AGR3 in Breast Cancer: Prognostic Impact and Suitable Serum-Based Biomarker for Early Cancer Detection
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{"title"=>"AGR3 in breast cancer: Prognostic impact and suitable serum-based biomarker for early cancer detection", "type"=>"journal", "authors"=>[{"first_name"=>"Stefan", "last_name"=>"Garczyk", "scopus_author_id"=>"56648162100"}, {"first_name"=>"Saskia", "last_name"=>"Von Stillfried", "scopus_author_id"=>"56394519200"}, {"first_name"=>"Wiebke", "last_name"=>"Antonopoulos", "scopus_author_id"=>"56623178200"}, {"first_name"=>"Arndt", "last_name"=>"Hartmann", "scopus_author_id"=>"7402943612"}, {"first_name"=>"Michael G.", "last_name"=>"Schrauder", "scopus_author_id"=>"55920718900"}, {"first_name"=>"Peter A.", "last_name"=>"Fasching", "scopus_author_id"=>"7003320928"}, {"first_name"=>"Tobias", "last_name"=>"Anzeneder", "scopus_author_id"=>"36665735700"}, {"first_name"=>"Andrea", "last_name"=>"Tannapfel", "scopus_author_id"=>"34573221000"}, {"first_name"=>"Yavuz", "last_name"=>"Ergönenc", "scopus_author_id"=>"36478547900"}, {"first_name"=>"Ruth", "last_name"=>"Knüchel", "scopus_author_id"=>"7004728010"}, {"first_name"=>"Michael", "last_name"=>"Rose", "scopus_author_id"=>"56174116400"}, {"first_name"=>"Edgar", "last_name"=>"Dahl", "scopus_author_id"=>"16149273600"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"25875093", "doi"=>"10.1371/journal.pone.0122106", "pui"=>"604107159", "issn"=>"19326203", "sgr"=>"84929484772", "scopus"=>"2-s2.0-84929484772"}, "id"=>"8923c102-b6db-3843-aa68-a939682f8632", "abstract"=>"Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.", "link"=>"http://www.mendeley.com/research/agr3-breast-cancer-prognostic-impact-suitable-serumbased-biomarker-early-cancer-detection-1", "reader_count"=>25, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Librarian"=>1, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>5, "Neuroscience"=>2, "Chemistry"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>2}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Ireland"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2022933"], "description"=>"<p>(<b>A</b>) Real-time PCR-based <i>AGR3</i> mRNA expression analysis of 62 breast tumour samples compared to 13 healthy breast tissue samples. Vertical lines: ± standard error of margin (SEM). (<b>B</b> and <b>C</b>) Box plots of the samples shown in A demonstrating a significant association of <i>AGR3</i> mRNA expression up-regulation with the IHC-defined luminal breast cancer subtype and lower grading (G1/G2). (<b>D</b>) <i>In silico AGR3</i> mRNA expression analysis of 516 PAM50-defined breast tumour samples depicted as heat map including normal breast tissues (<i>left</i>), and box plot (<i>right</i>). Red colour: high, black: intermediate, green: low <i>AGR3</i> mRNA expression. Horizontal lines: grouped medians. Boxes: 25–75% quartiles. Vertical lines: range, minimum and maximum. TNBC: triple negative breast cancer; ns: not significant, * <i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001.</p>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381438, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122106.g001", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Up_regulation_of_AGR3_mRNA_expression_in_G1_G2_grade_and_luminal_breast_carcinomas_/1381438", "title"=>"Up-regulation of <i>AGR3</i> mRNA expression in G1/G2 grade and luminal breast carcinomas.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-15 04:11:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2022950"], "description"=>"<p><sup>a</sup>According to Bloom and Richardson, as modified by Elston and Ellis [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref032\" target=\"_blank\">32</a>].</p><p><sup>b</sup>Log-rank test at the two-sided significance level of 0.05.</p><p><sup>c</sup>Median immunoreactive score (IRS) according to Remmele and Stegner [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref030\" target=\"_blank\">30</a>] was used as cut-off: AGR3 low (IRS 0–4), AGR3 high (IRS 6–12).</p><p><sup>d</sup>According to TNM classification by Sobin and Wittekind [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref058\" target=\"_blank\">58</a>].</p><p><sup>e</sup>Immunoreactive score (IRS) according to Remmele and Stegner [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref030\" target=\"_blank\">30</a>].