Assessment of Glial Scar, Tissue Sparing, Behavioral Recovery and Axonal Regeneration following Acute Transplantation of Genetically Modified Human Umbilical Cord Blood Cells in a Rat Model of Spinal Cord Contusion
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{"title"=>"Assessment of glial scar, tissue sparing, behavioral recovery and axonal regeneration following acute transplantation of genetically modified human umbilical cord blood cells in a rat model of spinal cord contusion", "type"=>"journal", "authors"=>[{"first_name"=>"Yana O.", "last_name"=>"Mukhamedshina", "scopus_author_id"=>"55414550500"}, {"first_name"=>"Ekaterina E.", "last_name"=>"Garanina", "scopus_author_id"=>"56624383300"}, {"first_name"=>"Galina A.", "last_name"=>"Masgutova", "scopus_author_id"=>"26027535800"}, {"first_name"=>"Luisa R.", "last_name"=>"Galieva", "scopus_author_id"=>"57188571047"}, {"first_name"=>"Elvira R.", "last_name"=>"Sanatova", "scopus_author_id"=>"57188683887"}, {"first_name"=>"Yurii A.", "last_name"=>"Chelyshev", "scopus_author_id"=>"6603614074"}, {"first_name"=>"Albert A.", "last_name"=>"Rizvanov", "scopus_author_id"=>"6507161167"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84962459622", "sgr"=>"84962459622", "doi"=>"10.1371/journal.pone.0151745", "pui"=>"609296236", "pmid"=>"27003408", "issn"=>"19326203"}, "id"=>"8f8c433f-f582-3612-85ab-55e903dfa11e", "abstract"=>"OBJECTIVE AND METHODS: This study investigated the potential for protective effects of human umbilical cord blood mononuclear cells (UCB-MCs) genetically modified with the VEGF and GNDF genes on contusion spinal cord injury (SCI) in rats. An adenoviral vector was constructed for targeted delivery of VEGF and GDNF to UCB-MCs. Using a rat contusion SCI model we examined the efficacy of the construct on tissue sparing, glial scar severity, the extent of axonal regeneration, recovery of motor function, and analyzed the expression of the recombinant genes VEGF and GNDF in vitro and in vivo. RESULTS: Transplantation of UCB-MCs transduced with adenoviral vectors expressing VEGF and GDNF at the site of SCI induced tissue sparing, behavioral recovery and axonal regeneration comparing to the other constructs tested. The adenovirus encoding VEGF and GDNF for transduction of UCB-MCs was shown to be an effective and stable vehicle for these cells in vivo following the transplantation into the contused spinal cord. CONCLUSION: Our results show that a gene delivery using UCB-MCs-expressing VEGF and GNDF genes improved both structural and functional parameters after SCI. Further histological and behavioral studies, especially at later time points, in animals with SCI after transplantation of genetically modified UCB-MCs (overexpressing VEGF and GDNF genes) will provide additional insight into therapeutic potential of such cells.", "link"=>"http://www.mendeley.com/research/assessment-glial-scar-tissue-sparing-behavioral-recovery-axonal-regeneration-following-acute-transpl", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>3, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4877257"], "description"=>"<p>Primers and probes for RT-PCR.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136195, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Primers_and_probes_for_RT_PCR_/3136195", "title"=>"Primers and probes for RT-PCR.", "pos_in_sequence"=>8, "defined_type"=>3, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877218"], "description"=>"<p>BBB locomotor scores of rats obtained for the SCI (A, red line), SCI UCB-MCs+Ad5-EGFP (B, red line), SCI UCB-MCs+Ad5-VEGF+Ad5-GDNF (B, black line) and Sham UCB-MCs+Ad5-VEGF+Ad5-GDNF (A, black line) groups. Statistically significant differences were detected between Sham UCB-MCs+Ad5-VEGF+Ad5-GDNF group and other groups for all days (P < 0.05). BBB scores were higher in the UCB-MCs+Ad5-EGFP (B, red line) group than in the SCI (A, red line) on at least 3 post-injury days (9, 11 and 13). *–P < 0.05, two-way ANOVA.