Search

Objective To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour (TURBT) and explore the risk factors of upgrading. Methods The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed. Comparative analysis of the tumour grade of biopsy and operation specimens was performed. Tumour grade changing from low-grade (LG) to high-grade (HG) with or without variant histology was defined as upgrading. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of upgrading. Results For the 205 patients, the concordance of tumour grade between biopsy and operation was 0.639. The concordance for patients who were preoperatively diagnosed with LG and HG was 0.504 and 0.912, respectively. Univariate and multivariate logistic regression analyses showed that older age, tumour multifocality, high neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte-to-monocyte ratio (LMR) were significantly associated with upgrading (odds ratio [OR] ranging from 0.412 to 4.364). The area under the curve of the different multivariate models was improved from 0.752 to 0.821, and decision curve analysis demonstrated a high net benefit when NLR, LMR, and PLR were added. Moreover, the nomogram was well calibrated. Conclusions Diagnostic cystoscopic biopsy may not accurately represent the true grade of new bladder cancer, especially for outpatients with LG. Moreover, older age, tumour multifocality, high NLR, PLR, and low LMR are risk factors of upgrading, and systemic inflammatory markers improve the predictive ability.

Background: Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC. Methods: The medical records of 224 patients with primary mHSPC were retrospectively reviewed. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS. Results: A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases was only 61.62%, and Cohen’s kappa coefficient was as low as 0.092. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all PP=0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P=0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P=0.008). Conclusion: NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.

Developments in deep learning have resulted in computer-aided diagnosis for many types of cancer. Previously, pathologists manually performed the labeling work in the analysis of colon tissues, which is both time-consuming and labor-intensive. Results are easily affected by subjective conditions. Therefore, it is beneficial to identify the cancerous regions of colon cancer with the assistance of computer-aided technology. Pathological images are often difficult to process due to their irregularity, similarity between cancerous and non-cancerous tissues and large size. We propose a multi-scale perceptual field fusion structure based on a dilated convolutional network. Using this model, a structure of dilated convolution kernels with different aspect ratios is inserted, which can process cancerous regions of different sizes and generate larger receptive fields. Thus, the model can fuse detailed information at different scales for better semantic segmentation. Two different attention mechanisms are adopted to highlight the cancerous areas. A large, open-source dataset was used to verify improved efficacy when compared to previously disclosed methods.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high incidence of metastasis and dismal prognosis. As a member of Gas-Gap gene, RASAL2 is involved in the hydrolysis of RAS-GTP to RAS-GDP and abnormal expression in human cancers. Here we firstly described the function of RASAL2 on PDAC to enrich the knowledge of RAS family.We interestingly observed that RASAL2 expression was upregulated in PDAC at both mRNA and protein levels, and high expression of RASAL2 predicted a poor prognosis in PDAC patients. Additionally, RASAL2 promoted malignant behaviors of PDAC in vitro and in vivo. To determine the mechanistic roles of RASAL2 signaling and its potential as a therapeutic target in PDAC, we clarified that RASAL2 could accumulate the TIAM1 expression in different level through inhibiting YAP1 phosphorylation, increased TIAM1 mRNA expression and suppressed ubiquitination of TIAM1 protein. In conclusion, RASAL2 enhances YAP1/TIAM1 signaling and promotes PDAC development and progression.

Supplementary Figure 1 from Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

Supplementary Figure 3 from Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

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.

