Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets
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{"title"=>"Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets", "type"=>"journal", "authors"=>[{"first_name"=>"Amorsolo L.", "last_name"=>"Suguitan", "scopus_author_id"=>"14631286300"}, {"first_name"=>"Josephine", "last_name"=>"McAuliffe", "scopus_author_id"=>"7006073544"}, {"first_name"=>"Kimberly L.", "last_name"=>"Mills", "scopus_author_id"=>"8951134600"}, {"first_name"=>"Hong", "last_name"=>"Jin", "scopus_author_id"=>"7403072773"}, {"first_name"=>"Greg", "last_name"=>"Duke", "scopus_author_id"=>"7005311175"}, {"first_name"=>"Bin", "last_name"=>"Lu", "scopus_author_id"=>"7401752245"}, {"first_name"=>"Catherine J.", "last_name"=>"Luke", "scopus_author_id"=>"7005674355"}, {"first_name"=>"Brian", "last_name"=>"Murphy", "scopus_author_id"=>"35395818900"}, {"first_name"=>"David E.", "last_name"=>"Swayne", "scopus_author_id"=>"35768368400"}, {"first_name"=>"George", "last_name"=>"Kemble", "scopus_author_id"=>"35474594000"}, {"first_name"=>"Kanta", "last_name"=>"Subbarao", "scopus_author_id"=>"7102213212"}], "year"=>2006, "source"=>"PLoS Medicine", "identifiers"=>{"issn"=>"15491277", "scopus"=>"2-s2.0-33748993450", "pui"=>"44455265", "doi"=>"10.1371/journal.pmed.0030360", "isbn"=>"1549-1676 (Electronic)\\r1549-1277 (Linking)", "sgr"=>"33748993450", "pmid"=>"16968127"}, "id"=>"54a19bb0-c7d5-3e00-a16d-4f71596e54f2", "abstract"=>"BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6) 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.", "link"=>"http://www.mendeley.com/research/live-attenuated-influenza-h5n1-candidate-vaccines-provide-broad-crossprotection-mice-ferrets", "reader_count"=>59, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>15, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>3, "Student > Bachelor"=>4, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>40, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>40}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "United States"=>1, "China"=>1, "Denmark"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/956533"], "description"=>"<p>The H5N1 2004 <i>ca</i> virus, unlike the H5N1 2004 <i>wt</i> parent virus, is undetectable in the brain. Influenza A/Beijing/95 <i>ca,</i> an H1N1 <i>ca</i> reassortant virus, was also undetectable in the brains of mice. The lower limit of detection is indicated by the dashed horizontal line. Four mice per group were euthanized at each time point (days 2, 4, 6, 8, 10, and 12). Data from days 6 through 12 are combined in the figure because virus was not detected in any of the brain tissues harvested on these days.</p>", "links"=>[], "tags"=>["h5n1", "2004", "viruses", "brains"], "article_id"=>626801, "categories"=>["Microbiology", "Infectious Diseases", "Virology"], "users"=>["Amorsolo L Suguitan Jr.", "Josephine McAuliffe", "Kimberly L Mills", "Hong Jin", "Greg Duke", "Bin Lu", "Catherine J Luke", "Brian Murphy", "David E Swayne", "George Kemble", "Kanta Subbarao"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030360.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_H5N1_2004_ca_and_2004_wt_Viruses_in_the_Brains_of_Mice_/626801", "title"=>"Replication of H5N1 2004 <i>ca</i> and 2004 <i>wt</i> Viruses in the Brains of Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:14:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/956609"], "description"=>"<p>Groups of eight mice that received a single dose of 10<sup>6</sup> TCID<sub>50</sub> of the H5N1 1997 <i>ca</i> (▪), H5N1 2003 <i>ca</i> (▵), H5N1 2004 <i>ca</i> (̂), or AA <i>ca</i> (○) viruses, or were mock-immunized (L-15 medium; ♦) were challenged with the H5N1 1997 <i>wt</i> (A–C) or H5N1 2004 <i>wt</i> virus (D–F) at 50 (A and D), 500 (B and E), or 5,000 (C and F) LD<sub>50</sub>. The mice were monitored daily for 21 d p.i. Immunization with the H5N1 1997 <i>ca,</i> H5N1 2003 <i>ca,</i> and H5N1 2004 <i>ca</i> viruses resulted in 100% survival of the mice following challenge, so the symbols for these groups are superimposed.</p>", "links"=>[], "tags"=>["mice", "immunized", "h5n1", "candidates", "lethal", "1997", "2004"], "article_id"=>626876, "categories"=>["Microbiology", "Infectious Diseases", "Virology"], "users"=>["Amorsolo L Suguitan Jr.", "Josephine McAuliffe", "Kimberly L Mills", "Hong Jin", "Greg Duke", "Bin Lu", "Catherine J Luke", "Brian Murphy", "David E Swayne", "George Kemble", "Kanta Subbarao"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030360.