bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication and Use of Nanopipettes in Chemical Analysis
Authors: Zhang Shudong , Li Mingzhi , Su Bin , Shao Yuanhua
Published: June 2018

This review summarizes progress in the fabrication, modification, characterization, and applications of nanopipettes since 2010. A brief history of nanopipettes is introduced, and the details of fabrication, modification, and characterization of nanopipettes are provided. Applications of nanopipettes in chemical analysis are the focus in several cases, including recent progress in imaging; in the study of single molecules, single nanoparticles, and single cells; in fundamental investigations of charge transfer (ion and electron) reactions at liquid/liquid interfaces; and as hyphenated techniques combined with other methods to study the mechanisms of complicated electrochemical reactions and to conduct bioanalysis.
An Approach to Linguistic Multiple Attribute Decision-Making Based on Unbalanced Linguistic Generalized Heronian Mean Aggregation Operator
Authors: Han Bing , Chen Huayou , Zhu Jiaming , Liu Jinpei
Published: June 2018

This paper proposes an approach to linguistic multiple attribute decision-making problems with interactive unbalanced linguistic assessment information by unbalanced linguistic generalized Heronian mean aggregation operators. First, some generalized Heronian mean aggregation operators with unbalanced linguistic information are proposed, involving the unbalanced linguistic generalized arithmetic Heronian mean operator and the unbalanced linguistic generalized geometric Heronian mean operator. For the situation that the input arguments have different degrees of importance, the unbalanced linguistic generalized weighted arithmetic Heronian mean operator and the unbalanced linguistic generalized weighted geometric Heronian mean operator are developed. Then we investigate their properties and some particular cases. Finally, the effectiveness and universality of the developed approach are illustrated by a low-carbon tourist instance and comparison analysis. A sensitivity analysis is performed as well to test the robustness of proposed methods.
Modelling the Embedded Control System Using iUML-B Pattern State Machine
Authors: Peng Han , Du Chenglie , Rao Lei , Liu Zhouzhou
Published: June 2018

Developing the formal model based on the Event-B design pattern is an excellent method to improve the development efficiency of the embedded control system and improve the reusability of the formal model. However, the instantiation of the Event-B design pattern requires the manual writing of a large number of model codes, which brings a great deal of learning cost and coding burden to the engineering staff. In this paper, we propose a modelling approach for formal development of control systems based on the application of iUML-B state machine patterns to model the four synchronization patterns of the typical control system. Then, we use the instantiation of iUML-B pattern state machine to establish a typical multilevel control system's Event-B model. The simulation results show that the event trace of the model obtained using our method is the same as that of the corresponding model obtained using the traditional Event-B design pattern. Compared with the traditional Event-B design pattern method, our method can greatly reduce the manual coding burden in the modelling process. The system model expressed using the iUML-B pattern state machine can be easily mapped to the labelled transition system so as to verify the behavioural properties of the model.
Predictive Value of Combined LIPS and ANG-2 Level in Critically Ill Patients with ARDS Risk Factors
Authors: Xu Zhi , Wu Guo-Ming , Li Qi , Ji Fu-Yun , Shi Zhong , Guo Hong , Yin Jin-Bo , Zhou Jian , Gong Liang , Mei Chun-Xia , Wang Guan-Song
Published: June 2018

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P<0.001, P<0.006, and P<0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.
Evidence That ADAM17 Mediates the Protective Action of CGRP against Angiotensin II-Induced Inflammation in Vascular Smooth Muscle Cells
Authors: Zeng Si-yu , Yang Li , Hong Chen-liang , Lu Hui-qin , Yan Qiu-jiang , Chen Yan , Qin Xu-ping
Published: June 2018

Calcitonin gene-related peptide (CGRP) has a potent protective action on the cardiovascular system; however, little is known about the role of CGRP in angiotensin II- (Ang II-) induced inflammation of vascular smooth muscle cells (VSMCs). This study is aimed at determining the anti-inflammatory effect of CGRP in Ang II-treated VSMCs and whether a disintegrin and metalloproteinase 17 (ADAM17) modulates this protective action. Small interference RNA (siRNA) and inhibitors of CGRP, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase 1/2 (ERK1/2) were adopted to investigate their effect on Ang II-induced inflammation in VSMCs. Here, we found that CGRP could inhibit inflammation and decrease ADAM17 expression and activation of EGFR and ERK1/2 in VSMCs stimulated with Ang II. Results of siRNA demonstrated that ADAM17 siRNA attenuated Ang II-induced inflammation and up-regulation of activities of EGFR and ERK1/2 in VSMCs. Furthermore, the EGFR-ERK1/2 pathway promoted Ang II-induced VSMC inflammation. In summary, these findings identify the anti-inflammatory effect of CGRP in VSMCs stimulated by Ang II and suggest that ADAM17 is involved in the protective effect of CGRP against Ang II-induced inflammation via the EGFR-ERK1/2 pathway in VSMCs.
Research on Supply Chain Coordination and Profit Allocation Based on Altruistic Principal under Bilateral Asymmetric Information
Authors: Gu Shuiliang , Guo Hongmei , Su Yingsheng
Published: June 2018

