Transformation of standardized clinical models based on OWL technologies: from CEM to OpenEHR archetypes

Introduction The semantic interoperability of electronic healthcare records (EHRs) systems is a major challenge in the medical informatics area. International initiatives pursue the use of semantically interoperable clinical models, and ontologies have frequently been used in semantic interoperability efforts. The objective of this paper is to propose a generic, ontology-based, flexible approach for supporting the automatic transformation of clinical models, which is illustrated for the transformation of Clinical Element Models (CEMs) into openEHR archetypes.Methods Our transformation method exploits the fact that the information models of the most relevant EHR specifications are available in the Web Ontology Language (OWL). The transformation approach is based on defining mappings between those ontological structures. We propose a way in which CEM entities can be transformed into openEHR by using transformation templates and OWL as common representation formalism. The transformation architecture exploits the reasoning and inferencing capabilities of OWL technologies.Results We have devised a generic, flexible approach for the transformation of clinical models, implemented for the unidirectional transformation from CEM to openEHR, a series of reusable transformation templates, a proof-of-concept implementation, and a set of openEHR archetypes that validate the methodological approach.Conclusions We have been able to transform CEM into archetypes in an automatic, flexible, reusable transformation approach that could be extended to other clinical model specifications. We exploit the potential of OWL technologies for supporting the transformation process. We believe that our approach could be useful for international efforts in the area of semantic interoperability of EHR systems.     

The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic perspectives

CYR61 (CNN1), a member of the cysteine rich 61/connective tissue growth factor/nephroblastoma overexpressed (CYR61/CTFG/NOV) family of growth regulators (CNN), is a pro-angiogenic factor that mediates diverse roles in development, cell proliferation, and tumorigenesis. We have recently shown that CYR61 is overexpressed in invasive and metastatic human breast cancer cells. Accordingly, elevated levels of CYR61 in breast cancer are associated with more advanced disease. Unfortunately, the exact mechanisms by which CYR61 promotes an aggressive breast cancer phenotype are still largely unknown. This review examines the functional role of CYR61 in breast cancer disease, presenting evidence that CYR61 signaling may play a major role in estrogen- as well as growth factor-dependent breast cancer progression. We also emphasize the functional significance of the molecular connection of CYR61 and its integrin receptor alpha(v)beta(3) enhancing breast cancer aggressiveness. Moreover, we describe experimental evidence that establishes a novel role for CYR61 determining the protection of human breast cancer cells against chemotherapy-induced apoptosis through its interactions with the integrin receptor alpha(v)beta(3). All these findings delineate a new noteworthy function of a CYR61/alpha(v)beta(3) autocrine-paracrine signaling pathway within both angiogenesis and breast cancer progression, which would allow a dual anti-angiogenic and anti-tumor benefit with a single drug.     

培多普利抑制心肌重构的动物实验研究

目的:本研究采用Wistar大鼠冠脉结扎心梗后心衰模型,以培多普利作为观察药物,探讨肾素血管紧张素系统(RAS)在心肌重构中的地位和血管紧张素转换酶抑制剂(ACEI)对心肌重构的干预作用.方法:将Wistar大鼠分为梗塞组、梗塞治疗组和假术组.梗塞组结扎左冠状动脉,梗塞治疗组在前者基础上用培多普利治疗2mg/kg/天,假手术组不结扎左冠状动脉.三月后测血流动力学参数,血液及组织内血管紧张素Ⅱ(AngⅡ)含量、血管紧张素转换酶(ACE)活性和观察组织形态学变化.结果:三月后,与假术组相比,梗塞组出现了克血性心衰(DHF)的血流动力学改变;心肌局部AngⅡ含量、ACE活性显著差增高,但血液AngⅡ含量和ACE活性无明显改变;心脏重量指数显著上升;残存心肌细胞肥大,间质增生,胶原蛋白沉积.培多普利可以改善血流动力学参数,减少AngⅡ的生成、抑制ACE活性并减轻心肌细胞肥大、间质增生和胶原蛋白沉积的程度.结论:心肌组织局部的RAS参与了心肌重构的病理生理过程,血液RAS与心肌重构无显著相关,ACEI可以有效地防治心肌重构及心衰.     

