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Transfer neural networks have been successfully applied in many domain adaptation tasks. The initiative of most of the current transfer networks, essentially, is optimizing a single distance metric between the source domain and target domain, while few studies integrate multiple metrics for training transfer networks. In this paper, we propose an architecture of transfer neural network equipped with hybrid representations of domain discrepancy, which could incorporate the advantages of different types of metrics as well as compensate their imperfections. In our architecture, the Maximum Mean Discrepancy (MMD) and H -divergence based domain adaptations are combined for simultaneous distribution alignment and domain confusion. Through extensive experiments, we find that the proposed method is able to achieve compelling transfer performance across the datasets with domain discrepancy from small scale to large scale. Especially, the proposed method can be promisingly used to predict the viewpoint of 3D-printed workpiece even trained without labels of real images. The visualization of learned features and adapted distributions by our transfer network highlights that the proposed approach could effectively learn the similar features between two domains and deal with a wide range of transfer tasks.

Unwinding the double helix of the DNA molecule is the basis of gene duplication and gene editing, and the acceleration of this unwinding process is crucial to the rapid detection of genetic information. Based on the unwinding of six-base-pair DNA duplexes, we demonstrate that a terahertz stimulus at a characteristic frequency (44.0 THz) can serve as an efficient, nonthermal, and long-range method to accelerate the unwinding process of DNA duplexes. The average speed of the unwinding process increased by 20 times at least, and its temperature was significantly reduced. The mechanism was revealed to be the resonance between the terahertz stimulus and the vibration of purine connected by the weak hydrogen bond and the consequent break in hydrogen bond connections between these base pairs. Our findings potentially provide a promising application of terahertz technology for the rapid detection of nucleic acids, biomedicine, and therapy.

Objective To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margins rate and 90-days postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusion Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

Terahertz (THz) waves show nontrivial interactions with living systems, but the underlying molecular mechanisms have yet to be explored. Here, we employ DNA origami as a model system to study the interactions between THz waves and DNA structures. We find that a 3-min THz illumination (35.2 THz) can drive the unwinding of DNA duplexes at ∼10 °C below their melting point. Computational study reveals that the THz wave can resonate with the vibration of DNA bases, provoking the hydrogen bond breaking. The cooperation of thermal and nonthermal effects allows the unfolding of undesired secondary structures and the THz illumination can generate diverse DNA origami assemblies with the yield (80%) ∼ 4-fold higher than that by the contact heating at similar temperatures. We also demonstrate the in situ assembly of DNA origami in cell lysate. This method enables remotely controllable assembly of intact biomacromolecules, providing new insight into the bioeffects of THz waves.

IntroductionTo assess the rate and location of residual tumor in re-transurethral resection of bladder tumor (re-TURBT) and develop a risk stratification tool to assist clinicians in making treatment decisions.Patients and MethodsThe data of 144 patients with high-risk bladder cancer who received re-TURBT were retrospectively reviewed. The rate and location of residual tumors was recorded. Logistic regression was performed to explore risk factors for residual tumors, and a risk classification tool was developed.ResultsAmong the 144 patients, the rates of residual tumor and tumor location at the base of the primary tumor were 22.2% and 10.4%, respectively. Non-urothelial carcinoma subspecialist, piecemeal resection and the absence of detrusor muscle in the first specimen were defined as risk factors. Patients were categorized into low-, intermediate-, and high-risk groups according to the number of risk factors. The rate of residual tumor in the high-risk group was significantly higher than that in the low- and intermediate-risk groups (50% vs. 7.8%, P=0.001; 50% vs. 18.6%, P=0.002). Moreover, high-risk patients benefitted more from a second resection at the base of the primary tumor due to the high rate of residual tumor located at this site than low- and intermediate-risk patients (23.5% vs. 2.0%, P=0.002; 23.5% vs. 10.2%, P=0.083).ConclusionsRisk stratification based on the subspecialist category, operative method, and presence or absence of detrusor muscle in the first specimen could help identify patients who benefit from re-TURBT and second resection the base of the primary tumor.

