FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2149249043> ?p ?o ?g. }

• W2149249043 endingPage "2052" @default.
• W2149249043 startingPage "2050" @default.
• W2149249043 abstract "There is extensive crosstalk between coagulation and inflammation in mounting an adequate immune response against potentially injurious stimuli [1Esmon C.T. Crosstalk between inflammation and thrombosis.Maturitas. 2004; 47: 305-14Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 2Levi M. Van Der Poll T. Buller H.R. Bidirectional relation between inflammation and coagulation.Circulation. 2004; 109: 2698-704Crossref PubMed Scopus (682) Google Scholar]. Indeed, coagulation proteases have significant immunomodulatory effects; vice‐versa, immune cells are important in the initiation of coagulation pathways and various inflammatory mediators are capable of altering hemostasis. It is not surprising for these two phylogenetically old responses to have widespread reciprocal activation and amplification, in particular when considering clotting and inflammation as possibly the oldest and most important host‐protective systems; for example, see the role of coagulation and inflammation in a fresh wound. Coagulation is immediately activated, and necessary for the formation of a clot to prevent the injured victim from bleeding to death. However, the role of the immune system is also clear because an adequate host defense is required to prevent the victim from an invasion of pathogens. As such, coagulation and inflammation are brothers‐in‐arms. In the lungs, both the coagulation system [3Gunther A. Mosavi P. Heinemann S. Ruppert C. Muth H. Markart P. Grimminger F. Walmrath D. Temmesfeld‐Wollbruck B. Seeger W. Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome.Am J Respir Crit Care Med. 2000; 161: 454-62Crossref PubMed Google Scholar, 4Schultz M.J. Millo J. Levi M. Hack C.E. Weverling G.J. Garrard C.S. Van Der Poll T. Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia.Thorax. 2004; 59: 130-5Crossref PubMed Scopus (117) Google Scholar] and the inflammation system [5Dehoux M.S. Boutten A. Ostinelli J. Seta N. Dombret M.C. Crestani B. Deschenes M. Trouillet J.L. Aubier M. Compartmentalized cytokine production within the human lung in unilateral pneumonia.Am J Respir Crit Care Med. 1994; 150: 710-6Crossref PubMed Google Scholar, 6Pugin J. Verghese G. Widmer M.C. Matthay M.A. The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome.Crit Care Med. 1999; 27: 304-12Crossref PubMed Google Scholar] can become very active. This should not cause surprise. First, bleeding into the airspaces of the lungs without doubt would cause major distress if not death. Abundant expression of tissue factor in the lungs allows for immediate activation of coagulation, preventing a breathtaking bleed. Second, the lungs are repeatedly exposed to respiratory pathogens, either via (micro‐) aspiration of microorganisms that colonize the oropharynx or by inhalation. Innate immune cells, including alveolar macrophages and recruited neutrophils, and proinflammatory mediators initiate a protective inflammatory reaction, preventing death due to overwhelming pneumonia caused by those pathogens that have passed the structural airway defenses and have entered into terminal airways. Also, a new‐formed clot may contain bacteria at the site of infection, while a microvascular clot occluding the draining venules may prevent bacteria from reaching the systemic circulation. Coagulation and inflammation are two comrades protecting the lungs. However, both the coagulation and inflammation systems can also react too strongly, resulting in unfavorable effects. Coagulation and inflammation may further amplify each other in a response that is too intensive. The detrimental effects of exaggerated clotting are best exemplified in the clinical syndrome of sepsis, characterized by systemic coagulation overactivation and systemic overproduction of proinflammatory mediators. The firm response