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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T12","span":{"begin":355,"end":360},"obj":"Body_part"},{"id":"T13","span":{"begin":918,"end":922},"obj":"Body_part"},{"id":"T14","span":{"begin":1116,"end":1120},"obj":"Body_part"},{"id":"T15","span":{"begin":1214,"end":1218},"obj":"Body_part"},{"id":"T16","span":{"begin":1344,"end":1350},"obj":"Body_part"},{"id":"T17","span":{"begin":1455,"end":1461},"obj":"Body_part"},{"id":"T18","span":{"begin":2140,"end":2158},"obj":"Body_part"},{"id":"T19","span":{"begin":2499,"end":2504},"obj":"Body_part"},{"id":"T20","span":{"begin":2529,"end":2534},"obj":"Body_part"}],"attributes":[{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A13","pred":"uberon_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A14","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A15","pred":"uberon_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A16","pred":"uberon_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"A17","pred":"uberon_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0001242"},{"id":"A19","pred":"uberon_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"},{"id":"A20","pred":"uberon_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/UBERON_0000062"}],"text":"POTENTIAL ADVERSE AND OFF-TARGET EFFECTS OF HEPARIN THERAPY\nThe use of heparin as a therapeutic anticoagulant is associated with a 10–15% risk of significant bleeding (11, 27). Factors that may increase bleeding risk are older age, worse illness severity, recent trauma or surgery, cardiopulmonary resuscitation, longer hospital stay, and decreased white blood cell and platelet counts (11, 27). Many of these risk factors for bleeding are commonly seen in patients with COVID-19. A second, albeit rare, complication of heparin therapy is HIT, which is estimated to occur in 0.2–3% of patients who receive heparin (4). This feared adverse effect is driven by the development of antibodies specific to the protein platelet factor 4, which leads to life-threatening thrombocytopenia and paradoxical development of thrombosis.\nIt is also possible that the intended effect of heparin (i.e., anticoagulation) can interrupt lung-protective processes of coagulation that may improve host survival in COVID-19. Although critical illness-associated intravascular thrombosis has been recognized as harmful in animal models of lung injury (44), coagulation occurring within alveoli and airways has generally been found to be lung protective (9, 34). This is particularly notable in animal models of viral pneumonia, in which transgenic loss of epithelial tissue factor markedly worsened animal mortality after influenza infection (3). Transgenic loss of endothelial tissue factor, conversely, had no effect on influenza-induced injury. It is therefore possible that intra-alveolar coagulation may serve a teleological function of isolating pulmonary pathogens, protecting the host from disseminated infection. Such divergent effects of intra-alveolar and intravascular coagulation may in part explain the muted benefits of anticoagulants [including inhaled heparin (6)] in randomized controlled studies of pneumonia.\nFinally, heparin may have many other unrecognized effects—both protective and harmful—arising from its heterogeneous structure. As noted, unfractionated heparin is composed of a mixture of distinct biologically derived (i.e., porcine intestinal mucosae) heparan sulfate polysaccharides, which on balance not only is enriched in a pentasaccharide sequence necessary for AT3 activation (and thus anticoagulation) but also displays a wide variety of other sulfation sequences. These non-anticoagulant sulfation sequences allow heparin binding to various growth factors, potentially exerting both organ-protective (46, 49) and organ-harmful (14, 20) effects."}

LitCovid-PubTator