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Survival_of_Mice_Immunized_with_a_Single_Dose_of_H5N1_ca_Vaccine_Candidates_Following_Lethal_Challenge_with_H5N1_1997_wt_or_H5N1_2004_wt_Viruses_/626876", "title"=>"Survival of Mice Immunized with a Single Dose of H5N1 <i>ca</i> Vaccine Candidates Following Lethal Challenge with H5N1 1997 <i>wt</i> or H5N1 2004 <i>wt</i> Viruses", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:15:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/956770"], "description"=>"<div><p>Ferrets were immunized with two doses of 10<sup>7</sup> TCID<sub>50</sub> of H5N1 1997 <i>ca</i> or H5N1 2004 <i>ca</i> viruses 1 mo apart and challenged 1 mo later with 10<sup>7</sup> TCID<sub>50</sub> of either H5N1 1997 <i>wt,</i> H5N1 2004 <i>wt,</i> or A/Indonesia/05/2005 (H5N1) <i>wt</i>. In order to determine the contribution of the internal protein genes of the AA <i>ca</i> virus to protection, an additional group of ferrets was immunized with H1N1 A/New Caledonia/99 <i>ca</i> and challenged with H5N1 1997 <i>wt</i>. These ferrets were not challenged with H5N1 2004 <i>wt</i> or A/Indonesia/05/2005 (H5N1) <i>wt</i>.</p>\n <p>Lungs, nasal turbinates, and brains were harvested 3 d after challenge and were homogenized and titered on MDCK cells. Three ferrets per group were evaluated. The lower limit of detection is indicated by the dashed line. *<i>p</i> < 0.05 compared to mock-immunized ferrets.</p></div>", "links"=>[], "tags"=>["ferrets", "doses", "h5n1", "viruses", "homologous", "heterologous"], "article_id"=>627034, "categories"=>["Microbiology", "Infectious Diseases", "Virology"], "users"=>["Amorsolo L Suguitan Jr.", "Josephine McAuliffe", "Kimberly L Mills", "Hong Jin", "Greg Duke", "Bin Lu", "Catherine J Luke", "Brian Murphy", "David E Swayne", "George Kemble", "Kanta Subbarao"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030360.g005", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Efficacy_in_Ferrets_of_Two_Doses_of_H5N1_ca_Viruses_against_Challenge_with_Homologous_and_Heterologous_H5N1_wt_Viruses_/627034", "title"=>"Efficacy in Ferrets of Two Doses of H5N1 <i>ca</i> Viruses against Challenge with Homologous and Heterologous H5N1 <i>wt</i> Viruses", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:17:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/956670"], "description"=>"<div><p>(A and B) Mice that received a single dose of 10<sup>6</sup> TCID<sub>50</sub> of the immunizing virus were challenged with 10<sup>5</sup> TCID<sub>50</sub> of H5N1 1997 <i>wt,</i> H5N1 2003 <i>wt,</i> or H5N1 2004 <i>wt</i> viruses on day 28 p.i. Replication of challenge virus is shown in the lungs (A) and nasal turbinates (B).</p>\n <p>(C and D) Mice that received two doses of the immunizing virus 4 wk apart were challenged with the H5N1 <i>wt</i> viruses on day 56 p.i. Replication of challenge virus is shown in the lungs (C) and nasal turbinates (D).</p>\n <p>Lungs were harvested 2 d following challenge, homogenized, and titrated on MDCK cells. Groups of mock-immunized (L-15) mice and mice immunized with the nonlethal 2003 <i>wt</i> virus (single dose) or with AA <i>ca</i> were included as control groups. Four mice were evaluated in each group. The lower limit of detection is indicated by the dashed horizontal line. Log-transformed viral titers were compared using the Mann-Whitney U test. * <i>p</i> ≤ 0.05 compared to mock-immunized mice.</p></div>", "links"=>[], "tags"=>["h5n1", "viruses", "mice", "immunized", "doses"], "article_id"=>626940, "categories"=>["Microbiology", "Infectious Diseases", "Virology"], "users"=>["Amorsolo L Suguitan Jr.", "Josephine McAuliffe", "Kimberly L Mills", "Hong Jin", "Greg Duke", "Bin Lu", "Catherine J Luke", "Brian Murphy", "David E Swayne", "George Kemble", "Kanta Subbarao"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030360.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Replication_of_H5N1_wt_Challenge_Viruses_in_Mice_Immunized_with_One_or_Two_Doses_of_H5N1_ca_Viruses_/626940", "title"=>"Replication of H5N1 <i>wt</i> Challenge Viruses in Mice Immunized with One or Two Doses of H5N1 <i>ca</i> Viruses", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:15:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/471712"], "description"=>"<div><h3>Background</h3><p>Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.