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关键词： colon epithelial cells   Gb3Cer   Gb4Cer   glycosphingolipids   Stx1a   Stx2a   Stx2e  

摘要： Shiga toxin (Stx) is released by enterohemorrhagic Escherichia coli (EHEC) into the human intestinal lumen and transferred across the colon epithelium to the circulation. Stx-mediated damage of human kidney and brain endothelial cells and renal epithelial cells is a renowned feature, while the sensitivity of the human colon epithelium towards Stx and the decoration with the Stx receptor glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer, Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer) and globotetraosylceramide (Gb4Cer, GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1Cer) is a matter of debate. Structural analysis of the globo-series GSLs of serum-free cultivated primary human colon epithelial cells (pHCoEpiCs) revealed Gb4Cer as the major neutral GSL with Cer (d18:1, C16:0), Cer (d18:1, C22:1/C22:0) and Cer (d18:1, C24:2/C24:1) accompanied by minor Gb3Cer with Cer (d18:1, C16:0) and Cer (d18:1, C24:1) as the dominant lipoforms. Gb3Cer and Gb4Cer co-distributed with cholesterol and sphingomyelin to detergent-resistant membranes (DRMs) used as microdomain analogs. Exposure to increasing Stx concentrations indicated only a slight cell-damaging effect at the highest toxin concentration of 1 mu g/mL for Stx1a and Stx2a, whereas a significant effect was detected for Stx2e. Considerable Stx refractiveness of pHCoEpiCs that correlated with the rather low cellular content of the high-affinity Stx-receptor Gb3Cer renders the human colon epithelium questionable as a major target of Stx1a and Stx2a.

关键词： Terrain reconstruction   Remote sensing image   Multispectral image   Convolutional neural network   Material classification  

摘要： For real-world simulation, terrain models must combine various types of information on material and texture in terrain reconstruction for the three-dimensional numerical simulation of terrain. However, the construction of such models using the conventional method often involves high costs in both manpower and time. Therefore, this study used a convolutional neural network (CNN) architecture to classify material in multispectral remote sensing images to simplify the construction of future models. Visible light (i.e., RGB), near infrared (NIR), normalized difference vegetation index (NDVI), and digital surface model (DSM) images were examined. This paper proposes the use of the robust U-Net (RUNet) model, which integrates multiple CNN architectures, for material classification. This model, which is based on an improved U-Net architecture combined with the shortcut connections in the ResNet model, preserves the features of shallow network extraction. The architecture is divided into an encoding layer and a decoding layer. The encoding layer comprises 10 convolutional layers and 4 pooling layers. The decoding layer contains four upsampling layers, eight convolutional layers, and one classification convolutional layer. The material classification process in this study involved the training and testing of the RUNet model. Because of the large size of remote sensing images, the training process randomly cuts subimages of the same size from the training set and then inputs them into the RUNet model for training. To consider the spatial information of the material, the test process cuts multiple test subimages from the test set through mirror padding and overlapping cropping;RUNet then classifies the subimages. Finally, it merges the subimage classification results back into the original test image. The aerial image labeling dataset of the National Institute for Research in Digital Science and Technology (Inria, abbreviated from the French Institut national de recherche en s

关键词： Ectopic   Primary hyperparathyroidism   Giant parathyroid adenoma   Water clear cell adenoma   Case report  

摘要： Background: Ectopic parathyroid gland is not uncommon, and is associated with primary hyperparathymidism. Giant parathyroid adenoma (PA) and concurrent presence of enlarged thyroid nodule increases the probability of ectopic location. The combination of a giant PA that is ectopic (within the strap muscle) in the neck is very rare, especially in cases with no previous surgery. The rare histopathological findings of the current case, water clear cell parathyroid adenoma (WCCPA), could explain the patient's presentation, since it has low endocrine function. Case presentation: A 56-year-old Qatari female on routine visit to primary health care physician for hypertension, was incidentally discovered to be hypercalcemic and was referred to the emergency department of our institution. Neck ultrasound showed a thyroid nodule on the left side, but Tc-99m-sestamibi scintigraphy identified a left PA. FNAC of the thyroid nodule showed that it was a colloid nodule. She underwent left hemithyroidectomy and excision of left PA. Intraoperatively, the PA was giant and in the sternohyoid muscle. Intraoperative monitoring of intact PTH (IOiPTH) confirmed successful excision. Discussion: Ectopic giant parathyroid adenoma is rare especially with the intramuscular location in sternohyoid muscle in the neck without previous neck surgeries. The presence of thyroid nodule could be a precipitating factor for migration of the PA. Preoperative assessment with the radiological image is crucial for diagnosis but sometimes fail to localized the PA. Conclusion: Giant asymptomatic PA with long standing low function before hyperfunctioning should raise the suspicion of WCCPA. If diagnosis is confirmed, metastasis from a clear cell renal cell carcinoma should be ruled out.