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T34","span":{"begin":947,"end":958},"obj":"http://purl.obolibrary.org/obo/GO_0050817"},{"id":"T35","span":{"begin":1134,"end":1145},"obj":"http://purl.obolibrary.org/obo/GO_0050817"},{"id":"T36","span":{"begin":1570,"end":1581},"obj":"http://purl.obolibrary.org/obo/GO_0050817"},{"id":"T37","span":{"begin":1758,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0050817"},{"id":"T38","span":{"begin":2359,"end":2368},"obj":"http://purl.obolibrary.org/obo/GO_0051923"},{"id":"T39","span":{"begin":2404,"end":2413},"obj":"http://purl.obolibrary.org/obo/GO_0051923"},{"id":"T40","span":{"begin":2457,"end":2463},"obj":"http://purl.obolibrary.org/obo/GO_0040007"}],"text":"POTENTIAL ADVERSE AND OFF-TARGET EFFECTS OF HEPARIN THERAPY\nThe use of heparin as a therapeutic anticoagulant is associated with a 10–15% risk of significant bleeding (11, 27). Factors that may increase bleeding risk are older age, worse illness severity, recent trauma or surgery, cardiopulmonary resuscitation, longer hospital stay, and decreased white blood cell and platelet counts (11, 27). Many of these risk factors for bleeding are commonly seen in patients with COVID-19. A second, albeit rare, complication of heparin therapy is HIT, which is estimated to occur in 0.2–3% of patients who receive heparin (4). This feared adverse effect is driven by the development of antibodies specific to the protein platelet factor 4, which leads to life-threatening thrombocytopenia and paradoxical development of thrombosis.\nIt is also possible that the intended effect of heparin (i.e., anticoagulation) can interrupt lung-protective processes of coagulation that may improve host survival in COVID-19. Although critical illness-associated intravascular thrombosis has been recognized as harmful in animal models of lung injury (44), coagulation occurring within alveoli and airways has generally been found to be lung protective (9, 34). This is particularly notable in animal models of viral pneumonia, in which transgenic loss of epithelial tissue factor markedly worsened animal mortality after influenza infection (3). Transgenic loss of endothelial tissue factor, conversely, had no effect on influenza-induced injury. It is therefore possible that intra-alveolar coagulation may serve a teleological function of isolating pulmonary pathogens, protecting the host from disseminated infection. Such divergent effects of intra-alveolar and intravascular coagulation may in part explain the muted benefits of anticoagulants [including inhaled heparin (6)] in randomized controlled studies of pneumonia.\nFinally, heparin may have many other unrecognized effects—both protective and harmful—arising from its heterogeneous structure. As noted, unfractionated heparin is composed of a mixture of distinct biologically derived (i.e., porcine intestinal mucosae) heparan sulfate polysaccharides, which on balance not only is enriched in a pentasaccharide sequence necessary for AT3 activation (and thus anticoagulation) but also displays a wide variety of other sulfation sequences. These non-anticoagulant sulfation sequences allow heparin binding to various growth factors, potentially exerting both organ-protective (46, 49) and organ-harmful (14, 20) effects."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T100","span":{"begin":0,"end":59},"obj":"Sentence"},{"id":"T101","span":{"begin":60,"end":176},"obj":"Sentence"},{"id":"T102","span":{"begin":177,"end":395},"obj":"Sentence"},{"id":"T103","span":{"begin":396,"end":480},"obj":"Sentence"},{"id":"T104","span":{"begin":481,"end":618},"obj":"Sentence"},{"id":"T105","span":{"begin":619,"end":823},"obj":"Sentence"},{"id":"T106","span":{"begin":824,"end":1002},"obj":"Sentence"},{"id":"T107","span":{"begin":1003,"end":1238},"obj":"Sentence"},{"id":"T108","span":{"begin":1239,"end":1423},"obj":"Sentence"},{"id":"T109","span":{"begin":1424,"end":1524},"obj":"Sentence"},{"id":"T110","span":{"begin":1525,"end":1698},"obj":"Sentence"},{"id":"T111","span":{"begin":1699,"end":1905},"obj":"Sentence"},{"id":"T112","span":{"begin":1906,"end":2033},"obj":"Sentence"},{"id":"T113","span":{"begin":2034,"end":2379},"obj":"Sentence"},{"id":"T114","span":{"begin":2380,"end":2560},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"POTENTIAL ADVERSE AND OFF-TARGET EFFECTS OF HEPARIN THERAPY\nThe use of heparin as a therapeutic anticoagulant