Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice
Publication Date
January 06, 2009
Journal
PLOS Neglected Tropical Diseases
Authors
Jennifer Keiser, Jacques Chollet, Shu Hua Xiao, Jin Yan Mei, et al
Volume
3
Issue
1
Pages
e350
DOI
https://dx.plos.org/10.1371/journal.pntd.0000350
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0000350
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/19125172
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600813
Europe PMC
http://europepmc.org/abstract/MED/19125172
Web of Science
000263301100002
Scopus
65549102140
Mendeley
http://www.mendeley.com/research/mefloquine-aminoalcohol-promising-antischistosomal-properties-mice
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Mendeley | Further Information

{"title"=>"Mefloquine - An aminoalcohol with promising antischistosomal properties in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Jennifer", "last_name"=>"Keiser", "scopus_author_id"=>"32867784000"}, {"first_name"=>"Jacques", "last_name"=>"Chollet", "scopus_author_id"=>"7006434795"}, {"first_name"=>"Shu Hua", "last_name"=>"Xiao", "scopus_author_id"=>"55583821800"}, {"first_name"=>"Jin Yan", "last_name"=>"Mei", "scopus_author_id"=>"19135204300"}, {"first_name"=>"Pei Ying", "last_name"=>"Jiao", "scopus_author_id"=>"7005966267"}, {"first_name"=>"Jürg", "last_name"=>"Utzinger", "scopus_author_id"=>"7003667858"}, {"first_name"=>"Marcel", "last_name"=>"Tanner", "scopus_author_id"=>"7202127772"}], "year"=>2009, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"issn"=>"1935-2735", "scopus"=>"2-s2.0-65549102140", "pui"=>"354579388", "doi"=>"10.1371/journal.pntd.0000350", "isbn"=>"1935-2735 (Electronic)\\r1935-2727 (Linking)", "sgr"=>"65549102140", "pmid"=>"19125172"}, "id"=>"34908bfb-b85d-3d22-b1cf-1da45cd79234", "abstract"=>"BACKGROUND: The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult Schistosoma mansoni or adult S. japonicum resulted in high or complete total and female worm burden reductions (72.3%-100%). Importantly, high worm burden reductions were also observed for young developing stages of S. mansoni and S. japonicum harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent S. mansoni infection.\\n\\nCONCLUSIONS/SIGNIFICANCE: Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further in vitro and in vivo studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on S. haematobium and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.", "link"=>"http://www.mendeley.com/research/mefloquine-aminoalcohol-promising-antischistosomal-properties-mice", "reader_count"=>37, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Master"=>5, "Other"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Librarian"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Master"=>5, "Other"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>10, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>13}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Chemistry"=>{"Chemistry"=>13}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Brazil"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/450340", "https://ndownloader.figshare.com/files/450387", "https://ndownloader.figshare.com/files/450426", "https://ndownloader.figshare.com/files/450475", "https://ndownloader.figshare.com/files/450530"], "description"=>"<div><h3>Background</h3><p>The treatment and control of schistosomiasis, an often neglected tropical disease that exacerbates poverty, depends on a single drug, praziquantel. The large-scale use of praziquantel might select for drug-resistant parasites, hence there is a need to develop new antischistosomal compounds. Here, we report that the antimalarial drug mefloquine possesses promising antischistosomal properties in mice.</p><h3>Methodology/Principal Findings</h3><p>A single dose of mefloquine (200 or 400 mg/kg) administered orally to mice infected with adult <em>Schistosoma mansoni</em> or adult <em>S. japonicum</em> resulted in high or complete total and female worm burden reductions (72.3%–100%). Importantly, high worm burden reductions were also observed for young developing stages of <em>S. mansoni</em> and <em>S. japonicum</em> harbored in the mouse. Both mefloquine erythro-enantiomers resulted in high and comparable total and female worm burden reductions when given to mice with either a sub-patent or patent <em>S. mansoni</em> infection.</p><h3>Conclusions/Significance</h3><p>Our findings hold promise for the development of a novel antischistosomal drug based on an aminoalcohol functionality. Further <em>in vitro</em> and <em>in vivo</em> studies have been launched to elucidate the possible mechanism of action and to study the effect of mefloquine on <em>S. haematobium</em> and other trematodes. It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist.</p></div>", "links"=>[], "tags"=>["aminoalcohol", "antischistosomal", "properties", "mice"], "article_id"=>148756, "categories"=>["Cancer"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.s001", "https://dx.doi.org/10.1371/journal.pntd.0000350.s002", "https://dx.doi.org/10.1371/journal.pntd.0000350.s003", "https://dx.doi.org/10.1371/journal.pntd.0000350.s004", "https://dx.doi.org/10.1371/journal.pntd.0000350.