leads to consumption of clotting factors and widespread fibrin depositions, causing diffuse endothelial damage, multiple organ dysfunction, and eventually death. Over the last decade several anticoagulant therapies have been tested in randomized trials of patients with severe sepsis. While treatment with antithrombin (AT) [7Warren B.L. Eid A. Singer P. Pillay S.S. Carl P. Novak I. Chalupa P. Atherstone A. Penzes I. Kubler A. Knaub S. Keinecke H.O. Heinrichs H. Schindel F. Juers M. Bone R.C. Opal S.M. Caring for the critically ill patient. High‐dose antithrombin III in severe sepsis: a randomized controlled trial.JAMA. 2001; 286: 1869-78Crossref PubMed Google Scholar], tissue factor pathway inhibitor [8Abraham E. Reinhart K. Opal S. Demeyer I. Doig C. Rodriguez A.L. Beale R. Svoboda P. Laterre P.F. Simon S. Light B. Spapen H. Stone J. Seibert A. Peckelsen C. De Deyne C. Postier R. Pettila V. Artigas A. Percell S.R. et al.Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial.JAMA. 2003; 290: 238-47Crossref PubMed Scopus (809) Google Scholar] or heparin [9Jaimes F. De La Rosa G. Morales C. Fortich F. Arango C. Aguirre D. Munoz A. Unfractioned heparin for treatment of sepsis: a randomized clinical trial (The HETRASE Study).Crit Care Med. 2009; 37: 1185-96Crossref PubMed Scopus (126) Google Scholar] failed to show any benefit, the PROWESS trial showed that infusion of recombinant‐human activated protein C (rh‐aPC) resulted in a dampened inflammatory response and a better outcome for these patients [10Bernard G.R. Vincent J.L. Laterre P.F. LaRosa S.P. Dhainaut J.F. Lopez‐Rodriguez A. Steingrub J.S. Garber G.E. Helterbrand J.D. Ely E.W. Fisher Jr, C.J. Efficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med. 2001; 344: 699-709Crossref PubMed Scopus (5051) Google Scholar]. Too much clotting in the lungs may also be a bad thing. Indeed, excessive fibrin deposition within the airways is associated with compromised pulmonary integrity and function [11Abraham E. Coagulation abnormalities in acute lung injury and sepsis.Am J Respir Cell Mol Biol. 2000; 22: 401-4Crossref PubMed Google Scholar, 12Schultz M.J. Haitsma J.J. Zhang H. Slutsky A.S. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia‐‐a review.Crit Care Med. 2006; 34: 871-7Crossref PubMed Scopus (0) Google Scholar]. Therefore, it can be questioned whether anticoagulant treatment may also benefit patients with pneumonia or other forms of acute lung injury [12Schultz M.J. Haitsma J.J. Zhang H. Slutsky A.S. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia‐‐a review.Crit Care Med. 2006; 34: 871-7Crossref PubMed Scopus (0) Google Scholar]. There are several reasons to consider this. First, in the above‐mentioned study, rh‐aPC treatment led to more rapid resolution of respiratory failure [10Bernard G.R. Vincent J.L. Laterre P.F. LaRosa S.P. Dhainaut J.F. Lopez‐Rodriguez A. Steingrub J.S. Garber G.E. Helterbrand J.D. Ely E.W. Fisher Jr, C.J. Efficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med. 2001; 344: 699-709Crossref PubMed Scopus (5051) Google Scholar]. Second, patients with pneumonia as the source of sepsis benefited most from treatment with rh‐aPC [13Laterre P.‐.F. Garber G. Levy H. Wunderink R. Kinasewitz G.T. Sollet J.‐.P. Maki D.G. Bates B. Yan S.C.B. Dhainaut J.‐.F. Severe community‐acquired pneumonia as a cause of severe sepsis: data from the PROWESS study.Crit Care Med. 2005; 33: 952-61Crossref PubMed Scopus (0) Google Scholar]. While systemic rh‐aPC treatment did not affect ventilator‐free days in a recent study in patients with acute lung injury (ALI), it must be noted that the low number of recruited patients limited the statistical power to detect a difference [14Liu K.D. Levitt J. Zhuo H. Kallet R.H. Brady S. Steingrub J. Tidswell M. Siegel M.D. Soto G. Peterson M.W. Chesnutt M.S. Phillips C. Weinacker A. Thompson B.T. Eisner M.D. Matthay M.A. Randomized clinical trial of activated protein C for the treatment of acute lung injury.Am J Respir Crit Care Med. 2008; 178: 618-23Crossref PubMed Scopus (177) Google Scholar]. In the lungs there is widespread crosstalk between coagulation and inflammation [1Esmon C.T. Crosstalk between inflammation and thrombosis.Maturitas. 