Purpose: The docetaxel-based chemotherapy is the standard of care for castration-resistant prostate cancer (CRPC), inevitably, patients develop resistance and decease. Until now, the mechanism and predictive marker for chemoresistance are poorly understood.Experimental Design: Immortalized normal prostate and cancer cell lines stably manipulated with different DAB2IP expression levels were used and treated with chemotherapeutic drugs commonly used in prostate cancer therapy. Cell proliferation was measured using MTT assay; Western blot, quantitative PCR, and luciferase reporter assays were used to analyze Clusterin gene regulation by DAB2IP. Immunohistochemical analysis was conducted for evaluating DAB2IP, Clusterin and Egr-1 expression in human prostate cancer tissue.Results: DAB2IP Knockdown (KD) cells exhibited resistance to several chemotherapeutic drugs, whereas increased DAB2IP in C4-2 cells restored the drug sensitivity. Parallel, DAB2IP KD cells exhibited higher expression of Clusterin, an antiapoptotic factor, whereas elevated DAB2IP in C4-2 cells decreased Clusterin expression. Functionally, knocking down Clusterin by short-hairpin RNA or antisense oligonucleotide OGX-011 decreased drug resistance, whereas overexpressing Clusterin in C4-2 D2 enhanced drug resistance. Mechanistically, DAB2IP blocked the cross-talk between Wnt/β-catenin and IGF-I signaling, leading to the suppression of Egr-1 that is responsible for Clusterin expression. A similar result was observed in the prostate of DAB2IP knockout animals. In addition, we observed a significantly inverse correlation between DAB2IP and Egr-1 or Clusterin expression from clinical tissue microarray.Conclusions: This study unveils a new regulation of the Egr-1/Clusterin signaling network by DAB2IP. Loss of DAB2IP expression in CRPC cells signifies their chemoresistance. Clusterin is a key target for developing more effective CRPC therapy. Clin Cancer Res; 19(17); 4740–9. ©2013 AACR.

Supplementary Figure Legends from Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

Supplementary Figure 4 from Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

Supplementary Figure 2 from Chemopreventive and Chemotherapeutic Effects of Intravesical Silibinin against Bladder Cancer by Acting on Mitochondria

Intravesical chemotherapy is often used to prevent the recurrence of superficial bladder cancer after transurethral resection. A search for more effective and less toxic intravesical agents is urgently needed. We previously found the in vitro apoptotic effects of silibinin, a natural flavonoid, on high-risk bladder carcinoma cells. Here, we further explored the underlying mechanisms and examined the intravesical efficacy in the prevention and treatment of bladder cancer. Human bladder carcinoma cell line 5637, which has the same molecular features of high-risk superficial bladder cancer, was used as the model system in vitro and in vivo. Autochthonous rat model of bladder cancer induced by intravesical N-methyl-N-nitrosourea (MNU) was used to investigate its intravesical efficacy. Exposure of 5637 cells to silibinin resulted in growth inhibition and induction of caspase-dependent and -independent apoptosis, which was associated with disruption of mitochondrial membrane potential and selective release of cytochrome c, Omi/HtrA2, and apoptosis-inducing factor (AIF) from mitochondria. Silibinin also downregulated survivin and caused nuclear translocation of AIF. Oral silibinin suppressed the growth of 5637 xenografts, which was accompanied with the activation of caspase-3, downregulation of survivin, and increased translocation of AIF. Furthermore, intravesical silibinin effectively inhibited the carcinogenesis and progression of bladder cancer in rats initiated by MNU by reducing the incidence of superficial and invasive bladder lesions without any side effects, which was accompanied with proapoptotic effects. These findings identify the in vitro and in vivo antitumor efficacy of silibinin, and suggest silibinin as an effective and novel intravesical agent for bladder cancer. Mol Cancer Ther; 10(1); 104–16. ©2011 AACR.

Supplementary Methods and Legends - PDF file 114K, All the supplementary legends and methods

Figure S1. DAB2IP expression does not affect key repair factors in NHEJ (Ku70, Ku80) and HR (RAD51, BRCA1) and PARP-1 mRNA expression. Figure S2. RANBP2, TRIP12, and RNF40 interact with both DAB2IP and PARP-1. Figure S3. Radiotherapy of RCC xenograft models.

