Prophylactic and Therapeutic Efficacy of Avian Antibodies Against Influenza Virus H5N1 and H1N1 in Mice
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{"title"=>"Prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Huan H.", "last_name"=>"Nguyen", "scopus_author_id"=>"7403322574"}, {"first_name"=>"Terrence M.", "last_name"=>"Tumpey", "scopus_author_id"=>"6701520653"}, {"first_name"=>"Hae Jung", "last_name"=>"Park", "scopus_author_id"=>"16444525200"}, {"first_name"=>"Young Ho", "last_name"=>"Byun", "scopus_author_id"=>"35309508700"}, {"first_name"=>"Linh D.", "last_name"=>"Tran", "scopus_author_id"=>"57200093951"}, {"first_name"=>"Van D.", "last_name"=>"Nguyen", "scopus_author_id"=>"36786942900"}, {"first_name"=>"Paul E.", "last_name"=>"Kilgore", "scopus_author_id"=>"6701476914"}, {"first_name"=>"Cecil", "last_name"=>"Czerkinsky", "scopus_author_id"=>"7006154497"}, {"first_name"=>"Jacqueline M.", "last_name"=>"Katz", "scopus_author_id"=>"7403970287"}, {"first_name"=>"Baik Lin", "last_name"=>"Seong", "scopus_author_id"=>"7006077026"}, {"first_name"=>"Jae Min", "last_name"=>"Song", "scopus_author_id"=>"21743950700"}, {"first_name"=>"Young Bong", "last_name"=>"Kim", "scopus_author_id"=>"25923367800"}, {"first_name"=>"Hoa T.", "last_name"=>"Do", "scopus_author_id"=>"25823602400"}, {"first_name"=>"Tung", "last_name"=>"Nguyen", "scopus_author_id"=>"56293918300"}, {"first_name"=>"Cam V.", "last_name"=>"Nguyen", "scopus_author_id"=>"36117065100"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-77956302071", "sgr"=>"77956302071", "pui"=>"359482202", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"20405007", "doi"=>"10.1371/journal.pone.0010152"}, "id"=>"1b939e6c-be1e-30a2-978c-618c5fb69a8f", "abstract"=>"BACKGROUND: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs) have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY) found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV) strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1.\\n\\nMETHODS AND FINDINGS: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection.\\n\\nCONCLUSIONS: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus-specific IgY as affordable, safe, and effective alternative for the control of influenza outbreaks, including the current H1N1 pandemic.", "link"=>"http://www.mendeley.com/research/prophylactic-therapeutic-efficacy-avian-antibodies-against-influenza-virus-h5n1-h1n1-mice", "reader_count"=>46, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>14, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>4, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>2, "Librarian"=>2, "Researcher"=>14, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>2, "Student > Master"=>3, "Other"=>4, "Student > Bachelor"=>2, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>4, "Materials Science"=>1, "Agricultural and Biological Sciences"=>19, "Medicine and Dentistry"=>4, "Veterinary Science and Veterinary Medicine"=>3, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>5, "Earth and Planetary Sciences"=>2, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>4}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>3}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>1, "Denmark"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/854620"], "description"=>"<p>BALB/c mice were treated with PR8-specific IgY (anti PR8 IgY) - as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010152#s2\" target=\"_blank\">Materials & Methods</a> at 8 hours pre- and 16, 40, and 64 hours post-infection (<u>Pre- and post-infection treatments, Fig. 3A</u>); at 8, 32, 56, and 80 hours post-infection (<u>post-infection treatments, Fig. 3B</u>); or once at 6 hours before infection <u>(Single pre-infection treatment, Fig. 3C</u>. Five LD<sub>50</sub> of mouse-adapted PR8 and 50 µl of IgY were used for intranasal infection and treatment, respectively. Morbidity (body weight loss) and mortality were monitored daily until recovered animals regained their initial weight. The values are the mean of 5–10 mice in each group. Mortality is expressed as % of mice that survived the lethal infection. Virus titers in the lungs (TCID<sub>50</sub>) determined at day 3 after infection in mice treated with PR8 specific IgY at 6 hours before (−6 hrs) or after (+6 hrs) infection (Fig. 3D). The values are the mean of 8 mice in each group derived from 2 independent experiments. As control, a group of mice treated with mouse anti-PR8 serum (HI titer 1∶128) was included. All mice received the same amount of the IgY preparation of identical HI titer.