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136165, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/BBB_locomotor_scores_of_rats_after_SCI_or_Sham_in_experimental_group_/3136165", "title"=>"BBB locomotor scores of rats after SCI or Sham in experimental group.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877176"], "description"=>"<p>Visualization of the distribution of GFAP, CGRP and GAP43 at the site of spinal cord contusion lesion after SCI-only (C,D), transplantation of UCB-MCs+Ad5-EGFP (A,B) and UCB-MCs+Ad5-VEGF+Ad5-GDNF after SCI (E,F,K,M,N) and Sham (G,H). In the UCB-MCs+Ad5-EGFP group (A,B) CGRP and GAP-43 expression was located in the islet of lesion zone, surrounded by glial scar. The UCB-MCs at the injury site appeared to be very closely associated with GAP43<sup>+</sup> axons (K). The sections I,J present negative controls. Nuclei are stained with DAPI (blue). Scale bar: 100 (A-J) and 5 (K). (D) Mean labeling intensity of GAP43 of the rats in experimental groups in the SCI center. Differences were statistically significant between SCI and other experimental groups (*P < 0.01). Differences were also statistically significant between groups with injection of UCB-MCs (**P < 0.05). One-way ANOVA.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136138, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Expression_of_GFAP_CGRP_and_GAP43_in_the_lesion_site_of_spinal_cord_/3136138", "title"=>"Expression of GFAP, CGRP and GAP43 in the lesion site of spinal cord.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877152"], "description"=>"<p>Visualization of glial scar formation at the lesion site using GFAP in experimental groups: SCI UCB-MCs+Ad5-EGFP (A), SCI UCB-MCs+Ad5-VEGF+Ad5-GDNF (B), SCI (C) and Sham UCB-MCs+Ad5-VEGF+Ad5-GDNF (D). In the UCB-MCs+Ad5-VEGF+Ad5-GDNF-treated rats after SCI we detected a central zone of tissue without GFAP immunofluorescence. Scale bar: 750 μm. (E) Western-blotting analysis of GFAP on the 30th day after SCI with direct injection of UCB-MCs+Ad5-VEGF+Ad5-GDNF (1) and UCB-MCs+Ad5-EGFP (3), SCI without therapy (2), Sham operation with direct injection of UCB-MCs+Ad5-VEGF+Ad5-GDNF (4). Staining with Abs against GFAP revealed a band at 50 kDa in the samples. β-actin was used as a loading control. At day 30, western blot analysis shows reduced GFAP expression at the injury zone after UCB-MCs+Ad5-VEGF+Ad5-GDNF injection. Positive and negative controls were performed using Western Blotting control for GFAP antibodies and protein extracts from mononuclear umbilical cord blood cells, respectively. (F) Densitometry analysis demonstrated a significant change in GFAP levels relative to β-actin expression after SCI. Differences were statistically significant between SCI and other experimental groups (*P < 0.01). Differences were also statistically significant between groups with injection of UCB-MCs (**P < 0.05). One-way ANOVA.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136114, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Glial_scar_formation_at_the_lesion_site_indicated_by_GFAP_/3136114", "title"=>"Glial scar formation at the lesion site indicated by GFAP.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877098"], "description"=>"<p>Injured spinal cord 30 days after SCI without therapy (A), SCI with direct injection of UCB-MCs+Ad5-VEGF+Ad5-GDNF (B) and UCB-MCs+Ad5-EGFP (C), Sham operation with direct injection of UCB-MCs+Ad5-VEGF+Ad5-GDNF (D). Images are Azur-eosin cryosections. Scale bar: 750 μm. Volume of intact tissue (E) and cavity volume (F) relative to the Th8 area of intact rats remaining 30 days after SCI in experimental groups. *–P < 0.05, **–P < 0.01, one-way ANOVA followed by a Tukey’s <i>post hoc</i> test.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136051, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Tissue_analysis_in_experimental_groups_/3136051", "title"=>"Tissue analysis in experimental groups.