bluuebunny/crossref_metadata_2025 huggingface dataset:
Beneficial Effects of Rikkunshito, a Japanese Kampo Medicine, on Gastrointestinal Dysfunction and Anorexia in Combination with Western Drug: A Systematic Review
Authors: Mogami Sachiko , Hattori Tomohisa
Published: March 2014

Background. Kampo medicines are traditional herbal medicines which have been approved for medicinal use by the Japanese Ministry of Health and Welfare and are currently being used more and more, often in combination with Western drugs. Thus, the need for investigation of interactions between Kampo medicines and Western drugs is now widely recognized. Aim. To summarize the effects and drug interactions of rikkunshito, a Kampo medicine often prescribed for upper gastrointestinal disorders and anorexia. Methods. Animal and human studies were systematically reviewed to identify published data on rikkunshito. Results describing its effects were abstracted, with an emphasis on drug interactions. Results and Discussion. Rikkunshito ameliorates anorexia induced by anticancer drugs, improves quality of life scores, and can even prolong survival compared with monotherapy. Rikkunshito combined with proton pump inhibitor therapy is shown to be useful in the treatment of PPI‐refractory gastroesophageal reflux disease patients and patients with gastrointestinal symptoms after endoscopic submucosal dissection. Rikkunshito reduces antidepressant‐induced adverse events and improves quality of life without influencing antidepressant effects. Conclusions. Rikkunshito shows ameliorative effects on adverse reactions induced by various Western drugs and can achieve better results (e.g., anticancer drugs and proton pump inhibitor) without influencing the efficacy and bioavailability of Western drugs.
Clinical Characteristics ofAlternariaKeratitis
Authors: Hsiao Ching-Hsi , Yeh Lung-Kun , Chen Hung-Chi , Lin Hsin-Chiung , Chen Phil Y. F. , Ma David H. K. , Tan Hsin-Yuan
Published: March 2014

Purpose.Alternariaspp. are an uncommon cause of mycotic keratitis. Previous studies onAlternariakeratitis have generally been limited to case reports. We examined the clinical characteristics ofAlternariakeratitis in this study.Methods.The characteristics and outcomes of 7 patients with culture-provenAlternariakeratitis treated in our hospital were compared with 25 previously reported cases.Results.The risk factors forAlternariakeratitis were trauma in 5 patients and soft contact lenses in 1 patient. Six patients with early diagnosis (<2 weeks) were cured with medical antimicrobial treatment; a patch graft was required in 1 patient with perforation. When incorporated with previous reports onAlternariakeratitis(n=32), 14 (44%) infections followed trauma, 10 (31%) were associated with preexisting corneal disease or previous ocular surgery, and 5 (16%) occurred in soft contact lens wearers. Successful medical treatment was achieved in 23 (72%) patients, including 10 out of 21 eyes (48%) treated with natamycin and/or amphotericin B. Therapeutic penetrating keratoplasty was performed in 9 (28%) cases.Conclusions.Alternariakeratitis is generally associated with specific risk factors and responds to medical treatment when early diagnosis is performed and prompt antifungal treatment is initiated.
An Improved Proportionate Normalized Least-Mean-Square Algorithm for Broadband Multipath Channel Estimation
Authors: Li Yingsong , Hamamura Masanori
Published: March 2014

To make use of the sparsity property of broadband multipath wireless communication channels, we mathematically propose anlp-norm-constrained proportionate normalized least-mean-square (LP-PNLMS) sparse channel estimation algorithm. A generallp-norm is weighted by the gain matrix and is incorporated into the cost function of the proportionate normalized least-mean-square (PNLMS) algorithm. This integration is equivalent to adding a zero attractor to the iterations, by which the convergence speed and steady-state performance of the inactive taps are significantly improved. Our simulation results demonstrate that the proposed algorithm can effectively improve the estimation performance of the PNLMS-based algorithm for sparse channel estimation applications.
Diagnostic Accuracy of Contrast-Enhanced FLAIR Magnetic Resonance Imaging in Diagnosis of Meningitis Correlated with CSF Analysis
Authors: Vaswani Aneel Kumar , Nizamani Waseem Mehmood , Ali Muhammad , Aneel Geeta , Shahani Bhesham Kumar , Hussain Sajjad
Published: March 2014

