Medium Chain Acylcarnitines Dominate the Metabolite Pattern in Humans under Moderate Intensity Exercise and Support Lipid Oxidation
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{"title"=>"Medium chain acylcarnitines dominate the metabolite pattern in humans under moderate intensity exercise and support lipid oxidation", "type"=>"journal", "authors"=>[{"first_name"=>"Rainer", "last_name"=>"Lehmann", "scopus_author_id"=>"7202174335"}, {"first_name"=>"Xinjie", "last_name"=>"Zhao", "scopus_author_id"=>"55705192200"}, {"first_name"=>"Cora", "last_name"=>"Weigert", "scopus_author_id"=>"55982182800"}, {"first_name"=>"Perikles", "last_name"=>"Simon", "scopus_author_id"=>"8516066400"}, {"first_name"=>"Elvira", "last_name"=>"Fehrenbach", "scopus_author_id"=>"6603341655"}, {"first_name"=>"Jens", "last_name"=>"Fritsche", "scopus_author_id"=>"57197266296"}, {"first_name"=>"Jürgen", "last_name"=>"Machann", "scopus_author_id"=>"6603740526"}, {"first_name"=>"Fritz", "last_name"=>"Schick", "scopus_author_id"=>"7004668646"}, {"first_name"=>"Jiangshan", "last_name"=>"Wang", "scopus_author_id"=>"12773129900"}, {"first_name"=>"Miriam", "last_name"=>"Hoene", "scopus_author_id"=>"23090951900"}, {"first_name"=>"Erwin D.", "last_name"=>"Schleicher", "scopus_author_id"=>"55308377100"}, {"first_name"=>"Hans Ulrich", "last_name"=>"Häring", "scopus_author_id"=>"36038728300"}, {"first_name"=>"Guowang", "last_name"=>"Xu", "scopus_author_id"=>"7404264029"}, {"first_name"=>"Andreas M.", "last_name"=>"Niess", "scopus_author_id"=>"7003913975"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"359318752", "doi"=>"10.1371/journal.pone.0011519", "isbn"=>"1932-6203", "pmid"=>"20634953", "issn"=>"19326203", "scopus"=>"2-s2.0-77955399279", "sgr"=>"77955399279"}, "id"=>"9a97fef3-c8d6-30ae-844a-2030372760d1", "abstract"=>"BACKGROUND: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise.\\n\\nMETHODOLOGY AND PRINCIPAL FINDINGS: First, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT-) metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under these conditions medium and long chain acylcarnitines were found to be the most discriminant plasma biomarkers of moderately intense exercise. Immediately after a 60 min (at 93% V(IAT)) or a 120 min run (at 70% V(IAT)) a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial beta-oxidation was verified in skeletal muscle cell culture experiments by probing (13)C-palmitate metabolism. Further investigations in primary human myotubes and mouse muscle tissue revealed that octanoyl-, decanoyl-, and dodecanoyl-carnitine were able to support the oxidation of palmitate, proving more effective than L-carnitine.\\n\\nCONCLUSIONS: Medium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.", "link"=>"http://www.mendeley.com/research/medium-chain-acylcarnitines-dominate-metabolite-pattern-humans-under-moderate-intensity-exercise-sup", "reader_count"=>77, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>6, "Researcher"=>21, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>5, "Student > Master"=>10, "Other"=>6, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>6, "Researcher"=>21, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>5, "Student > Master"=>10, "Other"=>6, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Agricultural and Biological Sciences"=>29, "Chemistry"=>4, "Computer Science"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Materials Science"=>1, "Medicine and Dentistry"=>12, "Neuroscience"=>4, "Sports and Recreations"=>10, "Physics and Astronomy"=>1, "Psychology"=>1, "Social Sciences"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>10}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>4}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "reader_count_by_country"=>{"Netherlands"=>1, "Norway"=>1, "Japan"=>1, "United Kingdom"=>3, "Chile"=>1, "Germany"=>2, "Russia"=>2, "Spain"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/841430"], "description"=>"<p>Only metabolites showing significant changes are given.</p><p>*mass (m/z) represents a fragment of this metabolite.</p>", "links"=>[], "tags"=>["metabolites", "contributing", "clusters", "shown"], "article_id"=>511874, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.t003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Most_influential_metabolites_contributing_to_the_separation_of_the_clusters_of_the_exercise_and_recovery_phase_shown_in_Figure_1A_/511874", "title"=>"Most influential metabolites contributing to the separation of the clusters of the exercise and recovery phase shown in Figure 1A.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 00:39:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/841566"], "description"=>"<p>Only metabolites showing significant changes are given.</p>", "links"=>[], "tags"=>["metabolites", "contributing", "clusters", "pre", "shown"], "article_id"=>512011, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.t004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Most_influential_metabolites_contributing_to_the_separation_of_the_clusters_of_the_exercise_and_pre_run_phase_shown_in_Figure_1C_/512011", "title"=>"Most influential metabolites contributing to the separation of the clusters of the exercise and pre run phase shown in Figure 1C.