Most of the existing studies about airline crew scheduling problems focus on single-objective optimization or multi-objective optimization under simple constraints. In this paper, we propose an airline crew scheduling model based on a large number of constraints in actual scenarios, with multiple objectives for both saving airline company’s cost and improving the balance of crew working time. We then introduce an improved fast search multi-objective genetic algorithm, which is able to quickly find the feasible domain around optimal solution when confronting with a large number of crew data and constraints. We compare the results of our algorithm with the multi-objective greedy algorithm, which verifies the effectiveness of our algorithm on solving the airline crew scheduling problem.

To describe a green-laser marking technique to assist partial cystectomy, which allows accurate identification of tumour margins, and provide our initial experience with ten patients. Between January 2014 and February 2018, ten patients suspected with muscle-invasive bladder cancer and request of bladder-preserving treatment were selected. In each case, bilateral pelvic lymphadenectomy was performed before green-laser assisted laparoscopic partial cystectomy. Under the direct view of cystoscope, the front-firing green-laser incision was performed 0.5–1 cm away from the exterior margin of lesion with adequate depth into the fat tissue. Tumours were then en bloc removed via laparoscope under the tracing of laser beam. The location of 12 tumours in 10 patients was superior wall in 7 cases, lateral wall in 3 cases, anterior wall in 1 case, and posterior wall in 1 case. All procedures were completed without serious complications. The median operating time was 270 (210–360) min with a median haemoglobin decrease of 11 (3–38) g/L. Nine patients were high-grade transitional cell carcinoma and one patient was urachal carcinoma, and the clinical stage was pT1 in 1 case, pT2 in 4 cases, and pT3 in 5 cases. The pathological evaluation of tumour margins was negative in 10 patients. During the follow-up, no recurrence or metastasis were detected in 8 patients, but 2 patients presented regional recurrence. The use of green-laser marking technique during laparoscopic partial cystectomy is a feasible manoeuvre in assisting the accurate incision and minimizing injury to the remaining bladder.

Purpose: Renal cell carcinoma (RCC) is known to be highly radioresistant but the mechanisms associated with radioresistance have remained elusive. We found DOC-2/DAB2 interactive protein (DAB2IP) frequently downregulated in RCC, is associated with radioresistance. In this study, we investigated the underlying mechanism regulating radioresistance by DAB2IP and developed appropriate treatment. Experimental Design: Several RCC lines with or without DAB2IP expression were irradiated with ionizing radiation (IR) for determining their radiosensitivities based on colony formation assay. To investigate the underlying regulatory mechanism of DAB2IP, immunoprecipitation-mass spectrometry was performed to identify DAB2IP-interactive proteins. PARP-1 expression and enzymatic activity were determined using qRT-PCR, Western blot analysis, and ELISA. In vivo ubiquitination assay was used to test PARP-1 degradation. Furthermore, in vivo mice xenograft model and patient-derived xenograft (PDX) model were used to determine the effect of combination therapy to sensitizing tumors to IR. Results: We notice that DAB2IP-deficient RCC cells acquire IR-resistance. Mechanistically, DAB2IP can form a complex with PARP-1 and E3 ligases that is responsible for degrading PARP-1. Indeed, elevated PARP-1 levels are associated with the IR resistance in RCC cells. Furthermore, PARP-1 inhibitor can enhance the IR response of either RCC xenograft model or PDX model. Conclusions: In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC.

Fabrication-less integrated circuit (IC) design houses outsource fabrication to third-party foundries to reduce cost of manufacturing. The outsourcing of IC fabrication, beyond our expectation, raises concerns regarding intellectual property (IP) piracy and theft by rogue elements in the third-party foundries. Obfuscation techniques have been proposed to increase resistance to reverse engineering, IP recovery, IP theft, and piracy. However, prior work on obfuscation for IP protection has primarily applied to the gate level or the layout level. As a result, it can significantly impact the performance of the original design in addition to requiring redesign of standard cells. In this article, we propose a high-level synthesis and analysis (HLSA)-based obfuscation approach for IP protection. The proposed method is based on split manufacturing. Additional dummy units and MUXes can be added to further obfuscate the design. The proposed technique aligns with the standard-cell-based design methodologies and does not significantly impact the performance of the original design. Our experimental results confirm that the proposed approach can provide high levels of IC obfuscation with moderate area cost.

