Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters

<p>Abstract</p> <p>Background</p> <p>Surgical resection is one important curative treatment for hepatocellular carcinoma (HCC), but the prognosis following surgery differs substantially and such large variation is mainly unexplained. A review of the literature yields a number of clinicopathologic parameters associated with HCC prognosis. However, the results are not consistent due to lack of systemic approach to establish a prediction model incorporating all these parameters.</p> <p>Methods</p> <p>We conducted a retrospective analysis on the common clinicopathologic parameters from a cohort of 572 ethnic Chinese HCC patients who received curative surgery. The cases were randomly divided into training (n = 272) and validation (n = 300) sets. Each parameter was individually tested and the significant parameters were entered into a linear classifier for model building, and the prediction accuracy was assessed in the validation set</p> <p>Results</p> <p>Our findings based on the training set data reveal 6 common clinicopathologic parameters (tumor size, number of tumor nodules, tumor stage, venous infiltration status, and serum α-fetoprotein and total albumin levels) that were significantly associated with the overall HCC survival and disease-free survival (time to recurrence). We next built a linear classifier model by multivariate Cox regression to predict prognostic outcomes of HCC patients after curative surgery This analysis detected a considerable fraction of variance in HCC prognosis and the area under the ROC curve was about 70%. We further evaluated the model using two other protocols; leave-one-out procedure (n = 264) and independent validation (n = 300). Both were found to have excellent prediction power. The predicted score could separate patients into distinct groups with respect to survival (p-value = 1.8e-12) and disease free survival (p-value = 3.2e-7).</p> <p>Conclusion</p> <p>This described model will provide valuable guidance on prognosis after curative surgery for HCC in clinical practice. The adaptive nature allows easy accommodation for future new biomarker inputs, and it may serve as the foundation for future modeling and prediction for HCC prognosis after surgical treatment.</p

High-performance infrared photodetectors based on InAs/InAsSb/AlAsSb superlattice for 3.5 µm cutoff wavelength spectra

High-performance infrared p-i-n photodetectors based on InAs/InAsSb/AlAsSb superlattices on GaSb substrate have been demonstrated at 300K. These photodetectors exhibit 50% and 100% cut-off wavelength of ∼3.2 µm and ∼3.5 µm, respectively. Under -130 mV bias voltage, the device exhibits a peak responsivity of 0.56 A/W, corresponding to a quantum efficiency (QE) of 28%. The dark current density at 0 mV and -130 mV bias voltage are 8.17 × 10−2 A/cm2 and 5.02 × 10−1 A/cm2, respectively. The device exhibits a saturated dark current shot noise limited specific detectivity (D*) of 3.43 × 109 cm·Hz1/2/W (at a peak responsivity of 2.5 µm) under -130 mV of applied bias

Clinicopathologic and gene expression parameters predict liver cancer prognosis

<p>Abstract</p> <p>Background</p> <p>The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model.</p> <p>Methods</p> <p>Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction.</p> <p>Results</p> <p>HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis.</p> <p>Conclusion</p> <p>When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.</p

Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

Background: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. © 2011 Lamb et al.published_or_final_versio

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Dynamics characteristics analysis of coal plow system under starting and braking conditio

In view of problems of large impact of coal plow system under starting and braking condition，dynamic model of the coal plow system was established comprehensively considering factors of sprocket wheel polygon effect, horizontal vibration of drive sprocket shaft, and coupling characteristics between driving device and plow chain. Dynamic characteristics of the system under condition of starting, braking and reverse starting after braking were analyzed by numerical analysis method, and vibration characteristics curves of the front and rear chain tension were obtained. The analysis results show that the system dynamic characteristic are the most stationary by using reverse 'S' start scheme, the method is more advantageous to the coal plow system; the nearer the distance between the plow head and the machine head is，the larger plow chain tension impact is; due to time difference between nose and tail of the machine, tension in the front and back end of the chain has a great impact in the starting process; the plow chain tensions produce difference because of uneven distribution after the coal plow system barking，the plow chain tension of the front end has great impact at the reverse restart moment, and it falls with the starting process. The research results provide theoretical basis for designing reasonable start and brake system of the coal plow

