Evidence for the Complexity of MicroRNA-Mediated Regulation in Ovarian Cancer: A Systems Approach
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{"title"=>"Evidence for the complexity of Microrna-Mediated regulation in ovarian cancer: A systems approach", "type"=>"journal", "authors"=>[{"first_name"=>"Shubin W.", "last_name"=>"Shahab", "scopus_author_id"=>"55175065400"}, {"first_name"=>"Lilya V.", "last_name"=>"Matyunina", "scopus_author_id"=>"6506763886"}, {"first_name"=>"Roman", "last_name"=>"Mezencev", "scopus_author_id"=>"6603631387"}, {"first_name"=>"L. Ette", "last_name"=>"de Walker", "scopus_author_id"=>"47460996700"}, {"first_name"=>"Nathan J.", "last_name"=>"Bowen", "scopus_author_id"=>"7006490418"}, {"first_name"=>"Benedict B.", "last_name"=>"Benigno", "scopus_author_id"=>"6603264476"}, {"first_name"=>"John F.", "last_name"=>"McDonald", "scopus_author_id"=>"35319980800"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"79960648178", "pmid"=>"21811625", "scopus"=>"2-s2.0-79960648178", "issn"=>"19326203", "pui"=>"362190960", "doi"=>"10.1371/journal.pone.0022508"}, "id"=>"b318f639-67c6-341e-85f6-9b3ea982346e", "abstract"=>"MicroRNAs (miRNAs) are short ( approximately 22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted messenger RNAs (mRNAs) making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted mRNAs were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only approximately 11% of predicted target mRNAs. We demonstrate that this low inverse correlation between changes in levels of miRNAs and their target mRNAs in vivo is not merely an artifact of inaccurate miRNA target predictions but the likely consequence of indirect cellular processes that modulate the regulatory effects of miRNAs in vivo. Our findings underscore the complexities of miRNA-mediated regulation in vivo and the necessity of understanding the basis of these complexities in cancer cells before the therapeutic potential of miRNAs can be fully realized.", "link"=>"http://www.mendeley.com/research/evidence-complexity-micrornamediated-regulation-ovarian-cancer-systems-approach", "reader_count"=>33, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>3, "Student > Master"=>3, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>13, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>3, "Student > Master"=>3, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>23, "Medicine and Dentistry"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>23}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>4, "Japan"=>1, "United Kingdom"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/379563", "https://ndownloader.figshare.com/files/379625", "https://ndownloader.figshare.com/files/379680", "https://ndownloader.figshare.com/files/379726", "https://ndownloader.figshare.com/files/379767", "https://ndownloader.figshare.com/files/379782", "https://ndownloader.figshare.com/files/379798", "https://ndownloader.figshare.com/files/379814", "https://ndownloader.figshare.com/files/379833", "https://ndownloader.figshare.com/files/379850", "https://ndownloader.figshare.com/files/379868", "https://ndownloader.figshare.com/files/379888", "https://ndownloader.figshare.com/files/379903", "https://ndownloader.figshare.com/files/379931"], "description"=>"<div><p>MicroRNAs (miRNAs) are short (∼22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases including cancer. Previous studies have shown that miRNAs inhibit the translation and facilitate the degradation of their targeted messenger RNAs (mRNAs) making them attractive candidates for use in cancer therapy. However, the potential clinical utility of miRNAs in cancer therapy rests heavily upon our ability to understand and accurately predict the consequences of fluctuations in levels of miRNAs within the context of complex tumor cells. To evaluate the predictive power of current models, levels of miRNAs and their targeted mRNAs were measured in laser captured micro-dissected (LCM) ovarian cancer epithelial cells (CEPI) and compared with levels present in ovarian surface epithelial cells (OSE). We found that the predicted inverse correlation between changes in levels of miRNAs and levels of their mRNA targets held for only ∼11% of predicted target mRNAs. We demonstrate that this low inverse correlation between changes in levels of miRNAs and their target mRNAs <em>in vivo</em> is not merely an artifact of inaccurate miRNA target predictions but the likely consequence of indirect cellular processes that modulate the regulatory effects of miRNAs <em>in vivo.</em> Our findings underscore the complexities of miRNA-mediated regulation <em>in vivo</em> and the necessity of understanding the basis of these complexities in cancer cells before the therapeutic potential of miRNAs can be fully realized.</p> </div>", "links"=>[], "tags"=>["microrna-mediated", "ovarian", "systems"], "article_id"=>135012, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.s001", "https://dx.doi.org/10.1371/journal.pone.0022508.s002", "https://dx.doi.org/10.1371/journal.pone.0022508.s003", "https://dx.doi.org/10.1371/journal.pone.0022508.s004", "https://dx.doi.org/10.1371/journal.pone.0022508.s005", "https://dx.doi.org/10.1371/journal.pone.0022508.s006", "https://dx.doi.org/10.1371/journal.pone.0022508.s007", "https://dx.doi.org/10.1371/journal.pone.0022508.s008", "https://dx.doi.org/10.1371/journal.pone.0022508.s009", "https://dx.doi.org/10.1371/journal.pone.0022508.s010", "https://dx.doi.org/10.1371/journal.pone.0022508.s011", "https://dx.doi.org/10.1371/journal.pone.0022508.s012", "https://dx.doi.org/10.1371/journal.pone.0022508.s013", "https://dx.doi.org/10.1371/journal.pone.0022508.s014"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Evidence_for_the_Complexity_of_MicroRNA_Mediated_Regulation_in_Ovarian_Cancer_A_Systems_Approach/135012", "title"=>"Evidence for the Complexity of MicroRNA-Mediated Regulation in Ovarian Cancer: A Systems Approach", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-07-21 01:23:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/754071"], "description"=>"<p>An unsupervised hierarchical clustering of the CEPI and OSE samples was carried out using all detected probesets on the Ambion miRChip array, regardless of differential expression. Probesets with standard deviation <0.5 across all samples were removed prior to clustering. The clustering shows that the CEPI and OSE samples cluster into separate groups, which suggests the variance between the groups is greater than that within the groups.