2004; 47: 305-14Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 15Choi G. Schultz M.J. Levi M. Van Der Poll T. The relationship between inflammation and the coagulation system.Swiss Med Wkly. 2006; 136: 139-44PubMed Google Scholar]. Recognizing the connection between pulmonary coagulation and inflammation brought up the hypothesis that influencing either pathway could alter the other. Will a strategy dampening the procoagulant response also attenuate local proinflammatory reactions? Indeed, it has been suggested that next to anticoagulant effects, anti‐inflammatory effects of rh‐aPC in the lungs contribute to a better outcome [16Nick J.A. Coldren C.D. Geraci M.W. Poch K.R. Fouty B.W. O’Brien J. Gruber M. Zarini S. Murphy R.C. Kuhn K. Richter D. Kast K.R. Abraham E. Recombinant human activated protein C reduces human endotoxin‐induced pulmonary inflammation via inhibition of neutrophil chemotaxis.Blood. 2004; 104: 3878-85Crossref PubMed Scopus (0) Google Scholar, 17Van Der Poll T. Levi M. Nick J.A. Abraham E. Activated protein C inhibits local coagulation after intrapulmonary delivery of endotoxin in humans.Am J Respir Crit Care Med. 2005; 171: 1125-8Crossref PubMed Scopus (101) Google Scholar]. In this issue of the Journal of Thrombosis and Haemostasis, Takagi et al.[18Takagi T. Taguchi O. Aoki S. Toda M. Yamaguchi A. Fujimoto H. Boveda‐Ruiz D. Gil‐Bernabe P. Ramirez A.Y. Yano Y. D’Alessandro‐Gabazza C.N. Fujiwara A. Takei Y. Morser J. Gabazza E.C. Direct effects of protein S in ameliorating acute lung injury.J Thromb Haemost. 2009; 7: 2053-63Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar] report on a series of experiments evaluating the effect of protein S (PS) on acute lung injury in the mouse. Lung injury was induced by intratracheal instillation of lipopolysaccharide (LPS). Mice were treated with PS or saline by intraperitoneal injection 1 h before LPS instillation. LPS‐treated mice developed lung injury, associated with procoagulant and proinflammatory changes in bronchoalveolar fluids and lung histopathology. Mice with lung injury treated with PS had significantly decreased concentrations of tumor necrosis factor‐α, interleukin‐6 and monocyte chemoattractant protein‐1 and decreased levels of total protein in bronchoalveolar lavage fluids. Also, PS treatment attenuated the influx of neutrophil cells into the lungs, with subsequent lower local levels of myeloperoxidase. In additional in vitrostudies using a human alveolar epithelial cells line it was shown that PS directly activates one tyrosine kinase receptor (Axl), a receptor that is linked to inhibition of cytokine expression. In line with this finding, PS suppressed the secretion of monocyte chemoattractant protein‐1 and interleukin‐8 from the alveolar epithelial cells. The authors suggest that the inhibiting effect of PS on inflammation was not related to the anticoagulant activity of PS. While this may be the case, their assessment of anticoagulant activity was based on a single local concentration of thrombin‐antithrombin at 24 h following inhaled LPS. It would have been interesting if the authors had also assessed anticoagulant activity by measuring the extent of microvascular thrombosis and hyaline membrane formation in lung tissue using a fibrin‐specific stain. The results of this study are, at least in part, in line with results from other animal studies investigating anti‐inflammatory effects of anticoagulant compounds. Indeed, in various models of LPS‐induced lung injury, anticoagulant therapy, including treatment with AT or APC, was found to be able to reduce both pulmonary coagulopathy and inflammation, as well as to improve oxygenation [19Murakami K. Okajima K. Uchiba M. Johno M. Nakagaki T. Okabe H. Takatsuki K. Activated protein C prevents LPS‐induced pulmonary vascular injury by inhibiting cytokine production.Am J Physiol. 