Lattice-Based Model of Ductal Carcinoma In Situ Suggests Rules for Breast Cancer Progression to an Invasive State
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{"title"=>"Lattice-Based Model of Ductal Carcinoma In Situ Suggests Rules for Breast Cancer Progression to an Invasive State", "type"=>"journal", "authors"=>[{"first_name"=>"Eline", "last_name"=>"Boghaert", "scopus_author_id"=>"37076786000"}, {"first_name"=>"Derek C.", "last_name"=>"Radisky", "scopus_author_id"=>"6603819929"}, {"first_name"=>"Celeste M.", "last_name"=>"Nelson", "scopus_author_id"=>"7403704252"}], "year"=>2014, "source"=>"PLoS Computational Biology", "identifiers"=>{"pmid"=>"25473842", "issn"=>"15537358", "sgr"=>"84919683936", "pui"=>"601020723", "scopus"=>"2-s2.0-84919683936", "doi"=>"10.1371/journal.pcbi.1003997"}, "id"=>"7a426f25-2fcf-3222-95f7-aa06a0ea568b", "abstract"=>"Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.", "link"=>"http://www.mendeley.com/research/latticebased-model-ductal-carcinoma-situ-suggests-rules-breast-cancer-progression-invasive-state", "reader_count"=>43, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>8, "Other"=>6, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>2, "Student > Master"=>8, "Other"=>6, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>11, "Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>2, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>4, "Arts and Humanities"=>1, "Physics and Astronomy"=>2, "Computer Science"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>11}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>4}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>2, "United Kingdom"=>1, "France"=>2}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["http://files.figshare.com/1821602/Figure_3.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Varying cell division axis leads to increased development of multiple lumena.</p>", "figshare_url"=>"http://figshare.com/articles/_Varying_cell_division_axis_leads_to_increased_development_of_multiple_lumena_/1260203", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g003"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260203, "categories"=>["Uncategorised"], "description"=>"<p>Schematic of cell division with the cell division axis specified to be parallel to the epithelial cell layer (<b>A</b>) or random (<b>C</b>). Cells shown in pink undergo cell division. Varying the probability of apoptosis and mitosis frequency, we observe an increased emergence of multiple lumena when the cell division axis is parallel to the epithelial cell layer (<b>B</b>) or chosen randomly (<b>D</b>).</p>"}
  • {"files"=>["http://files.figshare.com/1821719/Table_1.xls"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Model parameters and variables.</p>", "figshare_url"=>"http://figshare.com/articles/_Model_parameters_and_variables_/1260285", "defined_type"=>3, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.t001"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260285, "categories"=>["Uncategorised"], "description"=>"<p>Model parameters and variables.</p>"}
  • {"files"=>["http://files.figshare.com/1824602/S1_Figure.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"Lattice-Based Model of Ductal Carcinoma <i>In Situ</i> Suggests Rules for Breast Cancer Progression to an Invasive State", "figshare_url"=>"http://figshare.com/articles/Lattice_Based_Model_of_Ductal_Carcinoma_In_Situ_Suggests_Rules_for_Breast_Cancer_Progression_to_an_Invasive_State/1261585", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.s001"], "published_date"=>"2014-12-04 14:41:35", "article_id"=>1261585, "categories"=>["Uncategorised"], "description"=>"<div><p>Ductal carcinoma <i>in situ</i> (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated <i>in vivo</i> since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct <i>in vivo</i> or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored <i>in vivo</i>.</p></div>"}
  • {"files"=>["http://files.figshare.com/1821675/Figure_5.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Invasion occurs preferentially at the ends of cylindrical ducts.