Arterial Oxygen Content Is Precisely Maintained by Graded Erythrocytotic Responses in Settings of High/Normal Serum Iron Levels, and Predicts Exercise Capacity: An Observational Study of Hypoxaemic Patients with Pulmonary Arteriovenous Malformations
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{"title"=>"Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: An observational study of hypoxaemic patients with pulmonary arteriovenous malformations", "type"=>"journal", "authors"=>[{"first_name"=>"Vatshalan", "last_name"=>"Santhirapala", "scopus_author_id"=>"56081109900"}, {"first_name"=>"Louisa C.", "last_name"=>"Williams", "scopus_author_id"=>"56092412200"}, {"first_name"=>"Hannah C.", "last_name"=>"Tighe", "scopus_author_id"=>"25029578100"}, {"first_name"=>"James E.", "last_name"=>"Jackson", "scopus_author_id"=>"7404117325"}, {"first_name"=>"Claire L.", "last_name"=>"Shovlin", "scopus_author_id"=>"7003333972"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372838529", "scopus"=>"2-s2.0-84898657842", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24637882", "sgr"=>"84898657842", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0090777"}, "id"=>"3dd4813e-f668-3536-83bd-ad85bc44f5f3", "abstract"=>"BACKGROUND: Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.\\n\\nMETHODOLOGY: 165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.\\n\\nPRINCIPAL FINDINGS: There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.\\n\\nSIGNIFICANCE: Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses.", "link"=>"http://www.mendeley.com/research/arterial-oxygen-content-precisely-maintained-graded-erythrocytotic-responses-settings-highnormal-ser", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>1, "Student > Ph. D. Student"=>2, "Other"=>2, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>1, "Design"=>1, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1422530"], "description"=>"<p><b>Demographics of the 165 PAVM Patients</b>. N, number of datasets: values <165 imply that data was not available for a subgroup of patients. †SaO<sub>2</sub> measured continuously at rest for 10 minutes standing breathing room air, with recordings at one minute intervals, and reported values the mean of the readings after 7, 8, 9 and 10 minutes. MCH, mean corpuscular haemoglobin. MCHC, mean corpuscular haemoglobin concentration. MCV, mean corpuscular volume. Δ Blood test timings were standardised to catch the afternoon peak in iron levels as described in the online supplement to Livesey et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090777#pone.0090777-Livesey1\" target=\"_blank\">[33]</a>.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "165", "unselected", "pavm"], "article_id"=>963712, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.t001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographics_of_165_consecutive_unselected_PAVM_patients_/963712", "title"=>"Demographics of 165 consecutive unselected PAVM patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422525"], "description"=>"<p>A) SaO<sub>2</sub> relationships. Error bars represent mean and standard deviation. Similar trends were observed for median and IQR (data not shown). B) Oxygen content, calculated by <i>SaO<sub>2</sub> x haemoglobin x 1.34/100</i>, where SaO<sub>2</sub> was expressed as a %, and 1.34mls is the amount of oxygen carried per gram of haemoglobin <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090777#pone.0090777-Pittman1\" target=\"_blank\">[1]</a>. Error bars represent mean and standard deviation, but a similar trend was observed for median and IQR (data not shown).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "pavm", "patients", "graded", "self-reported"], "article_id"=>963707, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_165_PAVM_patients_graded_according_to_self_reported_exercise_tolerance_/963707", "title"=>"165 PAVM patients graded according to self-reported exercise tolerance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422524"], "description"=>"<p>Oxygen content across all degrees of hypoxaemia, calculated by <i>SaO<sub>2</sub> x haemoglobin x 1.34/100</i>, where SaO<sub>2</sub> was expressed as a %, and 1.34mls is the amount of oxygen carried per gram of haemoglobin.<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090777#pone.0090777-Pittman1\" target=\"_blank\">[1]</a> The bold black line represents the regression line for all patients, irrespective of iron status (p = 0.69). Grey diamonds/dotted line/shaded 95% confidence interval represent patients without iron deficiency (p = 0.33). Red diamonds/dotted line/shaded 95% confidence interval represent patients with iron deficiency (p = 0.97).