Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses
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{"title"=>"Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses", "type"=>"journal", "authors"=>[{"first_name"=>"Edward H.", "last_name"=>"Schuchman", "scopus_author_id"=>"7004364820"}, {"first_name"=>"Yi", "last_name"=>"Ge", "scopus_author_id"=>"36016440100"}, {"first_name"=>"Alon", "last_name"=>"Lai", "scopus_author_id"=>"24166749800"}, {"first_name"=>"Yury", "last_name"=>"Borisov", "scopus_author_id"=>"55569436700"}, {"first_name"=>"Meghan", "last_name"=>"Faillace", "scopus_author_id"=>"41961106300"}, {"first_name"=>"Efrat", "last_name"=>"Eliyahu", "scopus_author_id"=>"6508320837"}, {"first_name"=>"Xingxuan", "last_name"=>"He", "scopus_author_id"=>"8982147600"}, {"first_name"=>"James", "last_name"=>"Iatridis", "scopus_author_id"=>"6701406118"}, {"first_name"=>"Helen", "last_name"=>"Vlassara", "scopus_author_id"=>"7005741880"}, {"first_name"=>"Gary", "last_name"=>"Striker", "scopus_author_id"=>"7102191882"}, {"first_name"=>"Calogera M.", "last_name"=>"Simonaro", "scopus_author_id"=>"6602972154"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84872875678", "pui"=>"368187467", "doi"=>"10.1371/journal.pone.0054459", "isbn"=>"2012177778", "sgr"=>"84872875678", "pmid"=>"23365668"}, "id"=>"3cc566ff-2953-37b2-8d68-b616df5082ce", "abstract"=>"BACKGROUND: Pentosan polysulfate (PPS) is an FDA-approved, oral medication with anti-inflammatory and pro-chondrogenic properties. We have previously shown that animal models of the mucopolysaccharidoses (MPS) exhibit significant inflammatory disease, contributing to cartilage degeneration. Enzyme replacement therapy (ERT) only partly reduced inflammation, and anti-TNF-alpha antibody therapy significantly enhanced clinical and pathological outcomes. Here we describe the use of PPS for the treatment of MPS type VI rats.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Treatment began during prenatal development and at 1 and 6 months of age. All animals were treated until they were 9 months old. Significant reductions in the serum and tissue levels of several inflammatory markers (e.g., TNF-alpha, MIP-1alpha and RANTES/CCL5) were observed, as was reduced expression of inflammatory markers in cultured articular chondrocytes. ADAMTS-5/aggrecanase-2 levels also were reduced in chondrocytes, consistent with an elevation of serum tissue inhibitor of metalloproteinase 1. Marked improvements in motility and grooming behavior occurred, along with a reduction in eye and nasal secretions and a lessening of the tracheal deformities. MicroCT and radiographic analyses further revealed that the treated MPS skulls were longer and thinner, and that the teeth malocclusions, misalignments and mineral densities were improved. MicroCT analysis of the femurs and vertebrae revealed improvements in trabecular bone mineral densities, number and spacing in a subset of treated MPS animals. Biomechanical assessments of PPS-treated spines showed partially restored torsional behaviors, suggesting increased spinal stability. No improvements were observed in cortical bone or femur length. The positive changes in the PPS-treated MPS VI rats occurred despite glycosaminoglycan accumulation in their tissues.\\n\\nCONCLUSIONS: Based on these findings we conclude that PPS could be a simple and effective therapy for MPS that might provide significant clinical benefits alone and in combination with other therapies.", "link"=>"http://www.mendeley.com/research/pentosan-polysulfate-novel-therapy-mucopolysaccharidoses", "reader_count"=>40, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>5, "Student > Bachelor"=>5, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>5, "Student > Bachelor"=>5, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>4, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>13, "Agricultural and Biological Sciences"=>12, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Chemistry"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Chemistry"=>{"Chemistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>5}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>2, "Brazil"=>1}, "group_count"=>9}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/478335", "https://ndownloader.figshare.com/files/478336", "https://ndownloader.figshare.com/files/478337", "https://ndownloader.figshare.com/files/478339", "https://ndownloader.figshare.com/files/478340"], "description"=>"<div><h3>Background</h3><p>Pentosan polysulfate (PPS) is an FDA-approved, oral medication with anti-inflammatory and pro-chondrogenic properties. We have previously shown that animal models of the mucopolysaccharidoses (MPS) exhibit significant inflammatory disease, contributing to cartilage degeneration. Enzyme replacement therapy (ERT) only partly reduced inflammation, and anti-TNF-alpha antibody therapy significantly enhanced clinical and pathological outcomes. Here we describe the use of PPS for the treatment of MPS type VI rats.