Physiological Functions of the Cello-Oligosaccharides Binding CebE in the Pathogenic Streptomyces sp. AMCC400023.

Potato common scab, an economically important disease worldwide, is caused by pathogenic Streptomyces strains mainly through the effects of thaxtomin. The cello-oligosaccharides binding protein CebE is proposed as a gateway to the pathogenic development of Streptomyces scabiei. In this study, two functional CebE encoding genes, GEO5601 and GEO7671, were identified in pathogenic Streptomyces sp. AMCC400023. With a higher binding affinity towards signal molecules, the deletion of GEO5601 severely impaired thaxtomin-producing capacity and reduced the strain's pathogenicity. Transcriptional analysis confirmed that CebE5601 is also responsible for the import and provision of carbon sources for cell growth. With lower binding affinity, the pathogenicity island (PAI)-localized CebE7671 may assume a new function of mediating the biological process of sporulation, given the significantly impaired formation of ΔGEO7671 spores. The mechanisms of action of CebE proteins unraveled in Streptomyces sp. AMCC400023 will help pave the way for more effective prevention of the potato common scab disease.

An Effective Hyperspectral Image Classification Network Based on Multi-Head Self-Attention and Spectral-Coordinate Attention.

In hyperspectral image (HSI) classification, convolutional neural networks (CNNs) have been widely employed and achieved promising performance. However, CNN-based methods face difficulties in achieving both accurate and efficient HSI classification due to their limited receptive fields and deep architectures. To alleviate these limitations, we propose an effective HSI classification network based on multi-head self-attention and spectral-coordinate attention (MSSCA). Specifically, we first reduce the redundant spectral information of HSI by using a point-wise convolution network (PCN) to enhance discriminability and robustness of the network. Then, we capture long-range dependencies among HSI pixels by introducing a modified multi-head self-attention (M-MHSA) model, which applies a down-sampling operation to alleviate the computing burden caused by the dot-product operation of MHSA. Furthermore, to enhance the performance of the proposed method, we introduce a lightweight spectral-coordinate attention fusion module. This module combines spectral attention (SA) and coordinate attention (CA) to enable the network to better weight the importance of useful bands and more accurately localize target objects. Importantly, our method achieves these improvements without increasing the complexity or computational cost of the network. To demonstrate the effectiveness of our proposed method, experiments were conducted on three classic HSI datasets: Indian Pines (IP), Pavia University (PU), and Salinas. The results show that our proposed method is highly competitive in terms of both efficiency and accuracy when compared to existing methods.

Automatic Detection and Identification of Defects by Deep Learning Algorithms from Pulsed Thermography Data.

Infrared thermography (IRT), is one of the most interesting techniques to identify different kinds of defects, such as delamination and damage existing for quality management of material. Objective detection and segmentation algorithms in deep learning have been widely applied in image processing, although very rarely in the IRT field. In this paper, spatial deep-learning image processing methods for defect detection and identification were discussed and investigated. The aim in this work is to integrate such deep-learning (DL) models to enable interpretations of thermal images automatically for quality management (QM). That requires achieving a high enough accuracy for each deep-learning method so that they can be used to assist human inspectors based on the training. There are several alternatives of deep Convolutional Neural Networks for detecting the images that were employed in this work. These included: 1. The instance segmentation methods Mask-RCNN (Mask Region-based Convolutional Neural Networks) and Center-Mask; 2. The independent semantic segmentation methods: U-net and Resnet-U-net; 3. The objective localization methods: You Only Look Once (YOLO-v3) and Faster Region-based Convolutional Neural Networks (Fast-er-RCNN). In addition, a regular infrared image segmentation processing combination method (Absolute thermal contrast (ATC) and global threshold) was introduced for comparison. A series of academic samples composed of different materials and containing artificial defects of different shapes and nature (flat-bottom holes, Teflon inserts) were evaluated, and all results were studied to evaluate the efficacy and performance of the proposed algorithms.

A nomogram model based on pre-treatment and post-treatment MR imaging radiomics signatures: application to predict progression-free survival for nasopharyngeal carcinoma.