关键词： Head and neck cancer   Human papillomavirus   Squamous cell carcinoma   Squamous cell carcinoma of unknown primary  

摘要： Purpose: To examine the potential benefit of reevaluation of original slides and p16 immunohistochemistry (IHC) of tonsillectomy specimens for primary tumor identification in cases of human papillomavirus (HPV) positive squamous cell carcinoma (SCC) of the head and neck of unknown primary. Materials and methods: Through a retrospective review, we identified all patients 18 or older who presented at our institution from 2003 to 2015 with histologically confirmed HPV-positive SCC in a cervical lymph node with unidentified primary tumor after initial workup. For patients for whom specimens were available, an expert head and neck pathologist re-reviewed original hematoxylin and eosin (H&E) slides to confirm absence of tumor and performed p16 IHC and deep sectioning of tissue blocks to identify potential tumor foci. Results: Among 735 patient records assessed, 80 were HPV-positive SCC with unknown primary, 28 of which did not have a primary tumor identified, and 20 with original specimens available. Upon re-review of 103 original H&E slides, invasive SCC was identified for 2 patients. Deep sectioning and p16 IHC did not identify additional primary tumors. Conclusion: Re-review of original slides by an expert head and neck pathologist, but not p16 staining or deeper H&E sections, was able to identify additional tumors.

关键词： oral cavity squamous cell carcinoma   T4b tumor   surgery   survival  

摘要： Objectives To describe patterns of primary surgical treatments in patients with T4b oral cavity squamous cell carcinoma (OCSCC). Study Design Historical cohort study. Setting National Cancer Database. Methods Review of the National Cancer Database between 2004 and 2017 for all T4b OCSCCs. Only patients with curative treatment methods were included in the survival analysis. Surgical and nonsurgical outcomes were compared by multivariable and propensity score matching analysis. Results A total of 1515 cases of T4b OCSCC were identified. A minority of patients (n = 363, 24.0%) underwent curative treatment;among these, 206 (56.7%) underwent primary surgery. Median length of follow-up was 24 months. The 90-day mortality of patients who underwent surgical treatment was 1.0%. The 2-year survival was higher for patients who underwent surgery + chemoradiotherapy (CRT) as compared with CRT (64.6% vs 45.2%, P < .001). On multivariable analysis, surgery + CRT was associated with longer survival. In a propensity score-matched cohort of 312 patients, 2-year survival remained higher in the surgical group versus the nonsurgical group (59.4% vs 45.5%, P = .02). Among patients who underwent surgery + CRT, there was no difference in 2-year survival between clinical T4a and T4b (59% vs 64.6%, P = .20). Conclusions A minority of patients with T4b OCSCC undergo treatments with curative intent. A subset of patients underwent primary surgical treatment, which was associated with longer survival. The T4b classification might entail a heterogenous group, and further studies in revision of this classification might be justified.

关键词： Glaucoma   Optineurin   RGCs   Human primary retinal cells   TBK1   TBK1 inhibitor   Amlexanox  

摘要： Studies carried out on the pathogenesis of glaucoma using murine cell lines and animal models require to be validated in human cells. Therefore, we explored the possibility of using human primary retinal cells (hPRCs) in culture as a model for molecular studies and testing of potential therapeutic drugs. For this purpose, central retinal tissue, obtained from the enucleated eyes of patients with anterior staphyloma, was digested with trypsin and grown in a medium containing supplements (basic fibroblast growth factor and fetal bovine serum). hPRCs at passage 1 and 2, show expression of either GFAP, a glial cell marker, or beta-III tubulin, a retinal ganglion cell (RGC)-specific marker. But at passages 3-5 nearly all of hPRCs express several RGC-specific markers (Brn3 proteins, Thy-1, beta-III tubulin, RBPMS and NeuN) but not GFAP. Expression of these markers indicated that these cells may have functional properties of RGCs. As RGCs are sensitive to glaucoma-associated mutants of OPTN, we analysed the survival of hPRCs upon overexpression of OPTN mutants. Glaucoma-associated mutants, E50KOPTN and M98K-OPTN, induced significantly higher cell death in hPRCs compared to WT-OPTN, whereas an amyotrophic lateral sclerosis-associated mutant, E478G-OPTN, did not. TBK1 inhibitor Amlexanox protected hPRCs from E50K-OPTN and M98K-OPTN induced cell death. M98K-OPTN induced cell death was suppressed by inhibitors of CaMKK beta and AMPK in hPRCs as well as in 661W, a mouse cell line that expresses several markers of RGCs and RGC precursor cells. Our results suggest that hPRCs under appropriate culture condition show RGClike properties. These cells can be used to explore the molecular mechanisms of cell death relevant for glaucoma pathogenesis and for testing of cytoprotective compounds.

