Electroencephalographic Studies of Human Pain Perception

Ph.DDOCTOR OF PHILOSOPH

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Circulating extracellular vesicle-derived MARCKSL1 is a potential diagnostic non-invasive biomarker in metastatic colorectal cancer patients

Abstract Extracellular vesicle-derived proteins are closely related to colorectal cancer metastasis, and early detection and diagnosis of colorectal cancer metastasis is very important to improve the prognosis. In this study, we evaluated the clinical significance of plasma EV-derived MARCKSL1 in differentiating patients with metastatic and nonmetastatic CRC. This study included 78 patients, including 40 patients with nonmetastatic colorectal cancer, 38 patients with metastatic colorectal cancer, and 15 healthy volunteers. The extracellular vesicles extracted from the participants' plasma were characterized through transmission electron microscopy, nanoparticle tracking analysis and western blotting. MARCKSL1 protein expression in the EVs was detected by ELISA, and the diagnostic efficacy of MARCKSL1 alone or in combination with CA125 and lymphocyte levels was evaluated by receiver operating characteristic curve (ROC) analysis. Pearson's correlation test was performed to detect the correlation between MARCKSL1, CA125, lymphocyte level and clinicopathological characteristics of tumors. The present study demonstrated that the level of circulating EV-derived MARCKSL1 in patients with metastatic colorectal cancer was significantly higher than that in patients with nonmetastatic colorectal cancer and healthy people. Combined with CA125 and lymphocyte levels, the best diagnostic effect was achieved, and the area under the ROC curve was 0.7480. Together, our findings indicated that circulating EV-derived MARCKSL1 could be used as a new potential diagnostic biomarker for metastatic CRC

Single-Trial Event-Related Potential Based Rapid Image Triage System

Searching for points of interest (POI) in large-volume imagery is a challenging problem with few good solutions. In this work, a neural engineering approach called rapid image triage (RIT) which could offer about a ten-fold speed up in POI searching is developed. It is essentially a cortically-coupled computer vision technique, whereby the user is presented bursts of images at a speed of 6–15 images per second and then neural signals called event-related potential (ERP) is used as the ‘cue’ for user seeing images of high relevance likelihood. Compared to past efforts, the implemented system has several unique features: (1) it applies overlapping frames in image chip preparation, to ensure rapid image triage performance; (2) a novel common spatial-temporal pattern (CSTP) algorithm that makes use of both spatial and temporal patterns of ERP topography is proposed for high-accuracy single-trial ERP detection; (3) a weighted version of probabilistic support-vector-machine (SVM) is used to address the inherent unbalanced nature of single-trial ERP detection for RIT. High accuracy, fast learning, and real-time capability of the developed system shown on 20 subjects demonstrate the feasibility of a brainmachine integrated rapid image triage system for fast detection of POI from large-volume imagery

Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs) onto the human acellular amniotic membrane (AAM). The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration

Trajectories of Emergent Central Sleep Apnea During CPAP Therapy.

BackgroundThe emergence of central sleep apnea (CSA) during positive airway pressure (PAP) therapy has been observed clinically in approximately 10% of obstructive sleep apnea titration studies. This study assessed a PAP database to investigate trajectories of treatment-emergent CSA during continuous PAP (CPAP) therapy.MethodsU.S. telemonitoring device data were analyzed for the presence/absence of emergent CSA at baseline (week 1) and week 13. Defined groups were as follows: obstructive sleep apnea (average central apnea index [CAI] < 5/h in week 1, < 5/h in week 13); transient CSA (CAI ≥ 5/h in week 1, < 5/h in week 13); persistent CSA (CAI ≥ 5/h in week 1, ≥ 5/h in week 13); emergent CSA (CAI < 5/h in week 1, ≥ 5/h in week 13).ResultsPatients (133,006) used CPAP for ≥ 90 days and had ≥ 1 day with use of ≥ 1 h in week 1 and week 13. The proportion of patients with CSA in week 1 or week 13 was 3.5%; of these, CSA was transient, persistent, or emergent in 55.1%, 25.2%, and 19.7%, respectively. Patients with vs without treatment-emergent CSA were older, had higher residual apnea-hypopnea index and CAI at week 13, and more leaks (all P < .001). Patients with any treatment-emergent CSA were at higher risk of therapy termination vs those who did not develop CSA (all P < .001).ConclusionsOur study identified a variety of CSA trajectories during CPAP therapy, identifying several different clinical phenotypes. Identification of treatment-emergent CSA by telemonitoring could facilitate early intervention to reduce the risk of therapy discontinuation and shift to more efficient ventilator modalities

Trajectories of Emergent Central Sleep Apnea During CPAP Therapy.