</p><p><sup>f</sup>Overexpression of the <i>ERBB2</i> gene (Her-2/neu) was diagnosed analogously to the threshold of the DAKO-Score system based on IHC assay. Significant P-values are marked in bold face.</p><p>Univariate analysis of clinico-pathological parameters influencing tumour-specific survival in the group of grade<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#t001fn001\" target=\"_blank\"><sup>a</sup></a> 1 and 2 breast tumours.</p>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381452, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122106.t001", "stats"=>{"downloads"=>4, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Univariate_analysis_of_clinico_pathological_parameters_influencing_tumour_specific_survival_in_the_group_of_grade_a_1_and_2_breast_tumours_/1381452", "title"=>"Univariate analysis of clinico-pathological parameters influencing tumour-specific survival in the group of grade<sup>a</sup> 1 and 2 breast tumours.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-15 04:11:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2022946"], "description"=>"<p>According to the median AGR3 IRS of 6, the two groups “low AGR3” (IRS = 0–4) and “high AGR3” (IRS = 6–12) were dichotomised. Univariate Kaplan-Meier survival curves displaying tumour-specific survival of patients with low AGR3 expression (grey line) in relation to high AGR3 expression (black line) in (<b>A</b>) all, (<b>B</b>) low and intermediate (G1 and G2) and (<b>C</b>) high-grade (G3) breast cancer cases.</p>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381449, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122106.g003", "stats"=>{"downloads"=>2, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_AGR3_protein_expression_is_associated_with_reduced_tumour_specific_survival_in_G1_and_G2_breast_cancer_patients_/1381449", "title"=>"Increased AGR3 protein expression is associated with reduced tumour-specific survival in G1 and G2 breast cancer patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-15 04:11:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2022945"], "description"=>"<p><b>(A)</b> Western blot detection of human recombinant AGR3 (rAGR3, 100ng) but not recombinant AGR2 (rAGR2, 100ng) by monoclonal AGR3 antibody used for IHC analysis. <b>(B)</b> Cytoplasmic staining of AGR3 in isolated cells of the normal breast epithelium. <b>(C)</b> Strong cytoplasmic AGR3 protein expression in epithelial cancer cells of an IHC-defined luminal breast tumour. <b>(D)</b> Absent and <b>(E)</b> weak cytoplasmic AGR3 expression in two different triple negative breast tumours. <b>(F)</b> Box plot analysis demonstrating a significant up-regulation of AGR3 in all tumours (n = 190) and the luminal subtype (n = 113), but a significant reduction of expression in the triple negative breast cancer cases (TNBC, n = 23) compared to normal breast tissues (n = 39). <b>(G)</b> Box plot analysis showing a highly significant up-regulation of AGR3 in G1 and G2 breast tumours (n = 104) compared to normal controls (n = 39). Horizontal lines: grouped medians. Boxes: 25–75% quartiles. Vertical lines: range, minimum and maximum. Ns: not significant, * <i>P</i> < 0.05, *** <i>P</i> < 0.001. IRS: immunoreactive score.</p>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381448, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122106.g002", "stats"=>{"downloads"=>2, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Up_regulation_of_AGR3_protein_in_G1_G2_grade_and_luminal_breast_cancer_/1381448", "title"=>"Up-regulation of AGR3 protein in G1/G2 grade and luminal breast cancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-15 04:11:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2022955", "https://ndownloader.figshare.com/files/2022956", "https://ndownloader.figshare.com/files/2022957", "https://ndownloader.figshare.com/files/2022958", "https://ndownloader.figshare.com/files/2022959", "https://ndownloader.figshare.com/files/2022960", "https://ndownloader.figshare.com/files/2022961", "https://ndownloader.figshare.com/files/2022962", "https://ndownloader.figshare.com/files/2022963"], "description"=>"<div><p>Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.