Background The aim of this study was to explore the impact of antiviral therapy (AVT) on short- and long-term outcomes after rehepatectomy for patients with recurrent hepatitis B virus (HBV)-related ...hepatocellular carcinoma (HCC). Study Design We analyzed data from 583 consecutive patients who underwent rehepatectomy for intrahepatic recurrence of HBV-related HCC after initial hepatectomy, between 2006 and 2011 at the Eastern Hepatobiliary Surgery Hospital. Tumor re-recurrence, recurrence to death survival (RTDS), and overall survival (OS) were compared using the Kaplan-Meier method and log-rank test. The independent risk factors of prognoses were analyzed using the Cox proportional hazards model. Postoperative viral reactivation, surgical morbidity, and mortality were also observed. Results Preoperative AVT reduced viral reactivation rate after rehepatectomy (5.8% for AVT patients, 16.3% and 16.6% for non-AVT patients with viral level ≤ or >2,000 IU/mL, respectively, p ≤ 0.028). Viral reactivation and non-AVT were independent risk factors of tumor re-recurrence (hazard ratios 1.446 and 1.778, respectively), RTDS (1.691 and 2.457, respectively), and OS (1.781 and 1.857, respectively). The AVT improved long-term outcomes as compared with non-AVT with a viral level of ≤ or >2,000 IU/mL (5-year re-recurrence rate: 69% vs 81% vs 96%, respectively; 5-year RTDS rate: 47% vs 27% vs 17%, respectively, all p ≤ 0.016). Pre- plus postoperative AVT achieved a better 5-year OS rate than postoperative AVT alone (83% vs 60%, p = 0.045); there were insignificant differences in 5-year re-recurrence and RTDS rates (61% vs 77%, p = 0.102; 50% vs 44%, p = 0.395). Conclusions Preoperative AVT decreased viral reactivation rate, and AVT initiated either before or after rehepatectomy contributed to better long-term prognoses after rehepatectomy for recurrent HBV-related HCC.
Background: Similar to that in other malignant tumors, distant metastasis is one of the most important causes of poor prognosis in nasopharyngeal carcinoma (NPC). However, the genetic hallmarks and ...networks that regulate the distant metastasis of NPC are not fully understood. Methods: In this study, we performed high-throughput screening of mRNA expression profiles in 92 NPC samples collected from 3hospitals and detected the mRNA expression levels of 31,503 genes in these samples. Gene functional enrichment analyses were performed using gene set enrichment analysis (GSEA). Least absolute shrinkage and selection operator (LASSO) was applied to select prognostic genes and a Cox proportional hazards regression model including these genes was constructed to predict prognosis. The Kaplan–Meier curve and time-dependent receiver operating characteristic (ROC) curve were plotted to assess the performance of this model. Univariate and multivariate analyses were performed using the Cox proportion hazard model to test the independence of prognostic effect of gene model and other clinical features. Results: A total of 1837 differentially expressed genes between patients with and without distant metastasis were identified in the training cohort, including 869 upregulated genes and 968 downregulated genes. Six gene sets, including the Wnt/β catenin signaling pathway, hedgehog (Hh) signaling pathway, Notch signaling pathway, mitotic spindle, apical surface, and estrogen response late, were enriched in patients with distant metastasis. A four-gene signature model was constructed in the training cohort, and according to the time-dependent ROC curve, this model had certain accuracy in predicting distant metastasis-free survival (DMFS) in both the training and validation cohorts. Conclusion: We developed a four-gene signature model that can evaluate the distant metastasis risk of NPC patients and may also provide novel therapeutic targets for NPC treatment in the near future.
Up to one-third of patients who undergo cardiac resynchronisation therapy (CRT) are not responders. To identify potential responders to CRT may be sometimes difficult and time-consuming. Forty-five ...patients who had undergone CRT implantation for standard indications were evaluated. Electrical left ventricular (LV) lead location was assessed by left ventricular activation time (LVAT), LV lead electrical delay (LVLED), and RV-LV interlead electrical delay (RVsense-LVsense). Anatomic LV pacing location was assessed as basal or mid-ventricular between 3:00 to 5:00 (traditionally optimal site), and all the other positions (traditionally non-optimal site). CRT response was defined as a decrease in LV end-systolic volume (LVESV) exceeding 15% at six months. LVLED was larger in the responder group than that in the non-responder group (67.3±8.5% vs. 55.3±8.1%, P < 0.001). In the multivariate analysis, LVLED and cLBBB morphology were the two independent predictors of positive echocardiographic response to CRT (OR=1.180, P =0.003; OR=7.497, P =0.04, respectively). A cutoff value of LVLED> 54.82% predicted responders with 96.3% sensitivity and 75.2% specificity and the area under the receiver operating characteristic (ROC) curve was 0.844 for LVLED ( P =0.002). No relationship was found between the anatomic LV pacing sites and response to CRT ( P =0.188). The larger left ventricular lead electrical delay may predict response to cardiac resynchronisation therapy.
The separation of skin friction from total boundary layer shear stress for flows over bed forms is critical in erosion and sediment transport studies. Close‐to‐bed velocity profiles and skin friction ...shear velocities have been measured over mobile sand ripples of different geometries in a series of flume experiments to investigate the effects of form drag and flow stress partitioning. As expected, higher and longer ripples produce stronger form drag and hence higher total shear velocities for a given mean flow velocity, but the skin friction shear velocity was found to decrease with the increase in ripple height and length. For a fixed ripple geometry, the ratio of the skin friction to the total shear stress is also found to increase with the flow strength. Results of the present study together with data from previous investigations are used to test and extend the stress partition model of Smith and McLean (1977) for rippled beds. The Smith and McLean model is found to give reasonable partition of the skin friction from the total shear stress over mobile sand ripples. Overall empirical relationships based on total shear velocity and ripple geometry have also been obtained to understand the mechanisms of skin friction variation and to simplify the stress partitioning in bottom boundary layer flows over sand ripples.
