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关键词： squamous cell carcinoma   parotid   treatment   prognosis   MAJOR SALIVARY-GLAND   RADIOTHERAPY   HEAD  

摘要： Squamous cell carcinoma (SCC) of the parotid gland is a rare aggressive malignancy with a poor prognosis. The clinical behaviour, histopathological characteristics, and treatment strategies for parotid SCC still need to be comprehensively demonstrated. In this study, a retrospective review of patients diagnosed with parotid SCC was performed, covering the past two decades. Twenty-nine patients with primary parotid SCC and 10 patients with recurrent parotid SCC were identified. The clinicopathological characteristics of parotid SCC were summarized. Imaging records were used to determine the extent of invasion of the parotid SCC. Histopathological alterations in the parotid resulting from the infiltration of SCC were demonstrated. A set of treatment strategies was developed, involving parotidectomy, neck dissection, facial nerve treatment, defect repair, adjuvant radiotherapy, and chemotherapy/targeted therapy. The median patient survival was 24 months for those with primary parotid SCC and 14.5 months for those with recurrent parotid SCC. Comparatively, patients with a larger tumour size of primary parotid SCC experienced poorer overall survival (hazard ratio 8.986; P = 0.013). Great efforts have been made over the past two decades to identify and treat parotid SCC. Consensus regarding therapeutic options for parotid SCC has not been widely achieved and there is still a great need for well-designed prospective studies.

关键词： Chimeric antigen receptor (CAR)-T cell therapy   Immunotherapy   Antigens   High-grade serous ovarian carcinoma   Ovarian cancer   Tumor-infiltrating lymphocytes   MESOTHELIN EXPRESSION   EPITHELIAL OVARIAN   T-CELLS   ALPHA   IMMUNOTHERAPY   RESPONSES   SURVIVAL   CA125  

摘要： Objective. Chimeric antigen receptor (CAR)-T cell strategies ideally target a surface antigen that is exclusively and uniformly expressed by tumors; however, no such antigen is known for high-grade serous ovarian carcinoma (HGSC). A potential solution involves combinatorial antigen targeting with AND or OR logic-gating. Therefore, we investigated co-expression of CA125, Mesothelin (MSLN) and Folate Receptor alpha (FOLRA) on individual tumor cells in HGSC. Methods. RNA expression of CA125, MSLN, and FOLR1 was assessed using TCGA (HGSC) and GTEx (healthy tissues) databases. Antigen expression profiles and CD3+, CD8+ and CD20+ tumor-infiltrating lymphocyte (TIL) patterns were assessed in primary and recurrent HGSC by multiplex immunofluorescence and immunohistochemistry. Results. At the transcriptional level, each antigen was overexpressed in >90% of cases; however, MSLN and FOLR1 showed substantial expression in healthy tissues. At the protein level, CA125 was expressed by the highest proportion of cases and tumor cells per case, followed by MSLN and FOLRA. The most promising pairwise combination was CA125 and/or MSLN (OR gate), with 51.9% of cases containing >-90% of tumor cells expressing one or both antigens. In contrast, only 5.8% of cases contained >-90% of tumor cells co-expressing CA125 and MSLN (AND gate). Antigen expression patterns showed modest correlations with TIL. Recurrent tumors retained expression of all three antigens and showed increased TIL densities. Conclusions. An OR-gated CAR-T cell strategy against CA125 and MSLN would target the majority of tumor cells in most cases. Antigen expression and T-cell infiltration patterns are favorable for this strategy in primary and recurrent disease. (C) 2020 Elsevier Inc. All rights reserved.

关键词： Mortality   Cardiovascular events   Systematic review   Meta-analysis   OPEN-LABEL   METFORMIN TREATMENT   JAPANESE PATIENTS   GLYCEMIC CONTROL   PARALLEL-GROUP   NAIVE PATIENTS   ADD-ON   GLARGINE   EXENATIDE   EFFICACY  