AAV8 transduction capacity is reduced by prior exposure to endosome-like pH conditions

Adeno-associated virus(AAV) is an essential instrument in the neuroscientist's toolkit, which allows delivery of DNA to provide labeling with fluorescent proteins or genetic instructions to regulate gene expression. In the field of neural regeneration, the transduction of neurons enables the observation and regulation of axon growth and regeneration, and in the future will likely be a mechanism for delivering molecular therapies to promote sprouting and regeneration after central nervous system injury. Traditional formulations of AAV preparations permit efficient viral transduction under physiologic conditions, but an improved understanding of the mechanistic limitations of AAV transduction may facilitate production of more resilient AAV strains for investigative and therapeutic purposes. We studied AAV transduction in the context of prior exposure of AAV serotype 8(AAV8) to environmental p H within the range encountered during endosomal endocytosis(p H 7.4 to p H 4.4), during which low p H-triggered structural and autoproteolytic changes to the viral capsid are believed to be necessary for endosome escape and virus uncoating. Due to the fundamental nature of these processes, we hypothesized that premature exposure of AAV8 particles to acidic p H would decrease viral transduction of HT1080 cells in vitro, as measured by fluorescent reporter gene expression using high-content imaging analysis. We found that increasingly acidic incubation conditions were associated with concomitant reductions in transduction efficiency, and that quantitative levels of reporter gene expression in transduced cells were similarly decreased. The biggest decrease in transduction occurred between p H 7.4 and p H 6.4, suggesting the possible co-occurrence of a p H-associated event and viral inactivation within that range. Taken together, these findings indicate that exposure of AAV8 to acidic p H for as little as 1 hour is deleterious to transduction ability. Future studies are necessary to understand the p H-associated causative mechanisms involved. This study was approved by the University of Miami Institutional Animal Care and Use Committee, USA(Protocol #18-108-LF) on July 12, 2018.     

Massive Plasmodium falciparum visceral sequestration: a cause of maternal death in Africa

Sequestration of Plasmodium falciparum-infected erythrocytes (PfIE) in the capillaries of the central nervous system (CNS) is the pathognomonic feature of cerebral malaria, a condition frequently leading to death. Sequestration of PfIE in the placental intervillous spaces is the characteristic feature of malaria in pregnancy and is associated with low birthweight and prematurity. Although both patterns of sequestration are thought to result from the expression of different parasite proteins involved in cytoadhesion to human receptors, scant information exists on whether both conditions can coexist and whether this can lead to death. We conducted a prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary-level referral hospital in Maputo, Mozambique, between October 2002 and December 2006. Extensive sampling of all major viscera was performed. All cases showing parasites in any of the viscera were included in the analysis. From 317 complete autopsies PfIEs were identified in ten women (3.2%). All cases showed massive accumulation of PfIE in small capillaries of the CNS but also in most visceral capillaries (heart, lung, kidney, uterus). Placental tissue, available in four cases, showed a massive accumulation of maternal PfIE in the intervillous space. Coma (six women) and dyspnoea (five women) were the most frequent presenting clinical symptoms. In conclusion, massive visceral sequestration of PfIE with significant involvement of the CNS is an infrequent but definite direct cause of maternal death in endemic areas of Africa. The PfIE sequestered in cerebral capillaries and the placenta coexist in these fatal cases.     

TomoDirect技术在全脑全脊髓放疗中的应用

目的 为全脑全脊髓放疗建立新的TomoDirect技术(TD)布野方案,并评价剂量学参数。方法 对本院收治的7例全脑全脊髓放疗患者进行回顾性研究,在Tomo计划系统分别设计5野TD、3野TD和螺旋断层治疗(helical tomotherapy, HT)计划,比较3种计划的靶区适形指数(CI)、均匀性指数(HI)、危及器官受量、治疗时间和机器跳数(MU)。结果 除3野TD计划外其余两者均能获得较好的靶区适形度和均匀性。其中5野TD计划靶区受量明显优于3野TD计划,但略逊于HT计划;危及器官受量则各有优势。5野TD、3野TD和HT计划的靶区平均CI分别为0.79、0.57和0.88;靶区HI分别为1.06、1.16和1.05;双肺V₂₀分别为1.99%、3.30%和2.16%;心脏平均剂量分别为6.17、12.38和10.72 Gy;肝脏平均剂量分别为5.21、5.14和4.62 Gy;左侧肾脏平均剂量分别为4.30、1.99和5.03 Gy;右侧肾脏平均剂量分别为4.42、2.09和4.91 Gy。靶区以外的正常组织V₅分别为46.80%、28.06%和55.54%。5野TD计划的治疗时间最短,5野TD、3野TD及HT计划的平均治疗时间分别为677、721和907 s,MU数分别是8 773、9 657和12 581。结论 5野的TD技术应用于全脑全脊髓放疗具有一定优势,适用于难以坚持长时间治疗,且希望减少低剂量范围的患者。