</p> <h3>Methodology/Principal Findings</h3><p>Treatment began during prenatal development and at 1 and 6 months of age. All animals were treated until they were 9 months old. Significant reductions in the serum and tissue levels of several inflammatory markers (e.g., TNF-alpha, MIP-1alpha and RANTES/CCL5) were observed, as was reduced expression of inflammatory markers in cultured articular chondrocytes. ADAMTS-5/aggrecanase-2 levels also were reduced in chondrocytes, consistent with an elevation of serum tissue inhibitor of metalloproteinase 1. Marked improvements in motility and grooming behavior occurred, along with a reduction in eye and nasal secretions and a lessening of the tracheal deformities. MicroCT and radiographic analyses further revealed that the treated MPS skulls were longer and thinner, and that the teeth malocclusions, misalignments and mineral densities were improved. MicroCT analysis of the femurs and vertebrae revealed improvements in trabecular bone mineral densities, number and spacing in a subset of treated MPS animals. Biomechanical assessments of PPS-treated spines showed partially restored torsional behaviors, suggesting increased spinal stability. No improvements were observed in cortical bone or femur length. The positive changes in the PPS-treated MPS VI rats occurred despite glycosaminoglycan accumulation in their tissues.</p> <h3>Conclusions</h3><p>Based on these findings we conclude that PPS could be a simple and effective therapy for MPS that might provide significant clinical benefits alone and in combination with other therapies.</p> </div>", "links"=>[], "tags"=>["pentosan", "mucopolysaccharidoses"], "article_id"=>154255, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.s001", "https://dx.doi.org/10.1371/journal.pone.0054459.s002", "https://dx.doi.org/10.1371/journal.pone.0054459.s003", "https://dx.doi.org/10.1371/journal.pone.0054459.s004", "https://dx.doi.org/10.1371/journal.pone.0054459.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pentosan_Polysulfate_A_Novel_Therapy_for_the_Mucopolysaccharidoses__/154255", "title"=>"Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-24 01:10:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/501013"], "description"=>"<p>Macrophage inflammatory protein-1alpha (MIP-1alpha), CCL5, regulated on activation normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-alpha), tissue inhibitors of metalloproteinases-1 (TIMP-1), and the advanced glycation endproducts (AGEs; <i>N</i><sup>e</sup>-carboxymethyl-lysine (CML) and methyglyoxal (MG)), were quantified by ELISA assays as described in the Materials and Methods. Hatched boxes, normal rats; white boxes, untreated MPS VI rats; light gray boxes, group 1 treated MPS VI rats; dark gray boxes, group 2 treated MPS VI rats; and black boxes, group 3 treated MPS VI rats. N = 10/group. The vertical lines in each column indicate the ranges. *P<0.05 comparing treated to untreated MPS VI rats.</p>", "links"=>[], "tags"=>["assays", "untreated", "pps-treated", "mps", "vi"], "article_id"=>171512, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_assays_in_normal_untreated_and_PPS_treated_MPS_VI_rats_/171512", "title"=>"Serum assays in normal, untreated and PPS-treated MPS VI rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:25:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/501152"], "description"=>"<p>A) TNF-alpha was visualized in liver and spleen sections by fluorescent immunohistochemistry as described in the Materials and Methods. Representative images from one untreated and treated (group 2) MPS VI rat are shown. Red = TNF-alpha. Blue = DAPI. B) Light microscopy and DAB staining was used to visualize TNF-alpha in the heart. Brown color indicates positive staining. Representative images from one untreated and two treated group 2 MPS VI rats are shown. Images are representative of multiple sections from at least 3 rats in each group. Similar reductions in TNF-alpha staining were seen in all treatment groups.