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关键词： Hypopituitarism   Autoimmunity   Anti-pituitary antibody   Cell mediated immune response  

摘要： Introduction Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland. Although largely investigated, the pathogenesis of PAH is not completely clarified. We aimed to investigate the immune response in PAHs. Material and methods Serum anti-pituitary and anti-hypothalamus antibodies (respectively APAs and AHAs) were investigated though an indirect immunofluorescence on monkey hypophysis and hypothalamus slides, serum cytokines though an array membrane and cell-mediated immunity though the white blood cells count. Results Nineteen PAH cases entered the study. APA or AHA were identified in all cases. APA were detected in 13 patients (68.4%) and AHA in 13 patients (68.4%). Ten patients (52.6%) were simultaneously positive for both APA and AHA. The prevalence of APAs and AHAs was higher as compared to those observed in 50 health controls (respectively 14% p < 0.001 and 24% p = 0.004) and in 100 not-secreting pituitary adenoma (NFPAs) (respectively 22% p = 0.002 and 8% p < 0.001). Similarly, the prevalence of simultaneous positivity for APA and AHA (52.9%) was higher as compared to the those detected in patients affected by NFPAs (0%; p < 0.001) and in health controls (16% p = 0.002). No differences were identified between PAHs and controls at qualitative and quantitative analysis of serum cytokines and white blood cells count. Conclusions This study suggest that APA and AHA may be detected in an high percentage of PAH cases and that their simultaneous identification may be useful for the differential diagnosis between PAH and NFPAs, in an appropriate clinical context.

关键词： Carcinogenesis   Colon cancer   Cytotoxicity   Genetic alterations   Heme iron   DNA-DAMAGE   EXPRESSION  

摘要： Heme, a molecule abundant in red meat, is assumed to exert carcinogenic effects on normal colonic cells and tumour suppressive effects on cancer cells, though the hypothesis has not been explicitly proven yet. The present study aims to investigate hemin induced cytotoxic, genetic and biological alterations in both normal and cancerous colonic epithelial cells, which may imply its carcinogenic and anticarcinogenic properties. Normal colonic epithelial cells and colon carcinoma cells were treated with a 0-500 mu M concentration of hemin for 1-4 days following which cytotoxicity and wound healing assays, western blot, rt-PCR and cell cycle analysis were performed. Interestingly, hemin was cytotoxic to normal colonic cells, but carcinoma cells were more resistant. Cell migration potential of both normal colonic cells and colon carcinoma cells was impeded by hemin. Hemin caused upregulation of both P53 and beta-catenin gene and proteins expression in normal colonic cells with concomitant cell cycle arrest at G1(Gap 1) and G2/M (Gap 2/ Mitosis). G1 and G2 cell cycle arrests were also observed in colon carcinoma cells. In conclusion, the present study confirms that hemin, a main heme molecule present in red meat, facilitates behavioural, genetic and cell cycle kinetic alterations in both normal colonic epithelial and colon carcinoma cells.

摘要： Objectives: To define the incidence, prognosis, and treatment patterns associated with multiple primary lower genital tract squamous cell carcinoma (LGTSCC). Methods: Surveillance, Epidemiology, and End Results (SEER) database patients diagnosed with synchronous cervical, vaginal, vulvar, and/or anal SCC from 2000-2016 were included. Incidence and mortality were evaluated using Kaplan-Meier curves. Multivariable Cox proportional hazards regression was used to identify treatment patterns, risk factors, and mortality associated with LGTSCC. Results: Among 15,424 women with any LGTSCC, 138 patients had multiple primary LGTSCC (0.89%). Vulvar and vaginal SCC was the most common combination (49.3%), and cervical with anal SCC was the least common (1.4%). Only one patient had 3 or more primary LGTSCC (vulvar, cervical, and anal). Multiple primary LGTSCC was independently associated with higher mortality compared to single site LGTSCC (adjusted hazards ratio [aHR]=1.67; p<0.001). Multiple primary LGTSCC was significantly associated with older age (63 vs. 58 years, p<0.001) and have lower stage (adjusted odds ratio [aOR]=0.38; p<0.001) and grade of disease (aOR=0.32; p<0.001). Patients with multiple primary LGTSCC were more likely to receive radiation overall (aOR=1.74, p=0.005) and were more likely to receive adjuvant radiation after primary surgical resection compared to single site LGTSCC (aOR=1.88, p=0.007). Receipt of any treatment including radiation (aHR=0.85; p<0.001), chemotherapy (aHR=0.50; p<0.001), and surgery (aHR=0.70; p<0.001) was independently associated with decreased mortality hazard. Conclusions: Multiple primary LGTSCC is rare but is associated with increased mortality, and higher rates of adjuvant radiation compared to single site LGTSCC despite lower stage and grade at diagnosis. More research is needed to define optimal therapy for patients with multiple primary LGTSCC.

