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The emerging network function virtualization is migrating traditional middleboxes, e.g., firewalls, load balancers, proxies, from dedicated hardware to virtual network functions (VNFs) running on commercial servers defined as network points of presence (N-PoPs). VNFs further chain up for more complex network services called service function chains (SFCs). SFCs introduce new flexibility and scalability which greatly reduce expenses and rolling out time of network services. However, chasing the lowest cost may lead to congestion on popular N-PoPs and links, thus resulting in performance degradation or violation of service-level agreements. To address this problem, we propose a novel scheme that reduces the operating cost and controls network congestion at the same time. It does so by placing VNFs and routing flows among them jointly. Given the problem is NP-hard, we design an approximation algorithm named candidate path selection (CPS) with a theoretical performance guarantee. We then consider cases when SFC demands fluctuate frequently. We propose an online candidate path selection (OCPS) algorithm to handle such cases considering the VNF migration cost. OCPS is designed to preserve good performance under various migration costs and prediction errors. Extensive simulation results highlight that CPS and OCPS algorithms perform better than baselines and comparably to the optimal solution.

Objective: There were many constraints produced by training time and joint injury to analyze the influence of the training intensity on the elbow and knee joints of athletes during the training process. Methods: An improved algorithm-based master component analysis (PCA) modeling method is proposed .1 4 4 athletes were selected in xxx and compared in three groups. Results: The improved PCA models for injury prediction were applied to athletes from group A, the traditional injury models for prediction were adopted for athletes from group B, and athletes from group C received the hospital physical examinations. The results showed that the accuracy of elbow injury in group A due to excessive exercise was 66.86%, the accuracy of hospital physical examination in group C was 67%, and the accuracy of the traditional algorithm in group B was 50%, finding that the accuracy of group A was obviously different from group B (P < 0.05). Compared with other injuries caused by excessive friction, the detection accuracy of knee injuries caused by excessive friction in group A was 62%, that in group B was 44%, and that in group C was 63%. There was a statistically marked difference between groups A and B (P < 0.05). Conclusions: A PCA - based model of athletes’ overtraining injury has high accuracy and adaptability, predicting elbow injury. Level of evidence II; Therapeutic studies - investigation of treatment results. RESUMO Objetivo: Houve uma grande quantidade de restrições produzidas pelo tempo de treinamento e lesão articular a fim de analisar a influência da intensidade do treinamento nas articulações do cotovelo e joelho dos atletas durante o processo de treinamento. Métodos: É proposto um método de modelagem aprimorado de análise de componentes mestre (PCA) baseado em algoritmo .1 4 4 atletas foram selecionados em xxx e comparados em três grupos. Resultados: Os modelos aprimorados de PCA para previsão de lesões foram aplicados a atletas do grupo A, os modelos tradicionais de lesões para previsão foram adotados para atletas do grupo B e os atletas do grupo C receberam os exames físicos hospitalares. Os resultados mostraram que a acurácia da lesão de cotovelo no grupo A devido ao exercício excessivo foi de 66,86%, a acurácia do exame físico hospitalar no grupo C foi de 67% e a acurácia do algoritmo tradicional no grupo B foi de 50%, achando que a acurácia do grupo A era obviamente diferente do grupo B (P

Xudong Zhu,1,2,&ast; Xingming Zhang,1,2,&ast; Guangxi Sun,1,2,&ast; Zhenhua Liu,1,2,&ast; Haoran Zhang,1,2 Yaojing Yang,1,2 Yuchao Ni,1,2 Jindong Dai,1,2 Sha Zhu,1,2 Junru Chen,1,2 Jinge Zhao,1,2 Zhipeng Wang,1,2 Hao Zeng,1,2 Pengfei Shen1,2 1Department of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei ShenDepartment of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaEmail cdhx510@163.comHao ZengDepartment of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaEmail kucaizeng@163.comPurpose: To investigate the survival benefit and safety of individualized schedules for sunitinib in patients with metastatic renal cell carcinoma (mRCC) through plasma concentration monitoring.Methods: A total of 105 patients with mRCC were enrolled. The schedule was adjusted in two ways: therapeutic drug monitoring (TDM) and toxicity-adjusted schedule (TAS). One group of patients were without any schedule adjustment (maintained schedule, MAS). Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared. The relationship between AEs and steady-state concentration or consecutive monitoring curves was explored. Further monitoring of individualized schedules was also conducted.Results: Based on the plasma concentration, the schedules of 18 patients were adjusted in the TDM group. The schedules were adjusted in 37 patients due to severe AEs in the TAS group, while 50 patients were without any schedule adjustment. The median PFS and OS were better in the TDM group than the other two groups (p = 0.001 and p = 0.004, respectively). Univariate and multivariate analyses indicated that TDM could decrease the risk of death independently (p = 0.026). Moreover, the incidence of grades 3/4 AEs decreased from 88.9% to 33.3% in the TDM group (p = 0.001). Sunitinib concentration in 150– 200ng/mL was regarded as a “transitional zone” due to severe AEs mainly happened when concentration elevated over it. After TDM, further plasma concentration monitoring indicated that individualized schedules enabled sunitinib concentration to fluctuate in a much safer range.Conclusion: Treatment-related toxicities could be minimized through plasma concentration monitoring. Patients with adjusted schedules by therapeutic drug monitoring could achieve better survival benefits.Keywords: sunitinib, plasma concentration, metastatic renal cell carcinoma, individualized schedule adjustment, clinical outcomes

Background To use ddPCR to quantify plasma exosomal class III β‐tubulin (βIII‐tubulin, TUBB3, encoded by the TUBB3 gene) mRNA expression in metastatic castration‐resistant prostate cancer (mCRPC) patients, and study the association of this expression with abiraterone efficacy. Methods Blood samples were prospectively collected from 52 mCRPC patients using abiraterone as first‐line therapy to measure plasma exosomal TUBB3 mRNA expression value before the initiation of abiraterone. Study endpoints were PSA response rate, PSA‐progression‐free survival (PSA‐PFS), and overall survival (OS, from CRPC to death). Results Patients with positive exosomal TUBB3 expression showed shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3: 11.0 vs. 7.9 months; p = 0.014). Further analysis demonstrated that patients with strongly positive exosomal TUBB3 (>20 copies/20 µl) was associated with even shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3 [20 copies/20 µl]: 11.0 vs. 8.3 vs. 3.6 months, p = 0.005). In multivariate analyzes, TUBB3 (+) (HR: 2.114, p = 0.033) and ECOG score >2 (HR: 3.039, p = 0.006) were independent prognosticators of poor PSA‐PFS. PSA response and OS did not present significant differences. Conclusion The exosomal TUBB3 mRNA expression level is associated with poor PSA‐PFS of abiraterone in mCRPC patients. The detection of exosomal TUBB3 can be valuable in their management., In this study, we presented this novel, non‐invasive biomarker for abiraterone resistance in mCRPC patients using a ddPCR approach to quantificationally measure the exosomal TUBB3 mRNA expression. We found that a higher TUBB3 level is correlated with shorter progression time after first‐line abiraterone treatment in mCRPC patients.