</p>", "links"=>[], "tags"=>["immunology", "genetics and genomics", "rheumatology"], "article_id"=>171662, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TNF_alpha_immunohistochemistry_/171662", "title"=>"TNF-alpha immunohistochemistry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:27:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/501310"], "description"=>"<p>Articular chondrocytes were grown for 3 weeks as described in the Materials and Methods. Western blot analysis was then used to reveal the levels of TNF-alpha, p38, Cox-2 and ADAMTS-5. Each of these proteins was elevated in the untreated MPS VI rats (MPS) compared to normal (Nor) rats, and the levels were reduced to normal in the treated rats. Two animals each are shown for each of the three treatment groups. beta-actin was used as a loading control.</p>", "links"=>[], "tags"=>["blot", "articular", "chondrocytes", "pps-treated"], "article_id"=>171812, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blot_analysis_of_articular_chondrocytes_from_PPS_treated_and_control_rats_/171812", "title"=>"Western blot analysis of articular chondrocytes from PPS-treated and control rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:30:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/501401"], "description"=>"<p>Images of tracheas from normal, untreated MPS VI (MPS), and a representative animal from each PPS treatment group is shown. Note that the tracheas of untreated rats had thinner cartilage walls and smaller openings than normal rats, and that in the treated MPS VI rats the tracheal openings were wider.</p>", "links"=>[], "tags"=>["pps-treated"], "article_id"=>171911, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tracheas_from_PPS_treated_and_control_rats_/171911", "title"=>"Tracheas from PPS-treated and control rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:31:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/501487"], "description"=>"<p>Rotarod performance was assessed monthly in the untreated and PPS-treated MPS VI rats. Data is shown for all animals (n = 10/group) at 9 months of age, prior to sacrifice. White boxes, untreated MPS VI rats; light gray boxes, group 1 treated MPS VI rats; dark gray boxes, group 2 treated MPS VI rats; and black boxes, group 3 treated MPS VI rats. The vertical lines in each column indicate the ranges. The dotted horizontal line depicts the length of time that normal rats could remain on the rotarod at all speeds (120 s). In each of the treatment groups there was a significant improvement in the rotarod performance compared to untreated MPS VI rats (*P<0.05). This occurred at all speeds. Note that at or above 30 rpm the untreated MPS VI rats could not remain on the rotating bar.</p>", "links"=>[], "tags"=>["untreated", "pps-treated", "mps", "vi"], "article_id"=>171987, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rotarod_analysis_of_untreated_and_PPS_treated_MPS_VI_rats_/171987", "title"=>"Rotarod analysis of untreated and PPS-treated MPS VI rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/501599"], "description"=>"<p>A) Representative photographic images showing an untreated and PPS-treated (group 2) MPS VI rat. Black arrows indicate the eye and nasal secretions, which were reduced in the treated rats, and the ears, which were more erect in the treated animals. Also note the longer, thinner skulls. B) Representative radiograph and reconstructed microCT images of the skulls from a normal, untreated and treated MPS VI (group 2) rat. The longer and thinner snouts also are evident in these images. C) Quantitative radiographic measurements for all rats at 9 months of age. The skull and snouts lengths were statistically longer in all treated groups (*P<0.05). MicroCT reconstructions were carried out for at least 4 animals from each group.