To ensure supply chain coordination and equitable profit allocation when there is bilateral asymmetric information, a supply chain consisting of one manufacturer with private manufacturing cost information and one retailer with private selling cost information is considered. A bilateral adverse selection model is established with a virtual altruistic principal as the coordination subject, for which the supply chain coordination conditions and an allocation rule for the supply chain surplus are then given. It was found that contract coordination depended on the costs and risk rates of both parties and market demand; that is, the lower the costs and the risk rate, the easier the supply chain coordination. Second, the trading volume distortion degree was positively correlated with production cost, sales cost, and price sensitivity and negatively correlated with the market environment parameter. Third, the allocation proportion for the supply chain surplus was determined. Finally, under a specific cost distribution assumption, a numerical example was given to simulate the contract execution and analyze the relationships between costs and profit.
Parameter Estimation on a Stochastic SIR Model with Media Coverage
Authors: Li Changguo , Pei Yongzhen , Zhu Meixia , Deng Yue
Published: June 2018

Media coverage reduces the transmission rate from infective to susceptible individuals and is reflected by suitable nonlinear functions in mathematical modeling of the disease. We here focus on estimating the parameters in the transmission rate based on a stochastic SIR epidemic model with media coverage. In order to reduce the computational load, the Newton-Raphson algorithm and Markov Chain Monte Carlo (MCMC) technique are incorporated with maximum likelihood estimation. Simulations validate our estimation results and the necessity of a model with media coverage when modeling the contagious diseases.
Dynamic Stability and Control of a Manipulating Unmanned Aerial Vehicle
Authors: Liu Yunping , Huang Xijie , Zhang Yonghong , Zhou Yukang
Published: June 2018

This paper focuses on the dynamic stability analysis of a manipulator mounted on a quadrotor unmanned aerial vehicle, namely, a manipulating unmanned aerial vehicle (MUAV). Manipulator movements and environments interaction will extremely affect the dynamic stability of the MUAV system. So the dynamic stability analysis of the MUAV system is of paramount importance for safety and satisfactory performance. However, the applications of Lyapunov’s stability theory to the MUAV system have been extremely limited, due to the lack of a constructive method available for deriving a Lyapunov function. Thus, Lyapunov exponent method and impedance control are introduced, and the Lyapunov exponent method can establish the quantitative relationships between the manipulator movements and the dynamics stability, while impedance control can reduce the impact of environmental interaction on system stability. Numerical simulation results have demonstrated the effectiveness of the proposed method.
How Could We Influence Systemic Inflammation in Allergic Rhinitis? The Role of H1 Antihistamines
Authors: Muntean Ioana Adriana , Bocsan Ioana Corina , Miron Nicolae , Buzoianu Anca Dana , Deleanu Diana
Published: June 2018

The aim of the study was the analysis of adhesion molecules’ profile (ICAM‐1, VCAM‐1, and E‐selectin) in patients with allergic rhinitis and the influence of H1 antihistamines on those markers. Seventy‐nine patients with persistent allergic rhinitis (PAR) and 30 healthy volunteers were included in the study. The patients with PAR were treated with desloratadine 5 mg/day or levocetirizine 5 mg/day for 4 weeks. The clinical (rhinitis symptoms and total symptoms score (TSS), type of sensitization) and biological evaluation (total IgE, eosinophils, ICAM‐1, VCAM‐1, and E‐selectin) as well as fractionate nitric oxide in exhaled air (FeNO) measurement was performed before and after treatment. The plasmatic levels of ICAM‐1, VCAM‐1, total IgE, and eosinophils and FeNO were significantly increased in patients with PAR compared to healthy volunteers. H1 antihistamines significantly improved TSS, with no differences between the investigated drugs. There was a significant decrease of eosinophils, total IgE, and FeNO after treatment. H1 antihistamines significantly decreased the plasmatic levels of ICAM‐1 and E‐selectin but not VCAM‐1 compared to basal values. There is no difference between levocetirizine and desloratadine in the reduction of CAMs. A systemic inflammation characterized by increased levels of CAMs is present in patients with PAR. H1 antihistamines improve symptoms and reduce CAMs and FeNO levels after 1 month of treatment. H1 antihistamines might reduce the systemic inflammation which could be responsible to asthma occurrence in patients with PAR.
Modification of Medium Composition for Enhancing the Production of Antifungal Activity fromXenorhabdus stockiaePB09 by Using Response Surface Methodology
Authors: Sa-uth Chirayu , Rattanasena Paweena , Chandrapatya Angsumarn , Bussaman Prapassorn
Published: June 2018