Background: Inferior vena cava (IVC) filters are commonly used in China to prevent pulmonary embolisms in patients with deep vein thrombosis. However, IVC filter removal is complicated when the filter has penetrated the IVC wall and endovascular techniques usually fail. The purpose of this study was to evaluate the effectiveness and safety of retroperitoneal laparoscopic-assisted retrieval of wall-penetrating IVC filters after endovascular techniques have failed. Patients and Methods: We retrospectively evaluated a series of 8 patients who underwent retroperitoneal laparoscopic-assisted retrieval of a wall-penetrating IVC filter between December 2017 and November 2019. All patients had experienced at least 1 failure with endovascular retrieval before the study. The filters were slanted and the proximal retrieval hooks penetrated the posterior lateral IVC wall in all patients on computed tomography. Demographic information, operation parameters, and complications were recorded and analyzed. All patients were followed up for at least 12 months. Results: The procedure was successful in all patients. The median surgery time was 53.6 ± 12.7 min and the average blood loss was 45.0 ± 13.5 ml. No serious complication occurred during the patients’ hospitalization, which was an average of 6.4 days. The median follow-up time was 15.1 months, and no patient had deep vein thrombosis recurrence. Conclusions: Retroperitoneal laparoscopic-assisted retrieval is a feasible and effective technique, particularly when proximal retrieval hooks penetrate the posterior lateral wall of the IVC after endovascular techniques have failed. To some extent, the development of this technique at our institution has increased the success rate of filter removal and improved patient satisfaction.

OBJECTIVE The aim of this study was to compare a traditional cervical cage with a zero-profile (ZP) fixation device in patients who underwent three-level anterior cervical decompression and fusion (ACDF) in terms of patient-reported outcomes (visual analog scale [VAS], Japanese Orthopaedic Association [JOA], and Neck Disability Index [NDI] scores), radiographic findings (sagittal alignment 2 years after surgery and likelihood of fusion), and complications. METHODS This study was a retrospective case series. Between January 2012 and December 2016, 58 patients with cervical spondylotic myelopathy (CSM) who required three-level ACDF procedures, as identified by spinal surgeons, were treated with three-level ACDF and an anterior cage-plate construct (ACPC) (n = 38) or a three-level stand-alone ZP device (n = 20). On the basis of patient choice, patients were divided into two groups (ACPC group and ZP group). All patients completed a minimum of 2 years of follow-up. Patient-reported outcome scores included VAS, JOA, and NDI scores. The radiographic findings included sagittal alignment and likelihood of fusion 2 years after surgery. Data related to patient-reported outcomes and sagittal alignment were collected preoperatively, postoperatively, and at the final follow-up. Intraoperative and postoperative complications were also documented and analyzed. RESULTS The clinical outcomes, including VAS, JOA, and NDI scores, showed improvement in both groups, and no significant difference was observed between the two groups. Sagittal alignment and height of the fused segments were restored in all patients. However, the authors found no differences between the ZP and ACPC groups, and the groups exhibited similar fusion rates. The authors found no differences in complications, including dysphagia, adjacent-segment degeneration, and postoperative hematoma, between the groups. CONCLUSIONS Use of ZP implants yielded satisfactory long-term clinical and radiological outcomes that were similar to those of the standard ACPC. Additionally, the rates of complications between the groups were not significantly different. Although the best surgical option for multilevel CSM remains controversial, the results of this work suggest that ACDF with the ZP device is feasible, safe, and effective, even for multilevel CSM.

Background Multidisciplinary team (MDT) management is a popular treatment paradigm in managing cancer patients, which provides fully-discussed, interdisciplinary treatment recommendations for patients. However, there has been a lack of data on its actual impact on the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients. mCRPC is the end stage of prostate cancer, facing a treatment dilemma of overwhelming options; therefore, we hypothesize dynamic MDT discussions can be helpful in comprehensively managing these patients. Methods We retrospectively collected 422 mCRPC patients' clinical information from 2013 to 2020 from our institute. Patients can voluntarily choose whether to enroll in the dynamic MDT group, which includes discussions at CRPC diagnosis and subsequent disease progression. All patients were followed up regularly, and OS from CRPC diagnosis to death was set as the endpoint of this study. Results Participating in MDT discussions is a favorable independent indicator of longer overall survival (median OS: MDT (+): 39.7 months; MDT (-): 27.0 months, hazard ratio: 0.549, p = .001). Moreover, this survival benefit of MDT remained in subgroups with first-line therapy [median OS: MDT (+): not reached; MDT (-): 27.0 months, p = .001) and with multi-line therapy until the end of follow-up (median OS: MDT (+): 36.7 months; MDT (-): 25.6 months, p = .044). Conclusion Therefore, regular MDT discussions are valuable in the management of mCRPC patients. Clinicians are encouraged to tailor MDT discussions dynamically to provide mCRPC patients with a better and more individualized treatment plan and more prolonged survival. Take-home messages ● The MDT model is defined as dynamic MDT discussions at the time of mCRPC diagnosis and each time they progressed later on throughout the disease management. ● Prostate cancer MDT usually includes specialists in urologic oncology, pathology, chemotherapy, radiotherapy, ultrasound, imaging and nuclear medicine. ● MDT model can benefit mCRPC patients in terms of overall survival.

Up to 40% of papillary thyroid cancer (PTC) patients have lymph node metastasis, a condition that implies persistent, recurrent, or progressive disease. However, the American Joint Committee on Cancer Manual states that there is no reliable examination for adequate lymph node staging. Therefore, our aim is to develop a lymphatic imaging technique using ultrasonography to address this challenge. We consecutively enrolled PTC patients who underwent ultrasound (US) lymphatic imaging via the peritumoral injection of contrast media. Identification of the sentinel lymph nodes and the targeted sentinel lymph nodes was separately based on the lymphatic drainage pathway and the enhancement patterns. Every identified targeted node was assigned a score, according to the features on conventional US and enhancement patterns, and was referred for ultrasound-guided fine-needle aspiration. Cytological and histopathologic results represented the statuses of the targeted lymph nodes and overall central lymph nodes, respectively, which were applied to evaluate the diagnostic performance of US lymphatic imaging. In total, 100 PTC patients were included. On the basis of the cytological results, the sensitivity (97.1%, 95% confidence interval [CI]: 84.7–99.9%) of detecting positive targeted nodes by US lymphatic imaging significantly increased by 45.5% at a threshold of 4 or higher (p = 0.0001), without loss of specificity (p = 1.0000). The surgical results showed that the metastatic degree was positively correlated with an increase in the score (τ: 0.671, p < 0.001). Ultrasound lymphatic imaging has a high diagnostic performance, and its corresponding scoring system facilitates grading of the nodal burden in the central compartment. • Ultrasound neck lymphatic imaging is an effective contrast-enhanced ultrasound (CEUS) technique (applied after the peritumoral injection of contrast media) for identifying sentinel lymph nodes in the central compartment by tracing the imaged afferent lymphatic vessel. • Lack of enhancement or perfusion defects is the typical enhancement pattern for recognizing the involved central lymph nodes. • Ultrasound lymphatic imaging for identification of positive central lymph nodes before surgery may effectively avoid complications associated with the surgical sentinel node procedure.

