Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets
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{"title"=>"Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets", "type"=>"journal", "authors"=>[{"first_name"=>"Judith M. A.", "last_name"=>"van den Brand"}, {"first_name"=>"Koert J.", "last_name"=>"Stittelaar"}, {"first_name"=>"Geert", "last_name"=>"van Amerongen"}, {"first_name"=>"Leslie", "last_name"=>"Reperant"}, {"first_name"=>"Leon", "last_name"=>"de Waal"}, {"first_name"=>"Albert D. M. E.", "last_name"=>"Osterhaus"}, {"first_name"=>"Thijs", "last_name"=>"Kuiken"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"1932-6203", "pmid"=>"22905124", "doi"=>"10.1371/journal.pone.0042343"}, "id"=>"fc1098a4-c921-30c9-aac6-b929d468b9ab", "abstract"=>"Humans may be infected by different influenza A viruses--seasonal, pandemic, and zoonotic--which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues--including the central nervous system--for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.", "link"=>"http://www.mendeley.com/research/comparison-temporal-spatial-dynamics-seasonal-h3n2-pandemic-h1n1-highly-pathogenic-avian-influenza-h-3", "reader_count"=>21, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>3, "Other"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>4, "Immunology and Microbiology"=>3, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Germany"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/595994"], "description"=>"<p>There is high antigen expression with associated lesions characterized by neutrophilic rhinitis in the olfactory epithelium of ferrets inoculated with pH1N1 on 1 and 4 dpi, and for H5N1 only on 4 dpi. There were no antigen expression and no lesions for H3N2. HE and immunoperoxidase counterstained with hematoxylin, 200×.</p>", "links"=>[], "tags"=>["histopathology", "nasal", "olfactory", "epithelium", "ferrets", "inoculated", "influenza"], "article_id"=>266477, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g005", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antigen_expression_and_histopathology_of_nasal_olfactory_epithelium_of_ferrets_inoculated_with_different_influenza_viruses_/266477", "title"=>"Antigen expression and histopathology of nasal olfactory epithelium of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:47:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/595328"], "description"=>"<p>The data are depicted as median values and standard errors of the mean (SEM). (A) Virus titers in nasal swabs demonstrate highest titers for pH1N1, intermediate titers for H3N2 and lowest titers for H5N1. (B) Virus titers in pharyngeal swabs demonstrate initially comparable virus titers for pH1N1 and H3N2 and lower titers for H5N1, and on 4 dpi comparable titers for pH1N1 and H5N1 and lower titers for H3N2. (C) Body temperatures in ferrets inoculated with pH1N1 and H5N1 are higher than for H3N2 and the sham-inoculated group. The large SEM for H5N1 is due to the low body temperatures of moribund animals. (D) Body weight loss in animals inoculated with pH1N1 and H5N1 was comparable and higher when compared to H3N2.</p>", "links"=>[], "tags"=>["ferrets", "inoculated", "influenza"], "article_id"=>265811, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_data_of_ferrets_inoculated_with_different_influenza_viruses_/265811", "title"=>"Clinical data of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:36:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/596980"], "description"=>"<p>The number of leucocytes in the alveolar lumina (scores) and blood (×10<sup>9</sup>/L) are depicted as median values and standard errors of the mean. The number of mononuclear cells and neutrophils in the alveolar lumina and blood follow the same pattern for H3N2 and pH1N1. The increase of the number of mononuclear cells in the alveoli and decrease in the blood for pH1N1 demonstrates the demand in the alveoli. For pH1N1 there is a peak of neutrophils in the alveoli on 0.5 dpi followed by a dip and a response of myelopoiesis in the blood. For H5N1 the number of mononuclear cells is not elevated in the alveoli and blood, and the high demand for neutrophils in the alveoli is not followed by higher release of neutrophils in the blood. In negative control animals (non-inoculated) the median number (range) of mononuclear cells is 0.30 10<sup>9</sup>/L (0.13–0.37) in the blood and 17 (5–22) in the alveolar lumina, for neutrophils 4.33 (3.07–7.28) in the blood and 0.5 (0–2) in the alveolar lumina.</p>", "links"=>[], "tags"=>["counts", "alveoli", "ferrets", "inoculated", "influenza"], "article_id"=>267468, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g009", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Leucocyte_counts_in_alveoli_and_blood_of_ferrets_inoculated_with_different_influenza_viruses_/267468", "title"=>"Leucocyte counts in alveoli and blood of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 02:04:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/597323"], "description"=>"<p>Histopathology scores in ferrets inoculated with different influenza viruses.