Xenorhabdus stockiaePB09 bacterium has been shown to exhibit antifungal activity against several plant pathogens. To improve its efficacy, the optimization of the nutritional components in culture media was performed. The medium components that have significant effects on antifungal activity ofX. stockiaePB09 were initially identified using a fractional factorial design. Response surface methodology and central composite design were then used to create a model for optimizing the levels of carbon, nitrogen, and mineral sources that maximize antifungal activity ofX. stockiaePB09. After that, the suitable carbon, nitrogen, and mineral sources were selected and adjusted by the second-order polynomial regression model, which predicted that 98.62% of antifungal activity could be obtained when the medium contained sucrose, yeast extract, NaCl, and K2HPO4at 3.24, 23.71, 5.46, and 2.73 g/L, respectively. Laboratory verification of this recipe resulted in the antifungal activity at 97.95% in the shake flask experiment after 48-hour cultivation, which was significantly 27.22% higher than that obtained by using the TSB medium. In addition,X. stockiaePB09 cultured in the verified recipe by using 5 L fermenter could effectively inhibit the mycelial growth ofPhytophthorasp.,Rhizoctonia solani,Pythiumsp., andFusarium oxysporum. This study demonstrated that the RSM and CCD were shown to be valuable tools for optimizing the culture medium that maximize the antifungal activity ofX. stockiaePB09.
Effect of Rare-Earth Elements on the Corrosion Resistance of Flux-Cored Arc-Welded Metal with 10CrNi3MoV Steel
Authors: Wang Kai , Lu Qinghua , Jiang Zexin , Yi Yaoyong , Yi Jianglong , Niu Ben , Ma Jinjun , Hu Huiping
Published: June 2018

We modified the content of rare-earth elements (REE) in the flux-cored wire used to produce welds of high-strength low-alloy (HSLA) steel. The effect of REE addition on the microstructure as well as on the mechanical and electrochemical properties of the welded metal (WM) was investigated. REE-modified welded metals show very different responses during electrochemical impedance spectroscopy and the potentiodynamic polarization tests. The results indicate that the addition of REE of 0.3 wt.% facilitates a more uniform microstructure and improves both mechanical properties and corrosion resistance in welded metals.
In Vitro and In Vivo Immunomodulator Activities of Allium sativum L.
Authors: Moutia Mouna , Habti Norddine , Badou Abdallah
Published: June 2018

Allium Sativum L. (garlic), which is a species of the onion family, Alliaceae, is one of the most used plants in traditional medicine worldwide. More than 200 chemicals with diverse properties have been found in garlic extracts. Several garlic compounds were suggested to be efficient in improving various pathologies including certain types of cancer. This paper is an overview of data about garlic biological activities in vitro and/or in vivo on immune cells, on the development of certain inflammatory diseases, and on different types of carcinomas and sarcomas. Garlic and its compounds were found to have notable antioxidant properties. Garlic therapeutic potential has also been studied in several inflammatory diseases such as allergic‐airway inflammation, inflammatory bowel disease, arthritic rheumatism, and atherosclerosis. Furthermore, garlic was found to be able to maintain the immune system homeostasis and to exhibit beneficial effects on immune cells especially through regulation of proliferation and cytokine gene expression. Finally, we will show how major garlic components such as sulfur compounds and polyphenols might be responsible for the garlic biological activities revealed in different situations. If identified, specific compounds present in garlic could potentially be used in therapy.
Feasibility of Ideal Cardiovascular Health Evaluation in a Pediatric Clinic Setting
Authors: Blackett Piers , Farrell Kerry , Truong Minh , George Minu , Turner Peggy , Less Joane , Baldwin Jonathan D. , Knehans Allen W.
Published: June 2018

The feasibility of “point-of-care” screening for ideal cardiovascular health was explored in a pediatric specialty clinic setting. Children and adolescents aged 9–18 years (n=91) with treated and stabilized diseases were recruited at a pediatric endocrinology clinic. A table-top device was used to assay fingerstick samples for non-HDL cholesterol (non-HDL-C), which was used to divide participants into two groups based on the non-HDL-C threshold for comparison of the remaining metrics between groups. A significant number of children had low scores, and score frequency distribution was similar to larger retrospective studies, with few participants achieving none or all of the health metrics. Healthy diet was the metric least often achieved. Those with a non-HDL-C above the ideal threshold of 3.1 mmol/L (120 mg/dl) had a higher BMI percentile (p<0.01) and diastolic blood pressure percentile (p<0.05). We conclude that pediatric risk factor screening and scoring can be performed in a specialty clinic with meaningful cardiovascular health scores for patients and providers. Association of abnormal “point-of care” non-HDL-C levels with elevated BMI and blood pressure supports evidence for risk factor clustering and use of the ideal health construct in pediatric clinic settings.
Impact of Global Mean Normalization on Regional Glucose Metabolism in the Human Brain
Authors: Mortensen Kristian N. , Gjedde Albert , Thompson Garth J. , Herman Peter , Parent Maxime J. , Rothman Douglas L. , Kupers Ron , Ptito Maurice , Stender Johan , Laureys Steven , Riedl Valentin , Alkire Michael T. , Hyder Fahmeed
Published: June 2018

