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关键词： Augmentation   Bayesian optimization   Brain tumor   Convolutional neural networks   Deep learning   Image processing  

摘要： Detecting and classifying a brain tumor is a challenge that consumes a radiologist's time and effort while requiring professional expertise. To resolve this, deep learning techniques can be used to help automate the process. The aim of this paper is to enhance the accuracy of brain tumor classification using a new layered architecture of deep neural networks rather than the current state-of-the-art algorithms. In this paper, we propose automated tumor classification by concatenating two convolutional neural network structures of layers and tuning the hyperparameters by utilizing Bayesian optimization. The proposed solution focuses on enhancing the accuracy of classifying tumors to increase the level of trust in the technologies employed in the medical field. The work is tested and evaluated to predict the classification of magnetic resonance imaging inputs and achieving a higher accuracy (97.37%) than other similar works, with accuracies between 84.19% and 96.13%, for the same dataset.

关键词： Head and neck squamous cell carcinoma   Unknown primary   F-18-FDG PET   CT   Detection rate  

摘要： Purpose We performed a systemic review and meta-analysis to evaluate the performance of F-18-FDG-PET/CT as a next step in the search of occult primary tumors for patients with head and neck squamous cell carcinoma of unknown primary (HNSCC-UP). Methods PubMed and Embase databases were searched from the earliest available date of indexing through February 2021. Eligible studies were those using F-18-FDG-PET/CT to detect occult primary tumors for HNSCC-UP, of which the defining diagnostic workup had been limited to endoscopy with or without CT/MRI. The detection rates were meta-analytically pooled using a random-effects model. Subgroup analyses and meta-regression were performed to explore the source of heterogeneity. A pooled analysis evaluating the false-positive proportions was also performed. Results Sixteen studies with 724 patients were included in this meta-analysis. The pooled detection rate was 40% (95% CI 31-49%), with high heterogeneity (I-2 = 85.2%). No sources of heterogeneity were identified by analyzing multiple subgroups stratified by study design, sample size, ethnicity, use of contrast agent, defining diagnostic workup, image analysis, and reference standard (All P > 0.05). The most common sites of both true-positive cases and false-positive cases were tonsil and tongue base. The pooled false-positive proportion was 9% (95% CI 5-13%). Conclusions F-18-FDG PET/CT is useful as a next step in the search of occult primary tumors in HNSCC-UP patients defined by endoscopy with or without CT/MRI. However, in light of the high false-positive proportion, confirmatory histological investigations should be viewed as necessary practice upon positive PET/CT findings.

关键词： Gastrointestinal stromal tumors   Immunotherapy   Immune infiltrate   Programmed cell death-ligand 1  

摘要： Purpose To characterize the immune cell profile and expression of PD-1, PD-L1, and IDO in PDGFRA-mutant gastrointestinal stromal tumors (GISTs). Methods The clinicopathological data of PDGFRA-mutant GIST patients who received surgical resection in Zhongshan Hospital between January 2013 and August 2019 were reviewed retrospectively. The specimens of tissue chips were detected for immune cell infiltration and the expression of PD-1, PD-L1, and IDO by immunohistochemical staining. Results CD3(+), CD8(+), and CD68(+) cells were the main infiltrating immune cells in the 42 patients included in this study. In addition, CD4(+), CD56(+), Foxp3(+), and CD20(+) cells were also observed. A higher CD8(+) T cell count was associated with smaller tumor size and PDGFRA D842V mutation (P = 0.047, P = 0.005). A higher CD3(+) and CD68(+) cell count was associated with a higher mitotic index (P = 0.022, P = 0.006). CD4(+) and CD20(+) cell count was associated with tumor morphology (P = 0.002, P = 0.045). PD-1 expression was present in 37 (88%) samples. Eighteen samples were positive for PD-L1 expression, and it was higher in small vs. large tumors (P = 0.012) and epithelioid and mixed cell type vs. spindle cell type GISTs (P = 0.046). IDO expression was positive in all 42 patients. The number of CD4(+) cells was significantly greater in the specimens with high IDO expression (P = 0.012). Conclusion There were abundant infiltrating immune cells in PDGFRA-mutant GISTs. PD-L1 expression was negatively associated with tumor size. The immunotherapy targeting PD-1/PD-L1 checkpoint and IDO may be valuable.

