Integration of tools for binding archetypes to SNOMED CT

Background The Archetype formalism and the associated Archetype Definition Language have been proposed as an ISO standard for specifying models of components of electronic healthcare records as a means of achieving interoperability between clinical systems. This paper presents an archetype editor with support for manual or semi-automatic creation of bindings between archetypes and terminology systems. Methods Lexical and semantic methods are applied in order to obtain automatic mapping suggestions. Information visualisation methods are also used to assist the user in exploration and selection of mappings. Results An integrated tool for archetype authoring, semi-automatic SNOMED CT terminology binding assistance and terminology visualization was created and released as open source. Conclusion Finding the right terms to bind is a difficult task but the effort to achieve terminology bindings may be reduced with the help of the described approach. The methods and tools presented are general, but here only bindings between SNOMED CT and archetypes based on the openEHR reference model are presented in detail. Background The Archetype formalism and the associated Archetype Definition Language have been proposed as an ISO standard for specifying models of components of electronic healthcare records as a means of achieving interoperability between clinical systems. This paper presents an archetype editor with support for manual or semi-automatic creation of bindings between archetypes and terminology systems. Methods Lexical and semantic methods are applied in order to obtain automatic mapping suggestions. Information visualisation methods are also used to assist the user in exploration and selection of mappings. Results An integrated tool for archetype authoring, semi-automatic SNOMED CT terminology binding assistance and terminology visualization was created and released as open source. Conclusion Finding the right terms to bind is a difficult task but the effort to achieve terminology bindings may be reduced with the help of the described approach. The methods and tools presented are general, but here only bindings between SNOMED CT and archetypes based on the openEHR reference model are presented in detail.Original Publication: Erik Sundvall, Rahil Qamar, Mikael Nyström, Mattias Forss, Håkan Petersson, Hans Åhlfeldt and Alan Rector, Integration of Tools for Binding Archetypes to SNOMED CT, 2008, BMC Medical Informatics and Decision Making, (8), S7. http://dx.doi.org/10.1186/1472-6947-8-S1-S7 Licensee: BioMed Central http://www.biomedcentral.com/</p

Pim-1 Kinase Expression Predicts Radiation Response in Squamocellular Carcinoma of Head and Neck and Is under the Control of Epidermal Growth Factor Receptor

Pim-1 is an oncogenic serine/threonine kinase with poorly defined function in epithelial cancers. In this study, we determined 1) associations of Pim-1 expression with clinicopathological parameters including responsiveness to irradiation in squamocellular cancers of head and neck and 2) how Pim-1 expression is controlled subsequent to irradiation. Moderate to high expression of Pim-1 correlated to poor response to radiation therapy (P = .003). It is also associated to the expression of epidermal growth factor receptor (EGFR, P < .0001), which has been shown to be activated by irradiation. In radioresistant tumors, irradiation promoted nuclear translocation of Pim-1 (P < .005). When directly testing EGFR dependence of Pim-1 expression, up-regulation and nuclear translocation of Pim-1 could be induced through stimulation of EGFR with its ligands EGF or transforming growth factor a. Both ligand- and irradiation-induced changes in Pim-1 expression and localization could be inhibited by the monoclonal anti-EGFR antibody cetuximab and by the tyrosine kinase inhibitor gefitinib also targeting EGFR. These results suggest that irradiation-induced activation of EGFR upregulates Pim-1, and Pim-1 may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck.</p

The use of fasting vs. non-fasting triglyceride concentration for estimating the prevalence of high LDL-cholesterol and metabolic syndrome in population surveys

<p>Abstract</p> <p>Background</p> <p>For practical reasons it is not easy to obtain fasting samples in large population health surveys. Non-fasting triglyceride (Tg) values are difficult to interpret. The authors compared the accuracy of statistically corrected non-fasting Tg values with true fasting values and estimated the misclassification of subjects with high low-density lipoprotein cholesterol (LDL-C) and the metabolic syndrome.</p> <p>Methods</p> <p>Non-fasting blood was obtained from a population-based sample of 4282 individuals aged 24-75 years in the National FINRISK 2007 Study. Fasting blood samples were drawn from the same persons 3 months later. Non-fasting serum Tg values were converted into fasting values using previously published formula. LDL-C was calculated and classification of the metabolic syndrome was carried out according to three different latest guidelines.</p> <p>Results</p> <p>The median (25^th, 75th percentile) non-fasting serum Tg concentration was 1.18 (0.87, 1.72) mmol/L and after postprandial correction 1.06 (0.78, 1.52) mmol/L. The true-fasting serum Tg concentration was 1.00 (0.75, 1.38) mmol/L (<it>P </it>< 0.001) vs. non-fasting and corrected value. Bias of the corrected value was +5.9% compared with the true-fasting Tg. Of the true fasting subjects, 56.4% had LDL-C ≥3.00 mmol/L. When calculated using non-fasting serum Tg, the prevalence of high LDL-C was 51.3% and using statistically corrected Tg it was 54.8%. The prevalence of metabolic syndrome was 35.5% among fully fasted persons and among non-fasting subjects 39.7%, which after statistical correction of Tg decreased to 37.6% (P < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>Correction of non-fasting serum Tg to fasting values plays a minor role in population studies but nevertheless reduces misclassification of calculated high LDL-C from 5.1 to 1.6% and the metabolic syndrome from 4.2 to 2.1%.</p