Purpose Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Atrial fibrillation (AF) can cause a variety of heart diseases and its detection is insufficient in outside hospital. We proposed three methods for AF diagnosis in ambulatory settings. The first method is a convolutional neural network (CNN) trained on modified frequency slice wavelet transform (MFSWT) data. The second is a support vector machine (SVM) classifier trained on multiple AF features data. The third method is an SVM trained on the same feature set but extended by the predictive probability of the CNN. The proposed method (the third one) achieved the highest detection accuracy. MIT-BIH AF database was used as a training set with an accuracy of 97.87% for 30-s ECG episodes and 96.09% for 10-s ECG episodes from fivefold cross-validation. The trained model was tested on the PhysioNet/Computing in Cardiology (CinC) Challenge 2017 database, achieving an accuracy of 93.21% for 30-s episodes and 93.03% for 10-s ECG episodes. When tested on the China Physiological Signal Challenge (CPSC) 2018 database, the corresponding accuracies were 98.48% and 98.61%. The results on the wearable ECGs from a clinical AF patient were 99.21% and 97.04%. We retrained the model on the PhysioNet/CinC Challenge 2017 data set and tested on the other database to explore the generalization ability of the proposed method. Corresponding test results on the MIT-BIH AF database showed accuracies of 96.84% and 95.13%, on the CPSC 2018 database were 96.21% and 98.45%, on the wearable ECGs were 99.08% and 96.43%. The results proved that the proposed method could provide high accuracy and reliable recognition for AF events.

Background: The COVID-19 is a challenge for both patients and physicians in emergency department (ED). This study was aimed to report the impacts of the COVID-19 outbreak on visits and treatments for patients with ureteral stones in a general hospital ED. Methods: The patients with ureteral stones were collected from 24 January to 24 March 2020 during the COVID-19 outbreak in Beijing. Two periods were divided for study: 24 January to 24 February (Period 1) and 25 February to 24 March (Period 2). Data on patients’ characteristics, attendance, visual analog scale (VAS) scores, stone features, and final treatment choices were retrieved from the computer and compared with the data in the same periods in 2019. Results: The study included 376 patients with ureteral stones during the COVID-19 outbreak periods in 2020 and 343 patients during the same periods in 2019. Compared with the same periods in 2019, the number of patients with ureteral stones was less in Period 1 (137 vs 163) but had a rebound phenomenon in Period 2 (239 vs 180). The visit frequency was significantly reduced (2.6 ± 0.4 vs 3.6 ± 0.8, p Conclusion: These results showed that the COVID-19 outbreak can directly affect the visits and final treatment choices for patients with ureteral stones.

Introduction: Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare disease that may coexist with prostate stromal sarcoma (PSS). We aimed to analyze the histological and clinical features of STUMP. Methods: Twenty-three patients diagnosed with STUMP from 2008 to 2019 were included. Clinicopathological and follow-up information was collected. In the subgroup analysis, we divided the patients into a pure STUMP group (N = 18) and a mixed STUMP (STUMP coexisting with PSS) group (N = 5). Student’s t test was used to compare the 2 groups. Results: Patients had a mean age of 55.5 ± 19.4 years and an average follow-up time of 42.3 months. The mean prostate volume was 109.2 ± 73.5 cm3, and the mean prostate-specific antigen was 8.03 ± 10.5 ng/mL. In the subgroup analysis, 16.7% (2/12) of pure STUMP patients had disease progression, while 100% (3/3) of mixed STUMP patients suffered from recurrence. Compared with the pure STUMP group, the mixed STUMP group was younger (37.2 vs. 60.6 years, p = 0.013) and had lower expression of estrogen receptor and progesterone receptor (p = 0.004 and p < 0.001, respectively). Conclusion: STUMP is a rare disease with a relatively good prognosis. However, there is still a possibility of disease progression or coexistence with stromal sarcoma. Timely diagnosis and regular monitoring may be helpful in improving treatment outcomes.

Background A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis. Methods Literatures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients’ survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity. Results Seven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients’ overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) (P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18–0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than ‘immunoreactive score (IRS)>5’ and ‘IRS > 25′, high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30–0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country (P = 0.657), pathological type (P = 0.614), molecular type (P = 0.423), staining location (P = 0.481), or cut-off value (P = 0.509). Conclusions The protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.

Background The role of lipid metabolic status in tyrosine kinase inhibitors-treated patients with metastatic renal cell carcinoma is insufficient. Objective To analyse the influence of dynamic changes of lipid metabolism on survival outcomes in tyrosine kinase inhibitors-treated metastatic renal cell carcinoma. Patients and methods Serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol were collected, both before tyrosine kinase inhibitors therapy and at different time points of tyrosine kinase inhibitors treatment duration. Other clinicopathological and survival data were retrospectively reviewed. The clinical outcomes, including tumour response, progression-free survival and overall survival, were analysed. Kaplan–Meier survival curves were plotted and the log-rank test was used to analyse statistical significance. Results A total of 127 patients with metastatic renal cell carcinoma, initially treated with tyrosine kinase inhibitors as first-line systemic therapy, were included. In the whole cohort, the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol fluctuated but gradually increased during tyrosine kinase inhibitors treatment. In survival analysis, the higher serum level of lipid metabolism, the longer progression-free survival was observed. In terms of overall survival, all post-treatment lipid metabolism, including the percentages of increasing change, were correlated with better survival. Further multivariate analysis showed that patients with five components of treatment-related dysfunction of lipid metabolism had superior survival to those with less than five components. However, lipid metabolism was not correlated with tumour response. Conclusion Increasing parameters of lipid metabolism indicated improvement of survival in tyrosine kinase inhibitors-treated metastatic renal cell carcinoma, especially the increasing percentages.

Background Non-schistosoma-associated urinary bladder squamous cell carcinoma (SqCC) has low incidence and is associated with chronic inflammation. Due to its unique etiology and pathology, expression of programmed cell death ligand 1 (PD-L1) in SqCC could be different from that of urothelial carcinoma, which may contribute to different responses to immunotherapy. In this study, we intended to explore the expression profile and prognostic value of PD-L1 in non-schistosoma-associated urinary bladder SqCC under the consideration of tumor-infiltrating lymphocytes' (TILs) density. Methods We conducted a retrospective study to review 604 bladder cancer patients who received radical cystectomy (RC) from 2009 to 2013 in Peking University First Hospital. We enrolled 67 bladder SqCC patients in total, including pure SqCC (n=19) and mixed SqCC (n=48, with urothelial carcinoma). PD-L1 protein expression and TILs density were evaluated by immunohistochemistry. Results Nine female and 58 male patients (median age 67.4 years) were enrolled in the present study. There were 15 stage T1-2 patients and 52 stage T3-4 patients. 27 patients had N1-2 lymph node metastasis. Overall, 61.2% cases were PD-L1-positive. Dense TILs coincided with higher PD-L1 expression rate. Median survival time of PD-L1 positive cases was significantly higher than negative cases (P=0.026). During multivariate analysis, positive PD-L1 expression and dense TILs were independent protective factors affecting overall survival (OS, PD-L1: P=0.022; TILs: P=0.010) and progression free survival (PFS, PD-L1: P=0.018; TILs: P=0.009). Conclusions PD-L1 expression and dense TILs were frequently detected in urinary bladder SqCC tumors. Positive PD-L1 expression and dense TILs were correlated with better survival outcomes in non-schistosoma-associated urinary bladder SqCC. The immunotherapy targeting PD-L1 might be helpful to bladder SqCC patients.

