Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll-Like Receptor 4 Dependent
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{"title"=>"Heme-mediated induction of CXCL10 and depletion of CD34+ progenitor cells is toll-like receptor 4 dependent", "type"=>"journal", "authors"=>[{"first_name"=>"Carmen M.", "last_name"=>"Dickinson-Copeland", "scopus_author_id"=>"56006571900"}, {"first_name"=>"Nana O.", "last_name"=>"Wilson", "scopus_author_id"=>"56261663600"}, {"first_name"=>"Mingli", "last_name"=>"Liu", "scopus_author_id"=>"8921996700"}, {"first_name"=>"Adel", "last_name"=>"Driss", "scopus_author_id"=>"8504871800"}, {"first_name"=>"Hassana", "last_name"=>"Salifu", "scopus_author_id"=>"56005985900"}, {"first_name"=>"Andrew A.", "last_name"=>"Adjei", "scopus_author_id"=>"36536573200"}, {"first_name"=>"Michael", "last_name"=>"Wilson", "scopus_author_id"=>"57196691718"}, {"first_name"=>"Ben", "last_name"=>"Gyan", "scopus_author_id"=>"6602608075"}, {"first_name"=>"Daniel", "last_name"=>"Oduro", "scopus_author_id"=>"57039045800"}, {"first_name"=>"Kingsley", "last_name"=>"Badu", "scopus_author_id"=>"35328934200"}, {"first_name"=>"Felix", "last_name"=>"Botchway", "scopus_author_id"=>"57038869400"}, {"first_name"=>"Winston", "last_name"=>"Anderson", "scopus_author_id"=>"12768768700"}, {"first_name"=>"Vincent", "last_name"=>"Bond", "scopus_author_id"=>"7005411858"}, {"first_name"=>"Methode", "last_name"=>"Bacanamwo", "scopus_author_id"=>"6602268452"}, {"first_name"=>"Shailesh", "last_name"=>"Singh", "scopus_author_id"=>"56743734900"}, {"first_name"=>"Jonathan K.", "last_name"=>"Stiles", "scopus_author_id"=>"7101804755"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"607497543", "doi"=>"10.1371/journal.pone.0142328", "sgr"=>"84953269035", "pmid"=>"26555697", "scopus"=>"2-s2.0-84953269035"}, "id"=>"8ae3addf-b26f-365a-8b50-4e617383516e", "abstract"=>"Plasmodium falciparum infection can cause microvascular dysfunction, cerebral encephalopathy and death if untreated. We have previously shown that high concentrations of free heme, and C-X-C motif chemokine 10 (CXCL10) in sera of malaria patients induce apoptosis in microvascular endothelial and neuronal cells contributing to vascular dysfunction, blood-brain barrier (BBB) damage and mortality. Endothelial progenitor cells (EPC) are microvascular endothelial cell precursors partly responsible for repair and regeneration of damaged BBB endothelium. Studies have shown that EPC's are depleted in severe malaria patients, but the mechanisms mediating this phenomenon are unknown. Toll-like receptors recognize a wide variety of pathogen-associated molecular patterns generated by pathogens such as bacteria and parasites. We tested the hypothesis that EPC depletion during malaria pathogenesis is a function of heme-induced apoptosis mediated by CXCL10 induction and toll-like receptor (TLR) activation. Heme and CXCL10 concentrations in plasma obtained from malaria patients were elevated compared with non-malaria subjects. EPC numbers were significantly decreased in malaria patients (P < 0.02) and TLR4 expression was significantly elevated in vivo. These findings were confirmed in EPC precursors in vitro; where it was determined that heme-induced apoptosis and CXCL10 expression was TLR4-mediated. We conclude that increased serum heme mediates depletion of EPC during malaria pathogenesis.", "link"=>"http://www.mendeley.com/research/hememediated-induction-cxcl10-depletion-cd34-progenitor-cells-tolllike-receptor-4-dependent", "reader_count"=>12, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Librarian"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Librarian"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2435666"], "description"=>"<p>TLR4 mRNA expression was analyzed using student’s t-test. In HBVEC <i>p</i> = 0.002 in heme-treated versus NaOH vehicle and in CD34<sup>+</sup>-HSPC <i>p</i> = 0.005 in heme-treated versus NaOH vehicle. Data reported as mean fold-change relative to GAPDH.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599514, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heme_mediates_TLR_expression_in_vitro_/1599514", "title"=>"Heme mediates TLR expression <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435660"], "description"=>"<p>(A) CD34<sup>+</sup> hematopoietic stem and progenitor cell populations are significantly decreased in malaria patients. Median fluorescence intensity; 0.5 (IQR 0.3–0.9) in non-malaria, n = 8, vs. 0.2 (IQR 0.1–0.3) in malaria patients, n = 34, <i>p</i> = 0.0006. (B) Circulating EPC numbers (CD45<sup>-</sup>CD34<sup>+</sup>VEGFR2<sup>+</sup>) are decreased in malaria patients by 1.7-fold compared with non-malaria. Median fluorescence intensity; 0.3 (IQR 0.1–0.7) in non-malaria, n = 8 vs malaria 0.1(IQR 0.1–0.2), n = 34, <i>p</i> = 0.02. Data represented as median frequency and Interquartile Range (IQR). Mann-Whitney tests were used to calculate <i>p</i>-value.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599508, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD34_cell_populations_decreased_in_malaria_/1599508", "title"=>"CD34<sup>+</sup> cell populations decreased in malaria.