BACKGROUND: To establish a novel model using radiomics analysis of pre-treatment and post-treatment magnetic resonance (MR) images for prediction of progression-free survival in the patients with stage II-IVA nasopharyngeal carcinoma (NPC) in South China. METHODS: One hundred and twenty NPC patients who underwent chemoradiotherapy were enrolled (80 in the training cohort and 40 in the validation cohort). Acquiring data and screening features were performed successively. Totally 1133 radiomics features were extracted from the T2-weight images before and after treatment. Least absolute shrinkage and selection operator regression, recursive feature elimination algorithm, random forest, and minimum-redundancy maximum-relevancy (mRMR) method were used for feature selection. Nomogram discrimination and calibration were evaluated. Harrell's concordance index (C-index) and receiver operating characteristic (ROC) analyses were applied to appraise the prognostic performance of nomograms. Survival curves were plotted using Kaplan-Meier method. RESULTS: Integrating independent clinical predictors with pre-treatment and post-treatment radiomics signatures which were calculated in conformity with radiomics features, we established a clinical-and-radiomics nomogram by multivariable Cox regression. Nomogram consisting of 14 pre-treatment and 7 post-treatment selected features has been proved to yield a reliable predictive performance in both training and validation groups. The C-index of clinical-and-radiomics nomogram was 0.953 (all P < 0.05), which was higher than that of clinical (0.861) or radiomics nomograms alone (based on pre-treatment statistics: 0.942; based on post-treatment statistics: 0.944). Moreover, we received Rad-score of pre-treatment named RS1 and post-treatment named RS2 and all were used as independent predictors to divide patients into high-risk and low-risk groups. Kaplan-Meier analysis showed that lower RS1 (less than cutoff value, - 1.488) and RS2 (less than cutoff value, - 0.180) were easier to avoid disease progression (all P < 0.01). It showed clinical benefit with decision curve analysis. CONCLUSIONS: MR-based radiomics measured the burden on primary tumor before treatment and the tumor regression after chemoradiotherapy, and was used to build a model to predict progression-free survival (PFS) in the stage II-IVA NPC patients. It can also help to distinguish high-risk patients from low-risk patients, thus guiding personalized treatment decisions effectively.

Accelerating CO2 Electroreduction to Multicarbon Products via Synergistic Electric-Thermal Field on Copper Nanoneedles.

Electrochemical CO2 reduction is a promising way to mitigate CO2 emissions and close the anthropogenic carbon cycle. Among products from CO2RR, multicarbon chemicals, such as ethylene and ethanol with high energy density, are more valuable. However, the selectivity and reaction rate of C2 production are unsatisfactory due to the sluggish thermodynamics and kinetics of C-C coupling. The electric field and thermal field have been studied and utilized to promote catalytic reactions, as they can regulate the thermodynamic and kinetic barriers of reactions. Either raising the potential or heating the electrolyte can enhance C-C coupling, but these come at the cost of increasing side reactions, such as the hydrogen evolution reaction. Here, we present a generic strategy to enhance the local electric field and temperature simultaneously and dramatically improve the electric-thermal synergy desired in electrocatalysis. A conformal coating of ∼5 nm of polytetrafluoroethylene significantly improves the catalytic ability of copper nanoneedles (∼7-fold electric field and ∼40 K temperature enhancement at the tips compared with bare copper nanoneedles experimentally), resulting in an improved C2 Faradaic efficiency of over 86% at a partial current density of more than 250 mA cm-2 and a record-high C2 turnover frequency of 11.5 ± 0.3 s-1 Cu site-1. Combined with its low cost and scalability, the electric-thermal strategy for a state-of-the-art catalyst not only offers new insight into improving activity and selectivity of value-added C2 products as we demonstrated but also inspires advances in efficiency and/or selectivity of other valuable electro-/photocatalysis such as hydrogen evolution, nitrogen reduction, and hydrogen peroxide electrosynthesis.

Apparent diffusion coefficient for the prediction of tumor response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer.