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "stratified", "saturation"], "article_id"=>963706, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.g003", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Arterial_oxygen_content_stratified_by_oxygen_saturation_SaO_2_/963706", "title"=>"Arterial oxygen content stratified by oxygen saturation (SaO<sub>2</sub>).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422532"], "description"=>"<p>Patients stratified into those reporting and not reporting improved exercise tolerance. N, number with stated variable; IQR, interquartile range. PAP, pulmonary artery pressure; emb., embolisation. *P values calculated by logistic regression, and shown in bold where <0.05: Key odds ratios (and 95% confidence intervals) were 0.71 (0.56, 0.92) for albumin; 1.12 (1.01, 1.24) for PAP(systolic); 1.31 (1.04, 1.65) for PAP (diastolic); and 1.18 (1.01, 1.40) for PAP (mean). Note inverse associations are indicated by odds ratios <1.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "univariate", "associations", "embolisation", "98", "pavm"], "article_id"=>963714, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.t003", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographics_and_univariate_associations_with_improvement_in_exercise_capacity_post_embolisation_for_the_98_PAVM_patients_/963714", "title"=>"Demographics, and univariate associations with improvement in exercise capacity post embolisation for the 98 PAVM patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422527"], "description"=>"<p>Individuals with normal exercise tolerance (Grade 1) were subclassified into Grade 1a (athletes, grey symbols/lines, if participating in intense sporting activity such as rowing, football, distance cycling or gym activities at least three times per week), and Grade 1b (other normals, red symbols/lines, if they described dyspnoea only on strenuous exertion). All assignments were made blinded to physiological parameters <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090777#pone.0090777-Santhirapala1\" target=\"_blank\">[44]</a>. A) Haemoglobin (Hb) adjusted for SaO<sub>2</sub>, presented as (100*haemoglobin)/SaO<sub>2</sub>. Mann Whitney p value  =  0.0059. P values were also calculated by Kruskal Wallis across all exercise grades, when Dunn's post test correction comparing the athletic and non athletic normals gave a p value of<0.05. B) Serum iron. Mann Whitney p value  =  0.010. P values were also calculated by Kruskal Wallis across all exercise grades, when Dunn's post test correction comparing the athletic and non athletic normals gave a p value of<0.05.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "comparisons", "athletes", "individuals"], "article_id"=>963709, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.g005", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplot_comparisons_of_athletes_and_other_individuals_with_normal_exercise_tolerance_/963709", "title"=>"Boxplot comparisons of athletes and other individuals with normal exercise tolerance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422523"], "description"=>"<p>Three-way plots of relationships between SaO<sub>2</sub> (y axis), ferritin/iron (x axis), and haematinic index (z axis). The most hypoxaemic patients are at the bottom of each graph, and patients with the lowest ferritin/iron levels to the left. The z axis effectively provides a 3 dimensional plot in which contours range from blue (lowest value of modelled haematinic variable) to red (highest values). A–D) Serum ferritin/SaO<sub>2</sub> stratifications for the 105 PAVM patients with serum ferritin measurements: A) SaO<sub>2</sub>/ferritin/haemoglobin. B) SaO<sub>2</sub>/ferritin/haematocrit. C) SaO<sub>2</sub>/ferritin/MCHC. D) SaO<sub>2</sub>/ferritin/red cell count. Note that higher haemoglobin, haematocrit and MCHC are seen across the normal range for ferritin (10–150 or 20–300 µg/L, according to gender), but higher RBC number is only seen in patients with low or subnormal ferritin. E–H) Serum iron/SaO<sub>2</sub> stratifications for the 141 PAVM patients with serum iron measurements. E) SaO<sub>2</sub>/iron/haemoglobin. F) SaO<sub>2</sub>/iron/haematocrit. G) SaO<sub>2</sub>/iron/MCHC. D) SaO<sub>2</sub>/iron/red cell count. Although serum iron and serum ferritin were correlated (Spearman rho 0.34, p = 0.006), serum iron did not show the same relationships with hematinic indices as serum ferritin (contrast A and E; B and F; C and G; D and H). The highest haematinic indices were observed with serum iron above the normal range (7–27 µmol/L).