Purpose To assess the association between body fat components and survival status and tumor response for metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). Patients and Methods Patients with pathologically diagnosed and radiologically indicated mRCC were enrolled into the retrospective study. Three body fat components: total fat accumulation (TFA), visceral fat accumulation (VFA) and subcutaneous fat accumulation (SFA) were measured using standard CT scans. The clinical outcomes included progression-free survival (PFS), overall survival (OS), and tumor response rates. Univariate analysis and multivariate Cox proportion hazard regression models were used to find associated parameters and to calculate the adjusted hazard ratio (HR). Results A total of 146 patients were enrolled and the average age of patients was 56.5 years old. According to the univariate analysis, patients with an increased SFA and TFA had a longer PFS and OS. A similar phenomenon was observed among patients with ≥2 increasing body fat components about PFS and OS. As for multivariate analysis, SFA change (p=0.014) or the number of increasing body fat components (p=0.040) were independent indicators to predict PFS. In addition, SFA change (p=0.022) or the number of increasing body fat components (p=0.008) could independently predict OS. Moreover, a better disease control rate (p=0.028) was founded in patients with ≥2 increasing components. In the subgroup of patients with ≥2 metastasis sites, improved OS (p=0.017) and PFS (p=0.027) were found compared to those with

A novel dual-targeted CeO2-DNA nanosensor by modifying with folic acid (FA) and CD36 antibody was designed. This fluorescent nanosensor enables noninvasive imaging of alterations in H2O2in vitro and in vivo with good sensitivity and selectivity, accurately evaluating the inflammation level and providing early warning of plaque vulnerability.

Context: Radical cystectomy (RC) has complicated surgical procedures and various ways of urinary reconstruction. Aims: The aim of this study is to investigate whether the advantages of laparoscopy over open surgery were consistent in the perioperative recovery of different methods of urinary diversion after RC in the general and the elderly (>65 years) population. Settings and Design: A retrospective study reviewed 452 (elderly 261) patients who received RC from the year 2005–2012. Subjects and Methods: Of all, 88 patients underwent laparoscopic RC (LRC) and 364 patients underwent open RC (ORC). There were 325 patients received ileal conduit (IC), whereas 127 patients received cutaneous ureterostomy (CU). Statistical Analysis Used: We used different statistical methods (t-test, Chi-square, etc.) to compare variables outcomes. Results: For IC urinary diversion, the general patients undergoing LRC had less intra-operative blood loss (566.5 vs. 1320.3 ml, P < 0.001), lower blood transfusion rate (11.4 vs. 34.1%, P < 0.001), shorter gastrointestinal recovery time (5.7 vs. 6.7 days, P = 0.002) and shorter length of hospital stay (LOS) (21.7 vs. 26.0 days, P = 0.003) than patients receiving ORC. Similar trends were observed in older patients. For CU urinary diversion, the general and the elderly patients receiving LRC had a shorter mean time to gastrointestinal recovery (P = 0.017, P < 0.001, respectively) than patients receiving ORC. No differences were found between LRC and ORC in intra-operative blood loss, allogeneic blood transfusion rate and LOS. Conclusions: In the general and the elderly population, laparoscopic approach could result in more rapid rehabilitation for RC patients, especially in the IC patients.

We propose a novel absolute calibrate method for digital holographic microscopy with the sequential shift method using Chebyshev polynomials. We separate the object phase and the aberrations by sequential shifting the sample twice in vertical plane of the optical axis. The aberrations phase is then calculated using the high order Chebyshev polynomials. The correct phase is obtained by subtracting the aberrations from the original phase containing the aberration. This method can compensate for the complex aberrations including high-order aberrations without changing the traditional optical system. Meanwhile, it can effectively protect the medium and high frequency information of the specimen in the phase image. Numerical simulation and experimental results demonstrate the availability and advantages of the absolute calibrate method.

Internet of Things has remarkable effects in human’s daily life. It is important for users and sensors to securely access data collected by low-cost sensors via Internet in real-time IoT applications. There exist many authentication protocols for guaranteeing secure communication between users and sensors. However, in some protocols, the privacy of unattended sensors subjected to capture node attacks cannot be guaranteed. Moreover, the sensors subjected to physical tampering attacks can still execute normally the authentication process. Besides, an authentication protocol should be lightweight due to the restricted computing power and storage of the sensors. The idea of designing a more secure and lightweight authentication protocol engender this article. The proposed protocol can provide the physical security through physically unclonable function (PUF), require no additional phase to update challenge-response pairs (CRPs), and store a single CRP for each sensor. At the same time, the proposed protocol utilizes three factors, such as personal biometrics, smartcard and password, to strengthen the security contrasting with two factors, and manipulates some basic cryptographic operations, including bitwise-exclusive-OR (XOR) and hash function, to achieve the lightweight performance. Moreover, both formal security analysis based on Real-Or-Random (ROR) and informal security analysis demonstrate the security of the proposed protocol. Compared with the existing related protocols, the proposed protocol has the advantage in terms of security, functionality and computation costs. Finally, a NS3 simulation on measuring various network performance parameters indicates that the proposed protocol is practical in IoT environment.

Objective: To investigate the diagnostic role of magnetic resonance imaging (MRI)-targeted biopsy (TB) for prostate cancer (PCa) in biopsy-naïve men. Materials and Methods: Own control studies and randomized controlled trials (RCTs) up to December 2018 were identified via a systematic search of PubMed, Embase, Ovid, and the Cochrane Library. We pooled relative sensitivity (or risk ratio [RR]) to compare diagnostic efficiency for PCa and clinically significant PCa (csPCa) between TB and systematic biopsy (SB). The independent role of either biopsy pathway was evaluated for participants with positive/negative MRI. Results: Thirty-one studies consisting of 25 own control studies and 6 RCTs were included. We identified 4,020 biopsy-naïve men with positive MRI who underwent two biopsies concurrently, with PCa/csPCa detection rates of 65.90 and 45.13%, respectively. TB and SB did not differ in the detection of any PCa (RR 0.98, 95% confidence interval [CI] 0.92–1.05). However, TB detected more csPCa (RR 1.19, 95% CI 1.10–1.30) and more PCa with a Gleason score ≥3+4 (RR 1.20, 95% CI 1.07–1.34). Using a combined test as a reference, omitting SB resulted in detecting 12.81% less csPCa and 20.76% less clinically insignificant PCa (cinsPCa), and omitting TB resulted in detecting 25.69% less csPCa and 10.8% more cinsPCa. For patients with negative MRI, omitting SB led to underdetection of 30.29% of any PCa (10.9% of csPCa). Conclusions: Combining TB and SB increased the diagnostic accuracy of csPCa for biopsy-naïve men with positive MRI, and omitting SB for patients with a negative MRI would lead to the underdetection of nearly 10% of csPCa.