Objective: Our study aimed to detect whether 450 nm blue laser can be applied effectively and safely in endosocopic submucosal dissection (ESD) system for surgery in colonic tissue. Background data: Semiconductor blue laser has been applied in surgery due to its excellent cutting property, however, whether blue laser can be applied in colonic surgery has not been reported. Materials and methods: Porcine colon tissues were vaporized by 450 nm blue semiconductor laser at 10-25 W and at working distances from 0.5 to 3 mm, with a three-dimensional scanning system. Moreover, we designed an ESD model and applied blue laser at 10 W on porcine colonic tissues with this system. Dimensions of the vaporized tissues and coagulation zones were assessed under microscopy. Results: Since the thickness of colonic wall is no more than 1 mm, first we determined the cutting property and safety of blue laser on porcine colon tissue and found that blue laser at 10 W made lesions shallower than 1 mm and the depth of vaporization can be controlled effectively within muscularis mucosa and submucosa. Moreover, a large scale of porcine colonic tissue was vaporized precisely by blue laser at power of 10 W with the ESD system ex vivo. Conclusions: Our results indicate that 450 nm blue laser at 10 W can be well controlled for laser-tissue interaction with excellent cutting efficiency and less thermal damage in adjacent tissues especially side of the submucosa. Therefore, 450 nm semiconductor blue laser could be a safe alternative approach for colonic surgery.

Refresh schemes have been the default approach in NAND flash memory to avoid data losses. The critical issue of the refresh schemes is that they introduce additional costs on lifetime and performance. Recent work proposed to minimize the refresh costs by using uniform refresh frequencies based on the number of program/erase (P/E) cycles. However, from our investigation, we find that the refresh costs still have a high burden on the lifetime performance. In this paper, a novel refresh minimization scheme is proposed by exploiting the process variation (PV) of flash memory. State-of-the-art flash memory always has significant PV, which introduces large variations on the retention time of flash blocks. In order to reduce the refresh costs, we first propose a new refresh frequency determination scheme by detecting the supported retention time of flash blocks. If the detected retention time is large, a low refresh frequency can be applied to minimize the refresh costs. Second, considering that the retention time requirements of data are varied with each others, we further propose a data hotness and refresh frequency matching scheme. The matching scheme is designed to allocate data to blocks with right higher supported retention time. Through simulation studies, the lifetime and performance are significantly improved compared with state-of-the-art refresh schemes.

The intratumoral androgen synthesis is one of the mechanisms by which androgen receptor (AR) is aberrantly re-activated in castration-resistant prostate cancer (CRPC) after androgen ablation. However, pathways controlling steroidogenic enzyme expression and de novo androgen synthesis in prostate cancer (PCa) cells are largely unknown. In this study, we explored the potential roles of DAB2IP in testosterone synthesis and CRPC tumor growth. Indeed, DAB2IP loss could maintain AR transcriptional activity, PSA re-expression and tumor growth under castrated condition in vitro and in vivo, and reprogram the expression profiles of steroidogenic enzymes, including AKR1C3. Mechanistically, DAB2IP could dramatically inhibit the AKR1C3 promoter activity and the conversion from androgen precursors (i.e., DHEA) to testosterone through PI3K/AKT/mTOR/ETS1 signaling. Consistently, there was a high co-expression of ETS1 and AKR1C3 in PCa tissues and xenografts, and their expression in prostate tissues could also restore AR nuclear staining in castrated DAB2IP-/- mice after DHEA supplement. Together, this study reveals a novel regulation of intratumoral de novo androgen synthesis in CRPC, and provides the DAB2IP/ETS1/AKR1C3 signaling as a potential therapeutic target.