</p>", "links"=>[], "tags"=>["changes", "pps-treated", "mps", "vi"], "article_id"=>172109, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Skull_changes_in_the_PPS_treated_MPS_VI_rats_/172109", "title"=>"Skull changes in the PPS-treated MPS VI rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:35:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/501707"], "description"=>"<p>A) Reconstructed microCT images are shown for a representative normal, untreated MPS VI (MPS) and PPS-treated MPS VI (group 2) rat. The images to the right show a higher magnification to highlight the misalignment of the teeth in the untreated MPS VI rats (arrow), which was corrected in the treated animals. The skull microCT reconstructions were carried out for 6 rats each from groups 2 and 3, and similar observations were made. B) Tooth mineral densities (TMDs) were determined from the microCT analyses. Hatched boxes, normal rats; white boxes, untreated MPS VI rats; dark gray boxes, group 2 treated MPS VI rats; black boxes, group 3 treated MPS VI rats. Note that the TMDs were reduced in untreated rats compared to normal, and were significantly improved in each of the treatment groups (*P<0.05). C) Quantitative microCT measurements taken from reconstructed skull images from all of the analyzed PPS-treated group 2 and 3 rats (n = 12). Note the very significant posterior and anterior molar misalignment (PMM, AMM) evident in the untreated MPS VI rats, as well as the total misalignment (TtMis). In addition, the distance between the maxillary (upper) (maxM1–M1’ and maxM2–M2’) and mandibular (lower) (manM1–1′ and manM2–2′) molars in the untreated rats was wider than normal, and this was reduced in the treated rats. Finally, the nasal opening widths (NOW), which are moderately reduced in the untreated rats, were normalized in the treated rats, along with a ∼10% increase in nasal length (NL).</p>", "links"=>[], "tags"=>["changes", "pps-treated", "mps", "vi"], "article_id"=>172208, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dentition_changes_in_the_PPS_treated_MPS_VI_rats_/172208", "title"=>"Dentition changes in the PPS-treated MPS VI rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:36:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/501845"], "description"=>"<p>A) Representative reconstructed images from femurs showing mid-coronal and transverse growth plates (arrows). Note “detached” growth plates and condyles in MPS (white arrows) and non-responder animal (black arrows) which were improved in responder animals. B) Representative scaled 2D images from L2 vertebrae showing transverse, sagittal and coronal views. MPS vertebrae are shorter and wider than normal and are partially recovered with PPS treatment. Note that in the PPS-treated responder animal there were changes evident in the trabecular, but not in the cortical bone of both femurs and vertebrae.</p>", "links"=>[], "tags"=>["images", "femurs", "vertebrae", "pps-treated"], "article_id"=>172350, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MicroCT_images_of_femurs_and_vertebrae_of_PPS_treated_and_control_rats_/172350", "title"=>"MicroCT images of femurs and vertebrae of PPS-treated and control rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:39:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/501945"], "description"=>"<p>Values represent % of normal. Tra = trabecular, BV/TV = bone volume/total volume, Th = thickness, Spa = space, # = number, BMD = bone mineral density.</p><p>Values represent % of normal. Ct = cortical, Th = thickness, BMD = bone mineral density.</p>", "links"=>[], "tags"=>["microct"], "article_id"=>172457, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Femur_microCT_analyses_/172457", "title"=>"Femur microCT analyses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-24 00:40:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/501982"], "description"=>"<p>Values represent % of normal. Tra = trabecular, BV/TV = bone volume/total volume, Spa = space, # = space, TMD = total mineral density.</p><p>Values represent % of normal. Ct = cortical, Mar = margin, TMD = tissue mineral density.</p>", "links"=>[], "tags"=>["microct"], "article_id"=>172494, "categories"=>["Ecology", "Genetics", "Immunology"], "users"=>["Edward H. Schuchman", "Yi Ge", "Alon Lai", "Yury Borisov", "Meghan Faillace", "Efrat Eliyahu", "Xingxuan He", "James Iatridis", "Helen Vlassara", "Gary Striker", "Calogera M. Simonaro"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0054459.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vertebrae_microCT_analyses_/172494", "title"=>"Vertebrae microCT analyses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-24 00:41:34"}

PMC Usage Stats | Further Information

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Relative Metric

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