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mefloquine_An_Aminoalcohol_with_Promising_Antischistosomal_Properties_in_Mice/148756", "title"=>"Mefloquine—An Aminoalcohol with Promising Antischistosomal Properties in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-01-06 02:25:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/911423"], "description"=>"<p>Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.</p>", "links"=>[], "tags"=>["structures"], "article_id"=>581878, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemical_structures_of_mefloquine_quinine_halofantrine_and_lumefantrine_/581878", "title"=>"Chemical structures of mefloquine, quinine, halofantrine, and lumefantrine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-01-06 00:31:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/911518"], "description"=>"<p>Red squares: mefloquine 400 mg/kg, blue circles: praziquantel 400 mg/kg. The stage-specific susceptibilities of praziquantel and mefloquine on <i>S. mansoni</i> have been established in the laboratories of the Swiss Tropical Institute (Basel, Switzerland). The efficacy of praziquantel against <i>S. japonicum</i> has been reported by Yue et al. <a href=\"http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000350#pntd.0000350-Yue1\" target=\"_blank\">[51]</a> and that of mefloquine has been established at the laboratories of the National Institute of Parasitic Diseases (Shanghai, China).</p>", "links"=>[], "tags"=>["susceptibility", "mefloquine", "compared", "praziquantel"], "article_id"=>581965, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stage_specific_susceptibility_of_mefloquine_compared_to_praziquantel_in_the_S_mansoni_and_S_japonicum_mouse_models_/581965", "title"=>"Stage-specific susceptibility of mefloquine compared to praziquantel in the <i>S. mansoni-</i> and <i>S. japonicum</i>-mouse models.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-01-06 00:32:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/911635"], "description"=>"<p>SD, standard deviation.</p>", "links"=>[], "tags"=>["mefloquine", "administered", "mice", "infected"], "article_id"=>582090, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hepatic_shift_test_following_a_single_400_mg_kg_oral_dose_of_mefloquine_administered_to_mice_infected_with_S_mansoni_and_S_japonicum_/582090", "title"=>"Hepatic shift test following a single 400-mg/kg oral dose of mefloquine administered to mice infected with <i>S. mansoni</i> and <i>S. japonicum</i>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:34:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/911687"], "description"=>"<p>KW, Kruskal-Wallis; SD, standard deviation.</p>a<p>Two mice died on days 17 and 34 post-treatment.</p>", "links"=>[], "tags"=>["worm", "400", "aminomethanol", "antimalarials", "administered", "mice", "harboring", "49-day-old", "stratified"], "article_id"=>582123, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_on_worm_burden_of_a_single_400_mg_kg_oral_dose_of_four_selected_aminomethanol_antimalarials_administered_to_mice_harboring_a_49_day_old_adult_S_mansoni_infection_stratified_by_sex_and_worm_distribution_/582123", "title"=>"Effect on worm burden of a single 400 mg/kg oral dose of four selected aminomethanol antimalarials administered to mice harboring a 49-day-old adult <i>S. mansoni</i> infection, stratified by sex and worm distribution.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:35:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/911732"], "description"=>"<p>Worm burden is stratified by sex and worm distribution.</p><p>KW, Kruskal Wallis test; SD, standard deviation.</p>a<p>one mouse died 13 days post-treatment.</p>b<p>one mouse died 11 days post-treatment.</p>", "links"=>[], "tags"=>["mefloquine", "administered", "mice", "harboring", "21-day-old", "juvenile", "49-day-old"], "article_id"=>582185, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_response_relationship_of_mefloquine_administered_to_mice_harboring_a_21_day_old_juvenile_and_a_49_day_old_adult_S_mansoni_infection_/582185", "title"=>"Dose-response relationship of mefloquine administered to mice harboring a 21-day-old juvenile and a 49-day-old adult <i>S. mansoni</i> infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:36:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/911779"], "description"=>"<p>SD, standard deviation.</p>a<p>One mouse died on day 27 post-treatment.</p>b<p>Two mice died on days 1 and 2 post-treatment.</p>c<p>One mouse died on day 22 post-treatment.</p>d<p>Two mice died on days 27 and 30 post-treatment.</p>", "links"=>[], "tags"=>["worm", "antimalarials", "administered", "mice", "harboring", "49-day-old", "stratified"], "article_id"=>582225, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_on_worm_burden_of_a_single_oral_dose_of_seven_selected_antimalarials_administered_to_mice_harboring_a_49_day_old_adult_S_mansoni_infection_stratified_by_sex_and_worm_distribution_/582225", "title"=>"Effect on worm burden of a single oral dose of seven selected antimalarials administered to mice harboring a 49-day-old adult <i>S. mansoni</i> infection, stratified by sex and worm distribution.