</p>", "links"=>[], "tags"=>["h1n1"], "article_id"=>525069, "categories"=>["Virology", "Medicine", "Immunology"], "users"=>["Huan H. Nguyen", "Terrence M. Tumpey", "Hae-Jung Park", "Young-Ho Byun", "Linh D. Tran", "Van D. Nguyen", "Paul E. Kilgore", "Cecil Czerkinsky", "Jacqueline M. Katz", "Baik Lin Seong", "Jae Min Song", "Young Bong Kim", "Hoa T. Do", "Tung Nguyen", "Cam V. Nguyen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010152.g003", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protection_against_challenge_with_H1N1_PR8_/525069", "title"=>"Protection against challenge with H1N1 PR8.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:52:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/854295"], "description"=>"<p>BALB/c mice were treated with H5N1-specific IgY [anti H5N1 IgY or different batch of anti H5N1 IgY (vn045)] at 6 hours before and 18, 42, and 66 hours after infection with H5N2 virus (<u>Pre- and post-infection treatments, Fig. 1A</u>); at 6, 30, 54, and 78 hours after infection (<u>Post-infection treatments, Fig. 1B</u>); or once at 6 hours before infection <u>(Single pre-infection treatment, Fig. 1C</u>. Five LD<sub>50</sub> of mouse-adapted A/Aquatic bird/Korea/W81/2005 (H5N2) virus and 50 µl of IgY were used for intranasal infection and treatment, respectively. The values are the mean of 5–10 mice in each group.</p>", "links"=>[], "tags"=>["immunology/immunity to infections", "virology/emerging viral diseases", "virology/new therapies, including antivirals and immunotherapy"], "article_id"=>524730, "categories"=>["Virology", "Medicine", "Immunology"], "users"=>["Huan H. Nguyen", "Terrence M. Tumpey", "Hae-Jung Park", "Young-Ho Byun", "Linh D. Tran", "Van D. Nguyen", "Paul E. Kilgore", "Cecil Czerkinsky", "Jacqueline M. Katz", "Baik Lin Seong", "Jae Min Song", "Young Bong Kim", "Hoa T. Do", "Tung Nguyen", "Cam V. Nguyen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010152.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protection_against_challenge_with_A_Aquatic_bird_Korea_W81_2005_H5N2_/524730", "title"=>"Protection against challenge with A/Aquatic bird/Korea/W81/2005 (H5N2).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:50:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/854985"], "description"=>"<p>ND: Not done.</p><p>NA: Not available.</p><p>* A/PR/8/34 (PR8).</p><p>** A/Vietnam/1203/2004 (VN/1203 – H1N1).</p><p>*** A/Aquatic bird/Korea/W81/2005 (H5N2).</p>▴<p>Mean and SEM of log<sub>2</sub> titers.</p><p>Two hens were immunized with heat inactivated PR8 (as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010152#s2\" target=\"_blank\">Materials and Methods</a>) and IgY was pooled from 15 collected eggs. Sera of hens raised in Vietnam farms were tested individually (10 samples in each batch) and IgY was pooled from 10 eggs in each batch. If not otherwise indicated A/ck/Scotland/59 (H5N1) was used for H5 virus-specific HI titration. Sera from two unimmunized hens and IgY pooled from 10 eggs obtained in Korea were used as negative control. Titers of VN antibody were determined as the reciprocal of the highest dilution of specimens that neutralized 100 pfu or TCID<sub>50</sub> of virus in MDCK cell cultures.</p>", "links"=>[], "tags"=>["inhibition", "neutralization", "titers", "hen", "sera"], "article_id"=>525429, "categories"=>["Virology", "Medicine", "Immunology"], "users"=>["Huan H. Nguyen", "Terrence M. Tumpey", "Hae-Jung Park", "Young-Ho Byun", "Linh D. Tran", "Van D. Nguyen", "Paul E. Kilgore", "Cecil Czerkinsky", "Jacqueline M. Katz", "Baik Lin Seong", "Jae Min Song", "Young Bong Kim", "Hoa T. Do", "Tung Nguyen", "Cam V. Nguyen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010152.t001", "stats"=>{"downloads"=>4, "page_views"=>51, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Haemagglutination_inhibition_HI_and_virus_neutralization_VN_titers_in_hen_sera_and_egg_yolks_/525429", "title"=>"Haemagglutination inhibition (HI) and virus neutralization (VN) titers in hen sera and egg yolks.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:54:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/854856"], "description"=>"<p>PR8 virus neutralizing activity of PR8 specific IgY (anti-PR8 IgY) in the absence of anti-IgY serum was determined by microneutralization assay. VN titer of anti-PR8 IgY is 1∶320 at which the viral nuclear protein (NP) was not detected (Fig. 5A). In the presence of anti-IgY serum VN by anti-PR8 IgY was not abrogated by incubation with normal serum (Fig. 5B and 5D) or with anti-IgY serum (Figs. 5C and 5D). VN titer (1∶320) of anti-PR8 IgY was used in the assay. The optical density (O.D.) was determined at 450 nm (<i>A</i><sub>450</sub>).</p>", "links"=>[], "tags"=>["abs", "neutralizing"], "article_id"=>525304, "categories"=>["Virology", "Medicine", "Immunology"], "users"=>["Huan H. Nguyen", "Terrence M. Tumpey", "Hae-Jung Park", "Young-Ho Byun", "Linh D. Tran", "Van D. Nguyen", "Paul E. Kilgore", "Cecil Czerkinsky", "Jacqueline M. Katz", "Baik Lin Seong", "Jae Min Song", "Young Bong Kim", "Hoa T. Do", "Tung Nguyen", "Cam V. Nguyen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010152.