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435674", "https://ndownloader.figshare.com/files/2435675"], "description"=>"<div><p><i>Plasmodium falciparum</i> infection can cause microvascular dysfunction, cerebral encephalopathy and death if untreated. We have previously shown that high concentrations of free heme, and C-X-C motif chemokine 10 (CXCL10) in sera of malaria patients induce apoptosis in microvascular endothelial and neuronal cells contributing to vascular dysfunction, blood-brain barrier (BBB) damage and mortality. Endothelial progenitor cells (EPC) are microvascular endothelial cell precursors partly responsible for repair and regeneration of damaged BBB endothelium. Studies have shown that EPC’s are depleted in severe malaria patients, but the mechanisms mediating this phenomenon are unknown. Toll-like receptors recognize a wide variety of pathogen-associated molecular patterns generated by pathogens such as bacteria and parasites. We tested the hypothesis that EPC depletion during malaria pathogenesis is a function of heme-induced apoptosis mediated by CXCL10 induction and toll-like receptor (TLR) activation. Heme and CXCL10 concentrations in plasma obtained from malaria patients were elevated compared with non-malaria subjects. EPC numbers were significantly decreased in malaria patients (<i>P</i> < 0.02) and TLR4 expression was significantly elevated <i>in vivo</i>. These findings were confirmed in EPC precursors <i>in vitro</i>; where it was determined that heme-induced apoptosis and CXCL10 expression was TLR4-mediated. We conclude that increased serum heme mediates depletion of EPC during malaria pathogenesis.</p></div>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599522, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0142328.s001", "https://dx.doi.org/10.1371/journal.pone.0142328.s002"], "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heme_Mediated_Induction_of_CXCL10_and_Depletion_of_CD34_Progenitor_Cells_Is_Toll_Like_Receptor_4_Dependent_/1599522", "title"=>"Heme-Mediated Induction of CXCL10 and Depletion of CD34+ Progenitor Cells Is Toll-Like Receptor 4 Dependent", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435669"], "description"=>"<p>(A) CXCL10 mRNA expression is TLR4 dependent in HBVEC and CD34<sup>+</sup>-HSPC <i>in vitro</i>. CXCL10 mRNA expression was analyzed using analysis of variance followed by Tukey’s multiple comparisons test. In HBVEC and CD34<sup>+</sup>-HSPC, heme-treatment increased CXCL10 expression compared to vehicle (<i>p <</i> 0.0001 and 0.02, respectively). CXCL10 mRNA expression was decreased in the presence of anti-CD14 compared with heme alone (<i>p</i> = 0.0003 and <i>p</i> = 0.11, respectively). Data reported as mean fold-change relative to GAPDH. (B) CXCL10 expression is TLR4 dependent in supernatants of HBVEC and CD34<sup>+</sup>-HSPC <i>in vitro</i>. CXCL10 protein expression was analyzed using analysis of variance followed by Tukey’s multiple comparisons test. In HBVEC and CD34<sup>+</sup>-HSPC, heme-treatment increased CXCL10 expression compared to vehicle (<i>p</i> = 0.04 and 0.04, respectively). CXCL10 expression was decreased in the presence of TAK-242 compared with heme alone (<i>p</i> = 0.01, and 0.03, respectively). The 2(-Delta Delta C(T)) method was used to analysis relative gene expression data normalized to housekeeping gene, GAPDH, which was unaffected by experimental. Results are expressed as fold change relative to housekeeping gene in treatment versus vehicle-treated cultures.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599517, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g007", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heme_mediated_stimulation_of_CXCL10_expression_is_TLR4_dependent_/1599517", "title"=>"Heme-mediated stimulation of CXCL10 expression is TLR4 dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435665"], "description"=>"<p>Apoptosis was quantified using Guava TUNEL assay and analyzed by fluorescence-activated cell sorting (FACS). Apoptosis was analyzed using analysis of variance followed by Tukey’s multiple comparisons test; In HBVEC <i>p <</i> 0.0001 in heme-treated versus NaOH vehicle, and in CD34<sup>+</sup>-HSPC <i>p</i> = 0.0004 in heme-treated versus NaOH vehicle. CPT is a potent inducer of apoptosis used as positive control (<i>p</i> < 0.0001 in both cell types).</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599513, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heme_induces_apoptosis_in_HBVEC_and_CD34_HSPC_in_vitro_/1599513", "title"=>"Heme induces apoptosis in HBVEC and CD34<sup>+</sup>-HSPC <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435663"], "description"=>"<p>(A) TLR4 Expression is increased in EPC of malaria patients: Median Fluorescence Intensity in non-malaria subjects, 33.7 vs malaria patients, 40.9, <i>p</i> = 0.04. The EPC population was defined as being CD45<sup>-</sup>CD34<sup>+</sup>CD309<sup>+</sup>, (non-malaria n = 8, malaria n = 34). (B) Plasma CXCL10 is significantly increased in malaria patients compared to non-malaria subjects (non-malaria subjects, 178.6 pg/mL (IQR 100.7–333.4), malaria patients, 698.3 pg/mL (IQR 453.8–1143), <i>p</i> < 0.0001). Normal range of 49–811 pg/mL in non-malaria subjects.