1997; 272: L197-202PubMed Google Scholar, 20Okajima K. Antithrombin prevents endotoxin‐induced pulmonary vascular injury by inhibiting leukocyte activation.Blood Coagul Fibrinolysis. 1998; 9: S25-37PubMed Google Scholar, 21Giebler R. Schmidt U. Koch S. Peters J. Scherer R. Combined antithrombin III and C1‐esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin.Crit Care Med. 1999; 27: 597-604Crossref PubMed Google Scholar, 22Yasui H. Gabazza E.C. Tamaki S. Kobayashi T. Hataji O. Yuda H. Shimizu S. Suzuki K. Adachi Y. Taguchi O. Intratracheal administration of activated protein C inhibits bleomycin‐induced lung fibrosis in the mouse.Am J Respir Crit Care Med. 2001; 163: 1660-8Crossref PubMed Google Scholar]. The present study expands our knowledge on anti‐inflammatory effects of anticoagulant compounds in two ways. First, the relatively weak anticoagulant PS seems to have some beneficial effect, at least in local inflammation in the lungs. Second, this anti‐inflammatory effect, at least in part, seems to exist beyond, and not in crosstalk with, its anticoagulant effect. Several pathways have been mentioned by the authors [18Takagi T. Taguchi O. Aoki S. Toda M. Yamaguchi A. Fujimoto H. Boveda‐Ruiz D. Gil‐Bernabe P. Ramirez A.Y. Yano Y. D’Alessandro‐Gabazza C.N. Fujiwara A. Takei Y. Morser J. Gabazza E.C. Direct effects of protein S in ameliorating acute lung injury.J Thromb Haemost. 2009; 7: 2053-63Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. There are other animal studies, though, that do not show anti‐inflammatory effects of anticoagulant compounds in models of lung injury. Indeed, in models of infectious lung injury the anticoagulants APC, heparin and danaparoid were all found to attenuate pulmonary coagulopathy, while not affecting inflammation [23Choi G. Hofstra J.J. Roelofs J.J. Florquin S. Bresser P. Levi M. Van Der Poll T. Schultz M.J. Recombinant human activated protein C inhibits local and systemic activation of coagulation without influencing inflammation during Pseudomonas aeruginosa pneumonia in rats.Crit Care Med. 2007; 35: 1362-8Crossref PubMed Scopus (45) Google Scholar, 24Choi G. Hofstra J.J. Roelofs J.J. Rijneveld A.W. Bresser P. Van Der Zee J.S. Florquin S. Van Der Poll T. Levi M. Schultz M.J. Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats.Crit Care Med. 2008; 36: 204-10Crossref PubMed Scopus (0) Google Scholar, 25Hofstra J.J. Cornet A.D. Choi G. Van Der Poll T. Levi M. Schultz M.J. Locally Applied Antithrombin Inhibits Pulmonary Coagulopathy during Streptococcus pneumoniaePneumonia in rats.Crit Care. 2009; 13: R145Crossref PubMed Scopus (0) Google Scholar]. What is the explanation for the difference between the results from the study by Takagi et al.and those from these negative studies? None of the above‐mentioned negative studies used PS as an anticoagulant, and it may be that the found effects are unique for PS. One other explanation might be the difference between the models of lung injury: in the latter models of infectious lung injury, pneumonia was induced by installing live bacteria, which may better reflect the clinical syndrome of pneumonia [26Hofstra J.J. Juffermans N.P. Schultz M.J. Zweers M.M. Pulmonary coagulopathy as a new target in lung injury‐‐a review of available pre‐clinical models.Curr Med Chem. 2008; 15: 588-95Crossref PubMed Scopus (0) Google Scholar]. However, this may not be the only explanation, because, in one other negative study lung injury was induced by LPS, although administered intravenously and not intratracheally [27Hofstra J.J. Dixon B. Cornet A.D. Choi G. Van Der Poll T. Levi M. Schultz M.J. Nebulized Anticoagulants Limit Pulmonary Coagulopathy in Clinical and Experimental Acute Lung injury.J Aerosol Med Pulm Drug Deliv. 