Purpose. To determine the diagnostic accuracy of contrast enhanced FLAIR sequence of MRI brain in the diagnosis of meningitis.Subjects and Methods. A prospective study of 57 patients with signs and symptoms of meningitis, referred to the radiology department for MRI examination. Out of these, there were 30 males and 27 females. They underwent MRI brain with contrast including postcontrast T1W and FLAIR sequences. Cerebrospinal fluid (CSF) analysis obtained by lumbar puncture after MRI was considered the “reference standard” against which MRI findings were compared.Results. Of 57 patients, 50 were diagnosed as having meningitis on subsequent CSF analysis. Out of these 50, 49 were positive on postcontrast FLAIR images and 34 were positive on postcontrast T1W images. One patient was labeled false positive as CSF analysis showed malignant cells (leptomeningeal carcinomatosis). In the diagnosis of meningitis, the sensitivity of postcontrast FLAIR sequence was 96% and specificity 85.71%, whereas the sensitivity of postcontrast T1W sequence was 68% and specificity 85.71%.Conclusion. Contrast-enhanced FLAIR sequence is more sensitive and specific than contrast-enhanced T1W sequence in the diagnosis of meningitis. It should be routinely used in suspected cases of meningitis.
H∞ Guaranteed Cost Control for Networked Control Systems under Scheduling Policy Based on Predicted Error
Authors: Zhu Qixin , Lu Kaihong , Zhu Yonghong
Published: March 2014

Scheduling policy based on model prediction error is presented to reduce energy consumption and network conflicts at the actuator node, where the characters of networked control systems are considered, such as limited network bandwidth, limited node energy, and high collision probability. The object model is introduced to predict the state of system at the sensor node. And scheduling threshold is set at the controller node. Control signal is transmitted only if the absolute value of prediction error is larger than the threshold value. Furthermore, the model of networked control systems under scheduling policy based on predicted error is established by taking uncertain parameters and long time delay into consideration. The design method of H∞ guaranteed cost controller is presented by using the theory of Lyapunov and linear matrix inequality (LMI). Finally, simulations are included to demonstrate the theoretical results.
Overexpression of the Synthetic Chimeric Native-T-phylloplanin-GFP Genes Optimized for Monocot and Dicot Plants Renders Enhanced Resistance to Blue Mold Disease in Tobacco (N. tabacumL.)
Authors: Sahoo Dipak K. , Raha Sumita , Hall James T. , Maiti Indu B.
Published: March 2014

To enhance the natural plant resistance and to evaluate the antimicrobial properties of phylloplanin against blue mold, we have expressed a synthetic chimeric native-phylloplanin-GFP protein fusion in transgenicNicotiana tabacumcv. KY14, a cultivar that is highly susceptible to infection byPeronospora tabacina. The coding sequence of the tobacco phylloplanin gene along with its native signal peptide was fused with GFP at the carboxy terminus. The synthetic chimeric gene (native-phylloplanin-GFP) was placed between the modifiedMirabilis mosaic virusfull-length transcript promoter with duplicated enhancer domains and the terminator sequence from the rbcSE9 gene. The chimeric gene, expressed in transgenic tobacco, was stably inherited in successive plant generations as shown by molecular characterization, GFP quantification, and confocal fluorescent microscopy. Transgenic plants were morphologically similar to wild-type plants and showed no deleterious effects due to transgene expression. Blue mold-sensitivity assays of tobacco lines were performed by applyingP. tabacinasporangia to the upper leaf surface. Transgenic lines expressing the fused synthetic native-phyllopanin-GFP gene in the leaf apoplast showed resistance to infection. Our results demonstrate thatin vivoexpression of a synthetic fused native-phylloplanin-GFP gene in plants can potentially achieve natural protection against microbial plant pathogens, includingP. tabacinain tobacco.
A Comparative Systematic Review of the Optimal CD4 Cell Count Threshold for HIV Treatment Initiation
Authors: Olubajo Babatunde , Mitchell-Fearon Kathryn , Ogunmoroti Oluseye
Published: March 2014

HIV infection is no longer characterized by high morbidity, rapid progression to AIDS, and death as when the infection was first identified. While anti-retroviral drugs have improved the outcome of AIDS patients, clinical research on the appropriate time to initiate therapy continues to evolve. Optimal therapy initiation would maximize the benefits of these drugs, while minimizing side effects and drug resistance. Recent 2013 WHO guidelines changed HIV therapy initiation from 350 cells/μL to 500 cells/μL. This systematic review provides an evidence-based comparison of starting treatment at >500 cells/μL with starting treatment at the range between 350 cells/μL and 500 cells/μL. An 11% increase in risk was detected from initiation therapy at the 350–500 cells/μL range (0.37 [0.26, 0.53]), when compared with starting treatment before 500 cells/μL (0.33 [0.22, 0.48]). Most individual study comparisons showed a benefit for starting treatment at 500 cells/μL in comparison with starting at the 350–500 cells/μL range with risks ranging from 19% to 300%, though a number of comparisons were not statistically significant. Overall, the study provides evidence based support for initiating anti retroviral therapy at cell counts >500 cells/μL wherever possible to prevent AIDS mortality and morbidity.
Nanographene‐Based Saturable Absorbers for Ultrafast Fiber Lasers
Authors: Kuo Hsin-Hui , Hong Shuo-Fu
Published: March 2014

