Creating hospital-specific customized clinical pathways by applying semantic reasoning to clinical data

AbstractObjectiveClinical pathways (CPs) are widely studied methods to standardize clinical intervention and improve medical quality. However, standard care plans defined in current CPs are too general to execute in a practical healthcare environment. The purpose of this study was to create hospital-specific personalized CPs by explicitly expressing and replenishing the general knowledge of CPs by applying semantic analysis and reasoning to historical clinical data.MethodsA semantic data model was constructed to semantically store clinical data. After querying semantic clinical data, treatment procedures were extracted. Four properties were self-defined for local ontology construction and semantic transformation, and three Jena rules were proposed to achieve error correction and pathway order recognition. Semantic reasoning was utilized to establish the relationship between data orders and pathway orders.ResultsA clinical pathway for deviated nasal septum was used as an example to illustrate how to combine standard care plans and practical treatment procedures. A group of 224 patients with 11,473 orders was transformed to a semantic data model, which was stored in RDF format. Long term order processing and error correction made the treatment procedures more consistent with clinical practice. The percentage of each pathway order with different probabilities was calculated to declare the commonality between the standard care plans and practical treatment procedures. Detailed treatment procedures with pathway orders, deduced pathway orders, and orders with probability greater than 80% were provided to efficiently customize the CPs.ConclusionsThis study contributes to the practical application of pathway specifications recommended by the Ministry of Health of China and provides a generic framework for the hospital-specific customization of standard care plans defined by CPs or clinical guidelines

Cucurbitacin E inhibits the Yes‑associated protein signaling pathway and suppresses brain metastasis of human non‑small cell lung cancer in a murine model.

Human non‑small cell lung cancer (NSCLC) is associated with an extremely poor prognosis especially for the 40% of patients who develop brain metastasis, and few treatment strategies exist. Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid isolated from plants particularly of the family Cucurbitaceae, has shown anti‑tumorigenic properties in several types of cancer, yet the mechanism remains unclear. Yes‑associated protein (YAP), a main mediator of the Hippo signaling pathway, promotes tumorigenesis, drug resistance and metastasis in human NSCLC. The present study was designed to ascertain whether CuE inhibits YAP and its downstream gene expression in the human NSCLC cell lines H2030‑BrM3 (K‑rasG12C mutation) and PC9‑BrM3 (EGFRΔexon19 mutation), which have high potential for brain metastasis. The efficacy of CuE in suppressing brain metastasis of H2030‑BrM3 cells in a murine model was also investigated. It was found that after CuE treatment in H2030‑BrM3 and PC9‑BrM3 cells, YAP protein expression was decreased, and YAP signaling GTIIC reporter activity and expression of the downstream genes CTGF and CYR61 were significantly (P<0.01) decreased. CuE treatment also reduced the migration and invasion abilities of the H2030‑BrM3 and PC9‑BrM3 cells. Finally, our in vivo study showed that CuE treatment (0.2 mg/kg) suppressed H2030‑BrM3 cell brain metastasis and that mice treated with CuE survived longer than the control mice treated with 10% DMSO (P=0.02). The present study is the first to demonstrate that CuE treatment inhibits YAP and the signaling downstream gene expression in human NSCLC in vitro, and suppresses brain metastasis of NSCLC in a murine model. More studies to verify the promising efficacy of CuE in inhibiting brain metastasis of NSCLC and various other cancers may be warranted

3D Stretchable Arch Ribbon Array Fabricated via Grayscale Lithography.

Microstructures with flexible and stretchable properties display tremendous potential applications including integrated systems, wearable devices and bio-sensor electronics. Hence, it is essential to develop an effective method for fabricating curvilinear and flexural microstructures. Despite significant advances in 2D stretchable inorganic structures, large scale fabrication of unique 3D microstructures at a low cost remains challenging. Here, we demonstrate that the 3D microstructures can be achieved by grayscale lithography to produce a curved photoresist (PR) template, where the PR acts as sacrificial layer to form wavelike arched structures. Using plasma-enhanced chemical vapor deposition (PECVD) process at low temperature, the curved PR topography can be transferred to the silicon dioxide layer. Subsequently, plasma etching can be used to fabricate the arched stripe arrays. The wavelike silicon dioxide arch microstructure exhibits Young modulus and fracture strength of 52 GPa and 300 MPa, respectively. The model of stress distribution inside the microstructure was also established, which compares well with the experimental results. This approach of fabricating a wavelike arch structure may become a promising route to produce a variety of stretchable sensors, actuators and circuits, thus providing unique opportunities for emerging classes of robust 3D integrated systems

The therapeutic potential of GABA in neuron-glia interactions of cancer-induced bone pain

Abstract: The development of effective therapeutics for cancer-induced bone pain (CIBP) remains a tremendous challenge owing to its unclear mechanisms. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Emerging studies have shown that disinhibition in the spinal cord dorsal horn may account for the development of chronic pain. However, the role of GABA in the development of CIBP remains elusive. In addition, accumulating evidence has shown that neuroglial cells in the peripheral nervous system, especially astrocytes and microglial cells, play an important role in the maintenance of CIBP. In this study, we investigated the expression of GABA and Gamma-aminobutyric acid transporter-1 (GAT-1), a transporter of GABA. Our results demonstrate that GABA was decreased in CIBP rats as expected. However, the expression of glutamic acid decarboxylase (GAD) 65 was up-regulated on day 21 after surgery, while the expression of glutamic acid decarboxylase (GAD) 67 remained unchanged after surgery. We also found that the expression of GAT-1 was up-regulated mainly in the astrocytes of the spinal cord. Moreover, we evaluated the analgesic effect of exogenous GABA and the GAT-1 inhibitor. Intrathecal administration of exogenous GABA and NO-711(a GAT-1 selective inhibitor) significantly reversed CIBP-induced mechanical allodynia in a dose-dependent manner. These results firstly show that neuron-glia interactions, especially on the GABAnergic pathway, contribute to the development of CIBP. In conclusion, exogenous GABA and GAT-1 inhibitor might be alternative therapeutic strategies for the treatment of CIBP. Keywords: Cancer-induced bone pain; Gamma-Aminobutyric acid; Glutamic acid decarboxylases; GABA transporters; NO-711; Astrocyt