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:37:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/911827"], "description"=>"<p>Worm burden is stratified by sex and worm distribution.</p><p>KW, Kruskal Wallis test; SD, standard deviation.</p>", "links"=>[], "tags"=>["mefloquine", "administered", "mice", "harboring", "14-day-old", "juvenile", "35", "day-old"], "article_id"=>582272, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_response_relationship_of_mefloquine_administered_to_mice_harboring_either_a_14_day_old_juvenile_or_a_35_day_old_adult_S_japonicum_infection_/582272", "title"=>"Dose response relationship of mefloquine administered to mice harboring either a 14-day-old juvenile or a 35 day-old adult <i>S. japonicum</i> infection.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:37:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/911863"], "description"=>"<p>KW, Kruskal-Wallis test; SD, standard deviation.</p>", "links"=>[], "tags"=>["specificity", "400", "mefloquine", "administered", "mice", "infected", "stratified"], "article_id"=>582314, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stage_specificity_of_a_single_400_mg_kg_oral_dose_of_mefloquine_administered_to_mice_infected_with_S_japonicum_stratified_by_sex_/582314", "title"=>"Stage specificity of a single 400 mg/kg oral dose of mefloquine administered to mice infected with <i>S. japonicum</i>, stratified by sex.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:38:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/911920"], "description"=>"<p>KW, Kruskal-Wallis test; SD, standard deviation.</p>a<p>One mouse died several days post-treatment.</p>", "links"=>[], "tags"=>["400", "mefloquine", "administered", "mice", "infected", "stratified", "worm"], "article_id"=>582363, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stage_specificity_of_a_single_400_mg_kg_oral_dose_mefloquine_administered_to_mice_infected_with_S_mansoni_stratified_by_sex_and_worm_distribution_/582363", "title"=>"Stage-specificity of a single 400 mg/kg oral dose mefloquine administered to mice infected with <i>S. mansoni</i>, stratified by sex and worm distribution.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:39:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/911956"], "description"=>"<p>Worm burden is stratified by sex and worm distribution.</p><p>KW, Kruskal Wallis test; SD, standard deviation.</p>a<p>Two mice died at days 14 and 17 post-treatment.</p>", "links"=>[], "tags"=>["mefloquine", "enantiomer", "administered", "mice", "infected", "juvenile"], "article_id"=>582407, "categories"=>["Virology"], "users"=>["Jennifer Keiser", "Jacques Chollet", "Shu-Hua Xiao", "Jin-Yan Mei", "Pei-Ying Jiao", "Jürg Utzinger", "Marcel Tanner"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000350.t005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_mefloquine_and_enantiomer_administered_to_mice_infected_with_either_juvenile_or_adult_S_mansoni_/582407", "title"=>"Effect of mefloquine (+) and (−) enantiomer administered to mice infected with either juvenile or adult <i>S. mansoni.</i>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-01-06 00:40:07"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"30", "full-text"=>"35", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"13", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"6", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}

Relative Metric

{"start_date"=>"2009-01-01T00:00:00Z", "end_date"=>"2009-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Medicine and health sciences", "average_usage"=>[332, 584, 719, 824, 927, 1030, 1139, 1233, 1322, 1402, 1483, 1570, 1649, 1730, 1806, 1873, 1939, 2003, 2068, 2130, 2191, 2248, 2302, 2362, 2427, 2485, 2544, 2599, 2653, 2709, 2778, 2840, 2896, 2950, 3013, 3073, 3137, 3189, 3253, 3305, 3364, 3423, 3489, 3557, 3606, 3668, 3742, 3797, 3852, 3907, 3962, 4027, 4072, 4132, 4193, 4256, 4308, 4366, 4427, 4493, 4556]}, {"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[383, 606, 753, 875, 970, 1073, 1195, 1283, 1367, 1455, 1557, 1631, 1730, 1807, 1861, 1926, 1991, 2036, 2133, 2190, 2227, 2273, 2326, 2386, 2456, 2523, 2583, 2637, 2755, 2806, 2877, 2938, 3022, 3101, 3141, 3201, 3254, 3306, 3358, 3396, 3467, 3517, 3568, 3675, 3716, 3757, 3799, 3847, 3896, 3937, 3989, 4042, 4089, 4167, 4226, 4265, 4351, 4425, 4497, 4573, 4648, 4730]}, {"subject_area"=>"/People and places", "average_usage"=>[340, 621, 760, 868, 956, 1048, 1152, 1251, 1334, 1414, 1499, 1591, 1663, 1753, 1823, 1893, 1955, 2026, 2094, 2178, 2255, 2327, 2390, 2467, 2535, 2613, 2680, 2731, 2780, 2851, 2909, 2986, 3049, 3107, 3177, 3238, 3292, 3360, 3437, 3503, 3564, 3622, 3710, 3812, 3860, 3932, 4002, 4075, 4112, 4156, 4247, 4296, 4386, 4455, 4550, 4613, 4662, 4694, 4869, 4937, 4982]}, {"subject_area"=>"/People and places/Population groupings", "average_usage"=>[326, 591, 716, 814, 900, 987, 1120, 1224, 1289, 1374, 1460, 1550, 1643, 1734, 1802, 1864, 1932, 1993, 2048, 2125, 2213, 2285, 2353, 2413, 2485, 2557, 2605, 2660, 2740, 2788, 2845, 2907, 2959, 3036, 3109, 3163, 3228, 3286, 3351, 3404, 3482, 3562, 3633, 3707, 3749, 3842, 3924, 3985, 4080, 4118, 4176, 4261, 4333, 4379, 4458, 4529, 4578, 4632, 4711, 4767, 4817]}]}
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