In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified ...exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.
PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis.
At date cut-off of 24 March 2017, median follow-up was 31 months (range 23–41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 95% confidence interval (CI): 0.57, 0.77. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival 0.63 (95% CI: 0.45, 0.89) and newly collected samples 0.53 (95% CI: 0.38, 0.72). In patients with TPS ≥1%, PFS HRs were similar across archival 0.82 (95% CI: 0.66, 1.02) and newly collected samples 0.83 (95% CI: 0.68, 1.02).
Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples.
ClinicalTrials.gov: NCT01905657.
A memory cell consisting of a Pt/VO2/Pt switch element and a Pt/NiO/Pt memory element connected in series. By applying a voltage higher than Vth of 0.6 V, the switch element reaches the on state and ...the cell can be accessed. Since reset and set voltages are higher than Vth, information can be written by simply applying an appropriate voltage to a selected cell. By applying a voltage lower than Vth to the other cells, we can keep the other cells in the off state and prevent interference between the selected cell and the others.
We aimed to compare tissue-specific expression profiles and biological pathways of RNA from amniocytes and amniotic fluid supernatant (AFS) from second-trimester pregnancies by using transcriptome ...analysis. Additionally, we wanted to explore whether cell-free RNA from AFS exhibits a unique gene expression signature that more adequately reflects the fetal developmental process than amniocyte RNA.
Amniotic fluid samples were prospectively collected in the second trimester of pregnancy from euploid fetuses. Total RNA was extracted from amniocytes and AFS and hybridized to Affymetrix GeneChip Human Arrays. Significantly differentially expressed transcripts between amniocytes and AFS were obtained by using Welch's t-test. Unsupervised hierarchical clustering was used to visualize overall expression characteristics and differences in transcripts between AFS and amniocytes. The biological functions of selected genes were analyzed using various online Gene Ontology databases.
A total of 3,072 and 15,633 transcripts were detected in the second-trimester AFS and amniocytes, respectively. Hierarchical clustering revealed differential transcript expression between AFS and amniocytes. We found 353 genes that were specifically enriched in the AFS only, and tissue expression analysis showed enrichment of brain-specific genes in the AFS. Biological pathway analysis revealed that AFS-specific transcripts were mainly involved in embryonic development, cardiovascular development, and cellular morphology pathways.
This study demonstrated differential tissue-specific gene expression profiles and biological pathways between AFS and amniocytes. The results suggested that AFS is the preferred RNA source to investigate potential biomarkers of fetal neurodevelopment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigate collective modes in three dimensional (3D) gapless multi-Weyl semimetals with anisotropic energy band dispersions (i.e., with a positive integer J). For comparison, we also consider ...the gapless semimetals with the isotropic band dispersions (i.e. E ~ k
). We calculate analytically long-wavelength plasma frequencies incorporating interband transitions and chiral properties of carriers. For both the isotropic and anisotropic cases, we find that interband transitions and chirality lead to the depolarization shift of plasma frequencies. For the isotropic parabolic band dispersion the long-wavelength plasmons do not decay via Landau damping, while for the higher-order band dispersions the long-wavelength plasmons experience damping below a critical density. For systems with the anisotropic dispersion the density dependence of the long-wavelength plasma frequency along the direction of non-linear dispersion behaves like that of the isotropic linear band model, while along the direction of linear dispersion it behaves like that of the isotropic non-linear model. Plasmons along both directions remain undamped over a broad range of densities due to the chirality induced depolarization shift. Our results provide a comprehensive picture of how band dispersion and chirality affect plasmon behaviors in 3D gapless chiral systems with the arbitrary band dispersion.
RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are ...exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.
Epigenetic regulation by CpG methylation has an important role in tumorigenesis as well as in the response to cancer therapy. To analyze the mechanism of epigenetic control of radiosensitivity, the ...CpG methylation profiles of radiosensitive H460 and radioresistant H1299 human non-small cell lung cancer (NSCLC) cell lines were analyzed using microarray profiling. These analyses revealed 1091 differentially methylated genes (DMG) (absolute difference of mean beta-values, |Deltabeta |>0.5), including genes involved in cell adhesion, cell communication, signal transduction and transcriptional regulation. Among the 747 genes hypermethylated in radioresistant H1299 cells, CpG methylation of SERPINB5 and S100A6 in radioresistant H1299 cells was confirmed by methylation-specific PCR. Reverse transcriptase-PCR showed higher expression of these two genes in radiosensitive H460 cells compared with radioresistant H1299 cells. Downregulation of SERPINB5 or S100A6 by small interfering RNA in H460 cells increased the resistance of these cells to ionizing radiation. In contrast, promoter CpG sites of 344 genes, including CAT and BNC1, were hypomethylated in radioresistant H1299 cells. Suppression of CAT or BNC1 mRNA expression in H1299 cells also reduced the resistance of these cells to ionizing radiation. Thus, we identified DMGs by genome-wide CpG methylation profiling in two NSCLC cell lines with different responses to ionizing radiation, and our data indicated that these differences may be critical for epigenetic regulation of radiosensitivity in lung cancer cells.
We demonstrate a significant enhancement in the sensitivity of split ring resonator terahertz metamaterial dielectric sensors by the introduction of etched trenches into their inductive-capacitive ...gap area, both through finite element simulations and in experiments performed using terahertz time-domain spectroscopy. The enhanced sensitivity is demonstrated by observation of an increased frequency shift in response to overlaid dielectric material of thicknesses up to 18 µm deposited on to the sensor surface. We show that sensitivity to the dielectric is enhanced by a factor of up to ∼2.7 times by the incorporation of locally etched trenches with a depth of ∼3.4 µm, for example, and discuss the effect of the etching on the electrical properties of the sensors. Our experimental findings are in good agreement with simulations of the sensors obtained using finite element methods.
Objectives
High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in ...the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population.
Methods
This study used cross-sectional data from adult subjects aged 50–75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V–VII (2010–2011 and 2014–2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010–2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010–2011 dataset and any site SR-OA in the 2014–2016 dataset.
Results
Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (<2, 2–3, 3–4, 4–5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio OR = 1.64, 95% confidence interval CI 1.03–2.62) compared to the reference group (3–4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10–3.10) compared with the reference group. Regarding SR-OA at any site in the 2014–2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders.
Conclusions
This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.
Prediction of the
(IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our ...aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
Ninety-three patients with World Health Organization grade II gliomas with known
mutation and 1p/19q-codeletion status (18
wild-type, 45
mutant and no 1p/19q codeletion, 30
mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the
-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for
wild-type tumors and 1p/19q-codeletion status in
-mutant subgroups were evaluated using the least absolute shrinkage and selection operator.
Various histogram and texture parameters differed significantly according to
-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an
wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in
-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807.
Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
In mobile communication systems, the channel state information (CSI) is severely affected by the noise effect of the receiver. The adaptive subcarrier grouping (ASG) for sample matrix inversion (SMI) ...based minimum mean square error (MMSE) adaptive array has been previously proposed. Although it can reduce the additive noise effect by increasing samples to derive the array weight for co-channel interference suppression, it needs to know the signal-to-noise ratio (SNR) in advance to set the threshold for subcarrier grouping. This paper newly proposes adaptive zero padding (AZP) in the time domain to improve the weight accuracy of the SMI matrix. This method does not need to estimate the SNR in advance, and even if the threshold is always constant, it can adaptively identify the position of zero-padding to eliminate the noise interference of the received signal. Simulation results reveal that the proposed method can achieve superior bit error rate (BER) performance under various Rician K factors.
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