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877128"], "description"=>"<p>Visualization of grafted cells in the SCI zone 30 days after transplantation of UCB-MCs+Ad5-EGFP (A) and UCB-MCs+Ad5-VEGF+Ad5-GDNF (B). Localization of transplanted UCB-MCs+Ad5-VEGF+Ad5-GDNF after Sham operation (C). (A) HNu<sup>+</sup> cells (red) surviving in the spinal cord contusion area, and forming cell bridges within the traumatic centromedullary cavity. The dashed boxes indicate enlarged area of A”. Arrows show some the HNu and DAPI overlap cells which were used for analysis. (A’) The same area, labeled by dashed boxes, in subsequent serial sections was stained as negative control. (B) In UCB-MCs+Ad5-VEGF+Ad5-GDNF-treated rats the contusion area with spared tissue contained mostly HNu<sup>+</sup> cells, which expressed VEGF and GDNF. (C) HNu<sup>+</sup>/VEGF<sup>+</sup>/GDNF<sup>+</sup> cells arranged accordingly to the nerve fibers 30 days after Sham with injection of UCB-MCs+Ad5-VEGF+Ad5-GDNF. Nuclei are stained with DAPI (blue). Scale bar: 200 (A), 10 (A’, A”), 2,5 (B) and 20 (C) μm.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136084, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Visualization_of_grafted_cells_at_day_30_after_transplantation_/3136084", "title"=>"Visualization of grafted cells at day 30 after transplantation.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877053"], "description"=>"<p>VEGF, GDNF (A) and EGFP (B) mRNA expression on day 30 after SCI or Sham followed by injection of transduced UCB-MCs. The levels of VEGF, GDNF and EGFP mRNA expression in SCI group was considered 100%. Differences were statistically significant between SCI-group and other experimental groups (*–P < 0.05, **–P < 0.01, Student’s t-test).</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136021, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/VEGF_GDNF_and_EGFP_mRNA_expression_in_vivo_/3136021", "title"=>"VEGF, GDNF and EGFP mRNA expression in vivo.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877281"], "description"=>"<p>Primary and secondary antibodies used in immunofluorescent staining.</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3136219, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Primary_and_secondary_antibodies_used_in_immunofluorescent_staining_/3136219", "title"=>"Primary and secondary antibodies used in immunofluorescent staining.", "pos_in_sequence"=>9, "defined_type"=>3, "published_date"=>"2016-03-22 06:23:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/4877029"], "description"=>"<p>VEGF (A), GDNF (B) and EGFP (C) mRNA expression on day 5 after transduction of UCB-MCs concurrently with adenoviral vectors Ad5-VEGF/Ad5-GDNF and Ad5-EGFP, respectively. The levels of VEGF, GDNF and EGFP mRNA expression in UCB-MCs was considered 100%. Differences were statistically significant between UCB-MCs and the experimental groups in all cases (**–P < 0.01, Student’s t-test).</p>", "links"=>[], "tags"=>["Genetically Modified Human Umbilical Cord Blood Cells", "glial scar severity", "umbilical cord blood", "rat contusion SCI model", "Spinal Cord Contusion Objective", "cord.ConclusionOur results show", "GNDF genes", "axonal regeneration", "adenovirus encoding VEGF", "GDNF"], "article_id"=>3135997, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Pharmacology", "Biotechnology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Science Policy"], "users"=>["Yana O. Mukhamedshina", "Ekaterina E. Garanina", "Galina A. Masgutova", "Luisa R. Galieva", "Elvira R. Sanatova", "Yurii A. Chelyshev", "Albert A. Rizvanov"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0151745.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/VEGF_GDNF_and_EGFP_mRNA_expression_in_vitro_/3135997", "title"=>"VEGF, GDNF and EGFP mRNA expression in vitro.", "pos_in_sequence"=>1, "defined_type"=>1, "published_date"=>"2016-03-22 06:23:11"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
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  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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