Bladder cancer (BC) is among the most common urinary system tumors with a high morbidity and mortality worldwide. Despite advancements being made in the diagnosis and treatment of bladder cancer, targeted therapy remains the most promising treatment, and novel therapeutic targets are urgently required in to improve the outcomes of patients with BC. Kinesin family member 4A (KIF4A) is a plus‑end directed motor protein involved in the regulation of multiple cellular processes, such as mitosis and axon growth. Notably, KIF4A plays important roles in tumor growth and progression, and its expression is associated with the prognosis of several types of cancer. However, the potential role and molecular mechanisms of KIF4A in bladder cancer development remain unclear. The present study demonstrated that KIF4A was highly expressed in human BC tissues, and its expression was associated with patient clinicopathological characteristics, such as tumor stage (P=0.012) and with the prognosis of patients with BC. It was further found that KIF4A promoted the cell proliferation of bladder cancer both in vitro and in vivo. On the whole, the data presented herein provide evidence that KIF4A promotes the development of BC through the transcriptional activation of the expression of CDCA3. The present study indicates the involvement of KIF4A in the progression of BC and suggests that KIF4A may be a promising therapeutic target for the treatment of BC.

Significance Infrared neural stimulation (INS) is an emerging technology for neuromodulation and holds promise for clinical application. While most INS studies have been conducted at near-infrared wavelengths, whether midinfrared light with frequencies matching the chemical bond vibration of biomolecules can influence neuronal function remains unknown. We found that midinfrared light with low water absorption provides nonthermal and reversible modulation of neuronal spiking activity and sensorimotor behavior. Nonlinear resonance between light and chemical bond vibration at the selectivity sieve of the K+ channel directly enhances ion conductivity and thus regulates AP waveform and spiking activity. Together, our results reveal nonthermal effects of MIRS on functional biomolecules, neuronal signaling, and behavior state. Therefore, MIRS could serve as a form of physical neuromodulation., Various neuromodulation approaches have been employed to alter neuronal spiking activity and thus regulate brain functions and alleviate neurological disorders. Infrared neural stimulation (INS) could be a potential approach for neuromodulation because it requires no tissue contact and possesses a high spatial resolution. However, the risk of overheating and an unclear mechanism hamper its application. Here we show that midinfrared stimulation (MIRS) with a specific wavelength exerts nonthermal, long-distance, and reversible modulatory effects on ion channel activity, neuronal signaling, and sensorimotor behavior. Patch-clamp recording from mouse neocortical pyramidal cells revealed that MIRS readily provides gain control over spiking activities, inhibiting spiking responses to weak inputs but enhancing those to strong inputs. MIRS also shortens action potential (AP) waveforms by accelerating its repolarization, through an increase in voltage-gated K+ (but not Na+) currents. Molecular dynamics simulations further revealed that MIRS-induced resonance vibration of –C=O bonds at the K+ channel ion selectivity filter contributes to the K+ current increase. Importantly, these effects are readily reversible and independent of temperature increase. At the behavioral level in larval zebrafish, MIRS modulates startle responses by sharply increasing the slope of the sensorimotor input–output curve. Therefore, MIRS represents a promising neuromodulation approach suitable for clinical application.

Prostate-specific antigen nadir (nPSA) and time to nPSA (TTN) have been proved to be associated with the prognosis of prostate cancer. In this study, we explored the prognosis effect of nPSA and TTN during initial androgen deprivation therapy (ADT) in patients with metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel-based chemotherapy. The data of 153 mCRPC patients received docetaxel followed by ADT were retrospectively reviewed. Multivariate Cox regression analysis demonstrated that TTN (overall survival (OS): Hazard ratio [HR] 0.096, 95% confidence interval [CI] 0.045-0.206, p < .001; progression-free survival (PFS): HR 0.128, 95% CI 0.078-0.211, p < .001) and nPSA (OS: HR 2.849, 95% CI 1.318-6.157, p = .008; PFS: HR 1.573, 95% CI 1.008-2.454, p = .046) acted as independent predictors of chemotherapy prognosis. Kaplan-Meier analysis showed that patients with nPSA ≥ 0.2 ng/ml or TTN < 6.5 months had shorter OS and PFS. These results suggest that TTN and nPSA during ADT can affect the prognosis of docetaxel-based chemotherapy prognosis post-castration resistance in patients with mCRPC, and higher nPSA and shorter TTN lead to poor chemotherapy prognosis. What is more, TTN has a greater impact during ADT on the prognosis of chemotherapy than nPSA.