Purpose Breast cancer is the most common female tumor in the world. MicroRNA has been reported to play an important role in the progression of breast cancer. The purpose of this study was to explore the role of miR-937-3p in breast cancer. Patients and methods Expression of miR-937-3p in breast cancer tissues and serums was detected from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and patients' samples. Kaplan-Meier plotter identified the association between miR-937-3p and prognosis. Results The analysis of TCGA, GEO and qRT-PCR suggested that the level of miR-937-3p was increased in breast cancer tissues and serum compared with adjacent normal breast tissues and healthy persons, respectively. The decreased expression of miR-937-3p inhibited breast cancer proliferation, migration and invasion. CCRL2 was the target of miR-937-3p. In contrast to miR-937-3p, the level of CCRL2 was decreased in breast cancer tissues. Luciferase reporter assay revealed that miR-937-3p directly bound to the 3'-UTR of CCRL2. Double knockdown of CCRL2 and miR-937-3p promoted breast cancer cell proliferation, migration and invasion, suggesting that miR-937-3p promoted breast cancer cell proliferation, migration and invasion by targeting CCRL2. The Kaplan-Meier survival analysis suggested that breast cancer patients with high level of miR-937-3p or low level of CCRL2 had a reduced overall survival (OS). Conclusion miR-937-3p plays an important role in the diagnosis and prognosis of breast cancer. Inhibition of miR-937-3p expression may be a novel targeted therapy for breast cancer.

Glycoprotein non-metastatic protein B (GPNMB) promotes bone metastasis (BM) in various types of cancer. However, GPNMB expression and its function in patients with renal cell carcinoma (RCC) and BM is still unknown. Therefore, the clinical significance of GPNMB and its biological function in RCC with BM was investigated in the present study. A total of 31 patients with RCC and BM were retrospectively collected. The association between GPNMB protein expression level on the primary tumor and the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier analysis was used to investigate the association between GPNMB expression and the prognosis of the patients. The effects of GPNMB inhibition on cell proliferation, migration and invasion in RCC cells were investigated using short hairpin (sh)RNA. High GPNMB expression level was significantly associated with the number (P=0.001) and the extent of BM (P=0.001), Fuhrman grade (P=0.037), and ERK expression level (P=0.003) of the primary tumor. In addition, GPNMB overexpression was significantly associated with poor prognosis with respect to overall survival time (P=0.001). Furthermore, a specific shRNA sequence targeting the GPNMB gene was constructed and transduced into the ACHN cell line, using a lentivirus vector to obtain a stable cell line with low mRNA expression level of GPNMB. Low GPNMB expression level inhibited RCC cell proliferation, which was measured using a Cell Counting Kit-8 assay. Cell migration and invasion ability was significantly decreased in GPNMB knockdown RCC cells compared with that in cells transduced with the negative control shRNA. In addition, the protein expression levels of phosphorylated ERK were lower in the GPNMB shRNA-transduced ACHN cells compared with those in the control cells. Therefore, these results suggested that GPNMB plays an important role in tumor progression in RCC with BM. Furthermore, it might serve as a predictive marker for BM and as a poor prognostic factor in RCC with BM. GPNMB downregulation suppressed the proliferation, migration and invasion of the RCC cells, which may be mediated through the inhibition of the ERK signaling pathway.

Autonomic dysfunction (AutD) is one of the non-motor symptoms (NMSs) in Parkinson’s disease (PD). To investigate the prevalence and clinical features of AutD in Chinese patients with PD, a large multicenter cohort of 2,556 individuals with PD were consecutively involved in the Parkinson’s Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 1, 2017, and December 31, 2019. The assessment of AutD was performed using the Scale for Outcomes in Parkinson’s Disease for Autonomic Symptoms (SCOPA-AUT). The evaluation of motor symptoms and other NMSs were performed using well-established scales recommended by the Movement Disorder Society. We found that out of 2,556 patients with PD, 2,333 patients with PD (91.28%) had AutD. Compared with the group of patients with PD without AutD, the group of patients with PD with AutD had older age, older age of onset, longer disease duration, more severe motor symptoms, motor complications, and more frequent NMSs. As for partial correlation analysis, the total SCOPA-AUT score was significantly and positively associated with motor severity scales [Unified Parkinson’s Disease Rating Scale (UPDRS) total score] and some of the NMSs [Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBD), Epworth Sleepiness Scale, Hamilton Depression Scale], Fatigue Severity Scale, and Parkinson’s disease questionnaire. PD Sleep Scale was significantly and negatively correlated with AutD. With logistic regression analysis for potentially related factors, age, UPDRS total score, RBD, hyposmia, depression, and fatigue may be associated with PD with AutD. In conclusion, our multicenter cohort study reported the high prevalence of AutD in Chinese PD and revealed the associated factors of PD with AutD.

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.

Background: Skin flap transplantation is a common wound repair method in orthopedic surgery, but skin flap necrosis remains problematic. Memantine, an excitatory amino acid receptor antagonist, is currently used in the treatment of moderate to severe Alzheimer's disease, due to its ability to promote angiogenesis and reduce oxidative stress. This study investigated the effect of memantine on the survival of random skin flaps in Sprague-Dawley (SD) rats. Materials and methods: Thirty six male SD rats were divided into control, high-dose (20 mg/kg per day), and low-dose (10 mg/kg per day) groups and underwent a McFarland flap procedure. Seven days later, the survival of the flap was evaluated, The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, nuclear factor kappa B(NF-κB) and Mitogen-activated protein kinase（MAPK）were detected by immunohistochemistry. Oxidative stress was evaluated by measuring the levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Results: Compared with the control group, the flap survival area of memantine group, especially the high-dose group, was larger, VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the Memantine-H group than in the Memantine-L and control groups (P

Video captioning is a challenging task since it requires generating sentences describing various diverse and complex videos. Existing video captioning models lack adequate visual representation due to the neglect of the existence of gaps between videos and texts. To bridge this gap, in this paper, we propose a CLIP4Caption framework that improves video captioning based on a CLIP-enhanced video-text matching network (VTM). This framework is taking full advantage of the information from both vision and language and enforcing the model to learn strongly text-correlated video features for text generation. Besides, unlike most existing models using LSTM or GRU as the sentence decoder, we adopt a Transformer structured decoder network to effectively learn the long-range visual and language dependency. Additionally, we introduce a novel ensemble strategy for captioning tasks. Experimental results demonstrate the effectiveness of our method on two datasets: 1) on MSR-VTT dataset, our method achieved a new state-of-the-art result with a significant gain of up to 10% in CIDEr; 2) on the private test data, our method ranking 2nd place in the ACM MM multimedia grand challenge 2021: Pre-training for Video Understanding Challenge. It is noted that our model is only trained on the MSR-VTT dataset.

How to serve mobile users in rural areas by 5G networks is challenging due to the sparse distribution of base stations and poor connection to the cloud. Existing solutions focus on transmission frequency implementation such as frequency multiplexing, In this paper, we consider a decentralized caching scheme for two reasons. First, caching contents in the edge is an effective approach to reduce the transmission latency and improve the quality of service for mobile users. Second, the decentralized caching allows base stations to serve mobile users without any coordination of the cloud. Meanwhile, data privacy in the edge is critical for individual users. This paper aims to jointly determine the caching and routing policy in rural areas of 5G networks in a decentralized manner and simultaneously design a proper privacy-preserving mechanism. We tackle the challenges in two progressive steps. First, we design a decentralized algorithm with the convergence guarantee. Furthermore, we enhance the developed decentralized algorithm with a privacy-preserving mechanism based on (local) differential privacy and prove its privacy guarantee. We conduct extensive numerical simulations based on real-world traces to evaluate the proposed algorithms. Results highlight significant performance improvements compared to existing baselines.