2009; Google Scholar]. Several other, yet unrecognized, differences may exist. Although anti‐inflammatory effects of anticoagulants may be beneficial, several risks associated with altering pulmonary coagulation may need to be recognized. First, as mentioned above, clot formation may also be helpful in preventing spread of infection by containing invading pathogens at the site of infection within locally formed clots. Certain microorganisms even induce profibrinolytic mechanisms to escape from being contained in such a fibrin clot [28Lahteenmaki K. Kuusela P. Korhonen T.K. Bacterial plasminogen activators and receptors.FEMS Microbiol Rev. 2001; 25: 531-52Crossref PubMed Scopus (280) Google Scholar]. In addition, it has also been shown that heparin treatment facilitates spread of bacteremia [24Choi G. Hofstra J.J. Roelofs J.J. Rijneveld A.W. Bresser P. Van Der Zee J.S. Florquin S. Van Der Poll T. Levi M. Schultz M.J. Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats.Crit Care Med. 2008; 36: 204-10Crossref PubMed Scopus (0) Google Scholar]. These findings underline that coagulation and inflammation are closely related in pivotal host defense mechanisms, and interference with these pathways should be performed with great care. Second, systemic administration of anticoagulant compounds substantially increases the risk of bleeding. Indeed, in the PROWESS trial in patients with severe sepsis the incidence of serious bleeding was higher in the treatment group than in the placebo group (3.5% vs. 2.0%) [10Bernard G.R. Vincent J.L. Laterre P.F. LaRosa S.P. Dhainaut J.F. Lopez‐Rodriguez A. Steingrub J.S. Garber G.E. Helterbrand J.D. Ely E.W. Fisher Jr, C.J. Efficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med. 2001; 344: 699-709Crossref PubMed Scopus (5051) Google Scholar]. The effect of systemically administered high‐dose AT on the occurrence of bleeding events in patients with severe sepsis, especially when combined with heparin, was even stronger (22.0% vs. 12.8%) [7Warren B.L. Eid A. Singer P. Pillay S.S. Carl P. Novak I. Chalupa P. Atherstone A. Penzes I. Kubler A. Knaub S. Keinecke H.O. Heinrichs H. Schindel F. Juers M. Bone R.C. Opal S.M. Caring for the critically ill patient. High‐dose antithrombin III in severe sepsis: a randomized controlled trial.JAMA. 2001; 286: 1869-78Crossref PubMed Google Scholar]. Local treatment may be equally effective as systemic treatment in attenuating pulmonary procoagulant changes while leaving systemic coagulation unaltered. Local therapy may even allow higher dosages, leading to higher local concentrations. Indeed, several animal studies [25Hofstra J.J. Cornet A.D. Choi G. Van Der Poll T. Levi M. Schultz M.J. Locally Applied Antithrombin Inhibits Pulmonary Coagulopathy during Streptococcus pneumoniaePneumonia in rats.Crit Care. 2009; 13: R145Crossref PubMed Scopus (0) Google Scholar, 27Hofstra J.J. Dixon B. Cornet A.D. Choi G. Van Der Poll T. Levi M. Schultz M.J. Nebulized Anticoagulants Limit Pulmonary Coagulopathy in Clinical and Experimental Acute Lung injury.J Aerosol Med Pulm Drug Deliv. 2009; Google Scholar] and one pivotal clinical trial [29Dixon B. Santamaria J.D. Campbell D.J. A phase 1 trial of nebulised heparin in acute lung injury.Crit Care. 2008; 12: R64Crossref PubMed Scopus (64) Google Scholar] show this route of administration to be feasible and safe. Data from several preceding studies, as well as from the paper by Takagi et al., force us not to think off coagulation and inflammation as two independent pathways. It may be even naïve to see these pathways as two different systems. Instead of speaking of crosstalk between coagulation and inflammation we might want to consider the two systems as one, with both coagulant and inflammatory effects. Future research will have to tell us whether intervening with this system truly benefits patients. The authors state that they have no conflict of interest." @default.
• W2149249043 created "2016-06-24" @default.
• W2149249043 creator A5013315693 @default.
• W2149249043 creator A5049303332 @default.