关键词： Endocannabinoids   Cannabinoid system   Granulosa cells   Fertility   Folliculogenesis   Apoptosis   ACID AMIDE HYDROLASE   CANNABINOID RECEPTORS   EARLY-PREGNANCY   EXPRESSION   SYSTEM   WOMEN   LOCALIZATION   INVOLVEMENT  

摘要： The endocannabinoid system (ECS) plays a crucial role in human reproduction. Changes in anandamide (AEA) levels affect reproductive events and has already been suggested as biomarker of reproductive potential of male and female gametes. Although cannabinoid-receptor 1 (CB1) was already identified in human granulosa cells (hGCs) the ECS was not characterized on granulosa cells line COV434 nor the effects of AEA on GCs viability and function depicted. Therefore, the aim of this study was to characterize the ECS elements and explore the effects of AEA on both COV434 and hGCs. Our results revealed that hGCs express the full enzymatic machinery responsible for AEA metabolism as well as cannabinoid receptors. In addition, AEA induced a reduction in both COV434 and hGCs viability in a concentration and time-dependent manner. Nevertheless, the effects of AEA in cell viability was independent of either CB1 or CB2 receptors. There was no ROS release in both cell models; however, AEA induced morphological changes, presenting chromatin condensation at 72 h, and variation on mitochondrial membrane potential. Moreover, AEA induced an increase in caspase-3/-7 activities in both cell models, but in hGCs there was also an increase in caspase 8 activity. This study supports the idea that ECS balance is crucial for folliculogenesis and oocyte quality as dysregulated AEA levels may compromise female fertility.

关键词： Large-eddy simulation (LES)   Facade geometrical details   Wind speed   Pressure coefficient   Balcony geometry   High-rise building   CONVECTIVE HEAT-TRANSFER   LARGE-EDDY SIMULATION   FIELD POLLUTANT DISPERSION   AIR-FLOW   INTERUNIT DISPERSION   NATURAL VENTILATION   NIGHT-VENTILATION   URBAN-ENVIRONMENT   CATCHERS IMPACT   LES  

摘要： The presence of building balconies can significantly modify the near-facade wind flow pattern and surface pressures. The present study evaluates the impact of building balcony geometry on mean wind speed on balcony spaces and wind-induced mean surface pressure for generic high-rise buildings. The focus is on balconies that extend along the entire width of the building facade. Large-eddy simulations (LES), validated with wind tunnel experiments, are conducted to investigate the impact of (i) balconies present or not, (ii) balcony depth, (iii) balcony parapet walls, (iv) balcony partition walls, and (v) density of balconies. The results indicate that the balcony geometry can greatly affect the mean wind speed on balcony spaces and the local and facade-averaged mean pressure coefficient (Cp). The presence of balconies can increase the facade-averaged Cp over the windward and leeward facades by 5.2% and 8.9%, respectively. These numbers rise to 23.5% and 23.3% when two partition walls are added at the lateral edges of the facades. Adding five partition walls can reduce the overall areaaveraged wind speed on balcony spaces by 68.0% compared to the case without partition walls. These findings can be useful in developing, designing and constructing buildings with facade geometrical details that improve building ventilation, air quality and wind comfort.