BackgroundThe emergence of central sleep apnea (CSA) during positive airway pressure (PAP) therapy has been observed clinically in approximately 10% of obstructive sleep apnea titration studies. This study assessed a PAP database to investigate trajectories of treatment-emergent CSA during continuous PAP (CPAP) therapy.MethodsU.S. telemonitoring device data were analyzed for the presence/absence of emergent CSA at baseline (week 1) and week 13. Defined groups were as follows: obstructive sleep apnea (average central apnea index [CAI] < 5/h in week 1, < 5/h in week 13); transient CSA (CAI ≥ 5/h in week 1, < 5/h in week 13); persistent CSA (CAI ≥ 5/h in week 1, ≥ 5/h in week 13); emergent CSA (CAI < 5/h in week 1, ≥ 5/h in week 13).ResultsPatients (133,006) used CPAP for ≥ 90 days and had ≥ 1 day with use of ≥ 1 h in week 1 and week 13. The proportion of patients with CSA in week 1 or week 13 was 3.5%; of these, CSA was transient, persistent, or emergent in 55.1%, 25.2%, and 19.7%, respectively. Patients with vs without treatment-emergent CSA were older, had higher residual apnea-hypopnea index and CAI at week 13, and more leaks (all P < .001). Patients with any treatment-emergent CSA were at higher risk of therapy termination vs those who did not develop CSA (all P < .001).ConclusionsOur study identified a variety of CSA trajectories during CPAP therapy, identifying several different clinical phenotypes. Identification of treatment-emergent CSA by telemonitoring could facilitate early intervention to reduce the risk of therapy discontinuation and shift to more efficient ventilator modalities

Adherence to Positive Airway Therapy After Switching From CPAP to ASV: A Big Data Analysis.

STUDY OBJECTIVES:There is a lack of data regarding adherence trajectories when switching from continuous positive airway pressure (CPAP) to adaptive servoventilation (ASV) in the context of persistent or treatment-emergent central sleep apnea (CSA). This study investigated 90-day adherence rates in patients with sleep apnea based on the type of positive airway pressure (PAP) device used and any switching of PAP modality over time. METHODS:Telemonitoring data were obtained from a United States PAP database. Eligible patients were a 30% random sample who started PAP, plus all who started ASV, from January 1, 2015 to October 2, 2015. All received PAP and had at least one session with usage of 1 hour or more. Adherence and device usage were determined in three groups: started on CPAP and stayed on CPAP (CPAP only); started on ASV and stayed on ASV (ASV only); started on CPAP, switched to ASV (Switch). The United States Medicare definition of adherence was used. RESULTS:The study included 198,890 patients; 189,724 (CPAP only), 8,957 (ASV only) and 209 (Switch). In the Switch group, average apnea-hypopnea index decreased significantly on ASV versus CPAP. At 90 days, adherence rates were 73.8% and 73.2% in the CPAP only and ASV only groups. In the Switch group, CPAP adherence was 62.7%, improving to 76.6% after the switch to ASV. Mean device usage at 90 days was 5.27, 5.31, and 5.73 h/d in the CPAP only, ASV only, and Switch groups, respectively. CONCLUSIONS:Treatment-emergent or persistent CSA during CPAP reduced therapy adherence, but adherence improved early after switching from CPAP to ASV

A Novel Fault-Tolerant Approach for Dynamic Redundant Path Selection Service Migration in Vehicular Edge Computing

Vehicular Edge Computing (VEC) provides users with low-latency and highly responsive services by deploying Edge Servers (ESs) close to applications. In practice, vehicles are usually moving rapidly. To ensure the continuity of services, edge service migration technology is in high need, by which an application, infrastructure or any edge-hosted applications or services are not locked into a single vendor and allowed to shift between different edge resource vendors. Nevertheless, due to their complex and dynamic nature, real edge computing environments are error and fault prone and thus the reliability of edge service migrations can be easily compromised if the proactive measures are not taken to counter failures at different levels. In this paper, we propose a novel fault-tolerant approach for Dynamic Redundant Path Selection service migration (DRPS). The DRPS approach consists of path selection algorithm and service migration algorithm. The path selection algorithm is capable of evaluating time-varying failure rates of ESs by leveraging a sliding window-based model and identifying a set of service migration paths. The service migration algorithm incorporates resubmission and replication mechanisms as well and decides edge service migration schemes by choosing multiple redundant migration paths. We also conduct extensive simulations and show that our proposed method outperforms traditional solutions by 17.45%, 13.17%, and 7.22% in terms of ACT, TCR, and AFC, respectively