BACKGROUND: Patients with locally advanced rectal cancer generally have different response rates to preoperative neoadjuvant chemo-radiotherapy. This study investigated the value of the apparent diffusion coefficient (ADC) as a predictor to forecast the response to neoadjuvant chemo-radiotherapy in patients with locally advanced rectal cancer. METHODS: Ninety-one locally advanced rectal cancer patients who underwent neoadjuvant chemo-radiotherapy between 2015 and 2018 were enrolled. Diffusion-weighted magnetic resonance imaging was performed before treatment and within 4 weeks after the completion of neoadjuvant chemo-radiotherapy. Mean ADC values of regions of interest were evaluated by two radiologists. The tumor response was evaluated according to RESCIST 1.1. The cut-off value for the mean ADC and increasing percentage (ΔADC%) after neoadjuvant chemo-radiotherapy was calculated using the receiver operating characteristic curve. The response rate of pre-ADC and ΔADC% above/below the cut-off values was determined using the chi-square test, respectively. Primary tumor progression-free survival (PFS) was analyzed using the Kaplan-Meier method, based on the pre-ADC and ΔADC% cut-off values. RESULTS: The cut-off value of mean pre-ADC and ΔADC% was 0.94 × 10-3 mm2/s (80.36% sensitivity, 74.29% specificity) and 26.0% (73.21% sensitivity, 77.14% specificity), respectively. Lower mean pre-ADC values were related to a better response rate (83.3% vs 29.7%, P < 0.001) and PFS (26.12 vs 17.70 months, P = 0.004). ΔADC% above the cut-off value was also related to a better response rate (83.7% vs 35.7%, P < 0.001) and PFS (26.93 vs 15.65 months, P = 0.034). CONCLUSIONS: The mean ADC pre-treatment value and ΔADC% were potential predictors for the tumor response in locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy.

Mean apparent diffusion coefficient in a single slice may predict tumor response to whole-brain radiation therapy in non-small-cell lung cancer patients with brain metastases.

OBJECTIVES: This study aimed to access the performance of apparent diffusion coefficient (ADC) as a predictor for treatment response to whole-brain radiotherapy (WBRT) in patients with brain metastases (BMs) from non-small-cell lung cancer (NSCLC). METHODS: A retrospective analysis was conducted of 102 NSCLC patients with BMs who underwent WBRT between 2012 and 2016. Diffusion-weighted MRI were performed pre-WBRT and within 12 weeks after WBRT started. Mean single-plane ADC value of ROIs was evaluated by two radiologists blinded to results of each other. The treatment response rate, intracranial progression-free survival (PFS), and overall survival (OS) were analyzed based on the ADC value and ΔADC respectively. At last, we used COX and logistic regression to do the multivariate analysis. RESULTS: There was good inter-observer agreement of mean ADC value pre-WBRT, post-WBRT, and ΔADC between the 2 radiologists (Pearson correlation 0.915 [pre-WBRT], 0.950 [post-WBRT], 0.937 [ΔADC], p < 0.001, for each one). High mean ADC value were related with better response rate (72.2% vs 37.5%, p = 0.001) and iPFS (7.6 vs 6.4 months, p = 0.031). High ΔADC were related with better response rate (73.6% vs 36.7%, p < 0.001). Multivariate analysis shows that histopathology, BMs number, high ADC value pre-WBRT, and high ΔADC post-WBRT were related to better treatment response of WBRT, and KPS, BMs number, and low ADC value pre-WBRT increased the risk of developing intracranial relapse. CONCLUSIONS: The mean single-plane ADC value pre-WBRT and ΔADC post-WBRT were potential predictor for intracranial tumor response to WBRT in NSCLC patients with brain metastases. KEY POINTS: • ADC value is a potential predictor of intracranial treatment response to WBRT in NSCLC patients with brain metastases. • Higher mean ADC value pre-WBRT and ΔADC post-WBRT of brain metastases were related to better intracranial tumor response. • Prediction of response before WBRT using ADC value can help oncologists to make better therapy plans and avoid missing opportunities for rescue therapy.

Prediction of Clinical Outcome at Discharge After Rupture of Anterior Communicating Artery Aneurysm Using the Random Forest Technique.