The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network–International Prognostic Index. According to the molecular features, increased MPEG1 mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-β signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase >3 upper limit of normal was an independent adverse prognostic factor for OS, and ATM mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.

Terahertz video SAR can perform high-resolution imaging of targets in a short period of time, which is conducive to detection and tracking of ground moving targets. A new method is proposed in this paper for moving target shadow detection and tracking, which is verified on terahertz band data for the first time. According to the specific characteristics of terahertz video SAR images, this method is realized by change detection through background modeling and image difference. In the experiment, the effectiveness of proposed method is verified by the terahertz video-SAR images.

BACKGROUND: Adaptive thermogenesis is an iron-demanding pathway, significantly contributing to whole-body energy expenditure. However, the effects of iron-deficient diets on adaptive thermogenesis and obesity remain unknown. OBJECTIVES: We aimed to determine the impact of dietary iron deficiency on iron homeostasis in adipocytes, adaptive thermogenic capacity, and metabolic consequences in obesity. METHODS: C57BL/6 male mice were assigned to either the iron-adequate (IA, 35 ppm) or the iron-deficient group (ID, 3 ppm) at weaning. Upon 8 wk of age, both IA and ID groups received an isocaloric high-fat diet (45% kcal from fat) for 10 wk, maintaining the same iron content. Mice (n = 8) were used to determine the iron status at the systemic and tissue levels and lipid metabolism and inflammatory signaling in adipose tissue. The same mice were used to evaluate cold tolerance (4°C) for 3 h. For assessing adaptive thermogenesis, mice (n = 5) received an intraperitoneal injection of β3-adrenoceptor agonist CL316243 (CL) for 5 d. RESULTS: Compared with the IA group, the ID group had nonanemic iron deficiency, lower serum ferritin (42.8%, P

Intervention is the most direct link to improve and enhance the learning effect of learning analysis technology, and it is crucial to maintain the learning state. In order to clarify the development prospect of learning intervention research in China, this paper first takes six Chinese core journals in the field of educational technology from 2016 to 2020 as literature sources, and selects 24 papers as research samples to compile a coding table of learning intervention research. The paper samples were quantitatively analyzed from the intervention object, learning situation, learners and intervention model. Then, it explains that learning intervention can support adaptive and personalized learning, facilitate collaborative learning, provide precise teaching services, and improve learning quality. Finally, the future development direction of learning intervention is proposed to further promote the development and application of learning intervention in the field of learning analysis.

Cloud computing is becoming one of the ubiquitous computing paradigms for enterprises and organizations in recent years. Due to the volatility of system states such as cloud resource price and workload demand, it is challenging to provision cloud resources efficiently. This paper studies online cloud resource provisioning problems under cost budget where no accurate or distributional future information is available. We develop an algorithmic framework and design online algorithms based on the framework. We prove the competitive ratio of the proposed algorithms. We further show the proposed algorithms have better performance than a prominent existing algorithm named CR-Pursuit. While prior works on the problem require the objective functions to be concave, the proposed algorithms work for non-convex and non-concave objective functions. We conduct real-world trace-driven simulations. Results highlight the proposed algorithms outperform baselines significantly over a wide range of settings.

BackgroundTo explore whether patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to standard first-line therapy among patients with metastatic castration resistant prostate cancer (mCRPC).MethodsWe retrospectively analyzed data of 170 mCRPC patients receiving abiraterone (ABI) or docetaxel (DOC) as first-line therapy between 2014 and 2019. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed and compared based on the presence of IDC-P and its sub-patterns.ResultsTotally, IDC-P was confirmed in 91/170 (53.5%) patients. Among them, 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P pattern 1 and pattern 2, respectively. The presence of IDC-P was confirmed to be associated with poor prognosis in the whole cohort. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both ABI and DOC treatment. However, compared to patients with IDC-P pattern 1 and without IDC-P, IDC-P pattern 2 had markedly poorer prognosis in either ABI (PSA-PFS: PPPPP=0.021; rPFS: P=0.027) or pattern 2 (PSA-PFS: P=0.003; rPFS: P=0.007) was significantly inferior to ABI.ConclusionCompared to DOC, ABI exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 still responded unsatisfactorily to either ABI or DOC therapy. Novel therapeutic strategies appropriate for IDC-P pattern 2 need to be further investigated in the future.

OBJECTIVES: Colorectal cancer (CRC) is one of the most prevalent cancer worldwide. Evidence from epidemiological studies shows that the incidence rate of CRC among elders with age ≥ 50 years is gradually decreased, whereas the rate continuously rise in adults with age

OBJECTIVES To investigate the genetic alterations of patients with prostate cancer (PCa) with and without intraductal carcinoma of the prostate (IDC-P). PATIENTS AND METHODS We performed targeted sequencing of plasma cell-free DNA on 161 patients with prostate adenocarcinoma (PAC) with IDC-P and 84 without IDC-P. Genomic alterations were compared between these two groups. The association between genetic alterations and patients' survival outcomes was also explored. RESULTS We identified that 29.8% (48/161) and 21.4% (18/84) of patients with and without IDC-P harboured genomic alterations in DNA repair pathways, respectively (P = 0.210). Pathogenic germline DNA repair alterations were frequently detected in IDC-P carriers compared to IDC-P non-carriers (11.8% [19/161] vs 2.4% [two of 84], P = 0.024). Germline BReast CAncer type 2 susceptibility protein (BRCA2) and somatic cyclin-dependent kinase 12 (CDK12) defects were specifically identified in IDC-P carriers relative to PAC (BRCA2: 8.7% [14/161] vs 0% and CDK12: 6.8% [11/161] vs 1.2% [one of 84]). Patients with IDC-P had a distinct androgen receptor (AR) pathway alteration, characterised by an enrichment of nuclear receptor corepressor 2 (NCOR2) mutations compared with patients with pure PAC (21.1% [34/161] vs 6.0% [five of 84], P = 0.004). Increased AR alterations were detected in patients harbouring tumours with an IDC-P proportion of ≥10% vs those with an IDC-P proportion of

As the computing power of modern hardware is increasing strongly, pre-trained deep learning models (e.g., BERT, GPT-3) learned on large-scale datasets have shown their effectiveness over conventional methods. The big progress is mainly contributed to the representation ability of transformer and its variant architectures. In this paper, we study the low-level computer vision task (e.g., denoising, super-resolution and deraining) and develop a new pre-trained model, namely, image processing transformer (IPT). To maximally excavate the capability of transformer, we present to utilize the well-known ImageNet benchmark for generating a large amount of corrupted image pairs. The IPT model is trained on these images with multi-heads and multi-tails. In addition, the contrastive learning is introduced for well adapting to different image processing tasks. The pre-trained model can therefore efficiently employed on desired task after fine-tuning. With only one pre-trained model, IPT outperforms the current state-of-the-art methods on various low-level benchmarks. Code is available at https://github.com/huawei-noah/Pretrained-IPT and https://gitee.com/mindspore/mindspore/tree/master/model_zoo/research/cv/IPT, CVPR 2021