Preparation, Physicochemical Characterization, and Antioxidant Activity of Naringin&ndash;Silk Fibroin&ndash;Alginate Microspheres and Application in Yogurt

Naringin is the major polyphenol in bitter orange peel with antioxidant property. However, its pH sensitivity, low solubility, and bitter taste limit its application in food. In this study, naringin&ndash;sodium alginate&ndash;silk fibroin microspheres were prepared by the ionic gel method. The loading capacity and encapsulation efficiency of naringin in microspheres were 13.2% and 77.6%, respectively. The morphology of microspheres was characterized by scanning electron microscopy. The X-ray diffractometry and differential scanning calorimetry results showed naringin was amorphous after encapsulation. Fourier-transform infrared spectroscopy and molecular docking analysis confirmed the intermolecular hydrogen bonds between naringin and sodium alginate. Naringin could release from the microspheres continuously under different pH conditions. Compared with free naringin, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and the stability of naringin microspheres were significantly improved. The application of naringin microspheres in yogurt indicated the precipitation of whey could be effectively reduced and the decline rate of pH was inhibited. The study suggested that naringin encapsulated microspheres were beneficial for improving the shelf life of this bioactive product as well as providing a new idea for functional yogurt

Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice

Background: Endometrial regenerative cells (ERCs) are mesenchymal-like stem cells that can be non-invasively obtained from menstrual blood and are easily grown /generated at a large scale without tumorigenesis. We previously reported that ERCs exhibit unique immunoregulatory properties in vitro, however their immunosuppressive potential in protecting the colon from colitis has not been investigated. The present study was undertaken to determine the efficacy of ERCs in mediating immunomodulatory functions against colitis. Methods: Colitis was induced by 4% dextran-sulfate-sodium (DSS, in drinking water) in BALB/c mice for 7 days. ERCs were cultured from healthy female menstrual blood, and injected (1 million/mouse/day, i.v.) into mice on days 2, 5, and 8 following colitis induction. Colonic and splenic tissues were collected on day 14 post-DSS-induction. Clinical signs, disease activity index (DAI), pathological and immunohistological changes, cytokine profiles and cell populations were evaluated. Results: DSS-induced mice in untreated group developed severe colitis, characterized by body-weight loss, bloody stool, diarrhea, mucosal ulceration and colon shortening, as well as pathological changes of intra-colon cell infiltrations of neutrophils and Mac-1 positive cells. Notably, ERCs attenuated colitis with significantly reduced DAI, decreased levels of intra-colon IL-2 and TNF-α, but increased expressions of IL-4 and IL-10. Compared with those of untreated colitis mice, splenic dendritic cells isolated from ERC-treated mice exhibited significantly decreased MHC-II expression. ERC-treated mice also demonstrated much less CD3+CD25+ active T cell and CD3+CD8+ T cell population and significantly higher level of CD4+CD25+Foxp3+ Treg cells. Conclusions: This study demonstrated novel anti-inflammatory and immunosuppressive effects of ERCs in attenuating colitis in mice, and suggested that the unique features of ERCs make them a promising therapeutic tool for the treatment of ulcerative colitis.Medicine, Faculty ofUrologic Sciences, Department ofNon UBCReviewedFacult

Extended-wavelength InGaAsSb infrared unipolar barrier detectors

We presented an extended-wavelength InGaAsSb infrared unipolar barrier detector working at room temperature. The detector with GaSb lattice-matched InGaAsSb absorb layer and AlGaAsSb unipolar barrier can achieve high material quality and low dark current. The dark current density was 2.29×10-5 A/cm2 at 0 bias at 77K. At room temperature the dark current at 0 bias was 4×10-3 A/cm2 and the R0A is high to 44 Ω · cm2. We fabricated the cone arrays in the InGaAsSb absorb layer to reduce the reflection of the radiation and extend the spectrum response to visible area. The extended-wavelength detector had the response from the wavelength of 0.4 μm. Further experiment showed the cone arrays also reduced the dark current of the detector at room temperature