</p>", "links"=>[], "tags"=>["hierarchical", "clustering", "cepi", "ose", "samples", "probesets", "ambion"], "article_id"=>424429, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Unsupervised_hierarchical_clustering_of_CEPI_and_OSE_samples_based_on_probesets_expressed_on_the_Ambion_miRChip_/424429", "title"=>"Unsupervised hierarchical clustering of CEPI and OSE samples based on probesets expressed on the Ambion miRChip.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-21 01:13:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/754190"], "description"=>"<p>(A) Hierarchical clustering of normal and cancer patient samples based on differentially expressed miRNAs between CEPI cells and OSE cells (p<0.01, ≥2fold change). The dendogram on the left shows that the probes cluster into two groups corresponding to the up-regulated and down-regulated miRNAs differentially expressed between normal and cancer. IDs of selected probes are given on the right (including the annotated human miRNAs, see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022508#pone.0022508.s005\" target=\"_blank\">Table S1</a> for a complete list). Key: hsa-miR-x: annotated human miRNAs; hsa-asg/cand-x: predicted candidate human miRNAs; ppy-: <i>Pongo pygmaeus</i> miRNA; cel-: <i>C. elegans</i> miRNA. (B) Confirmation of expression patterns for selected miRNAs by qPCR. The relative expression of each miRNA in logarithmic units in cells from 3 cancer patients is shown compared to cells from 3 normal ovaries after normalization to RNU6B (ΔΔCt method). These were found to be statistically significant by Relative Expression Software Tool (REST®) by a randomization method. Randomization was performed 5000 times. Consistent with the microarray results, miR-141, miR-205 and miR-429 were confirmed to be significantly up-regulated in cancer, while miR-320 and miR-383 were found to be significantly down-regulated. Error bars represent standard error of the mean.</p>", "links"=>[], "tags"=>["mirnas", "cepi", "cells", "ovarian", "cancer", "patients"], "article_id"=>424552, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_expressed_miRNAs_in_CEPI_cells_from_ovarian_cancer_patients_relative_to_OSE_/424552", "title"=>"Differentially expressed miRNAs in CEPI cells from ovarian cancer patients relative to OSE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-21 01:15:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/754279"], "description"=>"<p>Targets that were predicted by miRanda (M), TargetScan (TS), PicTar (PT) or any combination of the 3 programs and were down-regulated (FDR<5%, fold change≥−|1.4|) in miR-7 transfection or in miR-128 transfection were assumed to be experimentally validated targets. The direction of change of these same targets in CEPI vs. OSE were then used to calculate IC, NC and PC fractions using a p-value<0.005 and a fold change of at least 2 in the tissue microarray data.</p>", "links"=>[], "tags"=>["pc", "nc", "mrnas", "cepi", "ose", "mir-7", "mir-128", "targets"], "article_id"=>424640, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.t006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_values_of_IC_PC_and_NC_mRNAs_in_CEPI_vs_OSE_for_miR_7_and_miR_128_using_8220_experimentally_validated_8221_targets_only_/424640", "title"=>"Summary values of IC, PC and NC mRNAs in CEPI vs. OSE for miR-7 and miR-128 using “experimentally validated” targets only.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-21 01:17:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/754317"], "description"=>"<p>miRNA targets that were differentially expressed between miR-7 or miR-128 transfected cells compared to negative control miRNA transfected cells, based on fold change of at least 1.4 and false discovery rate threshold of 5% were classified as being IC or PC with their regulating miRNAs (while target genes that do not meet the above criteria are classified as NC). Total number of targets from miRanda (M), TargetScan (TS) and PicTar (PT) or their intersections (two at time and all three) present after removing probe sets with “Absent” calls in all samples is shown along with fraction of IC, PC and NC targets for each miRNA.</p>", "links"=>[], "tags"=>["pc", "nc", "targets", "transfection", "experiments", "targetscan", "pictar"], "article_id"=>424679, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.t005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_values_of_IC_PC_and_NC_targets_in_transfection_experiments_using_miRanda_TargetScan_and_PicTar_target_predictions_/424679", "title"=>"Summary values of IC, PC and NC targets in transfection experiments using miRanda, TargetScan and PicTar target predictions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-21 01:17:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/754358"], "description"=>"<p>miRNA targets that were differentially expressed between CEPI and OSE based on t-test p<0.005 and fold change of at least 2 were classified as being IC or PC with their regulating miRNAs (while target genes that do not meet the above criteria are classified as NC). Total number of targets from the intersection (M_TS_PT) of miRanda (M), TargetScan (TS) and PicTar (PT) predictions present after removing probe sets with “Absent” calls in all samples is shown along with fraction of IC, PC and NC targets for each miRNA. On average, 76.7% of the target mRNAs are “No Change”, or do not change significantly with miRNAs, 6.8% are “inversely correlated” and 16.5% are “positively correlated” with miRNAs.