Supplementary Figures - Supplementary Figures - PDF file 1005K, Fig S1. DAB2IP knockdown enhances Egr1 and sCLU expression. Fig S2. Wnt treatment enhances sCLU expression and Egr1 promoter activity in prostate cells. Fig S3. Wnt/beta-catenin regulates production of the IGF-1-sCLU expression axis. Fig S4. Deletion of NF-{kappa}B binding sites within the Egr1 promoter has no effect on its repression by DAB2IP. Fig S5. Egr1 and sCLU protein expression increased in PCa tissues following androgen-deprived therapy

Supplementary Methods, Figure Legend from PrLZ Protects Prostate Cancer Cells from Apoptosis Induced by Androgen Deprivation via the Activation of Stat3/Bcl-2 Pathway

Supplementary Figure 1 from PrLZ Protects Prostate Cancer Cells from Apoptosis Induced by Androgen Deprivation via the Activation of Stat3/Bcl-2 Pathway

Neuromodulation serves as a cornerstone for brain sciences and clinical applications. Recent reports suggest that mid-infrared stimulation (MIRS) causes non-thermal modulation of brain functions. Current understanding of its mechanism hampers the routine application of MIRS. Here, we examine how MIRS influences the sensorimotor transformation in awaking-behaving pigeons, from neuronal signals to behavior. We applied MIRS and electrical stimulation (ES) to the pretectal nucleus lentiformis mesencephali (nLM), an essential retinorecipient structure in the pretectum, and examined their influences on the optokinetic nystagmus, a visually guided eye movement. We found MIRS altered eye movements by modulating a specific gain depending on the strength of visual inputs, in a manner different than the effect of ES. Simultaneous extracellular recordings and stimulation showed that MIRS could either excite and inhibit the neuronal activity in the same pretectal neuron depending on its ongoing sensory responsiveness levels in awake-behaving animals. Computational simulations suggest that MIRS modulates the resonance of a carbonyl group of the potassium channel, critical to the action potential generation, altering neuronal responses to sensory inputs and as a consequence, guiding behavior. Our findings suggest that MIRS could be a promising approach toward modulating neuronal functions for brain research and treating neurological diseases.

ObjectivesTo be the first to apply a novel 450 nm blue diode laser in transurethral resection of bladder tumor (TURBt) to treat patients with non-muscle invasive bladder cancer (NMIBC) and evaluate its efficacy and safety during the preoperative period compared to the conventional plasmakinetic electrocautery.Materials and MethodsRandomized controlled trial (RCT) in five medical centers was designed as a non-inferiority study and conducted from October 2018 to December 2019. Patients with NMIBC were randomized to the blue laser or plasmakinetic electrocautery group for TURBt. As the first study to evaluate this novel blue laser device, the primary outcome was the effective resection rate of bladder tumors, including effective dissection and hemostasis. The secondary outcomes were the perioperative records, including surgical time, postoperative indwelling catheter time, hospital stay length, blood loss, reoperation rate, wound healing and adverse events.ResultsA total of 174 patients were randomized to either the blue laser group (85 patients) or plasmakinetic electrocautery group (89 patients). There was no statistical significance in the clinical features of bladder tumors, including tumor site, number and maximum lesion size. Both the blue laser and plasmakinetic electrocautery could effectively dissect all visible bladder tumors. The surgical time for patients in the blue laser group was longer (p=0.001), but their blood loss was less than that of patients in the control group (p=0.003). There were no differences in the postoperative indwelling catheter time, hospital stay length, reoperation rate or other adverse events. However, the patients undergoing TURBt with the blue laser showed a faster wound healing at 3 months after operation.ConclusionThe novel blue laser could be effectively and safely used for TURBt in patients with NMIBC, and this method was not inferior to plasmakinetic electrocautery during the perioperative period. However, TURBt with the blue laser may provide the benefit to reduce preoperative blood loss and accelerate postoperative wound healing. Moreover, longer follow-up to confirm recurrence-free survival benefit was required.

