Blood-Based Biomarkers of Aggressive Prostate Cancer

Purpose: Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods: Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results: Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion: In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an “active surveillance” strategy

Modality analysis and algorithm design of stator short-circuit fault set for large compressed air energy storage generators

Using salt caverns and caves to build compressed air energy storage power stations is an important development direction in the field of large-scale energy storage. With the continuous maturity of technology, compressed air energy storage generators have gradually developed into large-scale units with a single-unit capacity of 300 MW. Due to the increase of single-unit capacity, the internal short-circuit fault of the stator will cause very serious losses. In addition, the compressed air energy storage generator has complex operating conditions and is more prone to various internal short-circuit faults. In order to effectively ensure its safe and reliable operation, it is particularly necessary to study the effective main protection configuration scheme. The optimal design of the main protection configuration scheme is based on the analysis of the possible internal short-circuit faults of the generator. At present, the stator windings of large-scale compressed air energy storage generators generally adopt double-layer wave winding or double-layer tap winding structures. For these two winding structures, this paper analyzes in detail the characteristics of all fault modalities that may occur inside the large-capacity compressed air energy storage generator and designs a general algorithm that can form their respective fault sets. Finally, the application of the algorithm in the analysis of the stator fault modality in a compressed air energy storage power station is introduced

Whole blood transcriptome correlates with treatment response in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Treatment protocols for nasopharyngeal carcinoma (NPC) developed in the past decade have significantly improved patient survival. In most NPC patients, however, the disease is diagnosed at late stages, and for some patients treatment response is less than optimal. This investigation has two aims: to identify a blood-based gene-expression signature that differentiates NPC from other medical conditions and from controls and to identify a biomarker signature that correlates with NPC treatment response.</p> <p>Methods</p> <p>RNA was isolated from peripheral whole blood samples (2 x 10 ml) collected from NPC patients/controls (EDTA vacutainer). Gene expression patterns from 99 samples (66 NPC; 33 controls) were assessed using the Affymetrix array. We also collected expression data from 447 patients with other cancers (201 patients) and non-cancer conditions (246 patients). Multivariate logistic regression analysis was used to obtain biomarker signatures differentiating NPC samples from controls and other diseases. Differences were also analysed within a subset (n = 28) of a pre-intervention case cohort of patients whom we followed post-treatment.</p> <p>Results</p> <p>A blood-based gene expression signature composed of three genes — LDLRAP1, PHF20, and LUC7L3 — is able to differentiate NPC from various other diseases and from unaffected controls with significant accuracy (area under the receiver operating characteristic curve of over 0·90). By subdividing our NPC cohort according to the degree of patient response to treatment we have been able to identify a blood gene signature that may be able to guide the selection of treatment.</p> <p>Conclusion</p> <p>We have identified a blood-based gene signature that accurately distinguished NPC patients from controls and from patients with other diseases. The genes in the signature, LDLRAP1, PHF20, and LUC7L3, are known to be involved in carcinoma of the head and neck, tumour-associated antigens, and/or cellular signalling. We have also identified blood-based biomarkers that are (potentially) able to predict those patients who are more likely to respond to treatment for NPC. These findings have significant clinical implications for optimizing NPC therapy.</p

Engineering of the Core–Shell Boron Nitride@Nitrogen-Doped Carbon Heterogeneous Interface for Efficient Heat Dissipation and Electromagnetic Wave Absorption

The effective integration of multiple functions into electromagnetic wave-absorbing (EWA) materials is the future development direction but remains a huge challenge. A rational selection of components and the design of structures can make the material have excellent EWA performance and heat dissipation. Herein, the core–shell structured boron nitride@nitrogen-doped carbon (BN@NC) is prepared by using waterborne polyurethane (WPU) as the carbon source via a facile pyrolysis treatment process, where NC is used as the conductive loss shell, and BN serves as an impedance matching core and dominant heat transfer media. As a result, the BN@NC-900 filled with paraffin wax yields a minimum reflection loss of −42.2 dB at 2.2 mm and an effective absorbing bandwidth of 4.48 GHz at 1.8 mm, and its thermal conductivity reaches up to 0.92 W/m·K in epoxy resin. Most importantly, flexible BN@NC/WPU films are prepared and simultaneously achieve the dual-functional capability of efficiently dissipating heat and electromagnetic waves (−50.0 dB). Besides, an attractive multiband absorption feature (>99%) from C to Ku bands is realized and a strong absorbing over −27.0 dB at the S band (2.88 GHz) is even achieved. This study may pave a new route for the rational design of multifunctional EWA materials

High grade prostate cancer (Gleason score 8 and above) biomarker gene list and differential expression ratio in Cohort II verification sample set (80 disease and 102 controls).

<p># The 7 biomarkers were picked up from the 10 that were verified in Cohort II samples, using gene-ratio algorithm, based on the best AUC of combined gene-pair.</p>†<p>Determined by qRT-PCR analysis using SAMSN1 as a partner gene, gene ratio was calculated using delta delta Ct calculation.</p>‡<p>Calculated by Mann-Whitney test.</p>*<p>area under receiver-operating-characteristic curve.</p

Combined PSA and mRNA model.

<p>Inputs are CT values for genes and Log2 transformation of PSA in ng/ml.</p

Gene identification and validation process.

<p>Gene Identification using Affymetrix U133Plus 2.0 GeneChip oligonucleotide arrays was carried out in Toronto, Canada, and Penang, Malaysia, in parallel. In Toronto, analysis was conducted on 166 samples (G8 = 42, G0 = 124). At the Malaysian site, 89 samples were profiled (49 G8, 40 G0). From microarray data analysis, 85 genes identified at both sites were tested in a series of quantitative real-time PCR verification studies. Twenty genes were verified through a Cohort I study on several cohorts of EDTA samples (total 245). These 20 genes were further tested in a Cohort II series of experiments on PAXgene samples (total 182), executed independently in Penang, Malaysia. 10 of the genes were verified, of which 7 genes became our final biomarkers and also confirmed in another independent sample set-Cohort III test (total 121).</p