• W2149249043 date "2009-12-01" @default.
• W2149249043 modified "2023-10-17" @default.
• W2149249043 title "A breathtaking and bloodcurdling story of coagulation and inflammation in acute lung injury" @default.
• W2149249043 cites W1908907230 @default.
• W2149249043 cites W1967429254 @default.
• W2149249043 cites W1970660789 @default.
• W2149249043 cites W2008951161 @default.
• W2149249043 cites W2012906489 @default.
• W2149249043 cites W2015205968 @default.
• W2149249043 cites W2043042097 @default.
• W2149249043 cites W2059426768 @default.
• W2149249043 cites W2074488392 @default.
• W2149249043 cites W2075425755 @default.
• W2149249043 cites W2078851496 @default.
• W2149249043 cites W2084951871 @default.
• W2149249043 cites W2085122311 @default.
• W2149249043 cites W2108435955 @default.
• W2149249043 cites W2115301416 @default.
• W2149249043 cites W2115434263 @default.
• W2149249043 cites W2124551895 @default.
• W2149249043 cites W2133875691 @default.
• W2149249043 cites W2144380673 @default.
• W2149249043 cites W2146884753 @default.
• W2149249043 cites W2167351713 @default.
• W2149249043 cites W2168488250 @default.
• W2149249043 cites W2170885626 @default.
• W2149249043 cites W2322121630 @default.
• W2149249043 cites W4246370983 @default.
• W2149249043 doi "https://doi.org/10.1111/j.1538-7836.2009.03639.x" @default.
• W2149249043 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19817992" @default.
• W2149249043 hasPublicationYear "2009" @default.
• W2149249043 type Work @default.
• W2149249043 sameAs 2149249043 @default.
• W2149249043 citedByCount "5" @default.
• W2149249043 countsByYear W21492490432012 @default.
• W2149249043 countsByYear W21492490432016 @default.
• W2149249043 countsByYear W21492490432019 @default.
• W2149249043 crossrefType "journal-article" @default.
• W2149249043 hasAuthorship W2149249043A5013315693 @default.
• W2149249043 hasAuthorship W2149249043A5049303332 @default.
• W2149249043 hasBestOaLocation W21492490431 @default.
• W2149249043 hasConcept C126322002 @default.
• W2149249043 hasConcept C142724271 @default.
• W2149249043 hasConcept C2776914184 @default.
• W2149249043 hasConcept C2777714996 @default.
• W2149249043 hasConcept C2778382381 @default.
• W2149249043 hasConcept C71924100 @default.
• W2149249043 hasConceptScore W2149249043C126322002 @default.
• W2149249043 hasConceptScore W2149249043C142724271 @default.
• W2149249043 hasConceptScore W2149249043C2776914184 @default.
• W2149249043 hasConceptScore W2149249043C2777714996 @default.
• W2149249043 hasConceptScore W2149249043C2778382381 @default.
• W2149249043 hasConceptScore W2149249043C71924100 @default.
• W2149249043 hasIssue "12" @default.
• W2149249043 hasLocation W21492490431 @default.
• W2149249043 hasLocation W21492490432 @default.
• W2149249043 hasOpenAccess W2149249043 @default.
• W2149249043 hasPrimaryLocation W21492490431 @default.
• W2149249043 hasRelatedWork W1506200166 @default.
• W2149249043 hasRelatedWork W1995515455 @default.
• W2149249043 hasRelatedWork W2048182022 @default.
• W2149249043 hasRelatedWork W2054378706 @default.
• W2149249043 hasRelatedWork W2080531066 @default.
• W2149249043 hasRelatedWork W2748952813 @default.
• W2149249043 hasRelatedWork W2899084033 @default.
• W2149249043 hasRelatedWork W3031052312 @default.
• W2149249043 hasRelatedWork W3032375762 @default.
• W2149249043 hasRelatedWork W3108674512 @default.
• W2149249043 hasVolume "7" @default.
• W2149249043 isParatext "false" @default.
• W2149249043 isRetracted "false" @default.
• W2149249043 magId "2149249043" @default.
• W2149249043 workType "article" @default.