is associated with a 10–15% risk of significant bleeding (11, 27). Factors that may increase bleeding risk are older age, worse illness severity, recent trauma or surgery, cardiopulmonary resuscitation, longer hospital stay, and decreased white blood cell and platelet counts (11, 27). Many of these risk factors for bleeding are commonly seen in patients with COVID-19. A second, albeit rare, complication of heparin therapy is HIT, which is estimated to occur in 0.2–3% of patients who receive heparin (4). This feared adverse effect is driven by the development of antibodies specific to the protein platelet factor 4, which leads to life-threatening thrombocytopenia and paradoxical development of thrombosis.\nIt is also possible that the intended effect of heparin (i.e., anticoagulation) can interrupt lung-protective processes of coagulation that may improve host survival in COVID-19. Although critical illness-associated intravascular thrombosis has been recognized as harmful in animal models of lung injury (44), coagulation occurring within alveoli and airways has generally been found to be lung protective (9, 34). This is particularly notable in animal models of viral pneumonia, in which transgenic loss of epithelial tissue factor markedly worsened animal mortality after influenza infection (3). Transgenic loss of endothelial tissue factor, conversely, had no effect on influenza-induced injury. It is therefore possible that intra-alveolar coagulation may serve a teleological function of isolating pulmonary pathogens, protecting the host from disseminated infection. Such divergent effects of intra-alveolar and intravascular coagulation may in part explain the muted benefits of anticoagulants [including inhaled heparin (6)] in randomized controlled studies of pneumonia.\nFinally, heparin may have many other unrecognized effects—both protective and harmful—arising from its heterogeneous structure. As noted, unfractionated heparin is composed of a mixture of distinct biologically derived (i.e., porcine intestinal mucosae) heparan sulfate polysaccharides, which on balance not only is enriched in a pentasaccharide sequence necessary for AT3 activation (and thus anticoagulation) but also displays a wide variety of other sulfation sequences. These non-anticoagulant sulfation sequences allow heparin binding to various growth factors, potentially exerting both organ-protective (46, 49) and organ-harmful (14, 20) effects."}

LitCovid-PD-GlycoEpitope

{"project":"LitCovid-PD-GlycoEpitope","denotations":[{"id":"T15","span":{"begin":2160,"end":2175},"obj":"GlycoEpitope"}],"attributes":[{"id":"A15","pred":"glyco_epitope_db_id","subj":"T15","obj":"http://www.glycoepitope.jp/epitopes/EP0086"}],"text":"POTENTIAL ADVERSE AND OFF-TARGET EFFECTS OF HEPARIN THERAPY\nThe use of heparin as a therapeutic anticoagulant is associated with a 10–15% risk of significant bleeding (11, 27). Factors that may increase bleeding risk are older age, worse illness severity, recent trauma or surgery, cardiopulmonary resuscitation, longer hospital stay, and decreased white blood cell and platelet counts (11, 27). Many of these risk factors for bleeding are commonly seen in patients with COVID-19. A second, albeit rare, complication of heparin therapy is HIT, which is estimated to occur in 0.2–3% of patients who receive heparin (4). This feared adverse effect is driven by the development of antibodies specific to the protein platelet factor 4, which leads to life-threatening thrombocytopenia and paradoxical development of thrombosis.\nIt is also possible that the intended effect of heparin (i.e., anticoagulation) can interrupt lung-protective processes of coagulation that may improve host survival in COVID-19. Although critical illness-associated intravascular thrombosis has been recognized as harmful in animal models of lung injury (44), coagulation occurring within alveoli and airways has generally been found to be lung protective (9, 34). This is particularly notable in animal models of viral pneumonia, in which transgenic loss of epithelial tissue factor markedly worsened animal mortality after influenza infection (3). Transgenic loss of endothelial tissue factor, conversely, had no effect on influenza-induced injury. It is therefore possible that intra-alveolar coagulation may serve a teleological function of isolating pulmonary pathogens, protecting the host from disseminated infection. Such divergent effects of intra-alveolar and intravascular coagulation may in part explain the muted benefits of anticoagulants [including inhaled heparin (6)] in randomized controlled studies of pneumonia.