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 00:40:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/841227"], "description"=>"<p>Oxidation of <sup>3</sup>H-palmitate determined after 4 h in human myotubes in the presence of L-carnitine (L-C), acetylcarnitine (ActC), an equimolar mixture of C8:0-, C10:0- and C12:0-acylcarnitine (AC), or C8:0-(C8-AC), C10:0- (C10-AC) and C12:0-acylcarnitine (C12-AC) as indicated (A,B). Values of <sup>3</sup>H-palmitate oxidation of control cells were set as 1. (C) Palmitate oxidation in the presence of 50 µM L-carnitine and 1, 5, 10 or 100 µM AC. Values of <sup>3</sup>H-palmitate oxidation of cells solely incubated with 50 µM L-carnitine were set as 1; shown are means ± SEM from 4 independent experiments, * p<0.05 vs. L-carnitine; # p<0.05 vs acetyl-carnitine; † p<0.05 vs. C8-AC or C10-AC, respectively. (D) Oxidation of <sup>3</sup>H-palmitate in mouse soleus, extensor digitorum longus (EDL), tibialis (tib) or quadriceps (Q) muscle from three different mice determined after 90 min in the presence of an equimolar mixture of C8:0-, C10:0- and C12:0-acylcarnitine as indicated. Shown are means ± SEM, values of <sup>3</sup>H-palmitate oxidation in untreated tissues were set as 1, * p<0.05 vs. untreated tissues.</p>", "links"=>[], "tags"=>["acylcarnitines", "fatty", "oxidation", "skeletal", "cells", "extensor", "digitorum", "tibialis", "quadriceps", "muscles"], "article_id"=>511656, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.g004", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_acylcarnitines_on_fatty_acid_oxidation_in_primary_human_skeletal_muscle_cells_as_well_as_soleus_extensor_digitorum_longus_tibialis_and_quadriceps_muscles_from_mice_/511656", "title"=>"Effects of acylcarnitines on fatty acid oxidation in primary human skeletal muscle cells as well as soleus, extensor digitorum longus, tibialis and quadriceps muscles from mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 00:38:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/841472"], "description"=>"<p>Values are shown as mean ± SE.</p>a)<p>measured after 10 min of treadmill performance.</p><p>*p<0.05 vs. pre.</p><p>nd = not determined.</p>", "links"=>[], "tags"=>["plasma", "parameters", "points"], "article_id"=>511915, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.t002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Concentrations_of_conventional_clinical_chemical_plasma_parameters_at_different_time_points_of_the_first_exercise_study_/511915", "title"=>"Concentrations of conventional clinical chemical plasma parameters at different time points of the first exercise study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 00:40:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/841026"], "description"=>"<p>Comparison of the time course of intracellular (A) and extracellular (B) intensity levels of <sup>12</sup>C- and <sup>13</sup>C-palmitoyl-carnitine in an experiment with primary human myotubes incubated with a mixture of 125 µM [U-<sup>13</sup>C<sub>16</sub>]palmitate/125 µM palmitate for 30 min, 4 h and 20 h. (C) The time course of the <sup>12</sup>C- and <sup>13</sup>C-signal intensity of dodecanoyl-carnitine and (D) decanoyl-carnitine. The <sup>13</sup>C-signal of the respective acylcarnitine is marked by a dash dotted arrow, the <sup>12</sup>C-signal by a solid arrow.</p>", "links"=>[], "tags"=>["synthesis"], "article_id"=>511476, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_13_C_Acylcarnitine_synthesis_and_release_from_primary_human_myotubes_/511476", "title"=>"<sup>13</sup>C-Acylcarnitine synthesis and release from primary human myotubes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 00:37:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/840737"], "description"=>"<p>Comparison of the time-dependent changes in the plasma metabolome of 13 individuals after a 60 min treadmill run at 93% velocity at individual anaerobic threshold (V<sub>IAT</sub>; approximately 75% of VO<sub>2max</sub>), showing the metabolome at rest, immediately at the end of the physical activity and at two time points in the recovery phase. The analyses were performed by partial least squares-discriminant analysis (PLS-DA) and OSC-filtering. (A) OSC-filtered PLS-DA score plot showing pre-run (▪), immediately after run (○), three hours after run (Δ) and 24 hours after run (*); (B) OSC-filtered PLS-DA score plot showing pre run (▪) and immediately after run (○). (C,D) The corresponding S-plot to (A) and (B), respectively. The variables are labelled with <i>m/z</i> values. Potential metabolic biomarkers including the corresponding <i>m/z</i> values are presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011519#pone-0011519-t003\" target=\"_blank\">Table 3</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011519#pone-0011519-t004\" target=\"_blank\">Table 4</a>.