Because the human brain consumes a disproportionate fraction of the resting body’s energy, positron emission tomography (PET) measurements of absolute glucose metabolism (CMRglc) can serve as disease biomarkers. Global mean normalization (GMN) of PET data reveals disease-based differences from healthy individuals as fractional changes across regions relative to a global mean. To assess the impact of GMN applied to metabolic data, we compared CMRglc with and without GMN in healthy awake volunteers with eyes closed (i.e., control) against specific physiological/clinical states, including healthy/awake with eyes open, healthy/awake but congenitally blind, healthy/sedated with anesthetics, and patients with disorders of consciousness. Without GMN, global CMRglc alterations compared to control were detected in all conditions except in congenitally blind where regional CMRglc variations were detected in the visual cortex. However, GMN introduced regional and bidirectional CMRglc changes at smaller fractions of the quantitative delocalized changes. While global information was lost with GMN, the quantitative approach (i.e., a validated method for quantitative baseline metabolic activity without GMN) not only preserved global CMRglc alterations induced by opening eyes, sedation, and varying consciousness but also detected regional CMRglc variations in the congenitally blind. These results caution the use of GMN upon PET-measured CMRglc data in health and disease.
A Note on Marcinkiewicz Integrals along Submanifolds of Finite Type
Authors: Zhang Daiqing
Published: June 2018

We study the parametric Marcinkiewicz integrals along submanifolds of finite type with rough kernels. The kernels of our operators are allowed to be very rough both on the unit sphere and in the radial direction. Under the rather weakened size conditions on the integral kernels, the Lp bounds will be established for such operators. As applications, the corresponding results for parametric Marcinkiewicz integrals related to area integrals and Littlewood-Paley gλ⁎ functions are also given.
Biometrics Based Privacy‐Preserving Authentication and Mobile Template Protection
Authors: Yang Wencheng , Hu Jiankun , Wang Song , Wu Qianhong
Published: June 2018

Smart mobile devices are playing a more and more important role in our daily life. Cancelable biometrics is a promising mechanism to provide authentication to mobile devices and protect biometric templates by applying a noninvertible transformation to raw biometric data. However, the negative effect of nonlinear distortion will usually degrade the matching performance significantly, which is a nontrivial factor when designing a cancelable template. Moreover, the attacks via record multiplicity (ARM) present a threat to the existing cancelable biometrics, which is still a challenging open issue. To address these problems, in this paper, we propose a new cancelable fingerprint template which can not only mitigate the negative effect of nonlinear distortion by combining multiple feature sets, but also defeat the ARM attack through a proposed feature decorrelation algorithm. Our work is a new contribution to the design of cancelable biometrics with a concrete method against the ARM attack. Experimental results on public databases and security analysis show the validity of the proposed cancelable template.
Assessing the Difference in Measuring Bolt Stress: A Comparison of Two Optical Fiber Sensing Techniques
Authors: Chai Jing , Liu Qi , Liu Jinxuan , Zhang Guihua , Zhang Dingding , Qiu Fengqi
Published: June 2018

Monitoring the load level of the rock bolts is of great importance for assessing risk. Based on the mechanical transmission mechanism of grouting bolts, the bolt pull-out test was carried out in lab. The performance of the bolt under pull-out loading was measured using the pulse-pre-pump Brillouin optical time domain analysis (PPP-BOTDA) and fiber Bragg grating (FBG) sensing technologies. The distribution characteristic of axial stress along the bolt was analysed in combination with the measurements obtained by the two sensing technologies. The relative standard deviation for repeatability errors in the determination and the setting time of resin grout was investigated. The results show that the distribution of axial stress is nonuniform along the anchorage section. The maximum value of axial stress on the bolt is closed to the pull-out side. The relative standard deviation for repeatability errors obtained by PPP-BOTDA is less than that obtained by FBG. The comparison of the measurements obtained by the two methods indicates that when the drawing force is greater than 20 kN and the axial stress is more than 10 kN, the two methods have better consistency. In the field application, it is necessary to estimate the deformation of matrix, leaving at least 500 minutes for resin bond to work.
Thiol/Disulfide Balance in Patients with Familial Hypercholesterolemia
Authors: Şimşek Özgür , Çarlıoğlu Ayşe , Alışık Murat , Edem Efe , Biçer Cemile Koca
Published: June 2018

Objective. Herein, we investigated the balance of thiol/disulfide, with the hypothesis that the balance between disulfides and thiols, which are natural antioxidants, might be disrupted in patients with familial hypercholesterolemia, which eventually leads to endothelial damage. Methods. In this study, we evaluated 51 patients diagnosed with familial hypercholesterolemia and 81 healthy subjects. Blood samples were taken from the patients after a minimum of 12 hours of fasting; samples were immediately centrifuged, stored in Eppendorf tubes, and preserved at −80°C. Results. This study found that thiol levels are significantly lower in patients with familial hypercholesterolemia, whereas disulfide levels are higher (independent of age, gender, and body mass index). This means that in such patients, the thiol/disulfide balance changes in favour of disulfide. Conclusions. In this study, we found that the thiol/disulfide balance in patients with familial hypercholesterolemia is disrupted in favour of disulfide.
Synergetic Effects ofPlasmodium, Hookworm, andSchistosoma mansoniInfections on Hemoglobin Level among Febrile School Age Children in Jawe Worda, Northwest Ethiopia
Authors: Hailu Tadesse , Yimer Mulat , Mulu Wondemagegn , Abera Bayeh
Published: June 2018