</p>", "links"=>[], "tags"=>["scores", "ferrets", "inoculated", "influenza"], "article_id"=>267817, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t002", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathology_scores_in_ferrets_inoculated_with_different_influenza_viruses_/267817", "title"=>"Histopathology scores in ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:10:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/597515"], "description"=>"a<p>Virus titers of the other animals in the group could not be determined.</p>b<p>The range of the cut off values is the range of the cut off values of the individual animals.</p><p>nd, not determined.</p>", "links"=>[], "tags"=>["tissues", "ferrets", "inoculated", "influenza"], "article_id"=>268007, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t004", "stats"=>{"downloads"=>3, "page_views"=>41, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_isolation_from_tissues_in_ferrets_inoculated_with_different_influenza_viruses_/268007", "title"=>"Virus isolation from tissues in ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:13:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/311572"], "description"=>"<div><p>Humans may be infected by different influenza A viruses—seasonal, pandemic, and zoonotic—which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. Differences in spatial and temporal dynamics of these infections are poorly understood. Therefore, we inoculated ferrets with seasonal H3N2, pandemic H1N1 (pH1N1), and highly pathogenic avian H5N1 influenza virus and performed detailed virological and pathological analyses at time points from 0.5 to 14 days post inoculation (dpi), as well as describing clinical signs and hematological parameters. H3N2 infection was restricted to the nose and peaked at 1 dpi. pH1N1 infection also peaked at 1 dpi, but occurred at similar levels throughout the respiratory tract. H5N1 infection occurred predominantly in the alveoli, where it peaked for a longer period, from 1 to 3 dpi. The associated lesions followed the same spatial distribution as virus infection, but their severity peaked between 1 and 6 days later. Neutrophil and monocyte counts in peripheral blood correlated with inflammatory cell influx in the alveoli. Of the different parameters used to measure lower respiratory tract disease, relative lung weight and affected lung tissue allowed the best quantitative distinction between the virus groups. There was extra-respiratory spread to more tissues—including the central nervous system—for H5N1 infection than for pH1N1 infection, and to none for H3N2 infection. This study shows that seasonal, pandemic, and zoonotic influenza viruses differ strongly in the spatial and temporal dynamics of infection in the respiratory tract and extra-respiratory tissues of ferrets.</p> </div>", "links"=>[], "tags"=>["temporal", "spatial", "seasonal", "pandemic", "h1n1", "pathogenic", "avian", "influenza", "h5n1", "infections", "ferrets"], "article_id"=>121461, "categories"=>["Cancer", "Cell Biology"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Comparison_of_Temporal_and_Spatial_Dynamics_of_Seasonal_H3N2_Pandemic_H1N1_and_Highly_Pathogenic_Avian_Influenza_H5N1_Virus_Infections_in_Ferrets/121461", "title"=>"Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Virus Infections in Ferrets", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 00:24:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/597555"], "description"=>"<p>Leucocyte concentrations in the peripheral blood of ferrets inoculated with different influenza viruses.</p>", "links"=>[], "tags"=>["concentrations", "peripheral", "ferrets", "inoculated", "influenza"], "article_id"=>268038, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Leucocyte_concentrations_in_the_peripheral_blood_of_ferrets_inoculated_with_different_influenza_viruses_/268038", "title"=>"Leucocyte concentrations in the peripheral blood of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:13:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/595596"], "description"=>"<p>There is high antigen expression with associated lesions characterized by neutrophilic rhinitis in the nasal respiratory epithelium of ferrets inoculated with H3N2 and pH1N1 on 1 dpi and lower expression on 4 dpi, while for H5N1 there is only occasional expression on 1 dpi. HE and immunoperoxidase counterstained with hematoxylin, 200×.</p>", "links"=>[], "tags"=>["histopathology", "nasal", "respiratory", "epithelium", "ferrets", "inoculated", "influenza"], "article_id"=>266083, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antigen_expression_and_histopathology_of_nasal_respiratory_epithelium_of_ferrets_inoculated_with_different_influenza_viruses_/266083", "title"=>"Antigen expression and histopathology of nasal respiratory epithelium of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:41:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/595454"], "description"=>"<p>The data are depicted as median values and standard errors of the mean. Virus titers and antigen expression as demonstrated by immunohistochemistry scores are comparable for ferrets inoculated with H3N2 and pH1N1. Ferrets inoculated with H5N1 have highest antigen expression in the alveoli while virus titers are comparable for all parts of the respiratory tract, suggesting that most virus originated from the lower respiratory tract. The average cut-off values for the respiratory tissues are: nose 1.6 (range 1.3–1.8), trachea 1.6 (1.4–1.9), bronchus 1.6 (range 1.3–2.0) and lung 1.3 (range 0.9–1.4) log<sub>10</sub> TCID<sub>50</sub>. Immunohistochemistry scores in nose, trachea, bronchi, and bronchioles are scored from 0 to 3, and those in the alveoli are scored as a percentage.