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关键词： Blood endothelial cells   Lymphatic endothelial cells   Cell identity   Epigenetics   DNA methylation   Histone modifications   DIFFERENTIAL EXPRESSION ANALYSIS   DNA METHYLATION   GENE-EXPRESSION   BIOCONDUCTOR PACKAGE   TRANSCRIPTION   PROX1   ENHANCERS   VEGFR-3   SITES   MEF2C  

摘要： Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant advances in elucidating how the specification of lymphatic and blood vascular ECs is regulated at the transcriptional level during development, the key molecular mechanisms governing their lineage identity under physiological or pathological conditions remain poorly understood. To explore the epigenomic signatures in the maintenance of EC lineage specificity, we compared the transcriptomic landscapes, histone composition (H3K4me3 and H3K27me3) and DNA methylomes of cultured matched human primary dermal lymphatic and blood vascular ECs. Our findings reveal that blood vascular lineage genes manifest a more 'repressed' histone composition in lymphatic ECs, whereas DNA methylation at promoters is less linked to the differential transcriptomes of lymphatic versus blood vascular ECs. Meta-analyses identified two transcriptional regulators, BCL6 and MEF2C, which potentially govern endothelial lineage specificity. Notably, the blood vascular endothelial lineage markers CD34, ESAM and FLT1 and the lymphatic endothelial lineage markers PROX1, PDPN and FLT4 exhibited highly differential epigenetic profiles and responded in distinct manners to epigenetic drug treatments. The perturbation of histone and DNA methylation selectively promoted the expression of blood vascular endothelial markers in lymphatic endothelial cells, but not vice versa. Overall, our study reveals that the fine regulation of lymphatic and blood vascular endothelial transcriptomes is maintained via several epigenetic mechanisms, which are crucial to the maintenance of endothelial cell identity.

关键词： Skin   Staging   Squamous cell carcinoma   AJCC   Prognosis   Survival   THICKNESS  

摘要： Background: The last revision of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual included a specific system for cutaneous squamous cell carcinoma (CSCC) of the head and neck. Here, we assessed the prognostic performance of six candidate modified T-classification models in head and neck CSCC patients. Methods: Analysis of 916 patients with head and neck CSCC given treatment with curative intent at The University of Texas MD Anderson Cancer Center between 1995 and 2019 was performed. The main outcome was disease-specific survival (DSS), and the impact of depth of invasion (DOI) was analyzed using multivariable regression models. Candidate models were developed using the optimal DOI cut points for each AJCC T classification based on goodness of fit of the model and the simplicity of the model. Staging systems were compared using Harrell's concordance index. Results: Median age was 70 years (range, 19e97years) and median follow-up time of 22 months (range, 1-250months). The median DOI was 6.0 mm (range, 0.1-70.0 mm). The five-year DSS rate was 80.7% (95% CI, 77.4-83.7%). We found significant association between DOI (hazard ratio, 1.21 [95%CI: 1.01-1.43]) and DSS on multivariable analysis. Based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan eMeier curves, model 6 surpassed the AJCC staging system. Conclusions: Incorporation of DOI in the current AJCC staging system improves discrimination of T classifications in head and neck CSCC patients. Lay summary: The current staging system for head and neck cutaneous squamous cell carcinoma demonstrates wide prognostic variability and provides suboptimal risk stratification. Incorporation of depth of invasion in the T-classification system improves risk prediction and patient counseling. Precis: We propose improved head and neck cutaneous squamous cell carcinoma T staging that will include depth of invasion and should be considered in future versions of the Americ

关键词： Scene classification   deep neural network   remote sensing   multi-objective optimization   evolutionary algorithm   neural architecture search   OPTIMIZATION   RECOGNITION   SELECTION   FEATURES  

摘要： The scene classification approaches using deep learning have been the subject of much attention for remote sensing imagery. However, most deep learning networks have been constructed with a fixed architecture for natural image processing, and they are difficult to apply directly to remote sensing images, due to the more complex geometric structural features. Thus, there is an urgent need for automatic search for the most suitable neural network architecture from the image data in scene classification, in which a powerful search mechanism is required, and the computational complexity and performance error of the searched network should be balanced for a practical choice. In this article, a framework for scene classification network architecture search based on multi-objective neural evolution (SceneNet) is proposed. In SceneNet, the network architecture coding and searching are achieved using an evolutionary algorithm, which can implement a more flexible hierarchical extraction of the remote sensing image scene information. Moreover, the computational complexity and the performance error of the searched network are balanced by employing the multi-objective optimization method, and the competitive neural architectures are obtained in a Pareto solution set. The effectiveness of SceneNet is demonstrated by experimental comparisons with several deep neural networks designed by human experts.

关键词： AIH   Ig   IQR   PBC  

摘要： Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.

关键词： Somatic cell cryobank   Buffalo   Fibroblast cells   Somatic cell nuclear transfer   Farm animals   DEVELOPMENTAL COMPETENCE   EPIGENETIC STATUS   GENE-EXPRESSION   ESTABLISHMENT   LINE   CULTURE   QUALITY   EMBRYOS  

摘要： Buffalo is an important farm animal species in South and South-east Asian countries. Cryopreservation allows long-term storage of somatic cells, which can be made available to research communities. This study aimed to 1) establish and cryopreserve somatic cells from elite buffaloes, and 2) share stored somatic cells and their associated data with researchers. To achieve these targets, somatic cells were established successfully from tail-skin biopsies of 17 buffaloes. The informative data such as buffalo details (breed, date of birth, sex, and age at the time of tissue biopsy collection, and production traits), the number of cryovials stored, and freezing dates were recorded in an electronic file and a printed inventory record. The established somatic cells were flat, spindle-shaped morphology, and expressed vimentin (a fibroblast-like cell type marker) and the negative expression of cytokeratin-18 (an epithelial cell type marker). Altogether, we cryopreserved 970 cryovials (0.1 million cells per vial) from two buffalo breeds, namely Murrah and Nili-Ravi (at least 45 cryovials per animal), for cryobanking. Somatic cell nuclear transfer (SCNT) experiments demonstrated the utility of cryopreserved cells to produce cloned buffaloes. Importantly, these cryopreserved somatic cells are made available to scientific communities. This study encourages the cryopreservation of somatic cells of elite farm animals for their utilization in cell-based research.