The generation of femtosecond pulse laser in the erbium‐doped fiber laser system is presented by integrating of the nanographene‐based saturable absorbers (SAs). A simplified method of dispersed nanographene‐based SAs side‐polished fiber device with controllable polished length and depth was also developed. The dependence of geometry of a graphene‐deposited side‐polished fiber device on optical nonlinear characteristics and on the performance of the MLFL was screened. We found that the 10 mm polished length with 1.68 dB insertion loss had the highest modulation depth (MD) of 1.2%. A stable MLFL with graphene‐based SAs employing the optimized side‐polished fiber device showed a pulse width, a 3 dB bandwidth, a time‐bandwidth product (TBP), a repetition rate, and pulse energy of 523 fs, 5.4 nm, 0.347, 16.7 MHz, and 0.18 nJ, respectively, at fundamental soliton‐like operation. The femtosecond pulse laser is achieved by evanescent field coupling through graphene‐deposited side‐polished fiber devices in the laser cavity. This study demonstrates that the polished depth is the key fabrication geometric parameter affecting the overall optical performance and better results exist within the certain polished range.
Usalpharma: A Cloud-Based Architecture to Support Quality Assurance Training Processes in Health Area Using Virtual Worlds
Authors: García-Peñalvo Francisco J. , Cruz-Benito Juan , Maderuelo Cristina , Pérez-Blanco Jonás Samuel , Martín-Suárez Ana
Published: March 2014

This paper discusses how cloud-based architectures can extend and enhance the functionality of the training environments based on virtual worlds and how, from this cloud perspective, we can provide support to analysis of training processes in the area of health, specifically in the field of training processes in quality assurance for pharmaceutical laboratories, presenting a tool for data retrieval and analysis that allows facing the knowledge discovery in the happenings inside the virtual worlds.
Mitogenic Effects of Phosphatidylcholine Nanoparticles on MCF-7 Breast Cancer Cells
Authors: Gándola Yamila B. , Pérez Sebastián E. , Irene Pablo E. , Sotelo Ana I. , Miquet Johanna G. , Corradi Gerardo R. , Carlucci Adriana M. , Gonzalez Lorena
Published: March 2014

Lecithins, mainly composed of the phospholipids phosphatidylcholines (PC), have many different uses in the pharmaceutical and clinical field. PC are involved in structural and biological functions as membrane trafficking processes and cellular signaling. Considering the increasing applications of lecithin-based nanosystems for the delivery of therapeutic agents, the aim of the present work was to determine the effects of phosphatidylcholine nanoparticles over breast cancer cellular proliferation and signaling. PC dispersions at 0.01 and 0.1% (w/v) prepared in buffer pH 7.0 and 5.0 were studied in the MCF-7 breast cancer cell line. Neutral 0.1% PC-derived nanoparticles induced the activation of the MEK-ERK1/2 pathway, increased cell viability and induced a 1.2 fold raise in proliferation. These biological effects correlated with the increase of epidermal growth factor receptor (EGFR) content and its altered cellular localization. Results suggest that nanoparticles derived from PC dispersion prepared in buffer pH 7.0 may induce physicochemical changes in the plasma membrane of cancer cells which may affect EGFR cellular localization and/or activity, increasing activation of the MEK-ERK1/2 pathway and inducing proliferation. Results from the present study suggest that possible biological effects of delivery systems based on lecithin nanoparticles should be taken into account in pharmaceutical formulation design.
Cardiac Electrophysiological Alterations in Heart/Muscle-Specific Manganese-Superoxide Dismutase-Deficient Mice: Prevention by a Dietary Antioxidant Polyphenol
Authors: Sunagawa Tadahiro , Shimizu Takahiko , Matsumoto Akio , Tagashira Motoyuki , Kanda Tomomasa , Shirasawa Takuji , Nakaya Haruaki
Published: March 2014

Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2−/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2−/−mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2−/−mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2−/−LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K+current (IK1) was decreased in the LV cells of H/M-Sod2−/−mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2−/−mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density ofIK1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.
Robust H∞ Filtering for Networked Control Systems with Random Sensor Delay
Authors: Xiao Shenping , Wang Liyan , Zeng Hongbing , Kong Lingshuang , Qin Bin
Published: March 2014

The robust H∞ filtering problem for a class of network‐based systems with random sensor delay is investigated. The sensor delay is supposed to be a stochastic variable satisfying Bernoulli binary distribution. Using the Lyapunov function and Wirtinger’s inequality approach, the sufficient conditions are derived to ensure that the filtering error systems are exponentially stable with a prescribed H∞ disturbance attenuation level and the filter design method is proposed in terms of linear matrix inequalities. The effectiveness of the proposed method is illustrated by a numerical example.
Optimal Orientation Planning and Control Deviation Estimation on FAST Cable-Driven Parallel Robot
Authors: Li Hui , Yao Rui
Published: March 2014