e16505 Background: Bladder cancer is one of the most common malignancy in urinary system. Fibroblast growth factor receptor 3 (FGFR3) is the most common alteration gene in bladder cancer, occurring in approximately 70% of non-metastatic bladder cancer and 20% of metastatic bladder cancer. Anlotinib is a potent oral, multi-target tyrosine kinase inhibitor with a favorable safety which mainly targets vascular endothelial growth factor receptor (VEGFR), FGFR, platelet-derived growth factor receptors, and c-kit. This study aims to investigate the role of anlotinib in bladder cancer compared with FGFR3 inhibitor erdafitinib i n vitro and in vivo. Methods: MTT, colony formation, and Transwell assays were performed on bladder cancer cells (SW780 and UMUC14) to confirm the effects of anlotinib and erdafitinib on proliferation, migration and invasion. Apoptotic effect was evaluated by Annexin V/propidium iodide double staining, and the levels of the protein and mRNA were examined by RNA-seq, Western blotting and RT-qPCR. Finally, mice with palpable xenografts were treated either with anlotinib and erdafitinib for 8 days before they were sacrificed for measuring the sizes and weights of the tumors. Results: To assess the roles of anlotinib in bladder cancer, we treated SW780 cell line which had FGFR3-BALAP2L1 fusion mutation and UMUC-14 cell line which had a FGFR3 (MuS247C) mutation with DMSO, anlotinib and erdafitinib. As seen in MTT, colony formation and Transwell assays, anlotinib repressed cell proliferation, migration and invasion as erdafitinib. Compared with vehicle, Anlotinib promoted cell apoptosis of bladder cancer cells. To further explore the mechanism, anlotinib and erdafitinib suppressed p-Erk1/2 and p-AKT, while only anlotinib inhibited the expression of VEGF-a. Compared with erdafitinib, the inhibitory ability of anlotinib was weaker than that of erdafitinib in cell line with FGFR3 (MuS247C) mutation, on the contrary, it was much stronger in cell line with FGFR3-BALAP2L1 fusion mutation. In addition, the in vivo data from xenagrafts also supported that anlotinib could significantly repress tumor growth with FGFR3 fusion mutation, and the efficacy was better than erdafitinib. Conclusions: Anlotinib could repress the proliferation, migration and invasion of bladder cancer cells by inhibiting the phosphorylation of Erk1/2 and AKT, and the suppression VEGF-a expression, whose effects was better than erdafitinib in bladder cancer with FGFR3 fusion mutation. Therefore, anlotinib might be a potential novel targeted agent to treat the bladder cancer patients with FGFR3 fusion mutations, and clinical trials are needed for further investigation.

4580 Background: To evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin as neoadjuvant therapy for patients (pts) with clinical T2-T4aN0M0 (cT2-T4aN0M0) muscle-invasive bladder urothelial cancer (MIBC). Methods: This multicenter, open-label, single arm phase II study enrolled pts tolerated with the cisplatin therapy. Eligible pts received tislelizumab 200 mg in day 1 (D1), cisplatin 70 mg/m2 D2, and gemcitabine 1000 mg/m2 D1 and D8 every 21 days for four cycles. Radical cystectomy (RC) was performed within 6 weeks after last dose treatment. The primary end point was pathologic complete response (pCR, pT0N0M0). Secondary end points were pathologic downstaging (≤pT1N0M0), EFS, OS and safety. Simon two-stage design was used. If > 5 pts achieved pCR in the first stage (n = 22), study would proceed to the second stage and enroll 33 additional pts. If > 18 of 55 pts achieved pCR, we would deem the study to have met the primary endpoint. Results: We reported the results in the first stage. By Oct 2021, 23 eligible pts were enrolled. Eighteen pts have completed neoadjuvant therapy, with median age of 62 (48-72) years and 8 (44.4%) pts of PD-L1 positive, among whom 17 pts underwent RC and one declined RC. At the data cut off time of 14th Jan 2022, among 17 evaluable pts (12 cT2, 3 cT3, and 2 cT4a), 10 (58.8% [95% CI, 32.9-81.6]) pts achieved pCR and 13 (76.5% [95% CI, 50.1-93.2]) achieved pathologic downstaging. No significant differences were found in pCR (62.5% vs. 55.6%) and downstaging (75.0% vs. 77.8%) rates between pts with PD-L1 positive versus PD-L1 negative. Eighteen pts completed 71/72 cycles of tislelizumab, 68/72 cycles of cisplatin and 135/144 cycles of gemcitabine therapy. The rate of dose reduction (all due to AEs) of cisplatin and gemcitabine therapy was 25.0% (17/68 cycles) and 23.7% (32/135 cycles), respectively. The relative dose intensity of tislelizumab, cisplatin and gemcitabine were 93.6%, 84.5% and 85.9%, respectively. Most common neoadjuvant therapy related AEs of any grade were hematologic toxicities (94.4%), nausea (72.2%), vomiting (61.1%), decreased appetite (55.6%), fatigue (27.8%), pruritus (22.2%) and ALT/AST increased (22.2%). Grade ≥3 neoadjuvant therapy related AEs were neutropenia (n = 6), thrombocytopenia (n = 4), anemia (n = 2) and lymphocyte count decreased (n = 1). Eight pts experienced grade 1-2 immune related AEs, including pruritus (n = 4), rash (n = 2), ALT/AST increased (n = 4), GGT increased (n = 2), CPK increased (n = 1), hyperthyroidism (n = 1), hypothyroidism (n = 1). Conclusions: Neoadjuvant tislelizumab combined with gemcitabine and cisplatin showed promising anti-tumor activity with high pCR and well tolerance in MIBC pts. The target of first stage has been achieved, and enrollment is ongoing. At the data cut off 14th Jan 2022, 34 pts have been enrolled. Clinical trial information: ChiCTR2000037670.