Modeling healthcare authorization and claim submissions using the openEHR dual-model approach

<p>Abstract</p> <p>Background</p> <p>The TISS standard is a set of mandatory forms and electronic messages for healthcare authorization and claim submissions among healthcare plans and providers in Brazil. It is not based on formal models as the new generation of health informatics standards suggests. The objective of this paper is to model the TISS in terms of the openEHR archetype-based approach and integrate it into a patient-centered EHR architecture.</p> <p>Methods</p> <p>Three approaches were adopted to model TISS. In the first approach, a set of archetypes was designed using ENTRY subclasses. In the second one, a set of archetypes was designed using exclusively ADMIN_ENTRY and CLUSTERs as their root classes. In the third approach, the openEHR ADMIN_ENTRY is extended with classes designed for authorization and claim submissions, and an ISM_TRANSITION attribute is added to the COMPOSITION class. Another set of archetypes was designed based on this model. For all three approaches, templates were designed to represent the TISS forms.</p> <p>Results</p> <p>The archetypes based on the openEHR RM (Reference Model) can represent all TISS data structures. The extended model adds subclasses and an attribute to the COMPOSITION class to represent information on authorization and claim submissions. The archetypes based on all three approaches have similar structures, although rooted in different classes. The extended openEHR RM model is more semantically aligned with the concepts involved in a claim submission, but may disrupt interoperability with other systems and the current tools must be adapted to deal with it.</p> <p>Conclusions</p> <p>Modeling the TISS standard by means of the openEHR approach makes it aligned with ISO recommendations and provides a solid foundation on which the TISS can evolve. Although there are few administrative archetypes available, the openEHR RM is expressive enough to represent the TISS standard. This paper focuses on the TISS but its results may be extended to other billing processes. A complete communication architecture to simulate the exchange of TISS data between systems according to the openEHR approach still needs to be designed and implemented.</p

Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin

Therapeutic protocols including EGFR antibodies in the context of oxaliplatin-based regimens have variable clinical effect in colorectal cancer. Here, we tested the effect of the EGFR antibody cetuximab in different sequential combinations with oxaliplatin on the growth of colorectal cancer cells in vitro and in vivo. Cetuximab reduced the efficacy of oxaliplatin when administered before oxaliplatin but provided additive effect when administered after oxaliplatin regardless of the KRAS or BRAF mutation status of the cells. Systemic gene expression and protein phosphorylation screens revealed alternatively activated pathways regulating apoptosis, cell cycle and DNA damage response. Functional assays indicated that cetuximab-induced arrest of the cells into the G1 phase of the cell cycle was associated with reduced responsiveness of the cells to subsequent treatment with oxaliplatin. In contrast, oxaliplatin-enhanced responsiveness to subsequent treatment with cetuximab was associated with increased apoptosis, inhibition of STAT3 activity and increased EGFR down-regulation. This preclinical study indicates that optimizing the sequence of administration may enhance the antitumor effect of combination therapy with EGFR antibodies and oxaliplatin

Cell Death or Survival Promoted by Alternative Isoforms of ErbB4

The report demonstrates that two distinct isoforms of the ErbB4 receptor tyrosine kinase stimulate either proliferation or apoptosis by mechanisms involving differential transcriptional regulation of the PDGFRA gene. These data have implications for developing approaches to target ErbB4 signaling in cancer

Coordination and expertise foster legal textualism

Funding Information: ACKNOWLEDGMENTS. This research was supported by the Spanish Ministry of Science and Innovation (PID2020-119791RA-I00; RTI2018-098882-B-I00), the Polish National Science Centre (2020/36/C/HS5/00111; 2017/25/N/HS5/00944), the Swiss National Science Foundation (PZ00P1_179912), and the European Research Council (805498). Publisher Copyright: Copyright © 2022 the Author(s).A cross-cultural survey experiment revealed a dominant tendency to rely on a rule’s letter over its spirit when deciding which behaviors violate the rule. This tendency varied markedly across (k = 15) countries, owing to variation in the impact of moral appraisals on judgments of rule violation. Compared with laypeople, legal experts were more inclined to disregard their moral evaluations of the acts altogether and consequently exhibited stronger textualist tendencies. Finally, we evaluated a plausible mechanism for the emergence of textualism: in a two-player coordination game, incentives to coordinate in the absence of communication reinforced participants’ adherence to rules’ literal meaning. Together, these studies (total n = 5,794) help clarify the origins and allure of textualism, especially in the law. Within heterogeneous communities in which members diverge in their moral appraisals involving a rule’s purpose, the rule’s literal meaning provides a clear focal point—an identifiable point of agreement enabling coordinated interpretation among citizens, lawmakers, and judges.Peer reviewe

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391