Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation

Abstract Background Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients. Methods In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3–144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence. Results Thirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2–139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU. Conclusions Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.http://deepblue.lib.umich.edu/bitstream/2027.42/110306/1/13046_2015_Article_120.pd

Characterization of loss mechanisms in a fluxonium qubit

Using a fluxonium qubit with in situ tunability of its Josephson energy, we characterize its energy relaxation at different flux biases as well as different Josephson energy values. The relaxation rate at qubit energy values, ranging more than one order of magnitude around the thermal energy $k_B T$, can be quantitatively explained by a combination of dielectric loss and $1/f$ flux noise with a crossover point. The amplitude of the $1/f$ flux noise is consistent with that extracted from the qubit dephasing measurements at the flux sensitive points. In the dielectric loss dominant regime, the loss is consistent with that arises from the electric dipole interaction with two-level-system (TLS) defects. In particular, as increasing Josephson energy thus decreasing qubit frequency at the flux insensitive spot, we find that the qubit exhibits increasingly weaker coupling to TLS defects thus desirable for high-fidelity quantum operations

Titanium Nitride Film on Sapphire Substrate with Low Dielectric Loss for Superconducting Qubits

Dielectric loss is one of the major decoherence sources of superconducting qubits. Contemporary high-coherence superconducting qubits are formed by material systems mostly consisting of superconducting films on substrate with low dielectric loss, where the loss mainly originates from the surfaces and interfaces. Among the multiple candidates for material systems, a combination of titanium nitride (TiN) film and sapphire substrate has good potential because of its chemical stability against oxidization, and high quality at interfaces. In this work, we report a TiN film deposited onto sapphire substrate achieving low dielectric loss at the material interface. Through the systematic characterizations of a series of transmon qubits fabricated with identical batches of TiN base layers, but different geometries of qubit shunting capacitors with various participation ratios of the material interface, we quantitatively extract the loss tangent value at the substrate-metal interface smaller than $8.9 \times 10^{-4}$ in 1-nm disordered layer. By optimizing the interface participation ratio of the transmon qubit, we reproducibly achieve qubit lifetimes of up to 300 $\mu$s and quality factors approaching 8 million. We demonstrate that TiN film on sapphire substrate is an ideal material system for high-coherence superconducting qubits. Our analyses further suggest that the interface dielectric loss around the Josephson junction part of the circuit could be the dominant limitation of lifetimes for state-of-the-art transmon qubits

Feasibility of Deep Learning–Based PET/MR Attenuation Correction in the Pelvis Using Only Diagnostic MR Images

This study evaluated the feasibility of using only diagnostically relevant magnetic resonance (MR) images together with deep learning for positron emission tomography (PET)/MR attenuation correction (deepMRAC) in the pelvis. Such an approach could eliminate dedicated MRAC sequences that have limited diagnostic utility but can substantially lengthen acquisition times for multibed position scans. We used axial T2 and T1 LAVA Flex magnetic resonance imaging images that were acquired for diagnostic purposes as inputs to a 3D deep convolutional neural network. The network was trained to produce a discretized (air, water, fat, and bone) substitute computed tomography (CT) (CTsub). Discretized (CTref-discrete) and continuously valued (CTref) reference CT images were created to serve as ground truth for network training and attenuation correction, respectively. Training was performed with data from 12 subjects. CTsub, CTref, and the system MRAC were used for PET/MR attenuation correction, and quantitative PET values of the resulting images were compared in 6 test subjects. Overall, the network produced CTsub with Dice coefficients of 0.79 ± 0.03 for cortical bone, 0.98 ± 0.01 for soft tissue (fat: 0.94 ± 0.0; water: 0.88 ± 0.02), and 0.49 ± 0.17 for bowel gas when compared with CTref-discrete. The root mean square error of the whole PET image was 4.9% by using deepMRAC and 11.6% by using the system MRAC. In evaluating 16 soft tissue lesions, the distribution of errors for maximum standardized uptake value was significantly narrower using deepMRAC (−1.0% ± 1.3%) than using system MRAC method (0.0% ± 6.4%) according to the Brown–Forsy the test (P &lt; .05). These results indicate that improved PET/MR attenuation correction can be achieved in the pelvis using only diagnostically relevant MR images

A deep learning approach for 18F-FDG PET attenuation correction

Abstract Background To develop and evaluate the feasibility of a data-driven deep learning approach (deepAC) for positron-emission tomography (PET) image attenuation correction without anatomical imaging. A PET attenuation correction pipeline was developed utilizing deep learning to generate continuously valued pseudo-computed tomography (CT) images from uncorrected 18F-fluorodeoxyglucose (18F-FDG) PET images. A deep convolutional encoder-decoder network was trained to identify tissue contrast in volumetric uncorrected PET images co-registered to CT data. A set of 100 retrospective 3D FDG PET head images was used to train the model. The model was evaluated in another 28 patients by comparing the generated pseudo-CT to the acquired CT using Dice coefficient and mean absolute error (MAE) and finally by comparing reconstructed PET images using the pseudo-CT and acquired CT for attenuation correction. Paired-sample t tests were used for statistical analysis to compare PET reconstruction error using deepAC with CT-based attenuation correction. Results deepAC produced pseudo-CTs with Dice coefficients of 0.80 ± 0.02 for air, 0.94 ± 0.01 for soft tissue, and 0.75 ± 0.03 for bone and MAE of 111 ± 16 HU relative to the PET/CT dataset. deepAC provides quantitatively accurate 18F-FDG PET results with average errors of less than 1% in most brain regions. Conclusions We have developed an automated approach (deepAC) that allows generation of a continuously valued pseudo-CT from a single 18F-FDG non-attenuation-corrected (NAC) PET image and evaluated it in PET/CT brain imaging

Extracorporeal Shock Wave Rebuilt Subchondral Bone In Vivo and Activated Wnt5a/Ca2+ Signaling In Vitro

Background. This study aimed to identify the optimal extracorporeal shock wave (ESW) intensity and to investigate its effect on subchondral bone rebuilt in vivo and Wnt5a/Ca2+ signaling in vitro using an osteoarthritis (OA) rat model and bone marrow mesenchymal stem cells (BMMSCs), respectively. Methods. OA rats treated with (OA + ESW group) or without (OA group) ESW (n=12/group) were compared with healthy controls (control group, n=12). Gait patterns and subchondral trabecular bone changes were measured. Western blot and quantitative real-time polymerase chain reaction detected protein expression and gene transcription, respectively. Results. The gait disturbances of OA + ESW group were significantly improved compared with the OA group at 6th and 8th weeks. The micro-CT analysis indicated that the BMD, BSV/BV, BV/TV, Tr.S, and Tr.Th are significantly different between OA group and OA + ESW group. Expression of Wnt5a was increased rapidly after ESW treatment at 0.6 bar and peaked after 30 min. Conclusions. ESW were positive for bone remodeling in joint tibial condyle subchondral bone of OA rat. ESW prevented histological changes in OA and prevented gait disturbance associated with OA progression. Optimal intensity of ESW induced changes in BMMSCs via activation of the Wnt5a/Ca2+ signaling pathway