Background: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease. Anterior communicating artery (ACoA) aneurysm is the most frequent location of intracranial aneurysms. The purpose of this study is to predict the clinical outcome at discharge after rupture of ACoA aneurysms using the random forest machine learning technique. Methods: A total of 607 patients with ruptured ACoA aneurysms were included in this study between December 2007 and January 2016. In addition to basic clinical variables, 12 aneurysm morphologic parameters were evaluated. A multivariate logistic regression analysis was performed to determine the independent predictors of poor outcome. Of the 607 patients, 485 patients were randomly selected for training and the remaining for internal testing. The random forest model was developed using the training data set. An additional 202 patients from February 2016 to December 2017 were collected for externally validating the model. The prediction performance of the random forest model was compared with two radiologists. Results: Patients' age (odds ratio [OR] = 1.04), ventilated breathing status (OR = 4.23), World Federation of Neurosurgical Societies (WFNS) grade (OR = 2.13), and Fisher grade (OR = 1.50) are significantly associated with poor outcome. None of the investigated morphological parameters of ACoA aneurysm is an independent predictor of poor outcome. The developed random forest model achieves sensitivities of 78.3% for internal test and 73.8% for external test. The areas under receiver operating characteristic (ROC) curve of the random forest model were 0.90 for the internal test and 0.84 for the external test. Both sensitivities and areas under ROC curves of our model are superior to those of two raters in both internal and external tests. Conclusions: The random forest model presents good performance in predicting the outcome after rupture of ACoA aneurysms, which may aid in clinical decision making.

GDC-0349 inhibits non-small cell lung cancer cell growth.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related human mortality with a clear need for new therapeutic intervention. GDC-0349 is a potent and selective ATP-competitive mTOR inhibitor. In A549 cells and primary human NSCLC cells, GDC-0349 inhibited cell growth, proliferation, cell cycle progression, migration and invasion, while inducing significant apoptosis activation. Although GDC-0349 blocked Akt-mTORC1/2 activation in NSCLC cells, it also exerted cytotoxicity in Akt1-knockout A549 cells. Furthermore, restoring Akt-mTOR activation by a constitutively-active Akt1 only partially attenuated GDC-0349-induced A549 cell apoptosis, indicating the existence of Akt-mTOR-independent mechanisms. In NSCLC cells GDC-0349 induced sphingosine kinase 1 (SphK1) inhibition, ceramide accumulation, JNK activation and oxidative injury. Conversely, N-acetylcysteine, the JNK inhibitor and sphingosine 1-phosphate alleviated GDC-0349-induced NSCLC cell apoptosis. In vivo, daily oral administration of GDC-0349 potently inhibited NSCLC xenograft growth in mice. Akt-mTOR in-activation, SphK1 inhibition, JNK activation and oxidative stress were detected in NSCLC xenograft tissues with GDC-0349 administration. In summary, GDC-0349 inhibits NSCLC cell growth via Akt-mTOR-dependent and Akt-mTOR-independent mechanisms.

CircRNA BIRC6 promotes non-small cell lung cancer cell progression by sponging microRNA-145.

PURPOSE: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality world-wide. Recently, a number of circular RNAs (circRNAs) has been found to be differentially expressed in human NSCLCs, correlating with clinico-pathological features. As yet, the expression and potential role of circRNA BIRC6 (circBIRC6) in NSCLC have not been studied. METHODS: Expression of circBIRC6 and its target microRNA-145 (miR-145) in human NSCLC cells and tissues was assessed using qRT-PCR. In vitro genetic strategies were used to exogenously alter circBIRC6 and miR-145 expression. Their impact on in vitro and in vivo NSCLC cell behavior was studied. RESULTS: We found that circBIRC6 was upregulated in primary human NSCLC tissues and NSCLC cells, whereas its potential target, miR-145, was downregulated. In A549 NSCLC cells and primary human NSCLC cells, shRNA-induced silencing of circBIRC6 potently inhibited their growth, proliferation, migration and invasion. Conversely, we found that exogenous overexpression of circBIRC6 promoted these characteristics. Using RNA immunoprecipitation (RIP) in A549 cells, we found that Argonaute 2 (Ago2) immunoprecipitated together with both circBIRC6 and miR-145. Additional studies revealed that the miR-145 level increased after circBIRC6 silencing in A549 cells, but decreased after circBIRC6 overexpression. Of note, we found that the circBIRC6 silencing-induced anti-A549 activity could be attenuated by a miR-145 inhibitor. Lastly, we found that circBIRC6 silencing inhibited the growth of NSCLC xenografts in severe combined immunodeficient mice. CONCLUSIONS: From our data we conclude that circBIRC6 overexpression promotes NSCLC cell progression, possibly by sponging miR-145.