</p>", "links"=>[], "tags"=>["respiratory", "tracts", "ferrets", "inoculated", "influenza"], "article_id"=>265940, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g003", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Virus_distribution_in_the_respiratory_tracts_of_ferrets_inoculated_with_different_influenza_viruses_/265940", "title"=>"Virus distribution in the respiratory tracts of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:39:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/596235"], "description"=>"<p>There is moderate antigen expression with associated lesions characterized by bronchitis in bronchial and glandular epithelium of ferrets inoculated with pH1N1 on 1 and 4 dpi, and for H5N1 only on 4 dpi. There were no antigen expression and no lesions for H3N2. HE and immunoperoxidase counterstained with hematoxylin, 200×.</p>", "links"=>[], "tags"=>["histopathology", "bronchial", "epithelium", "ferrets", "inoculated", "influenza"], "article_id"=>266721, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antigen_expression_and_histopathology_of_bronchial_epithelium_of_ferrets_inoculated_with_different_influenza_viruses_/266721", "title"=>"Antigen expression and histopathology of bronchial epithelium of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:52:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/597110"], "description"=>"<p>On 0.5 dpi there was mild DAD that was characterized by neutrophils in the alveolar walls. On 1 dpi the alveolar walls were thickened with mild necrosis of the lining epithelium and increased number of neutrophils, in the lumina there were more mononuclear cells, little amount of edema fluid mixed with fibrin, hemorrhage and little cellular debris. On 2 dpi there was increased presence of necrosis, edema, hemorrhage and hyperplasia. On 3 dpi there were both new lesions with acute necrosis and old lesions with type II hyperplasia present, with increased amounts of edema and hemorrhage. On 4 dpi the type II hyperplasia and hypertrophy was more pronounced with increased amount of edema and high numbers of mononuclear cells. On 7 dpi there was severe epithelial hyperplasia and hypertrophy as well as intraluminal edema and hemorrhage. On 14 dpi the walls were mildly thickened. HE, 100× (first column), 400× (second column).</p>", "links"=>[], "tags"=>["changes", "alveoli", "ferrets", "inoculated"], "article_id"=>267600, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g010", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathologic_changes_in_the_alveoli_during_time_in_ferrets_inoculated_with_pH1N1_/267600", "title"=>"Histopathologic changes in the alveoli during time in ferrets inoculated with pH1N1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 02:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/597484"], "description"=>"<p><i>P</i>-values were calculated by using the Mann-Whitney test.</p>*<p><i>P</i>-value<0.05.</p>**<p><i>P</i>-value<0.01.</p>", "links"=>[], "tags"=>["analyses", "comparing", "pathology", "Virology", "scores", "ferrets", "inoculated", "influenza"], "article_id"=>267965, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t007", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Statistical_analyses_comparing_pathology_and_virology_scores_among_ferrets_inoculated_with_different_influenza_viruses_/267965", "title"=>"Statistical analyses comparing pathology and virology scores among ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:12:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/597362"], "description"=>"*<p>Antigen expression counts in the negative control animals are considered false positive counts due to the incapacity of the program to determine artifact staining.</p>", "links"=>[], "tags"=>["histopathology", "scores", "ferrets", "inoculated", "influenza"], "article_id"=>267851, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Digital_histopathology_scores_in_ferrets_inoculated_with_different_influenza_viruses_/267851", "title"=>"Digital histopathology scores in ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:10:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/596773"], "description"=>"<p>There was moderate to high antigen expression for pH1N1 and H5N1 on 1 and 4 dpi with associated lesions characterized by severe DAD and no expression and lesions for H3N2. HE and immunoperoxidase counterstained with hematoxylin, 400×.