</p></div>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381457, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0122106.s001", "https://dx.doi.org/10.1371/journal.pone.0122106.s002", "https://dx.doi.org/10.1371/journal.pone.0122106.s003", "https://dx.doi.org/10.1371/journal.pone.0122106.s004", "https://dx.doi.org/10.1371/journal.pone.0122106.s005", "https://dx.doi.org/10.1371/journal.pone.0122106.s006", "https://dx.doi.org/10.1371/journal.pone.0122106.s007", "https://dx.doi.org/10.1371/journal.pone.0122106.s008", "https://dx.doi.org/10.1371/journal.pone.0122106.s009"], "stats"=>{"downloads"=>30, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AGR3_in_Breast_Cancer_Prognostic_Impact_and_Suitable_Serum_Based_Biomarker_for_Early_Cancer_Detection_/1381457", "title"=>"AGR3 in Breast Cancer: Prognostic Impact and Suitable Serum-Based Biomarker for Early Cancer Detection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-04-15 04:11:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2022951"], "description"=>"<p><sup>a</sup>According to Bloom and Richardson, as modified by Elston and Ellis [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref032\" target=\"_blank\">32</a>].</p><p><sup>b</sup>Median immunoreactive score (IRS) according to Remmele and Stegner [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref030\" target=\"_blank\">30</a>] was used as cut-off: AGR3 low (IRS 0–4), AGR3 high (IRS 6–12).</p><p><sup>c</sup>According to TNM classification by Sobin and Wittekind [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#pone.0122106.ref058\" target=\"_blank\">58</a>]. Significant P-values are marked in bold face. HR, hazard ratio; CI, confidence interval.</p><p>Multivariate Cox regression analysis including all factors potentially influencing tumour-specific survival in grade<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122106#t002fn001\" target=\"_blank\"><sup>a</sup></a> 1 and 2 breast cancer samples.</p>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381454, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122106.t002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_Cox_regression_analysis_including_all_factors_potentially_influencing_tumour_specific_survival_in_grade_a_1_and_2_breast_cancer_samples_/1381454", "title"=>"Multivariate Cox regression analysis including all factors potentially influencing tumour-specific survival in grade<sup>a</sup> 1 and 2 breast cancer samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-15 04:11:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/2022948"], "description"=>"<p>Scatter plot demonstrating a highly significant elevation of (<b>A</b>) AGR3 and (<b>C</b>) AGR2 protein concentration in human serum samples from breast cancer patients (n = 40) in comparison with samples from healthy women (n = 40). ROC curve analysis for (<b>B</b>) AGR3, (<b>D</b>) AGR2 and (<b>E</b>) the combination of both proteins. ** <i>P</i> < 0.01, *** <i>P</i> < 0.001. ROC: receiver operating characteristic, AUC: area under the curve, 95% CI: 95% confidence interval.</p>", "links"=>[], "tags"=>["AGR 3 expression", "serum samples", "AGR 3", "breast cancer prognosis", "AGR 3 protein concentration", "roc", "AGR 3 protein expression correlates", "breast cancer detection", "multivariate hazard ratio", "breast cancer", "elisa", "ci", "breast cancer patients", "characterised AGR 3", "AGR 2 protein", "biomarker"], "article_id"=>1381451, "categories"=>["Uncategorised"], "users"=>["Stefan Garczyk", "Saskia von Stillfried", "Wiebke Antonopoulos", "Arndt Hartmann", "Michael G. Schrauder", "Peter A. Fasching", "Tobias Anzeneder", "Andrea Tannapfel", "Yavuz Ergönenc", "Ruth Knüchel", "Michael Rose", "Edgar Dahl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122106.g004", "stats"=>{"downloads"=>2, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_the_diagnostic_performance_of_candidate_serum_biomarkers_AGR3_AGR2_and_their_combination_/1381451", "title"=>"Evaluation of the diagnostic performance of candidate serum biomarkers AGR3, AGR2 and their combination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-15 04:11:56"}

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  • {"unique-ip"=>"20", "full-text"=>"17", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"23", "full-text"=>"27", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"21", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"9", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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