LINC02476 Promotes the Malignant Phenotype of Hepatocellular Carcinoma by Sponging miR-497 and Increasing HMGA2 Expression.

BACKGROUND: Long noncoding RNAs (lncRNAs) can promote hepatocellular carcinoma (HCC) initiation and progression. In this report, we examined the role of lncRNA LINC02476 in HCC. METHODS: The expression levels of different lncRNAs in HCC were explored using the TCGA database and lncRNA LINC02476 was selected for further study. The expression of LINC02476 in HCC tissues was determined by real-time PCR. The clinicopathological characteristics of HCC patients were analyzed relative to the expression of LINC02476. The expression of LINC02476 was downregulated in HCC cells using a lentiviral vector and different assays were performed to study cell growth, proliferation, invasion, apoptosis and the cell cycle. MiR-497 was selected as a miRNA that could interact with LINC02476 which was further tested by RNA immunoprecipitation. HMGA2 was selected as a possible target of miR-497, and their interaction was examined by a luciferase reporter assay. RESULTS: LINC02476 expression was elevated in HCC cell lines and HCC tissues. When LINC02476 was downregulated, the growth and the invasion of HCC cells decreased in vitro and in vivo. LINC02476 negatively regulated the expression of miR-497 by acting as a ceRNA. HMGA2 was directly targeted and inhibited by miR-497. CONCLUSION: The results indicate that LINC02476 functions through the miR-497/HMGA2 axis and that it has a role in the growth and metastasis of HCC cells. Therefore, LINC02476 could be an interesting new molecular target in HCC therapies.

Protein Expression Profile in Rat Silicosis Model Reveals Upregulation of PTPN2 and Its Inhibitory Effect on Epithelial-Mesenchymal Transition by Dephosphorylation of STAT3.

Silicosis is a chronic occupational lung disease caused by long-term inhalation ofcrystalline silica particulates. We created a rat model that closely approximates the exposure and development of silicosis in humans. Isobaric tags for relative and absolute quantitation (iTRAQ) technologies weused to identify proteins differentially expressed in activated rat lung tissue. We constructed three lentiviral knockdown vectorsand an overexpression vectorfor the protein tyrosine phosphatase non-receptor type 2 (PTPN2) geneto achieve stable long-term expression.A total of 471 proteins were differentially expressed in the silicosis group compared with controls. Twenty upregulated, and eight downregulated proteins exhibited a ≥ 1.5-fold change relative to controls. We next found that the PTPN2, Factor B, and VRK1 concentrations in silicotic rats silicosis and SiO2-stimulated MLE-12 cells were significantly higher than control groups.More importantly, we found that overexpression of PTPN2 simultaneously decreased the expression of phospho-signal transducer and activator of transcription 3 (p-STAT3) and Vimentin, while increasing E-cadherin expression. The opposite pattern was observed for PTPN2-gene silencing. We identified three proteins with substantially enhanced expression in silicosis. Our study also showed that PTPN2 can inhibit epithelial-mesenchymal transition by dephosphorylating STAT3 in silicosis fibrosis.

Ninjurin 2 overexpression promotes human colorectal cancer cell growth in vitro and in vivo.

