full-text"=>"38", "pdf"=>"17", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
- {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
- {"unique-ip"=>"32", "full-text"=>"36", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
- {"unique-ip"=>"24", "full-text"=>"35", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
- {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
- {"unique-ip"=>"22", "full-text"=>"21", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
- {"unique-ip"=>"72", "full-text"=>"85", "pdf"=>"47", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"38", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
- {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
- {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
- {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
- {"unique-ip"=>"11", "full-text"=>"16", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
- {"unique-ip"=>"25", "full-text"=>"23", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
- {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
- {"unique-ip"=>"13", "full-text"=>"17", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
- {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
- {"unique-ip"=>"12", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
- {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
- {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"2", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
- {"unique-ip"=>"9", "full-text"=>"5", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
- {"unique-ip"=>"14", "full-text"=>"19", "pdf"=>"7", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
- {"unique-ip"=>"24", "full-text"=>"28", "pdf"=>"14", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
- {"unique-ip"=>"14", "full-text"=>"17", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
- {"unique-ip"=>"12", "full-text"=>"17", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
- {"unique-ip"=>"22", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
- {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
- {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
- {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
- {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
- {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
- {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
- {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
- {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"4", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
- {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
- {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
- {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
- {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
- {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
- {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"1"}
- {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2015", "month"=>"11"}
- {"unique-ip"=>"19", "full-text"=>"18", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
- {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
- {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2016", "month"=>"3"}
- {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
- {"unique-ip"=>"15", "full-text"=>"24", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
- {"unique-ip"=>"15", "full-text"=>"19", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
- {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
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- {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
- {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
- {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
- {"unique-ip"=>"15", "full-text"=>"21", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"15", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
- {"unique-ip"=>"17", "full-text"=>"19", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
- {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
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- {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"5"}
- {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
- {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
- {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
- {"unique-ip"=>"10", "full-text"=>"14", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"1", "year"=>"2017", "month"=>"9"}
- {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
- {"unique-ip"=>"12", "full-text"=>"18", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
- {"unique-ip"=>"12", "full-text"=>"15", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
- {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
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- {"unique-ip"=>"21", "full-text"=>"24", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
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Relative Metric
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