Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women
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{"title"=>"Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women", "type"=>"journal", "authors"=>[{"first_name"=>"Thomas R.", "last_name"=>"Hawn", "scopus_author_id"=>"6601968346"}, {"first_name"=>"Delia", "last_name"=>"Scholes", "scopus_author_id"=>"7005242906"}, {"first_name"=>"Hongwei", "last_name"=>"Wang", "scopus_author_id"=>"35278621900"}, {"first_name"=>"Sue S.", "last_name"=>"Li", "scopus_author_id"=>"7409241103"}, {"first_name"=>"Ann E.", "last_name"=>"Stapleton", "scopus_author_id"=>"7006459049"}, {"first_name"=>"Marta", "last_name"=>"Janer", "scopus_author_id"=>"34770603500"}, {"first_name"=>"Alan", "last_name"=>"Aderem", "scopus_author_id"=>"7006519947"}, {"first_name"=>"Walter E.", "last_name"=>"Stamm", "scopus_author_id"=>"7102302258"}, {"first_name"=>"Lue Ping", "last_name"=>"Zhao", "scopus_author_id"=>"7404455170"}, {"first_name"=>"Thomas M.", "last_name"=>"Hooton", "scopus_author_id"=>"7006593838"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-77949512726", "pui"=>"359087692", "doi"=>"10.1371/journal.pone.0008300", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "sgr"=>"77949512726", "pmid"=>"20016852"}, "id"=>"1e1d8dad-4a36-338a-bdda-535e1c1b5b38", "abstract"=>"BACKGROUND: Although several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early in vivo urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria.\\n\\nMETHODOLOGY: We conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB) in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines.\\n\\nPRINCIPAL FINDINGS: Polymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65-7.17). Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P< or =0.0001). Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P< or =0.0001). In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004).\\n\\nCONCLUSIONS: TLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early in vivo human bladder immune responses prior to the development of symptomatic UTIs.", "link"=>"http://www.mendeley.com/research/genetic-variation-human-urinary-tract-innate-immune-response-asymptomatic-bacteriuria-women-2", "reader_count"=>31, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>5, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>2, "Student > Doctoral Student"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>5, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>2, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>2, "Student > Doctoral Student"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>7, "Social Sciences"=>1, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Sweden"=>1, "Norway"=>1, "United States"=>2, "United Kingdom"=>1, "Germany"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/871534"], "description"=>"a<p>P value for comparison of 3 ASB clinical groups (no ASB vs medium vs high). P values or comparisons less than 0.05 are in bold.</p>", "links"=>[], "tags"=>["urine", "chemokine"], "article_id"=>541984, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASB_and_urine_chemokine_levels_/541984", "title"=>"ASB and urine chemokine levels.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:33:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/871760"], "description"=>"a<p>For coding region SNPs, the name includes nucleotide numbering based on mRNA with start codon at 1. For non-coding region SNPs, the name is from the IIPGA database (<a href=\"http://innateimmunity.net/IIPGA2/index_html\" target=\"_blank\">http://innateimmunity.net/IIPGA2/index_html</a>) and designated with a ‘z” prefix. rs numbers from the dbSNP database are included when available. A log-additive model was used for analysis. P values ≤0.05 in bold.</p>b<p>no ASB: <10<sup>3</sup> CFU/ml, medium ASB: >10<sup>3</sup> and <10<sup>5</sup> CFU/ml; high ASB: >10<sup>5</sup> CFU/ml.</p>c<p>Polymorphism CXCR2_T997C had no variation and could not be analyzed further.</p>", "links"=>[], "tags"=>["tlr", "polymorphisms", "asb", "caused", "gram-negative"], "article_id"=>542208, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t003", "stats"=>{"downloads"=>7, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CXCR1_CXCR2_and_TLR_polymorphisms_and_ASB_caused_by_gram_negative_uropathogens_/542208", "title"=>"CXCR1, CXCR2, and TLR polymorphisms and ASB caused by gram-negative uropathogens.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:36:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/871623"], "description"=>"a<p>Women with ASB defined as those with > = 1000 CFU/ml of a uropathogen. Chemokine levels were analyzed by genotype for each polymorphism with a log-additive model.</p>", "links"=>[], "tags"=>["tlr", "polymorphisms", "chemokine", "levels", "women"], "article_id"=>542074, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CXCR1_CXCR2_and_TLR_polymorphisms_and_chemokine_levels_in_women_with_ASB_a_/542074", "title"=>"CXCR1, CXCR2, and TLR polymorphisms and chemokine levels in women with ASB<sup>a</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:34:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/871575"], "description"=>"a<p>For coding region SNPs, the name includes nucleotide numbering based on mRNA with start codon at 1. For non-coding region SNPs, the name is from the IIPGA database (<a href=\"http://innateimmunity.net/IIPGA2/index_html\" target=\"_blank\">http://innateimmunity.net/IIPGA2/index_html</a>) and designated with a ‘z” prefix. rs numbers from the dbSNP database are included when available. A log-additive model was used for analysis. P values ≤0.05 in bold.</p>b<p>no ASB: <10<sup>3</sup> CFU/ml, medium ASB: >10<sup>3</sup> and <10<sup>5</sup> CFU/ml; high ASB: >10<sup>5</sup> CFU/ml.</p>c<p>Polymorphisms CXCR2_T997C and TLR4_A896G (in the High ASB group) had no variation and could not be analyzed further.</p>", "links"=>[], "tags"=>["tlr", "polymorphisms", "asb", "caused", "gram-positive"], "article_id"=>542024, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CXCR1_CXCR2_and_TLR_polymorphisms_and_ASB_caused_by_gram_positive_uropathogens_/542024", "title"=>"CXCR1, CXCR2, and TLR polymorphisms and ASB caused by gram-positive uropathogens.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:33:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/871469"], "description"=>"<p>Urine CXCL-8 levels in women with ASB were stratified by CXCR1_G827C genotypes and analyzed by a log-additive model. The 90<sup>th</sup> percentile median values are plotted with sample size for each genotype indicated.