关键词： Gastrointestinal stromal tumors   Immunotherapy   Immune infiltrate   Programmed cell death-ligand 1   REGULATORY T-CELLS   IMATINIB   EFFICACY   BLOCKADE   SAFETY  

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： Wheat kernels   Spectrogram   SPGAN-PNAS   Classification   IMPACT-ACOUSTIC EMISSIONS   FEASIBILITY   MACHINE  

摘要： Quantity and quality of grain are both closely related to national development and social stability. Grain is lost during storage due to mildew and insects. Detection of damaged grain kernels not only can reduce the loss of grain, but also protect human beings from diseases caused by damaged grain. Therefore, research on the automatic detection of damaged grain is of continued urgency. In this paper, we propose a framework combining spectrogram generative adversarial network and progressive neural architecture search (SPGAN-PNAS) to detect and classify mildew-damaged wheat kernels (MDK), insect damaged wheat kernels (IDK) and undamaged wheat kernels (UDK). First, the spectrogram generative adversarial network (SPGAN) is designed to enlarge the data set. Second, we apply progressive neural architecture search (PNAS) to generate network structure to classify three types of wheat kernels. An F1 of 96.2% is obtained using the proposed method with 5-fold cross-validation. The results are superior to the classical neural networks for detection and classification of damaged wheat kernels. Experimental results show that the structure of SPGAN-PNAS is feasible and effective. (c) 2021 IAgrE. Published by Elsevier Ltd. All rights reserved.

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： Diabetes classification   Graph convolutional network   Data processing   LSTM   Attention mechanism   GLYCEMIC VARIABILITY  

摘要： The classification of type 1 and type 2 diabetes is currently performed based on biochemical indicators and clinical experience. However, considering the unsatisfactory efficiency and accuracy of the experience-based diabetes type classification, we aim to propose a data-driven diabetes classification model through exploiting features contained in flash glucose monitoring (FGM) data. In particular, we propose a novel data reorganization and topologization method to reasonably extract the features of glycemic variability influence. Furthermore, a graph convolutional network is adopted to learn the inter-day influence feature and a Long Short-Term Memory network to characterize intra-day glycemic variability, which enables simultaneous characterization of slow and fast dynamics in FGM data. Finally, to visualize the effectiveness of our model, a t-distributed stochastic neighbor embedding method is implemented. The effectiveness of the proposed model is evaluated through a crossvalidation approach using a dataset containing FGM records of 113 diabetic subjects. Compared with classical machine learning algorithms and neural networks, the proposed model achieved the highest specificity value (0.9943) in diabetes type classification, F-Measure (0.8824) and Matthews correlation coefficient score (0.8250). The obtained results indicate the feasibility of achieving diabetes classification by learning the patterns hidden in continuous glucose monitoring data.

关键词： Vehicle mobility model   Discrete element method   Smoothed particle hydrodynamics   Finite element method   Vehicle dynamics   Terramechanics   Computational mechanics   Soft soil model   Tire   Tracked vehicles   FINITE-ELEMENT-ANALYSIS   SOIL INTERACTION   SIMULATION   ALGORITHM   SHAPE   SAND  

摘要： The US army along with NATO member and partner nations' militaries need an accurate software tool for predicting ground vehicle mobility (such as speed-made-good and fuel-consumption) on world-wide ter-rains where military vehicles may be required to operate. Currently, the NATO Reference Mobility Model (NRMM) is the only NATO recognized tool for assessing ground vehicle mobility. NRMM was developed from the 1960s to the 1980s and relies on steady-state empirical formulas which may not be accurate for new military ground vehicles. A NATO research task group (RTG-248) was established from 2016 to 2018 to develop the NG-NRMM (next-generation NRMM) software tool requirements and an NG-NRMM pro-totype which uses high-fidelity "simple" or "complex" terramechanics models for the terrain/soil along with modern 3D multibody dynamics software tools for modeling the vehicle. NG-NRMM Complex Terramechanics (CT) models are those that utilize full 3D soil models capable of predicting the 3D soil reaction forces on the vehicle surfaces (including tires, tracks, legs, and under body) and the 3D flow and deformation of the soil including both elastic and plastic deformation under any 3D loading condi-tion. In Part 1 of this paper, an overview of the full spectrum of terramechanics models from the highest fidelity to the lowest fidelity is presented along with a literature review of CT ground vehicle mobility models. (c) 2021 ISTVS. Published by Elsevier Ltd. All rights reserved.