Plasmodium coinfection with hookworm and/orSchistosoma mansonihas detrimental effects on human’s hemoglobin level. This study aimed to determine the effects of plasmodium, hookworm, andS. mansoniinfections on hemoglobin level among febrile school age children in Northwest Ethiopia. A cross-sectional study was conducted from April 2016 to August 2016.Plasmodiumand helminths infections were detected using Giemsa stain and formol-ether concentration techniques, respectively. Hemoglobin level was determined using Hemocue method. Among 333 children, 143 (42.9%), 49 (14.75%), and 22 (6.6%) hadPlasmodium, hookworm, and Schistosoma mansoniinfections, respectively. The prevalence ofPlasmodium-hookworm andPlasmodium-Schistosoma mansonicoinfections was 18 (12.6%) and 4 (2.8%) in children, respectively. The overall prevalence of anaemia in children was 41.4%. Effect ofPlasmodium, hookworm, andSchistosoma mansonion hemoglobin level was high. Therefore, febrile children should be screened forPlasmodium, hookworm,Schistosoma mansoni,and anaemia simultaneously in malaria endemic areas.
Design, Analysis, Optimization, Manufacturing, and Testing of a 2U Cubesat
Authors: Ampatzoglou Andreas , Kostopoulos Vassilis
Published: June 2018

The design optimization, development, and verification by analysis and testing of the 1st Greek cubesat, developed by the University of Patras and Libre Space Foundation (UPSat (University of Patras Satellite)), is presented. The key innovative approach includes the replacement of the aluminum side faces with structural composite components, keeping the commonly used aluminum frame. A “hybrid” double-unit (2U) cubesat structure was optimized, built, and tested for all launch and thermal loads/specifications required for launch and mission operations as imposed from the EU-funded FP7-QB50 project. Results show that the new design of the structure using CFRP can offer similar levels of performance in terms of stiffness, while saving 30% of the mass, for the entire cubesat platform.
Inhibition of HER2 Increases JAGGED1-dependent Breast Cancer Stem Cells: Role for Membrane JAGGED1
Authors: Shah Deep , Wyatt Debra , Baker Andrew T. , Simms Patricia , Peiffer Daniel S. , Fernandez Michelle , Rakha Emad , Green Andrew , Filipovic Alexandra , Miele Lucio , Osipo Clodia
Published: June 2018

Purpose: HER2-positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as cancer stem cells (CSC). CSCs are implicated in radiotherapy, chemotherapy resistance, and tumor recurrence. NOTCH promotes breast CSC survival and self-renewal, and overexpression of NOTCH1 and the NOTCH ligand JAGGED1 predict poor outcome. Resistance to anti-HER2 therapy in HER2+ breast cancer requires NOTCH1, and that combination of trastuzumab and a gamma secretase inhibitor (GSI) prevents tumor relapse in xenograft models.

Experimental Design: The current study investigates mechanisms by which HER2 tyrosine kinase activity regulates NOTCH-dependent CSC survival and tumor initiation.

Results: Lapatinib-mediated HER2 inhibition shifts the population of HER2+ breast cancer cells from low membrane JAGGED1 expression to higher levels, independent of sensitivity to anti-HER2 treatment within the bulk cell population. This increase in membrane JAGGED1 is associated with higher NOTCH receptor expression, activation, and enrichment of CSCs in vitro and in vivo. Importantly, lapatinib treatment results in growth arrest and cell death of JAGGED1 low-expressing cells while the JAGGED1 high-expressing cells continue to cycle. High membrane JAGGED1 protein expression predicts poor overall cumulative survival in women with HER2+ breast cancer.

Conclusions: These results indicate that higher membrane JAGGED1 expression may be used to either predict response to anti-HER2 therapy or for detection of NOTCH-sensitive CSCs posttherapy. Sequential blockade of HER2 followed by JAGGED1 or NOTCH could be more effective than simultaneous blockade to prevent drug resistance and tumor progression. Clin Cancer Res; 24(18); 4566–78. ©2018 AACR.
DNA Methylation of Telomere-Related Genes and Cancer Risk
Authors: Joyce Brian T. , Zheng Yinan , Nannini Drew , Zhang Zhou , Liu Lei , Gao Tao , Kocherginsky Masha , Murphy Robert , Yang Hushan , Achenbach Chad J. , Roberts Lewis R. , Hoxha Mirjam , Shen Jincheng , Vokonas Pantel , Schwartz Joel , Baccarelli Andrea , Hou Lifang
Published: June 2018

