PurposeTo develop a cerebrospinal fluid (CSF) miRNA diagnostic biomarker for glioblastoma.Experimental DesignGlioblastoma tissue and matched CSF from the same patient (obtained prior to tumor manipulation) were profiled by TaqMan OpenArray® Human MicroRNA Panel. CSF miRNA profiles from glioblastoma patients and controls were created from three discovery cohorts and confirmed in two validation cohorts.ResultsmiRNA profiles from clinical CSF correlated with those found in glioblastoma tissues. Comparison of CSF miRNA profiles between glioblastoma patients and non-brain tumor patients yielded a tumor “signature” consisting of nine miRNAs. The “signature” correlated with glioblastoma tumor volume (p=0.008). When prospectively applied to cisternal CSF, the sensitivity and specificity of the ‘signature’ for glioblastoma detection were 67% and 80%, respectively. For lumbar CSF, the sensitivity and specificity of the signature were 28% and 95%, respectively. Comparable results were obtained from analyses of CSF extracellular vesicles (EVs) and crude CSF.ConclusionWe report a CSF miRNA signature as a “liquid biopsy” diagnostic platform for glioblastoma.
Background The survival trends and the patterns of clinical practice pertaining to radiation therapy and surgical resection for WHO grade I, II, and III astrocytoma patients remain poorly characterized. Methods Using the Surveillance, Epidemiology and End Results (SEER) database, we identified 2497 grade I, 4113 grade II, and 2755 grade III astrocytomas during the period of 1999–2010. Time-trend analyses were performed for overall survival, radiation treatment (RT), and the extent of surgical resection (EOR). Results While overall survival of grade I astrocytoma patients remained unchanged during the study period, we observed improved overall survival for grade II and III astrocytoma patients (Tarone-Ware P < .05). The median survival increased from 44 to 57 months and from 15 to 24 months for grade II and III astrocytoma patients, respectively. The differences in survival remained significant after adjusting for pertinent variables including age, ethnicity, marital status, sex, tumor size, tumor location, EOR, and RT status. The pattern of clinical practice in terms of EOR for grade II and III astrocytoma patients did not change significantly during this study period. However, there was decreased RT utilization as treatment for grade II astrocytoma patients after 2005. Conclusion Results from the SEER database indicate that there were improvements in the overall survival of grade II and III astrocytoma patients over the past decade. Analysis of the clinical practice patterns identified potential opportunities for impacting the clinical course of these patients.
A fundamental aspect of human beings is that they learn. The process of learning and what is learned are impacted by a number of factors, both cognitive and social; that is, humans are boundedly rational. Cognitive and social limitations interact, making it difficult to reason about how to provide information to impact what humans know, believe, and do. Herein, we use a multi-agent dynamicnetwork simulation system, Construct, to conduct such reasoning. In particular, we ask, What media should be used to provide information to most impact what people know, believe, and do, given diverse social structures? All simulated agents are boundedly rational both at the cognitive and social level, and so are subject to factors such as literacy, education, and the breadth of their social network. We find that there is no one most effective intervention; rather, to be effective, messages and the media used to spread the message need to be selected for the population being addressed. Typically, a multimedia campaign is critical.
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