To improve the tracking performance of the pan-tilt visual tracking system, a Predictive Active Disturbance Rejection Control (P-ADRC) with parameter optimization is proposed. In this approach, the impact of internal parameter uncertainties and external disturbances on the closed-loop system performance is suppressed. Advance prediction of the target dynamics is achieved by Singular Value Decomposition-Unscented Kalman Filter (SVD-UKF), which reduces response lag caused by Tracking Differentiator (TD) in ADRC and visual processing. To realize optimal performance of P-ADRC, the Adaptive Particle Swarm Optimization (APSO) is used to overcome the problems of numerous parameters and difficulty in tuning. Simulation results indicate that, realizing satisfactory transient response and anti-disturbance behavior, the proposed method drastically reduces the Root Mean Square (RMS) tracking error of the pan-tilt system compared to conventional ADRC.

The literature on behavioral public finance has tended to focus on the biases of taxpayers. However, politicians and government agents are human as well and can be expected to show the same biases that we are all subject to. This chapter will examine three examples of availability heuristic arguably influencing political actors and the unintended consequences of their reactions. The examples are all from US international tax rules: the foreign investment in real property tax act (FIRPTA) (1980), the exit tax on US citizens who expatriate (2008) and the enforcement of withholding tax on dividend equivalents (2010).

Objective To compare the safety and outcomes between green-light laser en bloc resection and transurethral resection of bladder tumor. Methods A single-center, randomized controlled trial was carried out from August 2014 to September 2018. Patients with initial non-muscle-invasive bladder cancer were randomized to green-light laser en bloc resection or transurethral resection of bladder tumor. The primary outcomes were pathological findings and perioperative events. The secondary outcome was tumor recurrence. Results A total of 233 patients were randomized to the transurethral resection of bladder tumor group (117 patients) and the green-light laser en bloc resection group (116 patients). The resection time was longer in the green-light laser en bloc resection group (P = 0.022); however, no differences were identified in overall operative time (P = 0.255). Nine patients (7.7%) had an obturator nerve reflex during transurethral resection of bladder tumor. The estimated volume of blood loss was significantly lower in the green-light laser en bloc resection group (P = 0.012). The green-light laser en bloc resection group had a higher rate of T1 bladder cancer (P = 0.031). A total of 104 patients (89.7%) treated with green-light laser en bloc resection had detrusor muscle presence in the specimen, whereas 37 (31.9%) patients had the presence of muscularis mucosae, which was significantly higher than the corresponding number of transurethral resection of bladder tumor patients (P = 0.005 and 0.002, respectively). After a median follow-up period of 48 months, just five patients had tumor recurrence (three in the transurethral resection of bladder tumor group and two in the green-light laser en bloc resection group), and there was no difference between these two groups. Conclusions Compared with transurethral resection of bladder tumor, green-light laser en bloc resection is more effective due to less obturator nerve reflex and the same recurrence rate. Most importantly, green-light laser en bloc resection can provide better tumor specimens for pathological examinations.