Researchers hypothesized that telomere shortening facilitates carcinogenesis. Previous studies found inconsistent associations between blood leukocyte telomere length (LTL) and cancer. Epigenetic reprogramming of telomere maintenance mechanisms may help explain this inconsistency. We examined associations between DNA methylation in telomere-related genes (TRG) and cancer. We analyzed 475 participants providing 889 samples 1 to 3 times (median follow-up, 10.1 years) from 1999 to 2013 in the Normative Aging Study. All participants were cancer-free at each visit and blood leukocytes profiled using the Illumina 450K array. Of 121 participants who developed cancer, 34 had prostate cancer, 10 melanoma, 34 unknown skin malignancies, and 43 another cancer. We examined 2,651 CpGs from 80 TRGs and applied a combination of Cox and mixed models to identify CpGs prospectively associated with cancer (at FDR < 0.05). We also explored trajectories of DNA methylation, logistic regression stratified by time to diagnosis/censoring, and cross-sectional models of LTL at first blood draw. We identified 30 CpGs on 23 TRGs whose methylation was positively associated with cancer incidence (β = 1.0–6.93) and one protective CpG in MAD1L1 (β = −0.65), of which 87% were located in TRG promoters. Methylation trajectories of 21 CpGs increased in cancer cases relative to controls; at 4 to 8 years prediagnosis/censoring, 17 CpGs were positively associated with cancer. Three CpGs were cross-sectionally associated with LTL. TRG methylation may be a mechanism through which LTL dynamics reflect cancer risk. Future research should confirm these findings and explore potential mechanisms underlying these findings, including telomere maintenance and DNA repair dysfunction. Cancer Prev Res; 11(8); 511–22. ©2018 AACR.
Association between the Frequency of Optic Disk Hemorrhage and Progression of NTG Related with the Initial Location of RNFL Defect
Authors: Cho Hyun-Kyung , Lee Min Gyu , Kee Changwon
Published: June 2018

Purpose: This study aimed to investigate the association of the frequency of optic disk hemorrhage (DH) and progression of normal tension glaucoma (NTG) between each group based on the location of the initial retinal nerve fiber layer (RNFL) defect. Methods: In this retrospective, observational cohort study, 142 NTG patients who underwent more than 5 reliable visual field tests with initial superior hemifield (group 2, n = 51), inferior hemifield (group 1, n = 44), or both hemifield (group 3, n = 47) defects were included. The number of DHs was inspected in serial optic disk photographs by 2 different ophthalmologists. Progression rates, which are the slope of mean thresholds from the 52 points, were calculated using a linear mixed effect model. Results: The mean follow-up period was 8.19 ± 3.30 years. DHs related with the initial RNFL defect occurred significantly more frequently in group 2 (35 in inferior hemifield) than in group 1 (6 in superior hemifield) (p = 0.009) or group 3 (6 in inferior hemifield) (p = 0.006). The progression rate in group 2 was significantly faster than in group 1 (p = 0.019) or the superior hemifield of group 3 (p = 0.001). The progression rate of subjects showing recurrent DH was significantly faster than those showing single DH from all groups (–0.5460 vs. –0.2867 dB/year, p = 0.0053). Conclusions: More careful examination and caution are required when NTG patients show recurrent DH in the inferior hemifield related to the initial RNFL defect.
Diagnostic Accuracy of Low and Ultra-Low Dose CT for Identification of Urinary Tract Stones: A Systematic Review
Authors: Rodger Flora , Roditi Giles , Aboumarzouk Omar M.
Published: June 2018

Background: Non-contrast computed tomography of the kidneys, ureters, and bladder (CT KUB) is the investigation of choice for renal colic; however, radiation exposure can be a concern. Aims: The study aimed to investigate the diagnostic accuracy of low dose (LD) and ultra-low dose (ULD) CT of the urinary tract for detection of urinary tract stones in patients with renal colic. Methods: A Cochrane style systematic review of the literature from 1995 to 2017 was carried out. Literature search and data extraction were conducted by 2 reviewers. Specificity and sensitivity values were calculated for LD (<3.5 mean radiation dose [mSv]) and ULD (<1.9 mSv) CT separately. Results: A total of 12 studies were included following screening. A total of 1,529 patients were included in the review (475 in the LD group and 1,054 in the ULD group). Using standard dose CT KUB as the reference standard, the sensitivity of LD CT KUB ranged from 90 to 98% and specificity from 88 to 100%. The sensitivity of ULD CT KUB ranged from 72 to 99% and the specificity ranged from 86 to 100%. The diagnostic accuracy for LD CT was 94.3% and for ULD CT was 95.5%. Conclusions: LD and ULD CT KUB provide effective methods of identifying urinary tract stones. High diagnostic accuracy, sensitivity, and specificity are maintained despite significant radiation dose reduction in comparison to standard dose CT.
Primate Brain Anatomy: New Volumetric MRI Measurements for Neuroanatomical Studies
Authors: Navarrete Ana F. , Blezer Erwin L.A. , Pagnotta Murillo , de Viet Elizabeth S.M. , Todorov Orlin S. , Lindenfors Patrik , Laland Kevin N. , Reader Simon M.
Published: June 2018