关键词： Glucagon‐   like peptide‐   1 receptor agonist   Lixisenatide   Pooled analysis  

摘要： Aims/Introduction The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin. Materials and Methods An individual-level pooled analysis of two multi-national phase III studies, GetGoal-L and GetGoal-L-C, was carried out to assess the efficacy of lixisenatide versus placebo as an add-on treatment to BI +/- metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2-h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control. Results Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference -0.49, 95% confidence interval -0.68 to - 0.30 and white patients least squares mean difference -0.45, 95% confidence interval -0.63 to - 0.26;P = 0.6287). Similarly, no significant difference was found in 2-h PPG reduction between both groups (least squares mean difference for Asian vs white patients: -3.37 vs -3.93;P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of -0.56% after adjustment of baseline HbA1c level in Asian patients, and -0.41% in white patients. Conclusions Adding lixisenatide to BI significantly reduced HbA1c and 2-h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.

关键词： metastatic RCC   systemic targeted therapy   sunitinib   rechallenge   clinical outcomes   #uroonc   #kcsm   #KidneyCancer  

摘要： Objective To assess the efficacy and tolerability of rechallenge with sunitinib and other targeted therapies (TTs) in patitents with relapsed recurrent renal cell carcinoma (RCC) in the advanced setting. Methods In this multi-institutional retrospective study, patients with relapsed RCC were rechallenged with sunitinib or other systemic TTs as a first-line therapeutic approach after failed adjuvant sunitinib treatment. Patient characteristics, treatments and clinical outcomes were recorded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR) and overall survival (OS). Results A total of 34 patients with relapses were recorded, and 25 of these (73.5%) were men. Twenty-five patients were treated with systemic TT: 65% of patients received TT against the vascular endothelial growth factor pathway (including sunitinib), 21.7% received mammalian target of rapamycin inhibitors and 13% received immunotherapy. The median (interquartile range) time to relapse was 20.3 (5.2-20.4) months from diagnosis, and 7.5 months (1.0-8.5) from the end of adjuvant suntinib treatment. At a median follow-up of 23.5 months, 24 of the 25 patients had progressed on first-line systemic therapy. The median PFS was 12.0 months (95% confidence interval [CI] 5.78-18.2). There were no statistical differences in PFS between different treatments or sunitinib rechallenge. PFS was not statistically different in patients relapsing on or after adjuvant suntinib treatment (<= 6 or >6 months after adjuvant suntinib ending). The ORR was 20.5%. The median OS was 29.1 months (95% CI 16.4-41.8). Conclusions Rechallenge with sunitinib or other systemic therapies is still a feasible therapeutic option that provides patients with advanced or metastastic RCC with additional clinical benefits with regard to PFS and OS after failed response to adjuvant sunitinib.

关键词： Endothelial-to-mesenchymal transition   Endothelial cells   Bone morphogenic protein-7   Transforming growth factor beta   Systemic sclerosis  

摘要： Background: Systemic sclerosis (SSc) is an autoimmune inflammatory and vascular disorder that causes tissue fibrosis of the skin and internal organs. Endothelial-to-mesenchymal transition (EndoMT) has been considered an important mechanism in the pathogenesis of vascular remodeling in SSc. Recent studies suggested that bone morphogenic protein 7 (BMP-7) has anti-fibrotic effects in several fibrotic diseases. Objectives: To investigate the mechanism of BMP-7 in inhibiting TGF-beta-induced EndoMT in systemic sclerosis (SSc). Methods: Skin tissues of both healthy controls and SSc patients were detected the distribution of BMP-7. TGF-beta was applied to induce the EndoMT model of human umbilical vein endothelial cells (HUVECs), and bleomycin was used to established the SSc mouse model. After treatment of BMP-7, the protein levels of endothelial specific markers, mesenchymal cell products, transcription factors and Akt signal pathway were examined by western blotting, immunofluorescence or immunohistochemistry both in vivo and in vitro. Results: The expression of BMP-7 was decreased in the basal layer of epidermis and dermis of SSc patients. EndoMT in TGF-beta-treated HUVECs and skins of SSc mouse model were markedly attenuated after treatment with rh-BMP-7. Moreover, Akt/mTOR/p70S6K phosphorylation was involved in EndoMT and BMP-7 suppressed TGF-beta- or bleomycin-induced theses phosphorylation in HUVECs or SSc mouse model. Conclusion: BMP-7 reduced the production of TGF-beta-induced EndoMT in HUVECs and SSc mouse model through Akt/mTOR/p70S6K signaling pathway. These findings suggested that BMP-7 could be employed as a promising antifibrotic therapy for SSc. (c) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

