Citations

Tumor-educated platelets (TEPs) are a potential method of liquid biopsy for the diagnosis and monitoring of cancer. However, the mechanism underlying tumor education of platelets is not known, and transcripts associated with TEPs are often not tumor-associated transcripts. We demonstrated that direct tumor transfer of transcripts to circulating platelets is an unlikely source of the TEP signal. We used CDSeq, a latent Dirichlet allocation algorithm, to deconvolute the TEP signal in blood samples from patients with glioblastoma. We demonstrated that a substantial proportion of transcripts in the platelet transcriptome are derived from nonplatelet cells, and the use of this algorithm allows the removal of contaminant transcripts. Furthermore, we used the results of this algorithm to demonstrate that TEPs represent a subset of more activated platelets, which also contain transcripts normally associated with nonplatelet inflammatory cells, suggesting that these inflammatory cells, possibly in the tumor microenvironment, transfer transcripts to platelets that are then found in circulation. Our analysis suggests a useful and efficient method of processing TEP transcriptomic data to enable the isolation of a unique TEP signal associated with specific tumors.

Abstract Objective : Blood flow waveforms—essential data for hemodynamic modeling—are often in practice unavailable to researchers. The objectives of this work were to assess the variability among the waveforms for a clinically relevant older population, and develop data-based methods for addressing the missing waveform data for hemodynamic studies. Approach : We analyzed 272 flow waveforms from the internal carotid arteries of older patients (73 ± 13 yr) with moderate cardiovascular disease, and used these data to develop methods to guide new approaches for hemodynamic studies. Main results : Profound variations in waveform parameters were found within the aged population that were not seen in published data for young subjects. Common features in the aged population relative to the young included a larger systole-to-diastole flow rate ratio, increased flow during late systole, and absence of a dicrotic notch. Eight waveforms were identified that collectively represent the range of waveforms in the older population. A relationship between waveform shape and flow rate was obtained that, in conjunction with equations relating flow rate to diameter, can be used to provide individualized waveforms for patient-specific geometries. The dependence of flow rate on diameter was statistically different between male and female patients. Significance : It was shown that a single archetypal waveform cannot well-represent the diverse waveforms found within an aged population, although this approach is frequently used in studies of flow in the cerebral vasculature. Motivated by these results, we provided a set of eight waveforms that can be used to assess the hemodynamic uncertainty associated with the lack of patient-specific waveform data. We also provided a methodology for generating individualized waveforms when patient gender, age, and cardiovascular disease state are known. These data-driven approaches can be used to devise more relevant in vitro or in silico intra-cranial hemodynamic studies for older patients.