关键词： Kidney neoplasms   Metastasis   Nephrectomy   Renal cell carcinoma   TARGETED THERAPY   PREDICT SURVIVAL   STRATIFICATION   TOOL  

摘要： Background: Clinical and pathological factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). Bim, a downstream pro-apoptotic molecule in the PD-1 signaling pathway, has recently been associated with survival in other malignancies. We sought to determine if tissue biomarkers including Bim, added to a previously reported clinical metastases score, improved prediction of cancer-specific survival (CSS) for patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990 and 2004 were identified using our institutional registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for Bim, PD-1, B7H1 (PD-L1), B7-H3, CA-IX, IMP3, Ki67, and survivin. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients: 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up was 9.6 years (IQR 4.2- 12.8), during which 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score, and were eligible for biomarker-specific model inclusion. After variable selection, high Bim (hazard ratio [HR] = 1.44; 95% confidence interval [CI] 1.16- 1.78; P < 0.001), high survivin (HR = 1.35; 95% CI 1.08- 1.68; P = 0.008), and the metastases score (HR = 1.13 per 1 point; 95% CI 1.10- 1.16; P < 0.001) were retained in the final multivariable model (c-index = 0.69). Conclusion: We created a prognostic model combining the clinical metastases score and 2 primary tumor tissue expression biomarkers, Bim and survivin, for patients with metastatic

关键词： Clear-cell renal cell carcinoma   Ga-68-PSMA-11 PET   CT   WHO   ISUP grade   Adverse pathology   MEMBRANE ANTIGEN   TUMOR NECROSIS   EXPRESSION   SYSTEM   PSMA  

摘要： Purpose To evaluate parameters derived from(68)Ga-PSMA-11 PET/CT images for discriminating pathological characteristics in primary clear-cell renal cell carcinoma (ccRCC). Methods The study retrospectively examined data for 36 ccRCC patients with preoperative(68)Ga-PSMA-11 PET/CT scan and surgical specimens. Radiological parameters including maximal tumor diameter, mean CT value, and maximal standard uptake value (SUVmax) were derived from PET/CT images. Pathological characteristics included WHO/ISUP grade and adverse pathology (tumor necrosis or sarcomatoid or rhabdoid feature). Values of radiological parameters were compared within subgroups of pathological characteristics. Receiver operating characteristic (ROC) curve analysis was used for the effectiveness of radiological parameters in differentiating pathological characteristics, estimating area under the ROC curve (AUC) and 95% confidence intervals (CIs). Results The WHO/ISUP grade distribution for 36 tumors was grade 1, 9 (25.0%); grade 2, 12 (33.3%); grade 3, 9 (25.0%); and grade 4, 6 (16.7%). Adverse pathology was positive for 15 (41.7%). Radiological tumor diameter and SUVmax significantly differed by WHO/ISUP grade, pT stage, and adverse pathology (allP < 0.05), with no difference by CT value. Tumor diameter demonstrated sensitivity 86% and specificity 88% for pT stage, with cutoff 6.70 and AUC 0.91 (95% CI, 0.79-1.00,P < 0.001). SUV(max)could effectively differentiate WHO/ISUP grade (3-4 vs. 1-2) and adverse pathology (positive vs. negative), with AUC 0.89 (95% CI, 0.81-0.98,P < 0.001), cutoff 16.4, sensitivity 100%, and specificity 71% and AUC 0.92 (95% CI, 0.85-0.99,P < 0.001), cutoff 18.5, sensitivity 94%, and specificity 87%, respectively. Conclusion Ga-68-PSMA-11 PET/CT could effectively identify aggressive pathological features of ccRCC.

关键词： VACCINATION   EXPERIENCE   DISEASE  

关键词： Electrophoretic deposition   Process parameters   Spinel coating   Oxidation behaviour   Cr migration   METALLIC INTERCONNECTS   ELECTRICAL-CONDUCTIVITY   PROTECTIVE-COATINGS   CHROMIUM DEPOSITION   OXIDATION BEHAVIOR   CATHODE   ALLOY   CU   KINETICS   FE  

摘要： This study aimed to investigate the colloidal stability of (Cu,Mn,Co)(3)O-4 spinel in various suspension media and suitable applied voltage for electrophoretic deposition (EPD). The performance of the coated SUS430 was evaluated in terms of oxidation behaviour, Cr migration and electrical conductivity. The (Cu,Mn,Co)(3)O-4 suspension prepared using a mixture of 50/50 isopropanol and acetylacetone presented the highest zeta potential (41.4 mV), which indicated a stable and well-dispersed suspension. An applied voltage of 80 V is recommended to produce a coating surface with uniform particle arrangement. The electrophoretically deposited (Cu,Mn, Co)(3)O-4 spinel coating could reduce the oxidation kinetics by three orders of magnitude and exhibited stable electrical conductivity during 200 h of oxidation. Cr element was not detected on the surface of the coated SUS430 and LSCF cathode after 200 h of oxidation. Therefore, the electrophoretically deposited (Cu,Mn,Co)(3)O-4 spinel coating could successfully inhibit Cr migration from the stainless steel interconnects to the cathode.