This paper presents a flexible module that utilizes the 3D position attention mechanism to extract contextual features from local regions of point cloud. The key point is to create an effective representation of local features. Due to the irregularity of point cloud, previous algorithms for point cloud processing have not fully explored how to enhance the extraction of local features. Inspired by the position attention mechanism in the 2D image segmentation algorithm, we propose a Point Attention Graph (PAG) module that can be used to improve the fusion of local features and make it better and faster. The PAG module uses the point attention mechanism to adaptively calculate the interaction between all nodes of the local graph. It can efficiently definite the relations of local points to enhance the performance of feature extraction both in accuracy and time efficiency, especially compared with some related models like PointWEB. Experiments show that our method can be effectively applied to semantic segmentation datasets.

Modern Industrial Internet-of-Things (IIoT) requires reliable interaction and integration of data in the network. Thus, time sensitive networking (TSN) is a promising technology due to deterministic latency guarantee mechanisms for data transmission. However, the multiple mechanisms are based on the networkwide precise time synchronization. In this paper, to achieve precise and reliable clock synchronization of TSN, we propose a hierarchical timing-frequency synchronization mechanism. Specifically, the network is divided into two layers according to the network clock synchronization function. The top layer adopts tree-based synchronization to provide a global clock and an interface with external standard clock synchronization, and the underlying one adopts a distributed synchronization protocol to improve the reliability, which obtains the reference clock by multiple nodes to avoid the single point of failure. To improve synchronization efficiency, a time-frequency fusion synchronization mechanism is proposed, which comprehensively considers the synchronization time slot difference and the time-frequency coupling relationship to improve the synchronization speed under the same synchronization period. Simulation results show that the proposed synchronization mechanism has higher synchronization efficiency than the traditional methods, and improves the clock synchronization speed and accuracy significantly.

In recent years, cervical cancer has been one of the most common diseases in women's cancer. The advanced diagnosis of cervical precancerous lesions is essential for preventing cervical cancer. Its effectiveness and efficiency can be greatly improved by computer aided diagnosis, while challenged by the imprecise conclusions and uninterpretable process of diagnosis. To solve this problem, we propose a novel deep learning-based interpretable diagnosis system for pathology images, consisting of three interrelated models: an image model, an attention model and a conclusion model.Computer aided diagnosis improves the effectiveness and efficiency of the proposed image model uses a convolutional neural network (CNN) to ex-tract semantic features. Combining the model with the semantic attribute attention model, it aims to capture the discriminant relationship between se-mantic attributes by predicting the conclusion label through long-term and short-term memory (LSTM). The network is trained in an end-to-end manner, with different weights for each model. Experimental results on cervical intraepithelial neoplasia images, diagnostic reports and label datasets show that the proposed method achieves a significant improvement over traditional methods with a better interpretability.

Background: This study aimed to describe the aberrations of DNA damage repair genes and other important driving genes in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) using circulating tumor (ctDNA) sequencing and to evaluate the associations between the clinical outcomes of multiple therapies and key genomic alterations in mCRPC, especially DNA damage repair genes. Patients and Methods: A total of 292 Chinese patients with mCRPC enrolled from 8 centers. Multigene targeted sequencing was performed on 306 ctDNA samples and 23 matched tumor biopsies. The frequency of genomic alterations were compared with the Stand Up to Cancer–Prostate Cancer Foundation (SU2C-PCF) cohort. The Kaplan-Meier method was used to evaluate progression-free survival (PFS) following standard systemic treatments for mCRPC. Cox regression analyses were performed to determine prognostic factors associated with PFS resulting from treatments for mCRPC. Results: In total, 33 of 36 (91.7%) mutations were found consistently between ctDNA and paired biopsy samples. The most common recurrent genomic alterations were found in AR (34.6%), TP53 (19.5%), CDK12 (15.4%), BRCA2 (13%), and RB1 (5.8%). The frequency of CDK12 alterations (15.4%) in our cohort was significantly higher than that in Western populations (5%–7%). AR amplification and TP53 and/or RB1 alterations were associated with resistance to abiraterone or docetaxel. Patients with a CDK12 defect showed rapid disease progression after abiraterone treatment. However, the clinical outcome after docetaxel treatment was similar between patients with and without CDK12 defects. In multivariate Cox regression analysis, a CDK12 defect was significantly associated with inferior PFS after abiraterone treatment. Patients with a BRCA2 defect showed marked response to both PARP inhibitors and platinum-based chemotherapy. Conclusions: Our study explored the genomic landscape of Chinese patients with mCRPC at different treatment stages using minimally invasive methods and evaluated the clinical implications of the driver genomic alterations on patients’ response to the most widely used therapies for mCRPC. We observed a significantly higher alteration frequency of CDK12 in our cohort compared with the SU2C-PCF cohort.