\nFinally, heparin may have many other unrecognized effects—both protective and harmful—arising from its heterogeneous structure. As noted, unfractionated heparin is composed of a mixture of distinct biologically derived (i.e., porcine intestinal mucosae) heparan sulfate polysaccharides, which on balance not only is enriched in a pentasaccharide sequence necessary for AT3 activation (and thus anticoagulation) but also displays a wide variety of other sulfation sequences. These non-anticoagulant sulfation sequences allow heparin binding to various growth factors, potentially exerting both organ-protective (46, 49) and organ-harmful (14, 20) effects."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T39","span":{"begin":539,"end":542},"obj":"Phenotype"},{"id":"T40","span":{"begin":764,"end":780},"obj":"Phenotype"},{"id":"T41","span":{"begin":1294,"end":1303},"obj":"Phenotype"},{"id":"T42","span":{"begin":1895,"end":1904},"obj":"Phenotype"}],"attributes":[{"id":"A39","pred":"hp_id","subj":"T39","obj":"http://purl.obolibrary.org/obo/HP_0011874"},{"id":"A40","pred":"hp_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/HP_0001873"},{"id":"A41","pred":"hp_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/HP_0002090"},{"id":"A42","pred":"hp_id","subj":"T42","obj":"http://purl.obolibrary.org/obo/HP_0002090"}],"text":"POTENTIAL ADVERSE AND OFF-TARGET EFFECTS OF HEPARIN THERAPY\nThe use of heparin as a therapeutic anticoagulant is associated with a 10–15% risk of significant bleeding (11, 27). Factors that may increase bleeding risk are older age, worse illness severity, recent trauma or surgery, cardiopulmonary resuscitation, longer hospital stay, and decreased white blood cell and platelet counts (11, 27). Many of these risk factors for bleeding are commonly seen in patients with COVID-19. A second, albeit rare, complication of heparin therapy is HIT, which is estimated to occur in 0.2–3% of patients who receive heparin (4). This feared adverse effect is driven by the development of antibodies specific to the protein platelet factor 4, which leads to life-threatening thrombocytopenia and paradoxical development of thrombosis.\nIt is also possible that the intended effect of heparin (i.e., anticoagulation) can interrupt lung-protective processes of coagulation that may improve host survival in COVID-19. Although critical illness-associated intravascular thrombosis has been recognized as harmful in animal models of lung injury (44), coagulation occurring within alveoli and airways has generally been found to be lung protective (9, 34). This is particularly notable in animal models of viral pneumonia, in which transgenic loss of epithelial tissue factor markedly worsened animal mortality after influenza infection (3). Transgenic loss of endothelial tissue factor, conversely, had no effect on influenza-induced injury. It is therefore possible that intra-alveolar coagulation may serve a teleological function of isolating pulmonary pathogens, protecting the host from disseminated infection. Such divergent effects of intra-alveolar and intravascular coagulation may in part explain the muted benefits of anticoagulants [including inhaled heparin (6)] in randomized controlled studies of pneumonia.\nFinally, heparin may have many other unrecognized effects—both protective and harmful—arising from its heterogeneous structure. As noted, unfractionated heparin is composed of a mixture of distinct biologically derived (i.e., porcine intestinal mucosae) heparan sulfate polysaccharides, which on balance not only is enriched in a pentasaccharide sequence necessary for AT3 activation (and thus anticoagulation) but also displays a wide variety of other sulfation sequences. These non-anticoagulant sulfation sequences allow heparin binding to various growth factors, potentially exerting both organ-protective (46, 49) and organ-harmful (14, 20) effects."}