Since the publication of the primate brain volumetric dataset of Stephan and colleagues in the early 1980s, no major new comparative datasets covering multiple brain regions and a large number of primate species have become available. However, technological and other advances in the last two decades, particularly magnetic resonance imaging (MRI) and the creation of institutions devoted to the collection and preservation of rare brain specimens, provide opportunities to rectify this situation. Here, we present a new dataset including brain region volumetric measurements of 39 species, including 20 species not previously available in the literature, with measurements of 16 brain areas. These volumes were extracted from MRI of 46 brains of 38 species from the Netherlands Institute of Neuroscience Primate Brain Bank, scanned at high resolution with a 9.4-T scanner, plus a further 7 donated MRI of 4 primate species. Partial measurements were made on an additional 8 brains of 5 species. We make the dataset and MRI scans available online in the hope that they will be of value to researchers conducting comparative studies of primate evolution.
Stroke Mortality in Kenya’s Public Tertiary Hospitals: A Prospective Facility-Based Study
Authors: Kaduka Lydia , Muniu Erastus , Oduor Chrispine , Mbui Jane , Gakunga Robai , Kwasa Judith , Wabwire Sylvanus , Okerosi Nathan , Korir Anne , Remick Scot
Published: June 2018

Background: Despite the increasing global burden of stroke, there are limited data on stroke from Kenya to guide in decision-making. Stroke occurrence in sub-Saharan Africa has been associated with poor health outcomes. This study sought to establish the stroke incidence density and mortality in Kenya’s leading public tertiary hospitals for purposes of informing clinical practice and policy. Methods: This is a prospective study conducted at Kenya’s leading referral hospitals, namely, Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH). Adult patients with confirmed cases of stroke were recruited from February 2015 to January 2016 and followed up for a minimum period of 1 year. The WHO 2006 Stroke STEPS instrument was used to collect data on incidence and mortality at days 10 and 28 and every 3 months for 24 months. The person-time of follow-up was computed from admission to death, loss to follow-up, or the end of the study. A survival regression analysis was done using the Cox proportional hazards model. Results: A total of 719 patients were recruited (KNH: n = 406 [56.5%]; MTRH: n = 313 [43.5%]). The mean age was 58.6 ± 18.7 years, and the male-to-female ratio was 1: 1.4. Ischemic stroke accounted for 56.1% of the stroke cases. The peak age for stroke was between 50 and 69 years, when 36.3% of the cases occurred. Mortality at day 10 and day 28 was 18.4 and 26.7%, respectively. The inpatient mortality rate was 21.6%. The stroke incidence density was 507 deaths per 1,000 person-years of follow-up. The mean survival time was significantly different between inpatients (13.9 months; 95% CI: 13.0–14.7) and outpatients (18.6 months; 95% CI: 17.2–19.9) (p < 0.001). A 1-year increase in age increased the hazard by 1.8%. Inpatients had a 3.9-fold increase in hazard compared to outpatients. Conclusions: Mortality due to stroke is high, with poor survival observed in the first year after stroke. The risk of death increases with increasing age and duration of hospital stay. There is need for attention to quality of care and long-term needs of stroke patients to mitigate the high mortality rates observed. Public health initiatives aimed at early screening and diagnosis should be enhanced. Further research is recommended to establish the true burden of stroke at the community level to inform appropriate mitigation measures.
Incidence of Macular Holes in the Fellow Eye without Vitreomacular Detachment at Baseline
Authors: Philippakis Elise , Astroz Polina , Tadayoni Ramin , Gaudric Alain
Published: June 2018

Purpose: To determine the rate of macular holes (MH) occurring in the fellow eyes of eyes with MH depending on the vitreomacular interface at baseline. Methods: This was a retrospective study of patients operated on for idiopathic MH, with persistent vitreofoveal attachment in the fellow eye assessed by spectral-domain optical coherence tomography (SD-OCT). Follow-up lasted 6 months or more, and the main outcome was the occurrence of an MH. Results: The 77 fellow eyes included had a mean follow-up of 34.11 ± 22.3 months (6–78.4). At baseline, 31 eyes had vitreomacular traction (VMT), 35 vitreomacular adhesion, and 11 no posterior vitreous detachment. MH occurred in 19.5% of the cases (15/77). The rate of MH was significantly higher among the eyes with VMT than among the eyes without VMT at baseline (35.5 vs. 8.7%; p = 0.009). Conclusion: One-third of eyes with VMT at baseline identified by SD-OCT will develop an MH in the following 5 years.
Trends in Radiation Practices for Female Ocular Oncologists in North America: A Collaborative Study of the International Society of Ocular Oncology
Authors: Shah Sona N. , Kogachi Kaitlin , Correa Zelia M. , Schefler Amy C. , Aronow Mary E. , Callejo Sonia A. , Cebulla Colleen M. , Day-Ghafoori Shelley , Francis Jasmine H. , Lally Sara , McCannel Tara A. , Paton Katherine E. , Phan Isabella T. , Pointdujour-Lim Renelle , Ramasubramanian Aparna , Rath Pamela , Shields Carol L. , Skalet Alison H. , Wells Jill R. , Jennelle Richard L. , Berry Jesse L. ,   for the Women in Ocular Oncology Consortium
Published: June 2018