Renal cell carcinoma (RCC) is the most lethal of the urologic malignancies. We previously discovered that DAB2IP, a novel Ras-GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. In this study, we determined the biological functions of DAB2IP in RCC and its potential mechanisms of action. Correlations between DAB2IP expression level and RCC tumor size and patient survival were analyzed, and the results showed that RCC patients with high DAB2IP mRNA level exhibited smaller tumor size and better survival than the patients with low DAB2IP. Compared to control cells, DAB2IP knockdown (KD) cells showed enhanced cell proliferation, promoted G1/S phase cell cycle progression and decreased expression of p27. Mechanism studies demonstrated that loss of DAB2IP promoted p27 protein phosphorylation, cytosolic sequestration and subsequently ubiquitination-mediated degradation in RCC cells. Further studies confirmed that the proline-rich domain in C terminal (CPR) of DAB2IP suppressed AKT phosphorylation and induced p27 phosphorylation on S10. Hence, DAB2IP is essential for p27 protein stabilization in RCC, which is at less partly mediated by PI3K/AKT signaling pathway.

Neuromodulation serves as a cornerstone for brain sciences and clinical applications. Mid-infrared stimulation (MIRS) has been recently reported to cause non-thermal modulation of brain functions. However little knowledge of mechanisms hampers its application. Here we bridge across ion channels, neuronal signals, and behavioral performances associated with sensorimotor transformation to provide evidence of how the alternation of neuronal activity by MIRS guides the change of behavioral performance in awake-behaving pigeons. We compared effects on visually-guided eye movements by applying MIRS and electrical stimulation (ES) in the pretectal nucleus lentiformis mesencephali (nLM). Distinct from ES, we found a specific gain modulation of MIRS to alter behavior in a manner of the strength of visual inputs. Our simultaneous extracellular recordings showed that MIRS can excite and inhibit the neuronal activity in the same pretectal neuron based on its ongoing sensory responsiveness levels in awake-behaving animals. We further applied computational simulations and found that MIRS can modulate the carbonyl group (-C=O) enriched on the potassium channel to resonate, and could affect action potential generation, alter neuronal responses to sensory inputs and then guide behavior. Our findings suggest that MIRS could be a promising approach for brain researches and neurological diseases, with gene free manipulation.

Prostate lymphoma (PL) is rarely observed and may be concurrently presented with prostate adenocarcinoma. Moreover, the appearance of PL on conventional imaging is similar with prostate adenocarcinoma. Thus, most of PL is diagnosed through prostate biopsy, or accidentally found in the specimens of surgery. Prostate-specific membrane antigen (PSMA) PET/CT has improved the management of prostate adenocarcinoma. While, the question regarding whether it benefits the discovery of the characteristics of PL is unknown. A 32-year-old man presented with worsening dysuria for 1 month, and the prostate-specific antigen (PSA) concentration was normal. While the pelvic MRI showed a mass in the prostate and multiple enlarged lymph nodes in the bilateral inguinal area. Then, the diagnosis of prostate adenocarcinoma was considered, but the serum PSA was normal and he was younger than most patients. So, 18F-PSMA PET/CT was then performed to further reveal the characteristics of the lesion and guide biopsy. However, there was no abnormal PSMA uptake in the lesion of the prostate and lymph nodes of the pelvic cavity and bilateral inguinal area. These lesions presented with increased glucose metabolism on fluorodeoxyglucose (FDG) PET/CT, and the prostate biopsy was then performed. PL was confirmed based on the results of the histopathologic examination, and the patient subsequently received systemic chemotherapy plus radiotherapy. Fortunately, the symptoms and the lesions completely disappeared after radiotherapy. The clinical symptoms of PL are atypical, and PL and adenocarcinoma may be concurrently presented. Moreover, distinguishing PL from prostate adenocarcinoma based on the appearance of conventional imaging is difficult. As opposed to prostate adenocarcinoma, a high FDG-avidity and low PSMA uptake by lymphoma either in the prostate or metastases are seen. So, PSMA PET/CT combined with FDG PET/CT can non-invasively identify the characteristics and origin of PL.