关键词： Focal segmental glomerulosclerosis   Serum immunoglobulin G   Class-switched memory B cells   Plasmablasts  

摘要： Background: Focal segmental glomerulosclerosis (FSGS) is a kidney-specific autoimmune disease, but its pathogenesis is not fully known. The present study detected the frequencies of circulating memory B cells and plasmablasts and other clinical parameters in FSGS. Methods: We monitored 16 primary FSGS patients and 23 healthy controls (HC). Flow cytometry was used to analyze circulating memory B cell and plasmablasts percentages. Serum IgG levels were detected using a cytometric bead array (CBA). Results: The proportions of CD27 + IgD-class-switched memory B cells (P = 0.0002), CD27 + IgD-IgG + class-switched memory B cells (P < 0.0001), CD27hiCD38hi plasmablasts (P < 0.0001) and CD138 + plasma cells (P < 0.0001) were markedly elevated in FSGS patients, and the frequency of CD38 + IgG + plasmablasts (P < 0.0001) and serum IgG levels (P < 0.0001) were lower compared to HC. In the FSGS patients, the frequency of CD27 + IgD-IgG + class-switched memory B cells negatively correlated with CD38 + IgG + plasmablasts (P = 0.0183, R = -0.3375), serum IgG levels (P = 0.0061, R = -0.4263) and estimated glomerular filtration rate (eGFR) (P = 0.0074, R = -0.4114) but positively correlated with 24-h urinary protein levels (P = 0.0077, R = 0.4085). The proportion of CD38 + IgG + plasmablasts positively correlated with serum IgG levels (P = 0.0151, R = 0.3538). Conclusions: We speculate that alterations in the frequencies of CD27 + IgD-IgG + class-switched memory B cells and plasmablasts may be responsible for the etiopathogenesis of FSGS.

关键词： Always on   clock-free multi-function detectors   event-driven architecture   Internet of Things (IoTs)   level-crossing ADC (LCADC)   random sparse events (RSEs)   software-defined functions   time shielding (TS) technique   ultra-low power (ULP)   wake up  

摘要： This work presents an ultra-low-power software-defined always-on wake-up system to drastically decrease the system power of Internet of Things (IoTs) devices, which usually operate in random-sparse-event (RSE) scenarios. It mainly thanks to a clock-free time-shielding level-crossing ADC (TS-LCADC), software-defined clock-free multi-function detectors, and an asynchronous pipelined event-driven architecture. First, by quantifying RSE noisy signals with clock-free adaptive sampling in a signal-noise-rejecting manner, the proposed TS-LCADC reduces number of sampling points and power, and consumes only 41 nW when on-call waiting for IoT events. Second, the proposed clock-free multi-function detectors with offline and online programmability are able to character the signal features of versatile IoTs events and allow versatile and dynamic wake-up functions. Third, the proposed asynchronous pipelined event-driven architecture minimizes the system activity and thus power, because a power-hungry high-performance system (HPS) is only woken up when a detected parameter crosses its corresponding threshold. As such, the long-term average power (LTA-power) is dominated by the always-on circuits in RSE scenarios. The measurement results achieve 71-75 nW for three typical applications, i.e., heart rate, epilepsy, and keyword envelope detection. The LTA power is only 57 nW when waiting for RSE events, which is 30x lower than a prior general-purpose wake-up chip. Compared with other works of dedicated voice and acoustic wake-up functions, this work consumes 2x and 17x less power, respectively, while featuring 16x higher signal bandwidth and a broader versatility.

关键词： incidence   nomogram   prognosis   pulmonary acinar cell carcinoma   SEER  

摘要： Purpose The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). Methods PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease-specific survival (DSS) were evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. Results A total of 2918 patients were identified with PACC. The mean age was 65.2 +/- 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1-4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1- and 5-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. Conclusion PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1- and 5-year OS and DSS.

摘要： Although adjuvant radiotherapy has been used for cutaneous squamous cell carcinoma, its outcome benefits, especially for patients with clear surgical margins, have not been statistically estimated, and the characteristics that can indicate patients who require adjuvant therapy need to be validated with more evidence. We conducted a systematic review and meta-analysis of literature on the survival outcomes and prognostic factors in patients with cSCC treated by surgery with or without adjuvant radiotherapy. Twenty related studies involving 2605 patients met our inclusion criteria. The significant survival outcomes of adjuvant radiotherapy included lower recurrence (OR, 0.56;95% CI, 0.36-0.85), longer disease-free survival (OR, 2.17;95% CI, 1.23-3.83) and longer overall survival (OR, 2.94;95% CI, 1.75-4.91). Significant prognostic factors for poor outcomes were perineural invasion (HR, 1.61;95% CI, 1.24-2.09), involved surgical margins (HR, 2.34;95% CI, 1.42-3.83) and immunosuppression (HR, 3.02;95% CI, 2.14-4.25) while adjuvant radiotherapy significantly contributed to better overall survival (HR, 0.47;95% CI, 0.34-0.65). In conclusion, this systematic review suggests that in cutaneous squamous cell carcinoma patients with risk factors, including metastasis to the parotid gland, perineural invasion and immunosuppression, the use of adjuvant radiotherapy may be beneficial irrespective of surgical margin status.