Eight G protein‐coupled P2Y receptor subtypes respond to extracellular adenine and uracil mononucleotides and dinucleotides. P2Y receptors belong to the δ group of rhodopsin‐like GPCRs and contain ...two structurally distinct subfamilies: P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 (principally Gq protein‐coupled P2Y1‐like) and P2Y12–14 (principally Gi protein‐coupled P2Y12‐like) receptors. Brain P2Y receptors occur in neurons, glial cells, and vasculature. Endothelial P2Y1, P2Y2, P2Y4, and P2Y6 receptors induce vasodilation, while smooth muscle P2Y2, P2Y4, and P2Y6 receptor activation leads to vasoconstriction. Pancreatic P2Y1 and P2Y6 receptors stimulate while P2Y13 receptors inhibits insulin secretion. Antagonists of P2Y12 receptors, and potentially P2Y1 receptors, are anti‐thrombotic agents, and a P2Y2/P2Y4 receptor agonist treats dry eye syndrome in Asia. P2Y receptor agonists are generally pro‐inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2Y receptor pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X‐ray crystallography, mutagenesis and modelling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting.
Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We ...characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions. We experimentally demonstrated the effects of several cross-tumor nonsynonymous RNA editing events on cell viability and provide the evidence that RNA editing could selectively affect drug sensitivity. These results highlight RNA editing as an exciting theme for investigating cancer mechanisms, biomarkers, and treatments.
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•A systematic analysis of genome-wide RNA editing events across tumor types was done•A considerable number of clinically relevant RNA editing events are revealed•The functional effects of cross-tumor nonsynonymous RNA editing events are shown•Evidence that nonsynonymous RNA editing may affect drug sensitivity is provided
Han et al. characterize global A-to-I RNA editing profiles across 17 cancer types and experimentally demonstrate the effects of several cross-tumor nonsynonymous RNA editing events on cell viability and drug sensitivity.
Organic semiconductors are studied intensively for applications in electronics and optics, and even spin-based information technology, or spintronics. Fundamental quantities in spintronics are the ...population relaxation time (T1) and the phase memory time (T2): T1 measures the lifetime of a classical bit, in this case embodied by a spin oriented either parallel or antiparallel to an external magnetic field, and T2 measures the corresponding lifetime of a quantum bit, encoded in the phase of the quantum state. Here we establish that these times are surprisingly long for a common, low-cost and chemically modifiable organic semiconductor, the blue pigment copper phthalocyanine, in easily processed thin-film form of the type used for device fabrication. At 5 K, a temperature reachable using inexpensive closed-cycle refrigerators, T1 and T2 are respectively 59 ms and 2.6 μs, and at 80 K, which is just above the boiling point of liquid nitrogen, they are respectively 10 μs and 1 μs, demonstrating that the performance of thin-film copper phthalocyanine is superior to that of single-molecule magnets over the same temperature range. T2 is more than two orders of magnitude greater than the duration of the spin manipulation pulses, which suggests that copper phthalocyanine holds promise for quantum information processing, and the long T1 indicates possibilities for medium-term storage of classical bits in all-organic devices on plastic substrates.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ability of a cell to dynamically switch its chromatin between different functional states constitutes a key mechanism regulating gene expression. Histone mark "readers" display distinct binding ...specificity to different histone modifications and play critical roles in regulating chromatin states. Here, we show a plant-specific histone reader SHORT LIFE (SHL) capable of recognizing both H3K27me3 and H3K4me3 via its bromo-adjacent homology (BAH) and plant homeodomain (PHD) domains, respectively. Detailed biochemical and structural studies suggest a binding mechanism that is mutually exclusive for either H3K4me3 or H3K27me3. Furthermore, we show a genome-wide co-localization of SHL with H3K27me3 and H3K4me3, and that BAH-H3K27me3 and PHD-H3K4me3 interactions are important for SHL-mediated floral repression. Together, our study establishes BAH-PHD cassette as a dual histone methyl-lysine binding module that is distinct from others in recognizing both active and repressive histone marks.
A small cluster of massive stars residing in the Galactic center, collectively known as IRS 13E, is of special interest due to its close proximity to the central supermassive black hole Sgr A* and ...the possibility that an embedded intermediate-mass black hole (IMBH) binds its member stars. It has been suggested that colliding winds from two member stars, both classified as Wolf-Rayet type, are responsible for the observed X-ray, infrared, and radio emission from IRS 13E. We have conducted an in-depth study of the X-ray spatial, temporal, and spectral properties of IRS 13E, based on 5.6 Ms of ultradeep Chandra observations obtained over 20 years. These X-ray observations show no significant evidence for source variability. We have also explored the kinematics of the cluster members, using Keck near-infrared imaging and spectroscopic data on a 14 yr baseline that considerably improve the accuracy of the stars' proper motions. The observations are interpreted using three-dimensional hydrodynamical simulations of colliding winds tailored to match the physical conditions of IRS 13E, leading us to conclude that the observed X-ray spectrum and morphology can be well explained by the colliding wind scenario, in the meantime offering no support for the presence of a putative IMBH. An IMBH more massive than a few 103 M is also strongly disfavored by the stellar kinematics.
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