</p>", "links"=>[], "tags"=>["pc", "nc", "targets", "cepi", "ose", "overlap", "targetscan", "pictar"], "article_id"=>424721, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_values_of_IC_PC_and_NC_targets_in_CEPI_vs_OSE_using_overlap_of_miRanda_TargetScan_and_PicTar_target_predictions_/424721", "title"=>"Summary values of IC, PC and NC targets in CEPI vs. OSE using overlap of miRanda, TargetScan and PicTar target predictions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-21 01:18:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/754399"], "description"=>"<p>Average fraction of IC, NC and PC targets in CEPI vs. OSE calculated for all 12 annotated miRNAs using miRanda, TargetScan (TS) or PicTar (PT) (See <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022508#pone-0022508-t002\" target=\"_blank\">Tables 2</a>, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022508#pone.0022508.s008\" target=\"_blank\">S4</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022508#pone.0022508.s009\" target=\"_blank\">S5</a> for details). The average IC, NC and PC fractions of the mean values calculated from these 3 different algorithms are also shown.</p>", "links"=>[], "tags"=>["pc", "nc", "fractions", "pictar", "targetscan"], "article_id"=>424761, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_average_IC_PC_and_NC_fractions_based_on_miRanda_PicTar_and_TargetScan_predicted_targets_/424761", "title"=>"Summary of average IC, PC and NC fractions based on miRanda, PicTar and TargetScan predicted targets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-21 01:19:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/754432"], "description"=>"<p>miRNA targets that were differentially expressed between CEPI and OSE based on t-test p<0.005 and fold change of at least 2 were classified as being IC or PC with their regulating miRNAs (while target genes that do not meet the above criteria are classified as NC). Total number of targets from miRanda algorithm present after removing probe sets with “Absent” calls in all samples is shown along with fraction of IC, PC and NC targets for each miRNA. On average, 78.6% of the target mRNAs are “No Change”, or do not change significantly with miRNAs, 11.2% are “inversely correlated” and 10.3% are “positively correlated” with miRNAs.</p>", "links"=>[], "tags"=>["pc", "nc", "targets", "cepi", "ose"], "article_id"=>424800, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_values_of_IC_PC_and_NC_targets_in_CEPI_vs_OSE_using_miRanda_/424800", "title"=>"Summary values of IC, PC and NC targets in CEPI vs. OSE using miRanda.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-21 01:20:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/754461"], "description"=>"a<p>mRNA microarray;</p>b<p>microRNA microarray;</p>c<p>real-time PCR.</p><p>Clinical information relevant to this study for each patient is shown. In addition, a legend is given to identify which patient was used for each microarray and qPCR experiment. Abbreviations used- Cerv: Cervix; Endo: Endometrium; Ov: Ovary; ca.: Carcinoma; hx: History.</p>", "links"=>[], "tags"=>["samples"], "article_id"=>424832, "categories"=>["Molecular Biology", "Biological Sciences", "Cancer", "Genetics"], "users"=>["Shubin W. Shahab", "Lilya V. Matyunina", "Roman Mezencev", "L. DeEtte Walker", "Nathan J. Bowen", "Benedict B. Benigno", "John F. McDonald"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0022508.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_information_of_patient_samples_used_in_this_study_/424832", "title"=>"Clinical information of patient samples used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-21 01:20:32"}

PMC Usage Stats | Further Information

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  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"38", "year"=>"2011", "pdf"=>"27", "unique-ip"=>"34", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"2"}
  • {"scanned-page-browse"=>"0", "month"=>"1", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"30", "unique-ip"=>"33", "pdf"=>"25", "year"=>"2012", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"2", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"23", "year"=>"2012", "pdf"=>"10", "unique-ip"=>"25", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"10"}
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  • {"month"=>"4", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"19", "year"=>"2012", "pdf"=>"14", "unique-ip"=>"19", "figure"=>"0", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"5", "cited-by"=>"0", "abstract"=>"1", "full-text"=>"14", "unique-ip"=>"15", "pdf"=>"6", "year"=>"2012", "figure"=>"2", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"6", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"0", "full-text"=>"11", "year"=>"2012", "pdf"=>"7", "unique-ip"=>"11", "figure"=>"4", "scanned-summary"=>"0", "supp-data"=>"0"}
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  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2012", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"10"}
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  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"21", "full-text"=>"17", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"11", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"29", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"14", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
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