Ninjurin 2 (NINJ2) is a novel adhesion molecule. Its expression and potential function in human colorectal cancer (CRC) cells are studied. We show that NINJ2 is overexpressed in established (HT-29) and primary CRC cells and in human colon cancer tissues. Its expression level is low in colon epithelial cells and normal colon tissues. NINJ2 shRNA or knockout (by CRSIPR/Cas9) potently inhibited human CRC cell survival and proliferation, while significantly inducing cell apoptosis. Conversely, lentivirus-mediated NINJ2 overexpression promoted CRC cell proliferation. NINJ2 co-immunoprecipitated with multiple RTKs (EGFR, PDGFRα/ß and FGFR) in CRC cells and human colon cancer tissues. In HT-29 cells, RTKs' downstream signalings, Akt and Erk, were significantly inhibited by NINJ2 shRNA or knockout, but augmented following ectopic NINJ2 overexpression. In vivo, NINJ2-silenced or NINJ2-knockout CRC xenografts grew significantly slower than the control xenografts. Akt-Erk activation was largely inhibited in CRC xenografts with NINJ2 silencing or knockout. Taken together, NINJ2 overexpression promotes CRC cell growth in vitro and in vivo.

Knockdown of lncRNA CCEPR suppresses colorectal cancer progression.

Long non-coding RNAs (lncRNAs) serve important roles in colorectal cancer. The aim of the present study was to investigate the expression and role of cervical carcinoma expressed PCNA regulatory (CCEPR) lncRNA in colorectal cancer progression. The results demonstrated that CCEPR expression was significantly higher in colorectal cancer tissues when compared with paired adjacent normal tissues. In addition, CCEPR expression was significantly higher in patients with advanced colorectal cancer (stage III/IV) than those with early-stage colorectal cancer (stage I/II). High CCEPR expression was significantly associated with poor differentiation, advanced clinical stage, positive lymph node metastasis and distant metastasis. Of particular note, patients with colorectal cancer exhibiting high CCEPR expression levels had shorter survival rates when compared with patients with low CCEPR expression. In vitro experiments demonstrated that the expression of CCEPR was increased in colorectal cancer cell lines when compared with a normal colon cell line. Knockdown of CCEPR significantly inhibited colorectal cancer cell proliferation, colony formation and cell cycle progression, as well as cell migration and invasion. Finally, silencing of CCEPR downregulated matrix metalloproteinase (MMP)-2 and MMP-9 expression and suppressed epithelial-mesenchymal transition in colorectal cancer cells. In conclusion, the results of the present study suggest that CCEPR may exert an oncogenic role in colorectal cancer, and CCEPR may be a promising molecular target for colorectal cancer treatment.

Circular RNA PRKCI promotes glioma cell progression by inhibiting microRNA-545.

We here tested expression and potential functions of circular RNA PRKCI (circPRKCI) in human glioma. Our results show that circPRKCI is upregulated in human glioma tissues and glioma cells, correlating with downregulation of its potential target, microRNA-545 (miR-545). In A172 and primary human glioma cells, shRNA-mediated silencing of circPRKCI inhibited cancer cell growth, survival, proliferation, and migration. Conversely, ectopic circPRKCI overexpression promoted A172 cell progression. miR-545 is the primary target of circPRKCI in glioma cells. Forced overexpression of miR-545 mimicked circPRKCI shRNA-induced actions, inhibiting glioma cell survival and proliferation. In contrast, miR-545 inhibition, by a lentiviral antagomiR-545 construct, reversed circPRKCI shRNA-induced anti-A172 cell activity. Importantly, neither circPRKCI shRNA nor circPRKCI overexpression was effective in miR-545-knockout (Cas9 method) A172 cells. Importantly, the subcutaneous and orthotopic A172 xenograft growth was significantly inhibited by circPRKCI silencing. Collectively, circPRKCI promotes human glioma cell progression possibly by inhibiting miR-545. Targeting circPRKCI-miR-545 cascade could efficiently inhibit human glioma cells.

Prediction of rupture risk in anterior communicating artery aneurysms with a feed-forward artificial neural network.