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "relationships", "haematinic", "indices"], "article_id"=>963705, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.g002", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Three_way_plots_of_relationships_between_haematinic_indices_and_SaO_2_/963705", "title"=>"Three-way plots of relationships between haematinic indices and SaO<sub>2</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422520"], "description"=>"<p>Univariate associations demonstrating individual patient data (small diamonds), linear regression lines, and 95% confidence intervals (shaded) for two way relationships. A–C): The polycythaemic response to hypoxaemia. A) Lower SaO<sub>2</sub> was associated with higher haemoglobin (the ‘polycythaemic response’). B) This polycythaemia was not attributable to increased haemoglobin concentration in red cells (mean corpuscular haemoglobin concentration, MCHC). C) Instead, the polycythaemia reflected increased red cell number (RBC), that is, secondary erythrocytosis, D–F) The anaemic response to iron deficiency: D) Lower serum iron concentrations were associated with lower haemoglobin (the ‘anaemic response’). E) This anaemic response to iron deficiency resulted from reduced haemoglobin concentration in red cells (MCHC), and not a change in red cell number (RBC) (F).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "polycythaemia", "anaemia", "responses", "pavm"], "article_id"=>963702, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Basis_of_polycythaemia_and_anaemia_responses_in_PAVM_patients_/963702", "title"=>"Basis of polycythaemia and anaemia responses in PAVM patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422531"], "description"=>"<p>Data are provided only where available at all comparative timepoints for stated variable: immediately pre embolisation (previous evening, or same morning); the morning following embolisation (“immediate post (day 1)”); and at late follow up (“late post”), which referred to the first post embolisation follow up clinic, 2–24 (median 7) months post final embolisation. Where several embolisations took place in a series (17 patients required two sessions and 3 required three sessions), data are only reported pre and post final embolisation. The day 1 arterial oxygen content was calculated using the day 1 SaO<sub>2</sub> and pre-embolisation haemoglobin. P values for three way comparisons were calculated by Friedman, except for two way pre post haemoglobin comparisons which were calculated by Mann Whitney. IQR, interquartile range. ns, non significant (exact figure not provided from Kruskal Walllis.)</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "pavm"], "article_id"=>963713, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.t002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_SaO_2_haemoglobin_and_oxygen_content_following_PAVM_embolisation_/963713", "title"=>"Changes in SaO<sub>2</sub>, haemoglobin, and oxygen content following PAVM embolisation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-17 02:49:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1422529"], "description"=>"<p>Post embolisation data were obtained at clinic follow up at a median of 7 months (range (2–24) months after the final embolisation. Shaded areas represent 95% confidence interval for quadratic regression line for all 52 patients with pre and post embolisation haemoglobin measurements (pseudo r<sup>2</sup> 0.44, p<0.0001). Open diamonds represent individuals with pre embolisation serum iron <4 µmol/L.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "cardiovascular system", "Circulatory physiology", "Respiratory system", "Respiratory physiology", "Physiological processes", "hematology", "anemia", "Iron deficiency anemia", "Heme synthesis", "nutrition", "Pulmonology", "Sports and exercise medicine", "pre"], "article_id"=>963711, "categories"=>["Medicine"], "users"=>["Vatshalan Santhirapala", "Louisa C. Williams", "Hannah C. Tighe", "James E. Jackson", "Claire L. Shovlin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0090777.g006", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blood_oxygen_content_pre_and_post_embolisation_/963711", "title"=>"Blood oxygen content pre and post embolisation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 02:49:35"}

PMC Usage Stats | Further Information

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