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.

Prostate cancer (PCa) growth and progression are uniquely dependent on androgens, making the androgen receptor pathway a prime target for therapy; however, cancer progression to androgen independence leads to treatment failure and poor prognosis. In recent years, alternative therapeutic pathways for PCa have been extensively explored, such as the PTEN/PI3K/AKT pathway, cell cycle, and DNA repair. In the present study, we discovered that RASAL2, a RAS-GTPase-activating protein, acted as an oncogene to regulate cancer cell proliferation and the cell cycle and contributed to tumorigenesis via the PI3K/AKT/cyclin D1 pathway. First, RASAL2 expression was higher in PCa tumour and metastatic lymph node tissues than in matched adjacent nontumor tissues and was associated with higher PCa tumour stage, Gleason score and poorer prognosis. Mechanistically, we found that RASAL2 promoted tumour cell proliferation, the transition from G1 to S phase in vitro and tumour growth in vivo. Furthermore, we demonstrated that RASAL2 facilitated phosphorylation of AKT, which in turn increased the expression of cyclin D1 encoded by the CCND1 gene. In addition, there was a positive correlation between the expression of RASAL2 and cyclin D1 in subcutaneous xenografts and clinical specimens. Taken together, these findings indicate that RASAL2 plays an oncogenic role in prostate cancer and may promote PCa tumorigenesis through PI3K/AKT signalling and cyclin D1 expression.

Metastasis and metabolic disorders contribute to most cancer deaths and are potential drug targets in cancer treatment. However, corresponding drugs inevitably induce myeloid suppression and gastrointestinal toxicity. Here, we report a nonpharmaceutical and noninvasive electromagnetic intervention technique that exhibited long-term inhibition of cancer cells. Firstly, we revealed that optical radiation at the specific wavelength of 3.6 μ m (i.e., 83 THz) significantly increased binding affinity between DNA and histone via molecular dynamics simulations, providing a theoretical possibility for THz modulation- (THM-) based cancer cell intervention. Subsequent cell functional assays demonstrated that low-power 3.6 μ m THz wave could successfully inhibit cancer cell migration by 50% and reduce glycolysis by 60%. Then, mRNA sequencing and assays for transposase-accessible chromatin using sequencing (ATAC-seq) indicated that low-power THM at 3.6 μ m suppressed the genes associated with glycolysis and migration by reducing the chromatin accessibility of certain gene loci. Furthermore, THM at 3.6 μ m on HCT-116 cancer cells reduced the liver metastasis by 60% in a metastatic xenograft mouse model by splenic injection, successfully validated the inhibition of cancer cell migration by THM in vivo . Together, this work provides a new paradigm for electromagnetic irradiation-induced epigenetic changes and represents a theoretical basis for possible innovative therapeutic applications of THM as the future of cancer treatments.

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.

Detecting the marking characters of industrial metal parts remains challenging due to low visual contrast, uneven illumination, corroded character structures, and cluttered background of metal part images. Affected by these factors, bounding boxes generated by most existing methods locate low-contrast text areas inaccurately. In this paper, we propose a refined feature-attentive network (RFN) to solve the inaccurate localization problem. Specifically, we design a parallel feature integration mechanism to construct an adaptive feature representation from multi-resolution features, which enhances the perception of multi-scale texts at each scale-specific level to generate a high-quality attention map. Then, an attentive refinement network is developed by the attention map to rectify the location deviation of candidate boxes. In addition, a re-scoring mechanism is designed to select text boxes with the best rectified location. Moreover, we construct two industrial scene text datasets, including a total of 102156 images and 1948809 text instances with various character structures and metal parts. Extensive experiments on our dataset and four public datasets demonstrate that our proposed method achieves the state-of-the-art performance., 11 pages, 9 figures, 7 tables

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.