The survival of patients diagnosed with metastatic renal cell carcinoma (RCC) is still limited and the current targeted therapies are only partially effective. Herein, we investigated the clinical value and functions of adiponectin receptors (AdipoR1 and AdipoR2) in metastatic renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). A total of 127 mRCC patients treated with first-line TKIs between 2008 and 2017 at a single institution were collected. AdipoR1 and AdipoR2 expression was assessed by immunohistochemistry. AdipoR1 was positively expressed in 87.4% (111/127) of tumors, especially, highly expressed in pulmonary and bone lesions. Patients with low-AdipoR1 expression in primary tumor tissues were more likely to suffer from progressive disease during TKIs treatment (40.0% vs. 11.1%, P = 0 .02), and with decreased progression-free survival (PFS: 19.5 vs. 37.8 mo, P = .001) and overall survival (OS: 62.3 vs 101.1 mo, P = .004) compared to those with high-AdipoR1 expression. Moreover, low-AdipoR1 expression in metastatic tissues was also associated with poor PFS (P = .006) and OS (P = .037). In contrast, AdipoR2 expression was neither associated with sunitinib response nor patient survival. In vitro, we found that adiponectin inhibited migration, invasion and sensitized RCC cells to sunitinib though interacting with AdipoR1, but not AdipoR2. Furthermore, we demonstrated that adiponentin-AdipoR1 axis inhibits tumor cells migration and invasion by blocking the GSK3β/β-Catenin pathway and enhances sunitinib sensitivity via abrogating PI3K/AKT/NF-κB signaling. Our results suggest that adiponentin-AdipoR1 axis may serve as a predictor of TKIs response and could be a potential therapeutic target in the future treatment for metastatic RCC.

Primary frequency control (PFC) is a fast- acting mechanism used to ensure high-quality power for the grid that is becoming an increasingly attractive option for load participation. Due to speed requirements and other considerations, it is often desirable to have distributed control laws. Current distributed PFC designs assume that the costs at each geographic location are independent . However, many networked systems, such as those for cloud computing, have interdependent costs across locations and, therefore, need geographic coordination. In this paper, distributed control laws are designed for interdependent, geo-distributed loads in PFC based on the optimality conditions of the global system. The controlled frequencies are provably stable, and the final equilibrium point is proven to strike an optimal balance between load participation and the frequency's deviation from its nominal set point. We evaluate the proposed control laws with realistic numerical simulations. Under current technology, the proposed control laws achieve a convergence time that is smaller than droop control alone and is comparable to that of distributed control without interdependent costs. Results also highlight significant cost savings over existing approaches under a variety of settings.

BACKGROUND The prognostic value of ductal adenocarcinoma of the prostate (DA) in nonmetastatic prostate cancer (PCa) has been identified in many studies. However, it remains unknown whether DA is an adverse prognostic factor in metastatic PCa (mPCa). METHOD Data from 634 mPCa patients histopathologically documented with DA or/and acinar adenocarcinoma of the prostate in our center between 2012 and 2018 were retrospectively analyzed. Propensity score matching (PSM) was used to balance the baseline features. Data from the Surveillance, Epidemiology, and End Results (SEER) database were utilized to validate our findings. Castration-resistant PCa-free survival (CFS), overall survival (OS), and cancer-specific survival (CSS) were set as endpoints. RESULTS DA was confirmed in 35 of 634 (5.5%) patients. Among the DA-positive patients, 7 of 35 (20%) and 28 of 35 (80%) harbored high (DA ≥ 50%) and low (DA

Xiang Tu,1,* Fan Wang,1,* Tiancong Chang,2,* Chichen Zhang,2 Mengni Zhang,3 Zhenhua Liu,1 Shi Qiu,1 Lu Yang,1 Qiang Wei11Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2West China School of Clinical Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Pathology and Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workObjective: To determine the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) for disease-free survival (DFS) in non-metastatic papillary renal cell carcinoma (pRCC) patients following partial or radical nephrectomy.Methods: We retrospectively analyzed 315 non-clear cell RCC patients who received curative surgery in our hospital from 2013 to 2018, from which 76 pRCC patients without metastasis (T1-3N0M0) were selected. The receiver operating characteristics (ROC) curve was drawn and an NLR cut-off of 2.5 was set to achieve maximum diagnostic accuracy for predicting DFS. Kaplan-Meier method and the Cox regression model was used to determine the relationship of NLR with DFS.Results: During a median follow-up of 28.0months (IQR 15.9–42.1, mean 31.4), disease recurred in 12 patients (15.8%) recording a median duration of 14.4months (IQR 8.6–22.9, mean 16.6). The 5-year DFS was 85.5% and 61.6% for the low (

We propose a numerical robust phase aberration compensation method in digital holographic microscopy, which is based on self-extension of holograms. We remove the fringes of the sample area in the hologram, then expand the fringe to fill the removed area of hologram by self-extension. The sample-free reference hologram is obtained which contain the total aberration of the system. The quantitative phase imaging of samples is separated from measurement phase data by the difference phase map of captured and reference hologram. Numerical simulation and experimental results demonstrate the availability of the proposed aberration compensation method in digital holographic microscopy.

A traceable ciphertext-policy attribute-based encryption (T-CPABE) scheme can trace a malicious user, who may leak her/his decryption privilege to a third party for some benefits. However, even if the malicious user is traced, the existing schemes cannot revoke her/him from the cryptosystems. Thus, it is necessary to embed a revocation mechanism into a T-CPABE scheme in practice. In this paper, we propose a ciphertext-policy attribute-based encryption scheme with white-box traceability and direct user revocation. In the proposed scheme, the ciphertext is related to an access structure and a revocation list R . The secret key is associated with an attribute set and a user’s identity assigned a leaf node in a binary tree. The value of a leaf node is used to trace a malicious user. Once a malicious user is caught, her/his identity is added in the revocation list R . Only the ciphertext components associated with the revocation list R are updated according to the new revocation list R ′ , and the updated ciphertext can provide forward security. Therefore, a user can decrypt a ciphertext if and only if she/he is not in the revocation list and her/his attribute set satisfies the access policy, simultaneously. Furthermore, our scheme is proved to be secure under selective access policy and chosen-plaintext attacks based on the decisional q -bilinear Diffie–Hellman exponent hardness assumption in the standard model.