摘要： Objectives: Clear Cell Ovarian Carcinoma (CCOC) is known for its chemoresistance, high rates of relapse, and poor overall survival. Despite this, upfront treatment has remained relatively unchanged for decades. The objective of this study was to compare demographic and pathologic characteristics of patients with rapidly progressive versus chemo-sensitive advanced stage (III or IV) CCOC in order to better identify a cohort of patients who may benefit from innovative upfront treatment strategies. Methods: After IRB approval, patients diagnosed with CCOC between 2008 and 2020 at our University were identified and reviewed. Demographic information including age, parity, and menopausal status at time of diagnosis was collected in addition to tumor data such as percent clear cell and the presence or absence of coexisting endometriosis. Those diagnosed with stage I or II disease and those who have not yet completed adjuvant therapy were excluded. Progression-free survival (time from chemotherapy completion to progression or death) was estimated with a Kaplan-Meier curve. Patients were divided into one of two cohorts: chemo-sensitive (lack of progression or death at one year from chemotherapy completion) or rapidly progressive (evidence of progression or death within one year) and cohorts were compared using Wilcoxon rank-sum tests and Fisher's exact tests. Results: Thirty-four patients met inclusion criteria. All subjects underwent surgical staging or debulking and adjuvant platinum/taxane chemotherapy. Median progression-free survival was 6.1 months (95% confidence interval: 3.3-24.3 months). Thirteen patients (43.3%) were identified as chemo-sensitive, and seventeen (56.7%) as rapid progressors. Four patients did not have enough follow-up to be classified. All rapid progressors recurred or progressed within seven months of primary chemotherapy completion. The cohort of patients with rapidly progressive disease were younger (median age 53 vs 64, p=0.048) and more likely t

关键词： AP-1   Chromatin remodeling   Human induced pluripotent stem cells   JDP2  

摘要： Human induced pluripotent stem cells (iPSCs) technology has been widely applied to cell regeneration and disease modeling. However, most mechanism of somatic reprogramming is studied on mouse system, which is not always generic in human. Consequently, the generation of human iPSCs remains inefficient. Here, we map the chromatin accessibility dynamics during the induction of human iPSCs from urine cells. Comparing to the mouse system, we found that the closing of somatic loci is much slower in human. Moreover, a conserved AP-1 motif is highly enriched among the closed loci. The introduction of AP-1 repressor, JDP2, enhances human reprogramming and facilitates the reactivation of pluripotent genes. However, ESRRB, KDM2B and SALL4, several known pluripotent factors promoting mouse somatic reprogramming fail to enhance human iPSC generation. Mechanistically, we reveal that JDP2 promotes the closing of somatic loci enriching AP-1 motifs to enhance human reprogramming. Furthermore, JDP2 can rescue reprogramming deficiency without MYC or KLF4. These results indicate AP-1 activity is a major barrier to prevent chromatin remodeling during somatic cell reprogramming.

摘要： Desmoplastic small round cell tumor (DSRCT) is a rare malignancy believed to originate from the serous membranes and it is highly aggressive with 5-year overall survival of 18.4%. Only a small number of DSRCT cases have been documented. Here, we report findings of DSRCT of the kidney on F-18-FDG PET/CT in a 30-year-old woman who presented with repetitive pulmonary infection and spontaneous pneumothorax. (C) 2021 Elsevier Inc.

关键词： airway epithelium   cell differentiation   cilia  

摘要： The alteration of the mucociliary clearance is a major hallmark of respiratory diseases related to structural and functional cilia abnormalities such as chronic obstructive pulmonary diseases (COPD), asthma and cystic fibrosis. Primary cilia and motile cilia are the two principal organelles involved in the control of cell fate in the airways. We tested the effect of primary cilia removal in the establishment of a fully differentiated respiratory epithelium. Epithelial barrier integrity was not altered while multiciliated cells were decreased and mucous-secreting cells were increased. Primary cilia homeostasis is therefore paramount for airway epithelial cell differentiation. Primary cilia-associated pathophysiologic implications require further investigations in the context of respiratory diseases.