</p> <h3>Methods and Findings</h3><p>Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type <em>(wt)</em> N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted <em>(ca)</em> influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 <em>ca</em> (H2N2), were generated by reverse genetics. The H5N1 <em>ca</em> vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the <em>ca</em> vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10<sup>6</sup> 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous <em>wt</em> H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous <em>wt</em> H5N1 viruses.</p> <h3>Conclusions</h3><p>The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 <em>ca</em> vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.</p> </div>", "links"=>[], "tags"=>["attenuated", "influenza", "h5n1", "vaccines", "cross-protection", "mice", "ferrets"], "article_id"=>153005, "categories"=>["Cancer", "Microbiology"], "users"=>["Amorsolo L Suguitan Jr.", "Josephine McAuliffe", "Kimberly L Mills", "Hong Jin", "Greg Duke", "Bin Lu", "Catherine J Luke", "Brian Murphy", "David E Swayne", "George Kemble", "Kanta Subbarao"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030360", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Live_Attenuated_Influenza_A_H5N1_Candidate_Vaccines_Provide_Broad_Cross_Protection_in_Mice_and_Ferrets/153005", "title"=>"Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2006-09-12 00:50:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/956723"], "description"=>"<p>Mice that received two doses of 10<sup>6</sup> TCID<sub>50</sub> of H5N1 1997 <i>ca,</i> H5N1 2003 <i>ca,</i> or H5N1 2004 <i>ca</i> viruses 4 wk apart were challenged on day 56 p.i. with 10<sup>5</sup> TCID<sub>50</sub> of homologous and heterologous H5N1 <i>wt</i> viruses, including A/Indonesia/05/2005, a clade 2 H5N1 <i>wt</i> virus. The lungs were harvested from these mice 4 d later and were homogenized and titered on MDCK cells. Four mice were evaluated in each group. The lower limit of detection is indicated by the dashed horizontal line. * <i>p</i> < 0.02 compared to mock-immunized mice.</p>", "links"=>[], "tags"=>["mice", "doses", "h5n1", "viruses", "provides", "replication", "homologous", "heterologous"], "article_id"=>626989, "categories"=>["Microbiology", "Infectious Diseases", "Virology"], "users"=>["Amorsolo L Suguitan Jr.", "Josephine McAuliffe", "Kimberly L Mills", "Hong Jin", "Greg Duke", "Bin Lu", "Catherine J Luke", "Brian Murphy", "David E Swayne", "George Kemble", "Kanta Subbarao"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.0030360.g004", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunization_of_Mice_with_Two_Doses_of_H5N1_ca_Viruses_Provides_Protection_against_Replication_of_Homologous_and_Heterologous_H5N1_wt_Viruses_in_the_Lungs_/626989", "title"=>"Immunization of Mice with Two Doses of H5N1 <i>ca</i> Viruses Provides Protection against Replication of Homologous and Heterologous H5N1 <i>wt</i> Viruses in the Lungs", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:16:36"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"11", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
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  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "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"=>"8", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
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  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
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  • {"unique-ip"=>"13", "full-text"=>"8", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
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  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
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  • {"unique-ip"=>"13", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"13", "full-text"=>"9", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"20", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
  • {"unique-ip"=>"10", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}
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Relative Metric

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