摘要： Aim: To evaluate the risk of all-cause and cardiovascular mortality, acute myocardial infarction, and stroke associated with insulin treatment in patients with type 2 diabetes. Methods: A systematic review with meta-analysis of randomized clinical trials (RCTs) was performed. EMBASE, Cochrane, and PubMed databases were searched for RCTs reporting mortality or cardiovascular events and comparing basal insulin to any treatment in patients with type 2 diabetes. Data were summarized with Mantel-Haenzel relative risk (RR). Trial sequential analysis (TSA) was used to evaluate the reliability of the results considering a 20% relative risk difference between treatments. PROSPERO Registry: CRD42018087336. Results: In total, 2351 references were identified, and 26 studies (24348 patients) were included. Most studies evaluated glargine insulin (69%), compared insulin to GLP-1 analogs (57%), and evaluated add-on therapy with metformin (77%). Insulin was not associated with increased all-cause mortality (RR 0.99; 95% confidence interval (CI) 0.92?1.06), cardiovascular mortality (RR 1.01; 95% CI 0.91?1.13), myocardial infarction (RR 1.02; 95% CI 0.92?1.15), or stroke (RR 0.87; 95% CI 0.68?1.12). Insulin treatment increased severe hypoglycemia risk (RR 2.98; 95% CI 2.47?3.61). All analyses had low statistical heterogeneity. TSA confirmed these findings: optimal sample size (myocardial infarction), futility boundary (all-cause mortality, cardiovascular mortality, and stroke) and harm boundary (hypoglycemia) were reached. Conclusion: Treatment with basal insulin of patients with type 2 diabetes does not increase the risk of cardiovascular events or death. Despite the increased risk of hypoglycemia, these findings reinforce that insulin is a safe option in the treatment of type 2 diabetes. ? 2021 Elsevier B.V. All rights reserved.

关键词： Neural architecture search   Deep convolutional neural networks   Surface defect classification  

摘要： Surface defect classification (SDC) is the visual inspection of the surface of an object to identify appearance defects. Efficient and accurate SDC is i mportant for improving the quality of industrial products. A manually designed convolutional neural network (CNN) is traditionally used for SDC. In this study, a simpler SDC scheme with a higher classification accuracy, named NAS-SDC, is developed based on the neural architecture search (NAS) technique. A max-pooling cell based on NASNet is introduced to reduce the search space and the number of network parameters, thus simplifying the candidate operators for the search. Two network architectures are proposed to stack the search candidates or the best cells. The proposed method can be used to automatically design an efficient CNN model for SDC on a specific dataset. Experimental results show that the proposed method can find the best cells in similar to 11 h using a single graphics processing unit (GPU) and achieves higher classification accuracies (99.98%, 99.8% and 99.26%) than state-of-the-art methods on the Northeastern University (NEU-CLS), DAGM, and bridge defect datasets. The number of network parameters used in the proposed method is only 0.35 M, and the average test time per sample is approximately 61 ms, thus achieving a balance between performance and speed.

摘要： A Correction to this paper has been published:

关键词： Merkel cell carcinoma   Radiotherapy   Surgery  

摘要： The standard treatment approach for localised Merkel cell carcinoma (MCC) is wide surgical excision followed by adjuvant radiotherapy. However extensive surgery for locally advanced MCC may cause morbidity and disfigurement, compromise function and delay adjuvant therapy. Since MCC is a highly radiosensitive tumour, an alternative treatment option for advanced MCCs, especially those in anatomically challenging locations, is radiotherapy. Complete and durable control is achieved in up to 90% of cases if the definitive treatment of primary MCC is with radiotherapy. It is generally less morbid than surgery and can produce excellent cosmetic and functional outcomes. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

关键词： Bioassay   Disposable   Mediated MFC   Point of need   Toxicity   Water quality   BIOSENSOR   WATER   BIOFILM   ANODE   WASTE   OPTIMIZATION   PERFORMANCE   GENERATION   ELECTRODES   SENSOR  

摘要： Three of the primary bottlenecks, which should be consider for practical, point-of-need use of microbial fuel cell (MFC) analytical devices were surpassed in this work: i) the use of a diffusive barrier, hence, an electrogenic biofllm; ii) longer enrichment/stabilization times to produce a biofllm, made in a laboratory environment, over the electrode; and iii) difficulty comparing results obtained from MFCs based on electrogenic biofllms with standardized bioassays, a setback to be adopted as a new method. Here we show an easy way to determine water toxicity employing planktonic bacteria as biorecognition agents. The paper-based MFC contain an electron carrier (or mediator) to facilitate charge transfer from bacteria to the anode. In this way, there is no need to use biofllms. As far as we know this is the first paper-based MFC containing P. putida KT2440, a well characterized non-pathogenic bacteria previously used in standardized water toxicity bioassays. Results were obtained in 80 min and an effective concentration 50 of 9.02 mg L-1, calculated for Zn2+ (a reference toxic agent), was successfully compared with previously published and ISO standardized bioassays, showing a promising future for this technology. The practical design and cost (less than one U.S. dollar) of the paper-based MFC toxicity test presented will open new market possibilities for rapid and easy-to-use MFC analytical devices. (C) 2020 Elsevier Ltd. All rights reserved.