OBJECTIVES: Anterior communicating artery (ACOM) aneurysms are the most common intracranial aneurysms, and predicting their rupture risk is challenging. We aimed to predict this risk using a two-layer feed-forward artificial neural network (ANN). MATERIALS AND METHOD: 594 ACOM aneurysms, 54 unruptured and 540 ruptured, were reviewed. A two-layer feed-forward ANN was designed for ACOM aneurysm rupture-risk analysis. To improve ANN efficiency, an adaptive synthetic (ADASYN) sampling approach was applied to generate more synthetic data for unruptured aneurysms. Seventeen parameters (13 morphological parameters of ACOM aneurysm measured from these patients' CT angiography (CTA) images, two demographic factors, and hypertension and smoking histories) were adopted as ANN input. RESULTS: Age, vessel size, aneurysm height, perpendicular height, aneurysm neck size, aspect ratio, size ratio, aneurysm angle, vessel angle, aneurysm projection, A1 segment configuration, aneurysm lobulations and hypertension were significantly different between the ruptured and unruptured groups. Areas under the ROC curve for training, validating, testing and overall data sets were 0.953, 0.937, 0.928 and 0.950, respectively. Overall prediction accuracy for raw 594 samples was 94.8 %. CONCLUSION: This ANN presents good performance and offers a valuable tool for prediction of rupture risk in ACOM aneurysms, which may facilitate management of unruptured ACOM aneurysms. KEY POINTS: • A feed-forward ANN was designed for the prediction of rupture risk in ACOM aneurysms. • Two demographic parameters, 13 morphological aneurysm parameters, and hypertension/smoking history were acquired. • An ADASYN sampling approach was used to improve ANN quality. • Overall prediction accuracy of 94.8 % for the raw samples was achieved.

Quantitative assessment on blood-brain barrier permeability of acute spontaneous intracerebral hemorrhage in basal ganglia: a CT perfusion study.

PURPOSE: Blood-brain barrier (BBB) damage aggravates perihematomal edema, and edema volume predicts prognosis independently. But the BBB permeability at the late stage of acute intracerebral hemorrhage (ICH) patients is uncertain. We aimed to assess the BBB permeability of spontaneous basal ganglia ICH using computed tomographic perfusion (CTP) and investigates its relationship with hematoma and perihematomal edema volume. METHODS: We performed CTP on 54 consecutive ICH patients within 24 to 72 h after symptom onset. Permeability-surface area product (PS) derived from CTP imaging was measured in hematoma, "high-PS spot," perihematoma, normal-appearing, hemispheric, and contralateral regions. Hematoma and edema volumes were calculated from non-contrast CT. RESULTS: "High-PS spot" and perihematoma regions had higher PS than the contralateral regions (p < 0.001). Hematoma PS was lower than that in the contralateral regions (p < 0.001). Perihematoma PS of the large-hematoma group was higher than that of the small-hematoma group (p = 0.011). Perihematomal edema volume correlated positively with hematoma volume (ß = 0.864, p < 0.001) and perihematoma PS (ß = 0.478, p < 0.001). Perihematoma PS correlated positively with hematoma volume (ß = 0.373, p = 0.005). CONCLUSIONS: Locally elevated perihematoma PS was found in most spontaneous basal ganglia ICH patients within 24 to 72 h after symptom onset. Perihematoma PS was higher in larger hematomas and was associated with larger edema volume. At this period, BBB leakage is likely to be an important factor in edema formation.

Definitive concurrent chemoradiotherapy with S-1 and cisplatin in elderly esophageal squamous cell carcinoma patients.