The paper is devoted theoretically to the optimal orientation planning and control deviation estimation of FAST cable-driven parallel robot. Regarding the robot characteristics, the solutions are obtained from two constrained optimizations, both of which are based on the equilibrium of the cabin and the attention on force allocation among 6 cable tensions. A kind of control algorithm is proposed based on the position and force feedbacks. The analysis proves that the orientation control depends on force feedback and the optimal tension solution corresponding to the planned orientation. Finally, the estimation of orientation deviation is given under the limit range of tension errors.
A New Approach on Helices in Pseudo-Riemannian Manifolds
Authors: Zıplar Evren , Yaylı Yusuf , Gök İsmail
Published: March 2014

A proper curveαin then-dimensional pseudo-Riemannian manifold(M,g)is called aVn-slant helix if the functiong(Vn,X)is a nonzero constant alongα, whereXis a  parallel vector field alongαandVnisnth Frenet frame. In this work, we study such curves and give important characterizations about them.
Preparation Method of Co3O4 Nanoparticles Using Degreasing Cotton and Their Electrochemical Performances in Supercapacitors
Authors: Xu Hongyan , Gao Libo , Zhang Qiang , Li Junyang , Diwu Jiangtao , Chou Xiujian , Tang Jun , Xue Chenyang
Published: March 2014

Co3O4 nanoparticles were fabricated by a novel, facile, and environment‐friendly carbon‐assisted method using degreasing cotton. Structural and morphological characterizations were performed using X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The component of the sample obtained at different temperatures was measured by Fourier transform infrared spectroscopy (FTIR) and X‐ray photoelectron spectroscopy (XPS). Nitrogen adsorption and desorption isotherms were utilized to reveal the specific surface areas. The formation mechanism of Co3O4 nanoparticles was also proposed, demonstrating that the additive degreasing cotton played an indispensable role in the process of synthesizing the sample. The resultant Co3O4 sample calcined at 600°C exhibited superior electrochemical performance with better specific capacitance and long‐term cycling life, due to its high specific surface areas and pores structures. Additionally, it has been proved that this facile synthetic strategy can be extended to produce other metal oxide materials (e.g., Fe3O4). As a consequence, the carbon‐assisted method using degreasing cotton accompanied a promising prospect for practical application.
Void Structures in Regularly Patterned ZnO Nanorods Grown with the Hydrothermal Method
Authors: Yao Yu-Feng , Shen Chen-Hung , Chen Wei-Fang , Shih Pei-Ying , Chou Wang-Hsien , Su Chia-Ying , Chen Horng-Shyang , Liao Che-Hao , Chang Wen-Ming , Kiang Yean-Woei , Yang C. C.
Published: March 2014

The void structures and related optical properties after thermal annealing with ambient oxygen in regularly patterned ZnO nanrorod (NR) arrays grown with the hydrothermal method are studied. In increasing the thermal annealing temperature, void distribution starts from the bottom and extends to the top of an NR in the vertical (c‐axis) growth region. When the annealing temperature is higher than 400°C, void distribution spreads into the lateral (m‐axis) growth region. Photoluminescence measurement shows that the ZnO band‐edge emission, in contrast to defect emission in the yellow‐red range, is the strongest under the n‐ZnO NR process conditions of 0.003 M in Ga‐doping concentration and 300°C in thermal annealing temperature with ambient oxygen. Energy dispersive X‐ray spectroscopy data indicate that the concentration of hydroxyl groups in the vertical growth region is significantly higher than that in the lateral growth region. During thermal annealing, hydroxyl groups are desorbed from the NR leaving anion vacancies for reacting with cation vacancies to form voids.
A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis
Authors: Daniela Perani , Orazio Schillaci , Alessandro Padovani , Mariano Nobili Flavio , Leonardo Iaccarino , Pasquale Anthony Della Rosa , Giovanni Frisoni , Carlo Caltagirone
Published: March 2014

PET based tools can improve the early diagnosis of Alzheimer’s disease (AD) and differential diagnosis of dementia. The importance of identifying individuals at risk of developing dementia among people with subjective cognitive complaints or mild cognitive impairment has clinical, social, and therapeutic implications. Within the two major classes of AD biomarkers currently identified, that is, markers of pathology and neurodegeneration, amyloid- and FDG-PET imaging represent decisive tools for their measurement. As a consequence, the PET tools have been recognized to be of crucial value in the recent guidelines for the early diagnosis of AD and other dementia conditions. The references based recommendations, however, include large PET imaging literature based on visual methods that greatly reduces sensitivity and specificity and lacks a clear cut-off between normal and pathological findings. PET imaging can be assessed using parametric or voxel-wise analyses by comparing the subject’s scan with a normative data set, significantly increasing the diagnostic accuracy. This paper is a survey of the relevant literature on FDG and amyloid-PET imaging aimed at providing the value of quantification for the early and differential diagnosis of AD. This allowed a meta-analysis and GRADE analysis revealing high values for PET imaging that might be useful in considering recommendations.
A Preliminary Study on the Relationship between Platelet Serotonin Transporter Functionality, Depression, and Fatigue in Patients with Untreated Chronic Hepatitis C
Authors: Franke Leonora , Therstappen Eric , Schlosser Beate , Biermer Michael , Berg Thomas , Schäfer Martin , Arck Petra , Uebelhack Ralf , Friebe Astrid
Published: March 2014

