Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion
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{"title"=>"Differential susceptibility to hypertension is due to selection during the out-of-Africa expansion", "type"=>"journal", "authors"=>[{"first_name"=>"J. Hunter", "last_name"=>"Young", "scopus_author_id"=>"7408525242"}, {"first_name"=>"Yen Pei C.", "last_name"=>"Chang", "scopus_author_id"=>"8158751700"}, {"first_name"=>"James Dae Ok", "last_name"=>"Kim", "scopus_author_id"=>"13103744900"}, {"first_name"=>"Jean Paul", "last_name"=>"Chretien", "scopus_author_id"=>"35767522800"}, {"first_name"=>"Michael J.", "last_name"=>"Klag", "scopus_author_id"=>"7103327135"}, {"first_name"=>"Michael A.", "last_name"=>"Levine", "scopus_author_id"=>"35397994900"}, {"first_name"=>"Christopher B.", "last_name"=>"Ruff", "scopus_author_id"=>"7005423421"}, {"first_name"=>"Nae Yuh", "last_name"=>"Wang", "scopus_author_id"=>"7404340658"}, {"first_name"=>"Aravinda", "last_name"=>"Chakravarti", "scopus_author_id"=>"35355137200"}], "year"=>2005, "source"=>"PLoS Genetics", "identifiers"=>{"sgr"=>"55449131653", "pmid"=>"16429165", "isbn"=>"1553-7404 (Electronic)", "scopus"=>"2-s2.0-55449131653", "issn"=>"15537390", "pui"=>"135775055", "doi"=>"10.1371/journal.pgen.0010082"}, "id"=>"8aa37dcd-9a16-38bb-b70c-c093706c5830", "abstract"=>"Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in short tandem repeat markers, control single nucleotide polymorphisms, or non-functional single nucleotide polymorphisms within the five genes. In addition, we show that latitude and one of these alleles, GNB3 (G protein beta3 subunit) 825T, account for a major portion of worldwide variation in blood pressure. These results suggest that the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate.", "link"=>"http://www.mendeley.com/research/differential-susceptibility-hypertension-due-selection-during-outofafrica-expansion", "reader_count"=>126, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>19, "Researcher"=>18, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>29, "Student > Postgraduate"=>7, "Student > Master"=>15, "Other"=>3, "Student > Bachelor"=>15, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>11}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>19, "Researcher"=>18, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>29, "Student > Postgraduate"=>7, "Student > Master"=>15, "Other"=>3, "Student > Bachelor"=>15, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>11}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Agricultural and Biological Sciences"=>57, "Arts and Humanities"=>2, "Business, Management and Accounting"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Computer Science"=>3, "Engineering"=>1, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>12, "Nursing and Health Professions"=>2, "Mathematics"=>2, "Medicine and Dentistry"=>21, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1, "Social Sciences"=>11, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>21}, "Social Sciences"=>{"Social Sciences"=>11}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>8}, "Environmental Science"=>{"Environmental Science"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>2}, "Engineering"=>{"Engineering"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>57}, "Computer Science"=>{"Computer Science"=>3}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Austria"=>1, "United States"=>7, "Brazil"=>2, "France"=>1, "Chile"=>1, "Switzerland"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/960249"], "description"=>"<p>Heat Adaptation Is Strongly Associated with Absolute Latitude, Temperature, and Precipitation among the 53 Populations of the CEPH HGDP Cell Line Panel</p>", "links"=>[], "tags"=>["adaptation", "precipitation", "53", "populations", "ceph", "hgdp"], "article_id"=>630244, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_Adaptation_Is_Strongly_Associated_with_Absolute_Latitude_Temperature_and_Precipitation_among_the_53_Populations_of_the_CEPH_HGDP_Cell_Line_Panel_/630244", "title"=>"Heat Adaptation Is Strongly Associated with Absolute Latitude, Temperature, and Precipitation among the 53 Populations of the CEPH HGDP Cell Line Panel", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:48:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/960444"], "description"=>"<p>Histogram of β Coefficients for the Association of Heat Stress with Functional Genotypes, Neutral STR Markers, and Control SNPs for the Seven African populations of the CEPH HGDP Cell Line Panel</p>", "links"=>[], "tags"=>["coefficients", "str", "snps", "african", "populations", "ceph", "hgdp"], "article_id"=>630438, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g005", "stats"=>{"downloads"=>4, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histogram_of_946_Coefficients_for_the_Association_of_Heat_Stress_with_Functional_Genotypes_Neutral_STR_Markers_and_Control_SNPs_for_the_Seven_African_populations_of_the_CEPH_HGDP_Cell_Line_Panel_/630438", "title"=>"Histogram of β Coefficients for the Association of Heat Stress with Functional Genotypes, Neutral STR Markers, and Control SNPs for the Seven African populations of the CEPH HGDP Cell Line Panel", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:50:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/472173", "https://ndownloader.figshare.com/files/472256", "https://ndownloader.figshare.com/files/472350", "https://ndownloader.figshare.com/files/472394", "https://ndownloader.figshare.com/files/472497"], "description"=>"<div><p>Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in short tandem repeat markers, control single nucleotide polymorphisms, or non-functional single nucleotide polymorphisms within the five genes. In addition, we show that latitude and one of these alleles, <em>GNB3</em> (G protein β3 subunit) <em>825T,</em> account for a major portion of worldwide variation in blood pressure. These results suggest that the current epidemic of hypertension is due to exposures of the modern period interacting with ancestral susceptibility. Modern populations differ in susceptibility to these new exposures, however, such that those from hot environments are more susceptible to hypertension than populations from cold environments. This differential susceptibility is likely due to our history of adaptation to climate.