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599511, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Malaria_patients_have_increased_expression_of_TLR4_and_plasma_CXCL10_/1599511", "title"=>"Malaria patients have increased expression of TLR4 and plasma CXCL10.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435662"], "description"=>"<p>(A) Malaria patients have increased expression of plasma heme (<i>p</i> < 0.0001) and (B) Heme Oxygenase-1 (HO-1) (<i>p</i> < 0.0001) compared to non-malaria subjects. Box plots representing medians with 25th and 75th percentiles, bars for 10th and 90th percentiles, and points for outliers of biomarker concentrations. Means indicated by (+) sign. Statistically significant <i>p</i>-values after Bonferroni adjustment are shown, n = 411. Normal range of 0–60 μM heme and 0–4 ng/mL HO-1 observed in non-malaria subjects.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599510, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g003", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_heme_and_HO_1_levels_increase_in_malaria_patients_/1599510", "title"=>"Plasma heme and HO-1 levels increase in malaria patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435659"], "description"=>"<p>HSPC are CD34<sup>+</sup> cells derived from the bone marrow, where they reside in the stromal layer until mobilized in response to chemokines and cytokines released from dysfunctional endothelium. In the peripheral blood, they are capable of differentiating into endothelial progenitor cells (EPC) that will home into cites of vascular dysfunction. The EPC retains the hematopoietic surface marker CD34 in addition to gaining the vascular endothelial cell surface marker CD309 or VEGFR2. These cells will differentiate into mature and circulating endothelial cells capable of incorporating into sites of compromised vasculature, and inducing neovascularization as well as proliferation of existing endothelial cells.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599507, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.g001", "stats"=>{"downloads"=>1, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hematopoietic_Stem_and_Progenitor_Cell_Populations_HSPC_are_vital_to_vascular_endothelial_repair_and_regeneration_/1599507", "title"=>"Hematopoietic Stem and Progenitor Cell Populations (HSPC) are vital to vascular endothelial repair and regeneration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435673"], "description"=>"<p>Continuous variables compared using Mann-Whitney test, values reported as median and Interquartile Range (IQR). Malaria subjects had significantly higher levels of heme, HO-1 and CXCL10 compared with non-malaria regardless of the age group.</p><p>*Among the 141 non-malaria subjects 89% (125/141) are ≤16 years of age and 11% (16/141) are >16 years of age.</p><p><b>†</b>Among the 270 malaria subjects 83% (223/270) are ≤16 years of age and 17% (47/270) are >16 years of age.</p><p>Plasma Heme, Heme-Oxyenase-1 and CXCL10 quantification.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599521, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.t002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_Heme_Heme_Oxyenase_1_and_CXCL10_quantification_/1599521", "title"=>"Plasma Heme, Heme-Oxyenase-1 and CXCL10 quantification.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-11-10 04:29:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2435671"], "description"=>"<p>Dichotomous variables compared using χ<sup>2</sup> and Fisher exact tests and continuous variables compared using Mann-Whitney tests. Values reported as percent and number of observations for dichotomous variables or median and Interquartile Range (IQR) for continuous variables. There was a significant difference in median age however the age ranges for both the Non-Malaria and Malaria groups were the same. There were no significant differences in sex of the participants in each group.</p><p>*42 samples were randomly selected for EPC analysis; non-malaria = 8, malaria = 34.</p><p>Demographic and hematological characteristics.</p>", "links"=>[], "tags"=>["serum heme mediates depletion", "epc", "Endothelial Progenitor Cells", "TLR 4 expression", "malaria patients", "CXCL 10 expression", "CXCL 10 induction", "malaria pathogenesis", "bbb", "apoptosi", "microvascular", "CXCL 10 concentrations"], "article_id"=>1599519, "categories"=>["Biological Sciences"], "users"=>["Carmen M. Dickinson-Copeland", "Nana O. Wilson", "Mingli Liu", "Adel Driss", "Hassana Salifu", "Andrew A. Adjei", "Michael Wilson", "Ben Gyan", "Daniel Oduro", "Kingsley Badu", "Felix Botchway", "Winston Anderson", "Vincent Bond", "Methode Bacanamwo", "Shailesh Singh", "Jonathan K. Stiles"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142328.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_and_hematological_characteristics_/1599519", "title"=>"Demographic and hematological characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-11-10 04:29:45"}

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  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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