Objective and Methods.Although the interaction between fatigue and depression in patients with chronic hepatitis C infection (HCV) has been recognized, the biological correlates of this observation have yet to be reported. We addressed this issue by examining serotonin transporter- (SERT-) driven [14C]-serotonin uptake rate (SUR) and serotonin content in platelets of 65 untreated HCV patients and 65 healthy control subjects (HCS). All patients completed report questionnaires for fatigue, depression, and general psychopathology. Structured interviews were conducted by a board-certified psychiatrist.Results.Whereas 36 of the patients experienced fatigue of moderate-to-severe intensity, only 16 reported symptoms of depression (BDI score > 10). Mean SUR in patients with depressive symptoms was significantly higher relative to the HCS, corresponding to a large Cohen’s effect size ofd=1.45(95%CI=0.66—1.83). Patients who rated their fatigue to have a marked impact on mood and activity displayed a moderate relationship between the BDI score and SUR (n=18,r=0.563,P=0.015), which becomes stronger after controlling for age, gender, and thrombocytopenia (rpart=0.710,P=0.003). In the univariate analysis, high fatigue interference score, thrombocytopenia, and high SUR were all significant predictors of depression.Conclusions.High SERT activity could be implicated in the expression of depressive symptoms especially in a subgroup of HCV patients who are feeling fatigue as markedly distressing.
Mean-Variance Portfolio Selection for Defined-Contribution Pension Funds with Stochastic Salary
Authors: Zhang Chubing
Published: March 2014

This paper focuses on a continuous-time dynamic mean-variance portfolio selection problem of defined-contribution pension funds with stochastic salary, whose risk comes from both financial market and nonfinancial market. By constructing a special Riccati equation as a continuous (actually a viscosity) solution to the HJB equation, we obtain an explicit closed form solution for the optimal investment portfolio as well as the efficient frontier.
Robust Decentralized Adaptive Neural Control for a Class of Nonaffine Nonlinear Large‐Scale Systems with Unknown Dead Zones
Authors: Wang Huanqing , Zhou Qi , Yang Xuebo , Karimi Hamid Reza
Published: March 2014

The problem of robust decentralized adaptive neural stabilization control is investigated for a class of nonaffine nonlinear interconnected large‐scale systems with unknown dead zones. In the controller design procedure, radical basis function (RBF) neural networks are applied to approximate packaged unknown nonlinearities and then an adaptive neural decentralized controller is systematically derived without requiring any information on the boundedness of dead zone parameters (slopes and break points). It is proven that the developed control scheme can ensure that all the signals in the closed‐loop system are semiglobally uniformly ultimately bounded in the sense of mean square. Simulation study is provided to further demonstrate the effectiveness of the developed control scheme.
E-Bike Injuries: Experience from an Urban Emergency Department—A Retrospective Study from Switzerland
Authors: Papoutsi Sylvana , Martinolli Luca , Braun Christian Tasso , Exadaktylos Aristomenis K.
Published: March 2014

Background. Between 2005 and 2012, annual sales of E-bikes in Switzerland increased from 1,792 to 52,941. This continuous and rapid transition from human-powered bicycles to an electric bicycle technology may indicate the increasing demand for low-cost transportation technology in combination with a healthy lifestyle.Material and Methods. In the present study, from April 2012 to September 2013, we retrospectively analysed E-bike accidents treated in the Emergency Department of our hospital by focusing on the following parameters: age, gender, time, period, and cause of the accident, as well as injury and outcome.Results. Patients were predominantly male. The mean age of injured E-cyclists was 47.5 years. The main causes of injury were self-accident. Most injuries were to the head/neck. The mean ISS was 8.48. The outcome showed that 9 patients were treated as outpatients, 9 were inpatients, and 5 patients were kept in the Intensive Care Unit (ICU). Only six patients underwent surgery (S).Discussion. This is the first attempt to evaluate E-bike injuries in Switzerland in an acute hospital setting. Since there is increasing popular preference for E-bikes as means of transportation and injuries to the head or neck are prevalent among E-cyclists, the hazard should not to be underestimated.
Novel Back Propagation Optimization by Cuckoo Search Algorithm
Authors: Yi Jiao-hong , Xu Wei-hong , Chen Yuan-tao
Published: March 2014

The traditional Back Propagation (BP) has some significant disadvantages, such as training too slowly, easiness to fall into local minima, and sensitivity of the initial weights and bias. In order to overcome these shortcomings, an improved BP network that is optimized by Cuckoo Search (CS), called CSBP, is proposed in this paper. In CSBP, CS is used to simultaneously optimize the initial weights and bias of BP network. Wine data is adopted to study the prediction performance of CSBP, and the proposed method is compared with the basic BP and the General Regression Neural Network (GRNN). Moreover, the parameter study of CSBP is conducted in order to make the CSBP implement in the best way.
A Maximal Element Theorem inFWC-Spaces and Its Applications
Authors: Lu Haishu , Hu Qingwen , Miao Yulin
Published: March 2014