BACKGROUND: To evaluate the feasibility and efficiency of definitive concurrent chemoradiotherapy (dCRT) with S-1 and cisplatin for elderly esophageal squamous cell carcinoma (ESCC) patients. METHODS: Fifty-six elderly patients were included from January 2012 to December 2014. Patients received S-1 (tegafur/gimeracil/oteracil) and cisplatin at doses of 70 mg/m2/day for two weeks and 75 mg/m2 on day 1, respectively, every 3 weeks. Radiotherapy was delivered at a dose of 180-200 cGy per day to a total dose of 54 Gy. After dCRT, additional chemotherapy was administered for two cycles. RESULTS: The median age was 74 years (range: 70-87 years) and 38 (67.9%) patients were staged with III-IVa. Totally, 38 patients completed dCRT as planned. An objective response rate (ORR) was seen in 47 (84.0%) patients. The median OS and PFS time were 18.2 and 13.9 months and the 3-year OS and PFS rates were 30.1% and 14.2%, respectively. The most frequent hematological toxicities were leucocytopenia and neutropenia with the incidence of 55.4% and 53.6%, respectively. A significantly higher incidence of severe leucocytopenia was observed between patients aged ≥75 and 70≤ age <75 years. The most common non-hematologic toxicity was esophagitis. CONCLUSIONS: dCRT with S-1 and cisplatin yielded satisfactory survival outcomes but treatment-related toxicities were relatively high, especially for patients aged over 75 years.

Computed Tomography Perfusion Deficits during the Baseline Period in Aneurysmal Subarachnoid Hemorrhage Are Predictive of Delayed Cerebral Ischemia.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is a frequent and fearful complication following aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study is to assess the diagnostic accuracy of computed tomography perfusion (CTP) during an admission baseline period for the prediction of DCI. METHODS: Fifty-four aSAH cases were screened by baseline CTP within 3 days after aSAH and were reexamined with CTP 7-17 days after aSAH. Relative cerebral blood volume, relative cerebral blood flow (CBF), and relative mean transit time were measured. DCI was confirmed by a combination of noncontrast CT, CTP reexamination, and clinical assessment of neurologic deficits. Quantitative baseline and reexamination CTP data for all patients were compared between DCI and without DCI groups using Student's t-tests. The quantitative baseline and reexamination CTP data of DCI patients were compared using paired Student's t-tests. The χ2 test was used to evaluate incidences of DCI between different baseline relative CBF levels. The optimal cutoff value for each parameter was established by receiver operating characteristic curve analysis. RESULTS: Of the patients included in this study, 33.3% (18 of 54) developed DCI. There was a significant difference in the incidence of DCI among different baseline relative CBF subsets (χ2 = 38.00, P < .05). A relative CBF of .84 had the highest specificity and sensitivity of predicting DCI. CONCLUSION: CTP parameters during the baseline period can be helpful for the early identification of aSAH patients who are at high risk for DCI.

Activity guided isolation and modification of juglone from Juglans regia as potent cytotoxic agent against lung cancer cell lines.

BACKGROUND: Juglans regia has been found to exhibit significant anticancer activity against various human cancer cell lines. This study was undertaken to isolate the active chemical constituent (Juglone) and to investigate its cytotoxic activity along with its various analogs against different human cancer cell lines. METHODS: Isolation of juglone, a napthoquinone, from the chloroform extract of the root part of Juglans regia was executed by flash chromatography using silica gel as stationary phase. The isolated Juglone was used as starting material for the further synthesis of a novel series of triazolyl analogs using click chemistry approach to investigate their cytotoxic potential against different human cancer cell lines using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. RESULTS: The different extracts of Juglans regia and the isolated compound (juglone) exhibited satisfactory cytotoxic activity against a panel of eight different human cancer cell lines namely, prostate colon (Colo-205 and HCT-116), breast (T47D), prostate (PC-3 and DU-145), skin (A-431) and lung (NCI-H322 and A549). Interestingly, all the synthesised analogs displayed enhanced and selective cytotoxic activity against lung cancer cell lines only. Of the synthesized derivatives, 15a and 16a displayed the best activity with IC50 of 4.72 and 4.67 µM against A549 cells. Both these derivatives exhibited superior potency to BEZ-235 against both the lung cancer cell lines. So far as the structural aspects are concerned, electron withdrawing substituents at the ortho position of R moiety of the triazolyl analogs seem to be essential for attaining better activity. CONCLUSION: The present study demonstrates the selective and enhanced cytotoxic activity of the triazolyl analogs of juglone against NCI-H322 and A549 human lung cancer cell lines. Some derivatives exhibited superior potency to BEZ-235, a commercially available anticancer agent.