The myelination of axons was the last major evolution in the vertebrate nervous system. Myelin promotes the speed of action potential by two orders, and modulates the conduction of neurons, important for learning new skills. However, the intrinsic mechanism for high-speed information propagation in myelin in the nervous systems is still unclear. We propose that myelinated nerve fibres serve as dielectric waveguides for the high-frequency electromagnetic information in a certain mid-infrared to terahertz spectral range. Based on the structure characteristics of myelinated nerve composed of periodic nodes of Ranvier and myelin sheath, the energy for the signal propagation is supplied and amplified when crossing the nodes of Ranvier via a periodic relay. In this work, we exploit the quasi-quantum model of amplification for neural terahertz/infrared information at the nodes of Ranvier, and prove the existence of biomolecular ensemble for three-energy-level amplification, revealing the essential mechanism of high-speed electromagnetic information transmitting in myelinated nerves.

INTRODUCTION AND OBJECTIVE:With the application of the next-generation AR pathway inhibitor (ARPIs), such as enzalutamide, patients with metastatic castration resistant prostate cancer (mCRPC) acqu...

To present our preliminary experience in managing patients with highly recurrent bladder neck contractures (BNCs) after transurethral resection of the prostate (TURP). Between February 2015 and March 2018, 28 patients with highly recurrent BNCs who had failed multiple prior to endoscopic treatments were managed with transurethral resection and intra- and post-operative triamcinolone acetonide injections. The scar tissue was resected to the circular fiber at the bladder neck, and triamcinolone acetonide (2 mL, 40 mg/mL) was injected at the incision sites (8 points) using a cystoscopic injection needle. The cystoscopy-guided injections were repeated every four weeks for total three times after surgery. The patients were followed up at 3, 6, 12 months after surgery, and in July–August 2019. The recurrent interval before the treatments was 2.2 ± 1.2 months, without any BNC recurrence in the first 12 weeks after transurethral resection. The urinary flow rate increased significantly and was maintained during the follow-up period. Adequate voiding function was reported in 25 of 28 patients at a median follow-up of 2.8 (1.7, 3.9) years. One of the three patients with decreased urinary flow rate had underactive detrusor and no BNC recurrence. The complications were mild and tolerable. Transurethral resection of the scar tissue combined with intra- and post-operative triamcinolone acetonide injections resulted in a success rate of 92.9% in patients with highly recurrent BNC following TURP. It is a simple, safe, and effective treatment for highly recurrent BNCs.

Curriculum learning has the potential to solve the problem of sparse rewards, a long-standing challenge in reinforcement learning, with greater sample efficiency than traditional reinforcement learning algorithms because curriculum learning enables agents to learn tasks in a meaningful order: from simple tasks to difficult ones. However, most curriculum learning in RL still relies on fixed hand-designed sequences of tasks. We present a novel scheme of automatic curriculum learning for reinforcement learning agents. A two-level hierarchical reinforcement learning framework, with a high-level policy called the curriculum generator and a low-level policy called the action policy, is proposed. During training, the curriculum generator automatically proposes curricula for the action policy to learn. Our training methods guarantee that the proposed curricula are always moderately difficult for the action policy. Both levels of policies are trained simultaneously and independently. After training, the low-level policy will be able to finish all tasks without the instructions given by the curriculum generator. Experiment results on a wide range of benchmark robotics environments demonstrate that our method accelerates convergence considerably and improves the training quality compared with the method without the curriculum generator.