A maximal element theorem is proved in finite weakly convex spaces (FWC-spaces, in short) which have no linear, convex, and topological structure. Using the maximal element theorem, we develop new existence theorems of solutions to variational relation problem, generalized equilibrium problem, equilibrium problem with lower and upper bounds, and minimax problem inFWC-spaces. The results represented in this paper unify and extend some known results in the literature.
Incidence and Paris Classification of Pediatric Inflammatory Bowel Disease
Authors: Eszter Müller Katalin , Laszlo Lakatos Peter , Papp Maria , Veres Gabor
Published: March 2014

New epidemiological data suggest that the incidence of inflammatory bowel disease (IBD) is increasing. As a result the burden of disease accounts for more strains to the health care system. The clinical variability queries whether disease characteristics are related to clinical outcome. Our aim was to delineate the latest results of incidence trends in pediatric IBD and to compare the first experiences with Paris Classification. Incidence of pediatric IBD has been increasing in Western Europe and in Eastern Europe. To better characterize IBD, Paris Classification was introduced and validated recently. Ileocolonic involvement is the most characteristic disease location in Crohn’s disease (CD) based on applying Paris Classification. The rate of perianal disease and complicated behaviour in CD was similar. It is of interest that CD patients with colonic involvement were less likely to have stricturing disease compared with patients with ileal involvement. In addition, pancolitis dominated in ulcerative colitis (UC). However, most countries lack prospective, nationwide epidemiological studies to estimate incidence trends. This review emphasizes the importance of nationwide registries that enroll all pediatric IBD cases serving reliable data for “everyday practice.” These first reports have shown that Paris Classification is a useful tool to determine the pediatric IBD phenotype.
Evaluation of Thermal Evolution Profiles and Estimation of Kinetic Parameters for Pyrolysis of Coal/Corn Stover Blends Using Thermogravimetric Analysis
Authors: Bhagavatula Abhijit , Huffman Gerald , Shah Naresh , Honaker Rick
Published: March 2014

The thermal evolution profiles and kinetic parameters for the pyrolysis of two Montana coals (DECS-38 subbituminous coal and DECS-25 lignite coal), one biomass sample (corn stover), and their blends (10%, 20%, and 30% by weight of corn stover) have been investigated at a heating rate of 5°C/min in an inert nitrogen atmosphere, using thermogravimetric analysis. The thermal evolution profiles of subbituminous coal and lignite coal display only one major peak over a wide temperature distribution, ~152–814°C and ~175–818°C, respectively, whereas the thermal decomposition profile for corn stover falls in a much narrower band than that of the coals, ~226–608°C. The nonlinearity in the evolution of volatile matter with increasing percentage of corn stover in the blends verifies the possibility of synergistic behavior in the blends with subbituminous coal where deviations from the predicted yield ranging between 2% and 7% were observed whereas very little deviations (1%–3%) from predicted yield were observed in blends with lignite indicating no significant interactions with corn stover. In addition, a single first-order reaction model using the Coats-Redfern approximation was utilized to predict the kinetic parameters of the pyrolysis reaction. The kinetic analysis indicated that each thermal evolution profile may be represented as a single first-order reaction. Three temperature regimes were identified for each of the coals while corn stover and the blends were analyzed using two and four temperature regimes, respectively.
Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression
Authors: Yang Rui , Zhang Hongbo , Wu Xiaoping , Yang Junle , Ma Mingyue , Gao Yanjun , Liu Hongsheng , Li Shengbin
Published: March 2014

Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients(n=12)both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.
Estimating Glomerular Filtration Rate in Older People
Authors: Garasto Sabrina , Fusco Sergio , Corica Francesco , Rosignuolo Maria , Marino Antonio , Montesanto Alberto , De Rango Francesco , Maggio Marcello , Mari Vincenzo , Corsonello Andrea , Lattanzio Fabrizia
Published: March 2014

We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting.
Patterns of Antimicrobial Resistance in the Causative Organisms of Spontaneous Bacterial Peritonitis: A Single Centre, Six-Year Experience of 1981 Samples
Authors: Sheikhbahaei Sara , Abdollahi Alireza , Hafezi-Nejad Nima , Zare Elham
Published: March 2014