Background: The aim of this study was to determine the known radiation exposure, attitudes, and consequent risk modifications among female ocular oncologists in North America who routinely administer radioactive plaque brachytherapy treatment and are members of the International Society of Ocular Oncology. Methods: Nineteen female ocular oncologists completed an anonymous 17-question radiation exposure survey. Results: Eleven of the participants chose to routinely wear lead protection during surgery; 8 did not. Fifteen of 19 participants reported using an unloaded “nonactive” template to prepare for plaque implantation. During pregnancy, 11 of 13 participants continued to perform plaque brachytherapy. Eight of these 11 undertook measures to decrease radiation exposure self-reported as lead wear and other. The average reported anxiety regarding fertility was 2.1 (SD, 2.2) on a scale from 1 to 10. Conclusion: This study corroborates prior literature that surgeons’ exposure to radiation during plaque brachytherapy is minimal. Nonetheless, there remains some anxiety regarding exposure risk to women, due to potential effects on fertility and fetal health. We found variability in exposure monitoring, required training, and precautions during pregnancy amongst this group of surgeons. Improved education and clearer pregnancy guidelines may equip female ocular oncologists with optimal knowledge regarding risk of radiation exposure.
Surveillance of Cystic Lesions of the Pancreas: Whom and How to Survey
Authors: Andrianello Stefano , Falconi Massimo , Salvia Roberto , Crippa Stefano , Marchegiani Giovanni
Published: June 2018

The sudden prevalence increase of pancreatic cystic neoplasms (PCN) related to the use of cross-sectional imaging has raised several concerns. Even if there is a tangible risk of progression towards pancreatic cancer (PC), surgical resection cannot be offered to all patients due to the high risk of morbidity and mortality. Available guidelines are useful tools to identify patients at higher risk for harboring cancer thanks to their sensitivity. Because of their low specificity, however, such a risk is often overestimated. Recent evidence deriving from large observational series of surveilled patients suggests that the overall risk of PC is low. A large proportion of patients affected by PCN can be safely observed over time. Several follow-up schedules have been proposed in guidelines but none of them proved to be the most cost-effective. Moreover, it must still be demonstrated that any surveillance protocol can be associated with a reduction in PC-related mortality. By now, with most studies reporting a lifelong risk of malignancy, the only evidence-based recommendation regarding surveillance is that follow-up should never be discontinued as repeated observations are crucial for PC risk stratification.
National Trends in Emergency Room Visits of Dialysis Patients for Adverse Drug Reactions
Authors: Chan Lili , Saha Aparna , Poojary Priti , Chauhan Kinsuk , Naik Nidhi , Coca Steven , Garimella Pranav S. , Nadkarni Girish N.
Published: June 2018

Background: Various medications are cleared by the kidneys, therefore patients with impaired renal function, especially dialysis patients are at risk for adverse drug events (ADEs). There are limited studies on ADEs in maintenance dialysis patients. Methods: We utilized a nationally representative database, the Nationwide Emergency Department Sample, from 2008 to 2013, to compare emergency department (ED) visits for dialysis and propensity matched non-dialysis patients. Log binomial regression was used to calculate relative risk of hospital admission and logistic regression to calculate ORs for in-hospital mortality while adjusting for patient and hospital characteristics. Results: While ED visits for ADEs decreased in both groups, they were over 10-fold higher in dialysis patients than non-dialysis patients (65.8–88.5 per 1,000 patients vs. 4.6–5.4 per 1,000 patients respectively, p < 0.001). The top medication category associated with ED visits for ADEs in dialysis patients is agents primarily affecting blood constituents, which has increased. After propensity matching, patient admission was higher in dialysis patients than non-dialysis patients, (88 vs. 76%, p < 0.001). Dialysis was associated with a 3% increase in risk of admission and 3 times the odds of in-hospital mortality (adjusted OR 3, 95% CI 2.7–2.3.3). Conclusions: ED visits for ADEs are substantially higher in dialysis patients than non-dialysis patients. In dialysis patients, ADEs associated with agents primarily affecting blood constituents are on the rise. ED visits for ADEs in dialysis patients have higher inpatient admissions and in-hospital mortality. Further studies are needed to identify and implement measures aimed at reducing ADEs in dialysis patients.
Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up
Authors: Vanoli Alessandro , La Rosa Stefano , Miceli Emanuela , Klersy Catherine , Maragliano Roberta , Capuano Francesca , Persichella Andrea , Martino Michele , Inzani Frediano , Luinetti Ombretta , Di Sabatino Antonio , Sessa Fausto , Paulli Marco , Corazza Gino Roberto , Rindi Guido , Bordi Cesare , Capella Carlo , Solcia Enrico
Published: June 2018

Background: Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. Methods: Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. Results: Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. Conclusions: Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease.
Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas
Authors: Raman Aadhithya , Lennon Anne Marie
Published: June 2018

Pancreatic cysts are common, and are identified in 2-13% of individuals undergoing cross-sectional imaging. Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are pancreatic cysts which are precursors to pancreatic adenocarcinoma. Currently available tools are imperfect at differentiating IPMNs and MCNs from other, benign types of pancreatic cysts. The role of molecular markers in the evaluation of pancreatic cysts and the identification of cysts with high-grade dysplasia or invasive adenocarcinoma is reviewed.