</p>", "figshare_url"=>"http://figshare.com/articles/_Invasion_occurs_preferentially_at_the_ends_of_cylindrical_ducts_/1260244", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g005"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260244, "categories"=>["Uncategorised"], "description"=>"<p>(<b>A</b>) 0.5% probability of apoptosis, mitosis every 48 MCS, and random cell division: morphology begins as micropapillary and develops into cribriform with necrotic cells in the center and some invasion. Eventually the tissue becomes comedo. (<b>B</b>) 1% probability of apoptosis, mitosis every 32 MCS, and random cell division: morphology begins as micropapillary and develops into cribriform. As the tissue expands there are some necrotic cells in the duct and some cells break through the myoepithelial layer. (<b>C</b>) 0.5% probability of apoptosis, mitosis every 48 MCS, random cell division, and preferential proliferation: morphology begins as micropapillary and develops into cribriform morphology in the duct region with comedo morphology and invasion at the ends. Eventually the entire tissue becomes comedo. (<b>D</b>) 1% probability of apoptosis, mitosis every 32 MCS, random cell division, and preferential proliferation: morphology begins as micropapillary and develops into cribriform. As the tissue expands there are some necrotic cells in the duct and some cells break through the MEP layer. Quantification of tissues with invasion at the end and the duct region of each tissue at (<b>E</b>) 2000 MCS, (<b>F</b>) 2500 MCS and (<b>G</b>) 3000 MCS. Simulations were run 20 times each for the parameters described in A–D. Invasion occurs preferentially at the ends of the tissues.</p>"}
  • {"files"=>["http://files.figshare.com/1821709/Figure_6.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Patterns of cell invasion depend on cell adhesion and contractility.</p>", "figshare_url"=>"http://figshare.com/articles/_Patterns_of_cell_invasion_depend_on_cell_adhesion_and_contractility_/1260277", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g006"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260277, "categories"=>["Uncategorised"], "description"=>"<p>In the absence of proliferation, changing the adhesion parameter and the focal point plasticity parameter does not significantly alter tissue structure. (<b>A</b>) Images were generated using <i>J<sub>LEP,LEP</sub></i>, <i>J<sub>MEP,LEP</sub></i>, and <i>J<sub>MEP,MEP</sub></i> values of −2, −1, −0.5; −10, −5, −2.5; −20, −10, −5; −40, −20, −10; and −100, −50, −25 with FPPP set to zero. (<b>B</b>) Images were generated using FPP parameters of 5 and 0.5, 25 and 2.5, 50 and 5, 75 and 7.5, and 100 and 10 for homotypic and heterotypic interactions, respectively. With high proliferation (mitosis every 65 MCS) and high apoptosis (1% probability), changing the adhesion parameter and the focal point plasticity parameter affects cell invasion. (<b>C</b>) When cell adhesion is decreased cells invade from the entire periphery of the tissue. Adhesion and FPP parameters were all set to 0. (<b>D</b>) Increased cell adhesion inhibits invasion. Adhesion parameters were set to −100, −50, and −25 for <i>J<sub>LEP,LEP</sub></i>, <i>J<sub>MEP,LEP</sub></i>, and <i>J<sub>MEP,MEP</sub></i>, respectively. (<b>E</b>) Quantification of tissues with invasion at the end and the duct region of each tissue at 3000 MCS. Simulations were run 20 times each for the parameters described in C–D. (<b>F</b>) When tissue contractility is decreased by lowering the <i>λ<sub>v,MEP</sub></i> and <i>λ<sub>v,LEP</sub></i> to 2 and 1, respectively and lowering FPPP to 1 and 0.1 for homotypic and heterotypic cell interactions, cell invasion is inhibited. (<b>G</b>) Increased tissue contractility increases invasion from the duct regions. <i>λ<sub>v,MEP</sub></i> and <i>λ<sub>v,LEP</sub></i> were set to 50 and 25, respectively and FPP parameters were increased to 100 and 10 for homotypic and heterotypic cell interactions. (<b>H</b>) Quantification of tissues with invasion at the end and the duct region of each tissue at 3000 MCS. Simulations were run 20 times each for the parameters described in F–G.</p>"}
  • {"files"=>["http://files.figshare.com/1821520/Figure_1.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>DCIS morphologies.</p>", "figshare_url"=>"http://figshare.com/articles/_DCIS_morphologies_/1260151", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g001"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260151, "categories"=>["Uncategorised"], "description"=>"<p>Shown are histology sections (left) and schematic representations (right). (<b>A</b>) Micropapillary tumors contain additional epithelial cells within the lumen. (<b>B</b>) Cribriform tumors are characterized by ducts filled with cells that form multiple lumena. (<b>C</b>) Solid tumors have completely filled ducts. (<b>D</b>) Comedo tumors are solid with a necrotic core resulting from nutrient insufficiency <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003997#pcbi.1003997-Silverstein1\" target=\"_blank\">[6]</a>, <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003997#pcbi.1003997-Jaffer1\" target=\"_blank\">[9]</a>, <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003997#pcbi.1003997-Norton1\" target=\"_blank\">[10]</a>. Basement membrane is shown in black, myoepithelial (MEP) cells in blue, luminal epithelial (LEP) cells in green, and necrotic cells in red. Scale bars, 100 µm.</p>"}