Background/Aims. Spontaneous bacterial peritonitis (SBP) is one of the leading causes of morbidity and mortality in patients with cirrhosis. This study aims to determine the microbial agents of SBP and the pattern of antibiotic resistance, in a large number of ascitic samples.Methodology. In a cross-sectional, single center, hospital based study, 1981 consecutive ascitic fluid samples were recruited from 2005 to 2011. Samples were dichotomized into three-year periods, in order to assess the trend of resistance to the first-line empirical antibiotics.Results. SBP was found in 482 (24.33%) of samples, of which 314 (65.15%) were culture positive. The most prevalent isolated pathogen wasE. coli(33.8%), followed bystaphylococcus aureus(8.9%) andEnterococcus(8.6%). No significant changes in the proportion of gram-negative/gram-positive infections occurred during this period. A percentage of resistant strains to cefotaxime (62.5%, 85.7%), ceftazidim (73%, 82.1%), ciprofloxacin (30, 59.8%), ofloxacin (36.8%, 50%), and oxacilin (35%, 51.6%) were significantly increased.E. coliwas most sensitive to imipenem, piperacillin-tazobactam, amikacin, ceftizoxime, and gentamicin.Conclusions. The microbial aetiology of SBP remains relatively constant. However, the resistance rate especially to the first-line recommended antibiotics was significantly increased. This pattern must be watched closely and taken into account in empirical antibiotic treatment.
Theory and Phenomenology of Space-Time Defects
Authors: Hossenfelder Sabine
Published: March 2014

Whether or not space-time is fundamentally discrete is of central importance for the development of the theory of quantum gravity. If the fundamental description of spacetime is discrete, typically represented in terms of a graph or network, then the apparent smoothness of geometry on large scales should be imperfect—it should have defects. Here, we review a model for space-time defects and summarize the constraints on the prevalence of these defects that can be derived from observation.
EGFR-Mediated Chromatin Condensation Protects KRAS-Mutant Cancer Cells against Ionizing Radiation
Authors: Wang Meng , Kern Ashley M. , Hülskötter Marieke , Greninger Patricia , Singh Anurag , Pan Yunfeng , Chowdhury Dipanjan , Krause Mechthild , Baumann Michael , Benes Cyril H. , Efstathiou Jason A. , Settleman Jeff , Willers Henning
Published: March 2014

Therapeutics that target the epidermal growth factor receptor (EGFR) can enhance the cytotoxic effects of ionizing radiation (IR). However, predictive genomic biomarkers of this radiosensitization have remained elusive. By screening 40 non–small cell lung cancer cell (NSCLC) lines, we established a surprising positive correlation between the presence of a KRAS mutation and radiosensitization by the EGFR inhibitors erlotinib and cetuximab. EGFR signaling in KRAS-mutant NSCLC cells promotes chromatin condensation in vitro and in vivo, thereby restricting the number of DNA double-strand breaks (DSB) produced by a given dose of IR. Chromatin condensation in interphase cells is characterized by an unexpected mitosis-like colocalization of serine 10 phosphorylation and lysine 9 trimethylation on histone H3. Aurora B promotes this process in a manner that is codependent upon EGFR and protein kinase C α (PKCα). PKCα, in addition to MEK/ERK signaling, is required for the suppression of DSB-inducible premature senescence by EGFR. Blockade of autophagy results in a mutant KRAS-dependent senescence-to-apoptosis switch in cancer cells treated with IR and erlotinib. In conclusion, we identify EGFR as a molecular target to overcome a novel mechanism of radioresistance in KRAS-mutant tumor cells, which stands in contrast to the unresponsiveness of KRAS-mutant cancers to EGFR-directed agents in monotherapy. Our findings may reposition EGFR-targeted agents for combination with DSB-inducing therapies in KRAS-mutant NSCLC. Cancer Res; 74(10); 2825–34. ©2014 AACR.
Oral Contraceptives and Breast Cancer Risk Overall and by Molecular Subtype Among Young Women
Authors: Beaber Elisabeth F. , Malone Kathleen E. , Tang Mei-Tzu Chen , Barlow William E. , Porter Peggy L. , Daling Janet R. , Li Christopher I.
Published: March 2014

Background: Evidence suggests that recent oral contraceptive (OC) use is associated with a small increased breast cancer risk; yet risks associated with contemporary OC preparations and by molecular subtype are not well characterized.

Methods: We conducted a population-based case–control study of invasive breast cancer among women ages 20 to 44 residing in the Seattle–Puget Sound area from 2004 to 2010 (985 cases and 882 controls). We collected information on contraceptive use and participant characteristics via an in-person interview. Multivariable-adjusted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results: Lifetime duration of OC use for ≥15 years was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.1–2.2). Current OC use (within 1 year of reference date) for ≥5 years was associated with an increased risk (OR, 1.6; 95% CI, 1.1–2.5) and there were no statistically significant differences in risk by OC preparation. Risk magnitudes were generally greater among women ages 20 to 39, and for estrogen receptor–negative (ER−) and triple-negative breast cancer (current use for ≥5 years among ages 20–39: ER− OR, 3.5; 95% CI, 1.3–9.0; triple-negative OR, 3.7; 95% CI, 1.2–11.8), although differences between groups were not statistically significant.

Conclusions: Long-term use of contemporary OCs and current use for ≥5 years was associated with an increased breast cancer risk among women ages 20 to 44. Risk may be greater among younger women and for ER− and triple-negative breast cancer, but these findings require confirmation.

