Unintended consequences of existential quantifications in biomedical ontologies

<p>Abstract</p> <p>Background</p> <p>The Open Biomedical Ontologies (OBO) Foundry is a collection of freely available ontologically structured controlled vocabularies in the biomedical domain. Most of them are disseminated via both the OBO Flatfile Format and the semantic web format Web Ontology Language (OWL), which draws upon formal logic. Based on the interpretations underlying OWL description logics (OWL-DL) semantics, we scrutinize the OWL-DL releases of OBO ontologies to assess whether their logical axioms correspond to the meaning intended by their authors.</p> <p>Results</p> <p>We analyzed ontologies and ontology cross products available via the OBO Foundry site <url>http://www.obofoundry.org</url> for existential restrictions (<it>someValuesFrom</it>), from which we examined a random sample of 2,836 clauses.</p> <p>According to a rating done by four experts, 23% of all existential restrictions in OBO Foundry candidate ontologies are suspicious (Cohens' <it>κ </it>= 0.78). We found a smaller proportion of existential restrictions in OBO Foundry cross products are suspicious, but in this case an accurate quantitative judgment is not possible due to a low inter-rater agreement (<it>κ </it>= 0.07). We identified several typical modeling problems, for which satisfactory ontology design patterns based on OWL-DL were proposed. We further describe several usability issues with OBO ontologies, including the lack of ontological commitment for several common terms, and the proliferation of domain-specific relations.</p> <p>Conclusions</p> <p>The current OWL releases of OBO Foundry (and Foundry candidate) ontologies contain numerous assertions which do not properly describe the underlying biological reality, or are ambiguous and difficult to interpret. The solution is a better anchoring in upper ontologies and a restriction to relatively few, well defined relation types with given domain and range constraints.</p

The possible role of a cardiac mast cell derived protease during adverse cardiac remodeling

Introduction: The role of cardiac mast cells (MC) in the progression to heart failure has recently become increasingly evident. Cathepsin g is a neutrophil- and mast cell- derived protease, which can convert angiotensin I to angiotensin II and thereby activate the TGF-β pathway resulting in myocyte necrosis, hypertrophy and increased fibrosis. This study focuses on mast cell-derived cathepsin g in the human heart during heart failure and following mechanical unloading by means of heart assist devices (LVADs). Methods: Myocardial tissue was obtained from 10 patients with end-stage cardiomyopathy at the time of LVAD implantation (pre-LVAD) and following orthotopic heart transplantation (post-LAVD). In addition, biopsies of 4 normal hearts served as a control group. Paraffin embedded sections were dual stained for cathepsin g and tryptase, a known marker for mast cells, using standard immunohistochemistry protocols. Total cathepsin g positive (pos.) mast cells were counted. Results: No cathepsin g pos. MCs were found in normal hearts. However, we found evidence for cathepsin g in cardiac MCs in heart failure tissues (Pre-LVAD). During heart failure 46% of total MCs were cathepsin g pos. as compared to after mechanical unloading where only 11% of total MCs were cathepsin g pos. (p<0.001). Conclusion: Heart failure causes an increase of myocardial MCs. Cathepsin g pos. MC accumulate during heart failure and their total percentage decreases after ventricular unloading. This coincides with the decrease in myocyte necrosis, hypertrophy and fibrosis. Thus, cathepsin g may play a role in the progression to heart failure by activating angiotensin II