2_test

{"project":"2_test","denotations":[{"id":"32519894-20442353-2138200","span":{"begin":168,"end":170},"obj":"20442353"},{"id":"32519894-1657248-2138201","span":{"begin":172,"end":174},"obj":"1657248"},{"id":"32519894-20442353-2138202","span":{"begin":387,"end":389},"obj":"20442353"},{"id":"32519894-1657248-2138203","span":{"begin":391,"end":393},"obj":"1657248"},{"id":"32519894-28416511-2138204","span":{"begin":615,"end":616},"obj":"28416511"},{"id":"32519894-11734456-2138205","span":{"begin":1129,"end":1131},"obj":"11734456"},{"id":"32519894-23033361-2138206","span":{"begin":1231,"end":1232},"obj":"23033361"},{"id":"32519894-25884207-2138207","span":{"begin":1234,"end":1236},"obj":"25884207"},{"id":"32519894-26947929-2138208","span":{"begin":1420,"end":1421},"obj":"26947929"},{"id":"32519894-27288618-2138209","span":{"begin":1855,"end":1856},"obj":"27288618"},{"id":"32519894-28187268-2138210","span":{"begin":2517,"end":2519},"obj":"28187268"},{"id":"32519894-28538085-2138211","span":{"begin":2521,"end":2523},"obj":"28538085"},{"id":"32519894-30720464-2138212","span":{"begin":2544,"end":2546},"obj":"30720464"},{"id":"32519894-32320623-2138213","span":{"begin":2548,"end":2550},"obj":"32320623"}],"text":"POTENTIAL ADVERSE AND OFF-TARGET EFFECTS OF HEPARIN THERAPY\nThe use of heparin as a therapeutic anticoagulant is associated with a 10–15% risk of significant bleeding (11, 27). Factors that may increase bleeding risk are older age, worse illness severity, recent trauma or surgery, cardiopulmonary resuscitation, longer hospital stay, and decreased white blood cell and platelet counts (11, 27). Many of these risk factors for bleeding are commonly seen in patients with COVID-19. A second, albeit rare, complication of heparin therapy is HIT, which is estimated to occur in 0.2–3% of patients who receive heparin (4). This feared adverse effect is driven by the development of antibodies specific to the protein platelet factor 4, which leads to life-threatening thrombocytopenia and paradoxical development of thrombosis.\nIt is also possible that the intended effect of heparin (i.e., anticoagulation) can interrupt lung-protective processes of coagulation that may improve host survival in COVID-19. Although critical illness-associated intravascular thrombosis has been recognized as harmful in animal models of lung injury (44), coagulation occurring within alveoli and airways has generally been found to be lung protective (9, 34). This is particularly notable in animal models of viral pneumonia, in which transgenic loss of epithelial tissue factor markedly worsened animal mortality after influenza infection (3). Transgenic loss of endothelial tissue factor, conversely, had no effect on influenza-induced injury. It is therefore possible that intra-alveolar coagulation may serve a teleological function of isolating pulmonary pathogens, protecting the host from disseminated infection. Such divergent effects of intra-alveolar and intravascular coagulation may in part explain the muted benefits of anticoagulants [including inhaled heparin (6)] in randomized controlled studies of pneumonia.\nFinally, heparin may have many other unrecognized effects—both protective and harmful—arising from its heterogeneous structure. As noted, unfractionated heparin is composed of a mixture of distinct biologically derived (i.e., porcine intestinal mucosae) heparan sulfate polysaccharides, which on balance not only is enriched in a pentasaccharide sequence necessary for AT3 activation (and thus anticoagulation) but also displays a wide variety of other sulfation sequences. These non-anticoagulant sulfation sequences allow heparin binding to various growth factors, potentially exerting both organ-protective (46, 49) and organ-harmful (14, 20) effects."}

PMC:7381711 / 16609-19169 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7381711 / 16609-19169 JSON TXT