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_IgY_Abs_do_not_block_neutralizing_activity_of_virus_specific_IgY_/525304", "title"=>"Anti-IgY Abs do not block neutralizing activity of virus specific IgY.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:53:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/854754"], "description"=>"<p>Anti IgY in the sera of mice immunized with normal IgY (IgY immunized), treated once intranasally with PR8-specific IgY 8 hours before (anti PR8 IgY −8 h) or three times after infection (anti PR8 IgY +8, 32, 56 h) (Fig. 4A). Endpoint titers (log<sub>2</sub>) were determined by ELISA. Morbidity and mortality of IgY-immunized mice treated with PR8-specific IgY (anti PR8 IgY) before (−6 hr) or after (+6 hr) infection with mouse-adapted PR8 (Fig. 4B). The values are the mean of 5–10 mice in each group.</p>", "links"=>[], "tags"=>["anti", "igy", "abs", "mice", "pre-existing"], "article_id"=>525198, "categories"=>["Virology", "Medicine", "Immunology"], "users"=>["Huan H. Nguyen", "Terrence M. Tumpey", "Hae-Jung Park", "Young-Ho Byun", "Linh D. Tran", "Van D. Nguyen", "Paul E. Kilgore", "Cecil Czerkinsky", "Jacqueline M. Katz", "Baik Lin Seong", "Jae Min Song", "Young Bong Kim", "Hoa T. Do", "Tung Nguyen", "Cam V. Nguyen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010152.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induction_of_anti_IgY_Abs_and_IgY_treatment_in_mice_with_pre_existing_anti_IgY_/525198", "title"=>"Induction of anti IgY Abs and IgY treatment in mice with pre-existing anti IgY.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:52:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/854476"], "description"=>"<p>Morbidity and mortality of BALB/c mice that were treated with H5N1-specific IgY [anti H5N1 IgY] at 6 hours pre- (−6 h) or post- (+6 h) infection with VN/1203 (H5N1) virus (<u>Single pre- or post-infection treatment, Fig. 2A</u> - 6 mice per group); or at 6, 24, 48, and 72 hours after infection (<u>Multiple post-infection treatments, Fig. 2C</u> – 5 mice per group). Ten LD<sub>50</sub> of VN/1203 H5N1 virus and 50 µl of H5N1-specific IgY were used for intranasal infection and treatment, respectively. The mice protected from disease did not die even after 3 weeks monitoring. Virus titers (EID<sub>50</sub>) in the lungs were determined on day 3 after infection (Fig. 2B and 2D). The values are the mean of 4 mice in each group. The group of mice receiving single pre-infection treatment was included as control.</p>", "links"=>[], "tags"=>["hpaiv"], "article_id"=>524920, "categories"=>["Virology", "Medicine", "Immunology"], "users"=>["Huan H. Nguyen", "Terrence M. Tumpey", "Hae-Jung Park", "Young-Ho Byun", "Linh D. Tran", "Van D. Nguyen", "Paul E. Kilgore", "Cecil Czerkinsky", "Jacqueline M. Katz", "Baik Lin Seong", "Jae Min Song", "Young Bong Kim", "Hoa T. Do", "Tung Nguyen", "Cam V. Nguyen"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010152.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protection_against_challenge_with_HPAIV_H5N1_/524920", "title"=>"Protection against challenge with HPAIV H5N1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:51:27"}

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  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
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  • {"unique-ip"=>"9", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"1", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"4", "full-text"=>"4", "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"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
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  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"2", "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"=>"13", "full-text"=>"12", "pdf"=>"3", "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"=>"9", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
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  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
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  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"13", "full-text"=>"16", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"16", "full-text"=>"11", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"21", "full-text"=>"25", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"35", "full-text"=>"36", "pdf"=>"12", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"29", "full-text"=>"39", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"39", "full-text"=>"43", "pdf"=>"17", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
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Relative Metric

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