</p>", "links"=>[], "tags"=>["cxcr1", "polymorphism", "urine", "cxcl-8", "levels", "women"], "article_id"=>541909, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_a_CXCR1_polymorphism_with_urine_CXCL_8_levels_in_women_with_ASB_/541909", "title"=>"Association of a CXCR1 polymorphism with urine CXCL-8 levels in women with ASB.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-12-15 00:31:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/871801"], "description"=>"a<p>For coding region SNPs, the name includes nucleotide numbering based on mRNA with start codon at 1. For non-coding region SNPs, the name is from the IIPGA database (<a href=\"http://innateimmunity.net/IIPGA2/index_html\" target=\"_blank\">http://innateimmunity.net/IIPGA2/index_html</a>) and designated with a ‘z” prefix. rs numbers from the dbSNP database are included when available. A log-additive model was used for analysis. P values ≤0.05 in bold.</p>b<p>no ASB: <10<sup>3</sup> CFU/ml, medium ASB: >10<sup>3</sup> and <10<sup>5</sup> CFU/ml; high ASB: >10<sup>5</sup> CFU/ml.</p>c<p>Polymorphism CXCR2_T997C had no variation and could not be analyzed further.</p>", "links"=>[], "tags"=>["tlr", "polymorphisms"], "article_id"=>542254, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t002", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CXCR1_CXCR2_and_TLR_polymorphisms_and_ASB_/542254", "title"=>"CXCR1, CXCR2, and TLR polymorphisms and ASB.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:37:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/432395", "https://ndownloader.figshare.com/files/432448", "https://ndownloader.figshare.com/files/432504", "https://ndownloader.figshare.com/files/432572", "https://ndownloader.figshare.com/files/432609"], "description"=>"<div><h3>Background</h3><p>Although several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early <em>in vivo</em> urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria.</p><h3>Methodology</h3><p>We conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB) in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines.</p><h3>Principal Findings</h3><p>Polymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65–7.17). Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P≤0.0001). Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P≤0.0001). In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004).</p><h3>Conclusions</h3><p>TLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early <em>in vivo</em> human bladder immune responses prior to the development of symptomatic UTIs.</p></div>", "links"=>[], "tags"=>["urinary", "tract", "innate", "asymptomatic", "bacteriuria", "women"], "article_id"=>145322, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0008300.s001", "https://dx.doi.org/10.1371/journal.pone.0008300.s002", "https://dx.doi.org/10.1371/journal.pone.0008300.s003", "https://dx.doi.org/10.1371/journal.pone.0008300.s004", "https://dx.doi.org/10.1371/journal.pone.0008300.s005"], "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genetic_Variation_of_the_Human_Urinary_Tract_Innate_Immune_Response_and_Asymptomatic_Bacteriuria_in_Women/145322", "title"=>"Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-12-15 01:28:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/871715"], "description"=>"a<p>Definitions: CFU/ml of uropathogen: No ASB <10<sup>3</sup>; Medium ASB: ≥10<sup>3</sup> & <10<sup>5</sup>; High ASB: ≥10<sup>5</sup>.</p>b<p>Numbers and percentages in ethnicity subcategories can be greater than total number due to selection of more than one category for an individual.</p>C<p>P≤0.01 or <sup>d</sup> P≤0.05, when compared to group with no ASB.</p>e<p>For microbiology, numbers without percentages listed. The number of samples without growth of a specific pathogen in the “No ASB” group is left blank since it is the remainder of the 1122 individuals who had culture data available, but did not meet Medium or High ASB criteria.</p>f<p>Not included in uropathogen definition for this study.</p>", "links"=>[], "tags"=>["microbiologic", "characteristics", "asb"], "article_id"=>542166, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_and_microbiologic_characteristics_of_ASB_study_groups_/542166", "title"=>"Demographic and microbiologic characteristics of ASB study groups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:36:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/871666"], "description"=>"a<p>Comparing Urine PMNs in those with and without ASB with “negative” PMN group as reference.</p>b<p>Positive = combination of +, ++, and +++ neutrophil counts.</p>c<p>Comparing chemokine values at different urine neutrophil levels.</p>", "links"=>[], "tags"=>["neutrophil", "asb", "chemokine"], "article_id"=>542113, "categories"=>["Immunology", "Medicine"], "users"=>["Thomas R. Hawn", "Delia Scholes", "Hongwei Wang", "Sue S. Li", "Ann E. Stapleton", "Marta Janer", "Alan Aderem", "Walter E. Stamm", "Lue Ping Zhao", "Thomas M. Hooton"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0008300.t006", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Urine_neutrophil_association_with_ASB_and_chemokine_levels_/542113", "title"=>"Urine neutrophil association with ASB and chemokine levels.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-12-15 00:35:13"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
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  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
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  • {"unique-ip"=>"17", "full-text"=>"18", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
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  • {"unique-ip"=>"25", "full-text"=>"60", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
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  • {"unique-ip"=>"33", "full-text"=>"37", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
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  • {"unique-ip"=>"32", "full-text"=>"32", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"36", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
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  • {"unique-ip"=>"16", "full-text"=>"23", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"5", "cited-by"=>"1", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"35", "full-text"=>"39", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"35", "full-text"=>"65", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"21", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
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Relative Metric

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