</p></div>", "links"=>[], "tags"=>["differential", "susceptibility", "hypertension", "out-of-africa"], "article_id"=>153095, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0010082.sg001", "https://dx.doi.org/10.1371/journal.pgen.0010082.sg002", "https://dx.doi.org/10.1371/journal.pgen.0010082.st001", "https://dx.doi.org/10.1371/journal.pgen.0010082.st002", "https://dx.doi.org/10.1371/journal.pgen.0010082.st003"], "stats"=>{"downloads"=>9, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Differential_Susceptibility_to_Hypertension_Is_Due_to_Selection_during_the_Out_of_Africa_Expansion/153095", "title"=>"Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-20 10:52:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/960547"], "description"=>"<p>Residual Plot Demonstrating the Association of <i>GNB3 825T</i> with Systolic Blood Pressure after Adjustment for Latitude among 35 INTERSALT Populations with Matching Genotype Data</p>", "links"=>[], "tags"=>["demonstrating", "systolic", "latitude", "35", "intersalt", "populations", "matching", "genotype"], "article_id"=>630539, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g006", "stats"=>{"downloads"=>2, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Residual_Plot_Demonstrating_the_Association_of_GNB3_825T_with_Systolic_Blood_Pressure_after_Adjustment_for_Latitude_among_35_INTERSALT_Populations_with_Matching_Genotype_Data_/630539", "title"=>"Residual Plot Demonstrating the Association of <i>GNB3 825T</i> with Systolic Blood Pressure after Adjustment for Latitude among 35 INTERSALT Populations with Matching Genotype Data", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:50:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/960328"], "description"=>"<p>Histogram of β Coefficients for the Association of Absolute Latitude with Functional Genotypes, Neutral STR Markers, and Control SNPs for the 53 Populations of the CEPH HGDP Cell Line Panel</p>", "links"=>[], "tags"=>["coefficients", "latitude", "str", "snps", "53", "populations", "ceph", "hgdp"], "article_id"=>630317, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histogram_of_946_Coefficients_for_the_Association_of_Absolute_Latitude_with_Functional_Genotypes_Neutral_STR_Markers_and_Control_SNPs_for_the_53_Populations_of_the_CEPH_HGDP_Cell_Line_Panel_/630317", "title"=>"Histogram of β Coefficients for the Association of Absolute Latitude with Functional Genotypes, Neutral STR Markers, and Control SNPs for the 53 Populations of the CEPH HGDP Cell Line Panel", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:49:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/960388"], "description"=>"<p>Heat Adaptation, <i>AGT G-217A,</i> and <i>ENaCγ</i> Are Strongly Associated with Heat Stress in Africa</p>", "links"=>[], "tags"=>["Evolutionary biology", "physiology", "genetics and genomics/population genetics", "genetics and genomics/genetics of disease", "genetics and genomics/complex traits"], "article_id"=>630387, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g004", "stats"=>{"downloads"=>7, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_Adaptation_AGT_G_217A_and_ENaC_947_Are_Strongly_Associated_with_Heat_Stress_in_Africa_/630387", "title"=>"Heat Adaptation, <i>AGT G-217A,</i> and <i>ENaCγ</i> Are Strongly Associated with Heat Stress in Africa", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:49:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/960690"], "description"=>"<p>The β coefficients represent those in the models listed in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010082#pgen-0010082-t003\" target=\"_blank\">Table 3</a>.</p>", "links"=>[], "tags"=>["relating", "latitude", "population-average", "systolic", "35", "intersalt", "populations", "matching", "genotype"], "article_id"=>630677, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g007", "stats"=>{"downloads"=>3, "page_views"=>78, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Epidemiologic_Model_Relating_Absolute_Latitude_and_Population_Average_GNB3_825T_Frequency_with_Each_Other_and_with_Population_Average_Systolic_Blood_Pressure_among_35_INTERSALT_Populations_with_Matching_Genotype_Data_/630677", "title"=>"Epidemiologic Model Relating Absolute Latitude and Population-Average <i>GNB3 825T</i> Frequency with Each Other and with Population-Average Systolic Blood Pressure among 35 INTERSALT Populations with Matching Genotype Data", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:51:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/960168"], "description"=>"<p>Worldwide Distribution of the 53 Populations of the CEPH Human Genome Diversity Cell Line Panel</p>", "links"=>[], "tags"=>["53", "populations", "ceph", "genome"], "article_id"=>630169, "categories"=>["Physiology", "Genetics", "Evolutionary Biology"], "users"=>["J. Hunter Young", "Yen-Pei C Chang", "James Dae-Ok Kim", "Jean-Paul Chretien", "Michael J Klag", "Michael A Levine", "Christopher B Ruff", "Nae-Yuh Wang", "Aravinda Chakravarti"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0010082.g001", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Worldwide_Distribution_of_the_53_Populations_of_the_CEPH_Human_Genome_Diversity_Cell_Line_Panel_/630169", "title"=>"Worldwide Distribution of the 53 Populations of the CEPH Human Genome Diversity Cell Line Panel", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 08:48:07"}

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  • {"unique-ip"=>"32", "full-text"=>"35", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
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  • {"unique-ip"=>"28", "full-text"=>"28", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
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  • {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
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  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"24", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"25", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
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  • {"unique-ip"=>"23", "full-text"=>"25", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
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  • {"unique-ip"=>"30", "full-text"=>"31", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
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  • {"unique-ip"=>"15", "full-text"=>"18", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"29", "full-text"=>"29", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
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  • {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"26", "full-text"=>"23", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"23", "full-text"=>"24", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"23", "full-text"=>"32", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"43", "full-text"=>"51", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"76", "full-text"=>"96", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"18", "full-text"=>"14", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"27", "full-text"=>"32", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2020", "month"=>"7"}
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Relative Metric

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