Intraductal carcinoma of the prostate is an adverse prognosticator of prostate cancer. However, the roles of proportion and architectural patterns of intraductal prostate carcinoma in patient outcomes remain unclear.We retrospectively analyzed data on 644 patients with de novo metastatic prostate cancer between 2010 and 2017. Intraductal carcinoma of the prostate was identified from 12-core prostate biopsy. We calculated the proportion of intraductal prostate carcinoma and identified patterns according to the 2016 WHO classification. Propensity score matching was performed to balance baseline characteristics between patients with and without intraductal prostate carcinoma. Kaplan-Meier curves and Cox regression were used for survival analyses. The end points were castration resistant prostate cancer-free survival and overall survival.Of the 644 patients 180 (28.0%) harbored intraductal carcinoma of the prostate. A 10% or greater incidence of the carcinoma was independently associated with worse prognosis (castration resistant prostate cancer-free survival HR 2.06, 95% CI 1.51-2.81, p0.001, and overall survival HR 2.52, 95% CI 1.52-4.16, p0.001), as was pattern 2 intraductal carcinoma of the prostate (HR 1.86, 95% CI 1.40-2.49, p0.001, and HR 2.12, 95% CI 1.29-3.46, p = 0.003, respectively). Based on these 2 risk factors all men were classified into 5 groups. Patients in group 0 (no intraductal carcinoma of the prostate) and prostate intraductal carcinoma group 1 (less than 10% intraductal carcinoma, pattern 1) had favorable median castration resistant prostate cancer-free survival (18.0 vs 16.9 months, p = 0.871) and median overall survival (neither reached, p = 0.698). Men in intraductal carcinoma of the prostate group 4 (10% or greater intraductal carcinoma, pattern 2) harbored the worst outcomes (median castration resistant prostate cancer-free and overall survival 8.4 and 29.9 months, respectively). Group 2 (less than 10% intraductal carcinoma, pattern 2, with median castration resistant prostate cancer-free and overall survival 14.2 and 45.9 months) and group 3 (10% or less prostate intraductal carcinoma, pattern 1, with median castration resistant prostate cancer-free and overall survival 11.9 and 39.7 months, respectively) had an intermediate prognosis.A 10% or greater proportion of intraductal carcinoma of the prostate and pattern 2 were 2 unfavorable prognosticators of metastatic prostate cancer. Pathological reporting criteria based on intraductal carcinoma of the prostate could improve the prediction of patient outcomes and optimize treatment decisions.

The cause of cervical spondylotic radiculopathy could be related to the intraforaminal ligaments (IFLs) of the cervical spine. The aim of this study is to identify and describe the IFLs and assess their clinical significance. Six intact cervical spine specimens from adult embalmed cadavers were dissected to expose the cervical nerve roots and their surrounding intraforaminal tissues fully. From the C1-C2 to the C7-T1 intervertebral foramina (IVF), the connective structures between each nerve root and its surrounding foraminal wall were examined under a surgical microscope. The morphology, number, and attachment points of the IFLs of each segment were documented, and the length, width, or diameter and thickness of the ligaments were measured with a vernier caliper. IFLs were observed in all 84 IVFs of the cervical spine. According to their locations, they can be divided into two categories: the first is entrance-zone IFLs, which are radially distributed around the nerve root; the second is mid-zone IFLs, which are thin, strip-shaped fibrous tissues intertwined around the nerve roots, the number of ligaments being considerable but difficult to quantify. Ligament structures have been identified in the IVF of the cervical spine. Under physiological conditions, they could be protective in maintaining the position, shape, and function of nerve roots. However, under pathological conditions, the IFLs of the cervical spine could aggravate the symptoms of cervical nerve root radicular pain associated with other types of compression. Clin. Anat. 32:654-660, 2019. © 2019 Wiley Periodicals, Inc.

Ciphertext-policy attribute-based encryption (CP-ABE) can offer fine-grained access control over encrypted data, which is suitable for complex commercial applications. However, since the same decryption privileges could be shared by multiple users in the one-to-many encryption mechanism, it is dangerous that a malicious user misuses his secret key but cannot be traced. In addition to further security, when the malicious user has been caught, it is required to revoke him from the system. To address these problems, we propose a novel updatable CP-ABE scheme supporting white-box traceability and traitor revocation. In the proposed scheme, a “fixed point” is embedded into the user's secret key to achieving the traceability and each user is assigned with a unique identifier for revocation. Moreover, the secret exponent used to encrypt a message is divided into two parts: one is assigned to access policy and the other to the revocation list. Therefore, only a part of the ciphertext components needs to be updated when the revocation list is changed, which greatly simplifies the process of ciphertext update. Compared to the previous works, our scheme is more efficient, and can achieve valid revocation and ciphertext update. In addition, the traceability of the proposed scheme is depended on the l-Strong Difffie-Hellman assumption, and the indistinguishability security under selective access policy and chosen-plaintext attacks in the standard model is reduced to the Decisional q-Bilinear Diffie-Hellman assumption. Furthermore, the experimental results show that the proposed scheme is efficient.

The deduplication based on attribute-based encryption can be well used in eHealth systems to save storage space and share medical records. However, the excessive computation costs of existing schemes lead to inefficient deduplication. In addition, the frequent changes of clients' attribute weaken the forward secrecy of data, and thus, how to achieve the attribute revocation in deduplication is a problem that remains to be solved. In this paper, we propose a variant of the attribute-based encryption scheme that supports efficient deduplication and attributes revocation for eHealth systems. Specifically, an efficient deduplication protocol based on the nature of prime number is used to alleviate the computation burden on the private cloud, and attribute revocation is realized by updating the attribute agent key and the ciphertext. Moreover, outsourcing decryption is introduced to reduce the computation overhead of clients. The security analysis argues that the proposed scheme can reach the desired security requirements, and the visual experiment result indicates the excellent performance of the proposed scheme while realizing deduplication and attribute revocation.

Background: Large cell neuroendocrine carcinoma (LCNEC) of the prostate is an extremely rare entity, and the clinicopathological course, potential effective treatment, and prognosis are yet to be elucidated. Materials and Methods: A systematic search in Pubmed, Embase, and Ovid from inception to January 2019 was conducted. We reviewed each individual case of prostatic LCNEC and summarized specific features and outcomes for this rare pathologic entity. Results: Thirteen studies with a total of 20 patients (mean age: 70.3, range 43–87) were included in our review. Seventeen patients harbored primary LCNEC of the prostate, of which 9 patients were diagnosed with de novo carcinoma, and 8 patients were with a history of prostatic adenocarcinoma treated with hormonal therapy (mean duration: 2.9 years, range 2–5). The other 3 patients were diagnosed with metastatic LCNEC originating from lung (2 cases) and bladder (1 case). All patients met the diagnostic criteria of the typical morphological features as well as immunohistochemical staining results. Nearly all primary de novo LCNEC of the prostate were at a late stage at initial diagnosis. The pattern of distant metastasis resembled that of prostatic adenocarcinoma with the most common sites as bone spread (8/16, 50%). Most patients received systematic chemotherapy after diagnosis; however, the prognosis remained poor and patients deteriorated rapidly but with exception. Three reported cases in the context of de novo LCNEC admixed with prostatic adenocarcinoma kept sustained response to androgen deprivation therapy (ADT) and achieved obviously better survival outcomes compared with other patients. Conclusions: LCNEC of the prostate is a rare entity that mostly occurs after long-standing hormonal therapy of prostatic adenocarcinoma. The prognosis was universally poor irrespective of the systematic chemotherapy. However, patients of de novo tumor mixed with prostatic adenocarcinoma may respond to ADT and harbor a better outcome than those of pure de novo or post-ADT LCNEC of the prostate.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.