Der Infektionsmarker Procalcitonin in der Herzchirurgie

Der Einsatz der extrakorporalen Zirkulation führt zu einer erheblichen Stimulation der proinflammatorischen Reaktion. Dies kann bewirken, daß die zeitgerechte Diagnosestellung einer Infektion postoperativ erschwert wird und zeigt den Bedarf nach einem zuverläßigeren Sepsismarker in der postoperativen Phase nach herzchirurgischen Eingriffen.  Wir bestimmten den neuen Sepsismarker Procalcitonin (PCT) in zwei unterschiedlichen Patientengruppen, die jeweils dem Kontakt mit extrakorporalen Kreislaufsystemen ausgesetzt waren. Die erste Gruppe (VAD-Gruppe) bestand aus 38 Patienten mit terminalem Herzversagen, die mit einem ventrikulären Unterstützungssystem Typ Berlin Heart versorgt wurden. Die zweite Gruppe (EKZ-Gruppe) bestand aus 713 Patienten, die einem konventionellen herzchirurgischen Operationsverfahren unterzogen wurden. PCT wurde vor Operation und täglich nach der Operation gemessen. In der VAD-Gruppe waren die präoperativen PCT-Werte in der Lage, Patienten im kardiogenen Schock zu identifizieren, die nach der Operation an einer Infektion verstarben. Darüberhinaus hatten die Patienten, die vor Herztransplantation immer noch erhöhte PCT-Werte aufwiesen, eine schlechte Prognose nach Transplantation.  In der EKZ-Gruppe hatte kein Patient erhöhte PCT-Werte vor Operation. Patienten mit erhöhten Werten am ersten postoperativen Tag hatten eine hohe Inzidenz von Komplikationen in ihrem weiteren Verlauf, während Patienten ohne PCT-Erhöhung einen unkomplizierten Verlauf nahmen.  Sowohl bei Patienten mit kardiogenem Schock als auch nach Einsatz der Herz-Lungen-Maschine ist Procalcitonin in der Lage, bakterielle und pilzbedingte Infektionen zu identifizieren. Daher kann es zur Beurteilung der Transplantabilität von Patienten an Kreislaufunterstützungssystemen herangezogen werden. Der PCT-Wert scheint vom Blutkontakt zu Fremdoberflächen nicht beeinflußt zu werden. Allerdings zeigen eine Reihe von Patienten nach herzchirurgischen Routineeingriffen einen PCT-Verlauf. Die Komplikationsinzidenz ist in dieser Gruppe deutlich erhöht. Möglicherweise ist der PCT-Anstieg auf eine intestinale Minderperfusion während der extrakorporalen Zirkulation zurückzuführen. The use of extracorporal circulation in open heart surgery causes profound stimulation of proinflammatory reaction. Therefore, timely diagnosis of infectious complications may become extremely difficult, and a more reliable marker of sepsis under these circumstances is needed.  We measured the new marker for sepsis Procalcitonin (PCT) in two distinct groups of patients exposed to extracorporeal circulatory devices. Group VAD consisted of 38 patients in end-stage heart failure supported with ventricular assist devices (VAD) Type Berlin Heart. Group EEC included 713 patients undergoing standard open heart surgery procedures. PCT was measured before operation and daily thereafter. PCT levels before operation were able to identify patients in cardiogenic shock who after device implantation died of infectious complications. Patients on VAD who showed elevated PCT levels before heart transplantation had a very unfavorable outcome. In the ECC group, none of the patients had elevated PCT levels before surgery. On day one after the procedure PCT was elevated in those patients who in their further postoperative course developed complications. Patients without PCT elevation after open heart surgery had an uncomplicated recovery.  Under the conditions of cardiogenic shock as well as the use of extracorporeal circulation, PCT is able to identify bacterial and fungal infections. It is helpful in evaluating the transplantability of patients on VADs. PCT seams to be unaffected by the use of extracorporeal circulatory circuits. However, a substantial number of patients exhibit PCT increase after ECC, and the PCT level has some prognostic value. The increase of PCT may be due to intestinal malperfusion

Procalcitonin in patients undergoing cardiopulmonary bypass in open heart surgery-first results of the Procalcitonin in Heart Surgery study (ProHearts)

To investigate procalcitonin (PCT) levels in patients undergoing cardiopulmonary bypass (CPB) in order to assess the prevalence and prognostic capacity of elevated PCT levels following CPB in open heart surgery. prospective observational study in consecutive patients. Twenty-four-bed ICU, department of thoracic and cardiovascular surgery, university hospital. Seven hundred and twenty two patients, 691 of whom underwent CPB, i.e., 476 had coronary bypass surgery (CABG), 130 valve replacement, 34 combined CABG and valve replacement and 23 thoracic aortic surgery. Standard perfusion techniques were used with cardioplegic arrest and mild hypothermia (28-32 degrees C). With the exception of thoracic aortic procedures, full-flow perfusion was performed. PCT was measured prior to surgery and daily thereafter until ICU discharge or death. PCT significantly increased at day 1 postoperatively compared to baseline values (0.25+/-1.65 vs 6.49+/-22.0 ng/ml, p5.0 ng/ml, compared to 39% in valve patients and 35% of patients with aortic surgery. An elevated PCT level >1.0-5.0 ng/ml at day 1 was highly predictive of mortality (P5.0 ng/ml were measured (P<0.002 vs<1.0 ng/ml). These results provide evidence that PCT might serve as an early prognostic marker in patients undergoing CPB in open heart surgery. It may be worth considering immunomodulating approaches in patients presenting elevated PCT levels in the early phase after CPB