Impact: Continued surveillance and pooled analyses of OC use and breast cancer risk by molecular subtype are needed as OC preparations evolve. Cancer Epidemiol Biomarkers Prev; 23(5); 755–64. ©2014 AACR.
In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas
Authors: Schalper Kurt A. , Velcheti Vamsidhar , Carvajal Daniel , Wimberly Hallie , Brown Jason , Pusztai Lajos , Rimm David L.
Published: March 2014

Purpose: Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas.

Experimental Design: The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I–III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence.

Results: On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor–negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099–0.721; P = 0.009).

Conclusions: PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1–targeted therapies in breast cancer. Clin Cancer Res; 20(10); 2773–82. ©2014 AACR.
ABCB1, ABCG2, and PTEN Determine the Response of Glioblastoma to Temozolomide and ABT-888 Therapy
Authors: Lin Fan , de Gooijer Mark C. , Roig Eloy Moreno , Buil Levi C.M. , Christner Susan M. , Beumer Jan H. , Würdinger Thomas , Beijnen Jos H. , van Tellingen Olaf
Published: March 2014

Purpose: Little is known about the optimal clinical use of ABT-888 (veliparib) for treatment of glioblastoma. ABT-888 is a PARP inhibitor undergoing extensive clinical evaluation in glioblastoma, because it may synergize with the standard-of-care temozolomide (TMZ). We have elucidated important factors controlling ABT-888 efficacy in glioblastoma.

Experimental Design: We used genetically engineered spontaneous glioblastoma mouse models and allograft models that were orthotopically transplanted into wild-type (WT) and Abcb1/Abcg2-deficient (KO) recipients.

Results: ABT-888/TMZ is not efficacious against p53;p16Ink4a/p19Arf;K-Rasv12;LucR allografts in wild-type recipients, indicating inherent resistance. Abcb1/Abcg2 mediated efflux of ABT-888 at the blood–brain barrier (BBB) causes a 5-fold reduction of ABT-888 brain penetration (P < 0.0001) that was fully reversible by elacridar. Efficacy studies in WT and KO recipients and/or concomitant elacridar demonstrate that Abcb1/Abcg2 at the BBB and in tumor cells impair TMZ/ABT-888 combination treatment efficacy. Elacridar also markedly improved TMZ/ABT-888 combination treatment in the spontaneous p53;p16Ink4a/p19Arf;K-Rasv12;LucR glioblastoma model. Importantly, ABT-888 does enhance TMZ efficacy in Pten deficient glioblastoma allografts and spontaneous tumors, even in Abcb1/Abcg2 proficient wild-type mice. Loss of PTEN occurs frequently in glioblastoma (36%) and in silico analysis on patient with glioblastoma samples revealed that it is associated with a worse overall survival (310 days vs. 620 days, n = 117).

Conclusions: The potential of ABT-888 in glioblastoma can best be demonstrated in patients with PTEN null tumors. Therefore, clinical trials with ABT-888 should evaluate these patients as a separate group. Importantly, inhibition of ABCB1 and ABCG2 (by elacridar) may improve the efficacy of TMZ/ABT-888 therapy in all glioblastoma patients. Clin Cancer Res; 20(10); 2703–13. ©2014 AACR.
A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity
Authors: Grabiner Brian C. , Nardi Valentina , Birsoy Kıvanç , Possemato Richard , Shen Kuang , Sinha Sumi , Jordan Alexander , Beck Andrew H. , Sabatini David M.
Published: March 2014

Genes encoding components of the PI3K–AKT–mTOR signaling axis are frequently mutated in cancer, but few mutations have been characterized in MTOR, the gene encoding the mTOR kinase. Using publicly available tumor genome sequencing data, we generated a comprehensive catalog of mTOR pathway mutations in cancer, identifying 33 MTOR mutations that confer pathway hyperactivation. The mutations cluster in six distinct regions in the C-terminal half of mTOR and occur in multiple cancer types, with one cluster particularly prominent in kidney cancer. The activating mutations do not affect mTOR complex assembly, but a subset reduces binding to the mTOR inhibitor DEPTOR. mTOR complex 1 (mTORC1) signaling in cells expressing various activating mutations remains sensitive to pharmacologic mTOR inhibition, but is partially resistant to nutrient deprivation. Finally, cancer cell lines with hyperactivating MTOR mutations display heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer mTOR pathway dependency.

Significance: We report that a diverse set of cancer-associated MTOR mutations confer increased mTORC1/2 pathway activity and that cells harboring these mutations are highly sensitive to rapamycin in culture and in vivo. These findings are clinically relevant as the MTOR mutations characterized herein may serve as biomarkers for predicting tumor responses to mTOR inhibitors. Cancer Discov; 4(5); 554–63. ©2014 AACR.

See related commentary by Rejto and Abraham, p. 513

This article is highlighted in the In This Issue feature, p. 495