</p>", "links"=>[], "tags"=>["metabolites", "reflecting", "changes", "metabolite"], "article_id"=>511159, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.g001", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_metabolites_reflecting_changes_in_the_metabolite_pattern_during_moderate_intensity_exercise_and_recovery_/511159", "title"=>"Identification of metabolites reflecting changes in the metabolite pattern during moderate intensity exercise and recovery.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 00:35:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/841324"], "description"=>"<p>mRNA expression of PGC-1α (A), CPT1b (B), CD36 (C), COX1 (D) and AngPL-4 (E) related to β-actin mRNA levels after incubation with 100 µM L-carnitine (L-C), an equimolar mixture of C8:0-, C10:0- and C12:0-acylcarnitine (total 100 µM; AC), 60 µM palmitate (p), or p and AC as indicated. Values are shown as fold changes compared with untreated (L-C, AC) or BSA-treated (p, p+AC) control cells, shown are means ± SEM; * significant increase with p<0.05 vs. control cells, † p = 0.06 vs. control cells; # significant decrease with p<0.05 vs. control cells. The broken black line indicates the 1-fold expression in control cells.</p>", "links"=>[], "tags"=>["skeletal", "cells"], "article_id"=>511768, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_in_primary_human_skeletal_muscle_cells_after_treatment_with_acylcarnitines_/511768", "title"=>"Gene expression in primary human skeletal muscle cells after treatment with acylcarnitines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 00:39:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/840850"], "description"=>"<p>(A) Time-dependent changes of acylcarnitine species during the exercise bout and in the recovery phase, based on non-targeted (NT-)metabolomics signal intensity data. The relative amounts of acylcarnitines are based on peak heights. Values are means ±SE. *<i>p<</i>0.05, significantly different from the pre run signal intensity; (<i>n = </i>13). (B) Time-dependent changes of 13 individual C10:0 carnitine levels based on NT-metabolomics data. (C) Quantitative analysis of time-dependent changes of plasma acylcarnitine concentrations investigated in eight individuals performing a continuous 120 min treadmill run at 70% V<sub>IAT</sub> in an independent second exercise study. Values are means ±SE. *<i>p<</i>0.05, significantly different from the pre-run concentrations. As a C8- instead of a C18-reversed phase UPLC-column was used to achieve the detection of the long-chain C16 (palmitoyl)-carnitine, the analysis of C2:0-carnitine was not possible in this experiment.</p>", "links"=>[], "tags"=>["acylcarnitine", "plasma", "levels"], "article_id"=>511293, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.g002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_course_for_the_acylcarnitine_species_plasma_levels_during_the_exercise_phase_and_under_recovery_conditions_/511293", "title"=>"Time-course for the acylcarnitine species plasma levels during the exercise phase and under recovery conditions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 00:36:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/841522"], "description"=>"<p>V<sub>IAT</sub> - velocity at individual anaerobic threshold,</p><p>VO<sub>2max</sub> - maximal oxygen consumption.</p>", "links"=>[], "tags"=>["diabetes and endocrinology", "biochemistry/small molecule chemistry", "chemistry/biochemistry", "physiology/muscle and connective tissue", "public health and epidemiology/exercise and sports", "public health and epidemiology/preventive medicine"], "article_id"=>511967, "categories"=>["Chemistry", "Medicine", "Physiology", "Biochemistry"], "users"=>["Rainer Lehmann", "Xinjie Zhao", "Cora Weigert", "Perikles Simon", "Elvira Fehrenbach", "Jens Fritsche", "Jürgen Machann", "Fritz Schick", "Jiangshan Wang", "Miriam Hoene", "Erwin D. Schleicher", "Hans-Ulrich Häring", "Guowang Xu", "Andreas M. Niess"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0011519.t001", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physical_characteristic_of_the_subjects_/511967", "title"=>"Physical characteristic of the subjects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 00:40:18"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"29", "full-text"=>"30", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
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  • {"unique-ip"=>"28", "full-text"=>"32", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
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  • {"unique-ip"=>"18", "full-text"=>"20", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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  • {"unique-ip"=>"18", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"27", "full-text"=>"23", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"9"}
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Relative Metric

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