  • {"files"=>["http://files.figshare.com/1821645/Figure_4.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Progression between DCIS morphologies.</p>", "figshare_url"=>"http://figshare.com/articles/_Progression_between_DCIS_morphologies_/1260217", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g004"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260217, "categories"=>["Uncategorised"], "description"=>"<p>(<b>A</b>) With no apoptosis and high proliferation (mitosis every 65 MCS, 15 mitotic events over 1000 MCS) we observe transitions from micropapillary to solid morphology and from solid to comedo morphology. Cell division axis was specified perpendicular to the epithelial layer. (<b>B</b>) With high apoptosis (1% probability) and high proliferation (mitosis every 38 MCS, 25 mitotic events over 1000 MCS) we observe transitions from the micropapillary to the cribriform morphology. Cell division axis was specified parallel to the epithelial layer. (<b>C</b>) With low apoptosis (0.5% probability) or (<b>D</b>) high apoptosis (1% probability) and low proliferation (mitosis every 65 MCS, 15 mitotic events over 1000 MCS) we observe only the micropapillary morphology. Cell division axis was random. LEP are capable of invading through the MEP layer from (<b>E</b>) micropapillary, (<b>F</b>) cribriform, (<b>G</b>) solid, and (<b>H</b>) comedo morphologies. The images shown here were generated under the following conditions: (<b>E</b> and <b>F</b>) 1% probability of apoptosis, mitosis every 32 MCS (30 mitotic events over 1000 MCS), and cell division axis parallel to the epithelial layer; (<b>G</b>) 0.5% probability of apoptosis, mitosis every 32 MCS (30 mitotic events over 1000 MCS), and random cell division axis; (<b>H</b>) 0.5% probability of apoptosis, mitosis every 38 MCS (25 mitotic events over 1000 MCS), and cell division axis parallel to the epithelial layer.</p>"}
  • {"files"=>["http://files.figshare.com/1821716/Figure_7.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Cells invade preferentially from the ends of bifurcating ducts.</p>", "figshare_url"=>"http://figshare.com/articles/_Cells_invade_preferentially_from_the_ends_of_bifurcating_ducts_/1260283", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g007"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260283, "categories"=>["Uncategorised"], "description"=>"<p>(<b>A</b>) In control tissues cells invade preferentially from the ends of bifurcating ducts. Decreasing contractility partially inhibits invasion, while increasing contractility causes delocalization of invasion. (<b>B</b>) Quantification of tissues with invasion at the end and the duct region of each tissue at 3000 MCS. Simulations were run with high proliferation (mitosis every 65 MCS) and high apoptosis (1% probability), 20 times for each of the parameters described in <a target=\"_blank\" href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003997#pcbi-1003997-g006\"><b>Fig. 6F&#8211;G</b></a>.</p>"}
  • {"files"=>["http://files.figshare.com/1821586/Figure_2.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "users"=>["Celeste M. Nelson", "Eline Boghaert", "Derek C. Radisky"], "links"=>[], "tags"=>["apoptosi", "tissue", "breast cancer progression", "model", "tumor cell behavior", "cribriform", "Cell proliferation", "Situ Suggests Rules", "Invasive State Ductal carcinoma", "vivo", "dcis", "comedo", "morphologie"], "title"=>"<p>Generation of morphologies based on number of mitotic events and probability of apoptosis.</p>", "figshare_url"=>"http://figshare.com/articles/_Generation_of_morphologies_based_on_number_of_mitotic_events_and_probability_of_apoptosis_/1260189", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pcbi.1003997.g002"], "published_date"=>"2014-12-04 03:04:42", "article_id"=>1260189, "categories"=>["Uncategorised"], "description"=>"<p>(<b>A</b>) Varying the probability of apoptosis and the mitosis frequency, we observe the emergence of solid and comedo morphologies at high proliferation rates with low apoptosis and micropapillary morphology at low proliferation rates with high apoptosis. (<b>B</b>) The cribriform morphology emerged occasionally, but not consistently for any of these conditions. Image shown from 1% apoptosis and 25 mitotic events. (<b>C</b>) Schematic of cell division when the division axis is specified to be perpendicular to the epithelial cell layer. Cells shown in pink undergo cell division.</p>"}

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  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[]}
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