</p>", "links"=>[], "tags"=>["histopathology", "alveolar", "epithelium", "ferrets", "inoculated", "influenza"], "article_id"=>267260, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g008", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antigen_expression_and_histopathology_of_alveolar_epithelium_of_ferrets_inoculated_with_different_influenza_viruses_/267260", "title"=>"Antigen expression and histopathology of alveolar epithelium of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 02:01:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/596517"], "description"=>"<p>There is high antigen expression with associated lesions characterized by bronchiolitis in bronchiolar epithelium of ferrets inoculated with pH1N1 on 1 dpi that was low on 4 dpi, consistent with severe loss of bronchiolar epithelium, and for H5N1 there was no expression on 1 dpi and moderate antigen expression with associated lesions on 4 dpi. There were no antigen expression and no lesions for H3N2. HE and immunoperoxidase counterstained with hematoxylin, 200×.</p>", "links"=>[], "tags"=>["histopathology", "bronchiolar", "epithelium", "ferrets", "inoculated", "influenza"], "article_id"=>266999, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g007", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Antigen_expression_and_histopathology_of_bronchiolar_epithelium_of_ferrets_inoculated_with_different_influenza_viruses_/266999", "title"=>"Antigen expression and histopathology of bronchiolar epithelium of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:56:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/595394"], "description"=>"<p>The data are depicted as median values and standard errors of the mean. (A) Percentages of affected lung tissue show highest values for H5N1, intermediate values for pH1N1 and lowest values for H3N2. (B) Percentages relative lung weight show highest values for H5N1, intermediate values for pH1N1 and lowest values for H3N2.</p>", "links"=>[], "tags"=>["pathology", "lungs", "ferrets", "inoculated", "influenza"], "article_id"=>265877, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gross_pathology_of_the_lungs_of_ferrets_inoculated_with_different_influenza_viruses_/265877", "title"=>"Gross pathology of the lungs of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 01:37:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/597435"], "description"=>"<p>URRT: upper regions of the respiratory tract (nose and trachea); DRRT: deeper regions of the respiratory tract (bronchi, bronchioles and alveoli).</p>", "links"=>[], "tags"=>["generalized", "linear", "models", "predicting", "viral", "excretion", "ferrets", "inoculated", "influenza"], "article_id"=>267923, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t006", "stats"=>{"downloads"=>0, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parameter_estimates_of_generalized_linear_models_predicting_viral_excretion_of_ferrets_inoculated_with_different_influenza_viruses_/267923", "title"=>"Parameter-estimates of generalized linear models predicting viral excretion of ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:12:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/597252"], "description"=>"<p>On 0.5 dpi there was infiltration of neutrophils in the bronchiolar epithelium and lumen with mild peribronchiolar cuffing. On 1 dpi the number of neutrophils increased with necrosis of the epithelium, intraluminal cellular debris and peribronchiolar cuffing. On 2 dpi the necrosis was more severe than on 1 dpi. On 3 dpi there was denudation of the basement membrane and little regeneration of the bronchiolar epithelium with hyperplasia, peribronchiolar cuffing and occasionally cellular debris in the lumen. On 4 dpi there was increased epithelial hyperplasia with moderate cuffing. On 7 dpi the epithelium covered the basement membrane of the bronchiole with hypertrophic cells and moderate cuffing. On 14 dpi the epithelium was slightly hypertrophic with little cuffing. HE, 200×.</p>", "links"=>[], "tags"=>["changes", "bronchioles", "ferrets", "inoculated"], "article_id"=>267741, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.g011", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathologic_changes_in_the_bronchioles_during_time_in_ferrets_inoculated_with_pH1N1_/267741", "title"=>"Histopathologic changes in the bronchioles during time in ferrets inoculated with pH1N1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-08 02:09:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/597399"], "description"=>"<p>Data also are provided for enlargement of the tracheo-bronchial lymph nodes, virus excretion from the rectum, and virus neutralization antibody titers in the serum.</p>a<p>Scores are based on individual animals.</p>b<p>The cut off values are <0.8 log<sub>10</sub> TCID<sub>50</sub>/ml).</p>", "links"=>[], "tags"=>["signs", "ferrets", "inoculated", "influenza"], "article_id"=>267890, "categories"=>["Virology", "Cell Biology", "Infectious Diseases"], "users"=>["Judith M. A. van den Brand", "Koert J. Stittelaar", "Geert van Amerongen", "Leslie Reperant", "Leon de Waal", "Albert D. M. E. Osterhaus", "Thijs Kuiken"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042343.t001", "stats"=>{"downloads"=>0, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Survival_and_clinical_signs_in_ferrets_inoculated_with_different_influenza_viruses_/267890", "title"=>"Survival and clinical signs in ferrets inoculated with different influenza viruses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-08 02:11:30"}

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Relative Metric

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