bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation between Gastric Cancer and Protein Oxidation, DNA Damage, and Lipid Peroxidation
Authors: Ma Yongsheng , Zhang Lin , Rong Shengzhong , Qu Hongyan , Zhang Yannan , Chang Dong , Pan Hongzhi , Wang Wenbo
Published: December 2013

Objects.The aim of this study is to evaluate protein oxidation, DNA damage, and lipid peroxidation in patients with gastric cancer and to investigate the relationship between oxidative stress and gastric cancer.Methods. We investigated changes in serum protein carbonyl (PC), advanced oxidation protein products (AOPP), and 3-nitrotyrosine (3-NT) levels, as indicators of protein oxidation, serum 8-hydroxydeoxyguanosine (8-OHdG), as a biomarker of DNA damage, and malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), and 8-ISO-prostaglandinF2α(8-PGF) in serum, as lipid peroxidation markers in gastric cancer (GC) patients and healthy control.Results. Compared with control, a statistically significant higher values of 8-OHdG, PC, AOPP, and 3-NT were observed in the GC patients (P<0.05). The products of lipid peroxidation, MDA, CD, 4-HNE, and 8-PGF, were significantly lower in the GC patients compared to those of control (P<0.05). In addition, the products of oxidative stress were similar between the Helicobacter pylori positive and the negative subgroups of GC patients.Conclusions. GC patients were characterized by increased protein oxidation and DNA damage, and decreased lipid peroxidation. Assessment of oxidative stress and augmentation of the antioxidant defense system may be important for the treatment and prevention of gastric carcinogenesis.
Microstrip Folded Dipole Antenna for 35 GHz MMW Communication
Authors: Hua Guang , Yang Chen , Lu Ping , Zhou Hou-Xing , Hong Wei
Published: December 2013

A microstrip asymmetric folded dipole antenna on chip is proposed in this paper. The construction of balun feed line is adopted to provide wideband. A new design procedure based on the odd-even mode method to calculate the input impedance of an asymmetric strip folded dipole antenna is presented. The folded dipole antenna has the advantage of small size, low profile, low cost, and so forth. The measured results show that a miniaturized antenna has the bandwidth of more than 14.2% (VSWR≤2); gain of the antenna is 5.7 dB at 35 GHz.
Methicillin ResistantStaphylococcus aureusProstatic Abscess with Bacteremia
Authors: Lachant Daniel J. , Apostolakos Michael , Pietropaoli Anthony
Published: December 2013

Prostatic abscess is traditionally considered a rare disease that is caused by Gram-negative bacteria. Methicillin resistantStaphylococcus aureus(MRSA) has recently emerged as an important cause of prostatic abscesses. Symptoms are nonspecific and include dysuria, urinary frequency, fever, chills, and perineal and low back pain. Morbidity and mortality increase with delays in identification and proper treatment. We present two cases of community acquired MRSA prostatic abscesses with bacteremia. One of these cases may be the first reported septic shock fatality resulting from a prostatic abscess source in an immunocompetent patient. As the number of community acquired MRSA bacteremia cases increases, this potential site of infection should be recognized.
Span Length Variance Effect on the Fatigue Life of FRP Bridge Deck
Authors: Park Ki-Tae , Yu Young-Jun , Shin Hyunseop
Published: December 2013

Fiber reinforced composite materials have the merits of light weight and durability for bridge deck and are estimated to be superior in economy to conventional deck materials considering the life-cycle cost of bridge. In this study, fatigue tests were conducted for the span lengths of 2.0 m and 2.5 m in order to investigate the change trend of fatigue characteristics of composite material deck according to the change in the span length. The result showed that the fatigue life rapidly reduces to about 25% when the span increases by 25%. However, considering that the fatigue performance safety margin was approximately 1.6 times more than the design axle load of the DB-24 design truck load in Korea, even at the span of 2.5 m, it is judged that the FRP decks being considered can be effectively used at a span length of 2.5 m.
Trauma as Pathogenesis of a Plantar Forefoot Fibrolipoma: First Case and Review of the Literature
Authors: Vasconcelos Juliana S. P. , Gharaibeh Faris , Nittinger Hans-Christoph
Published: December 2013

Lipomas and their variants are benign soft-tissue tumors that occur at any age and most frequently on the upper back and neck, shoulder, and abdomen. The foot is a relatively uncommon site for soft-tissue neoplasia and the etiology is not usually related to trauma. We describe a case of a pedunculated fibrolipoma of the forefoot that originated from a cut wound at the Atlantic Ocean. A brief review of the literature is also given.
An Implicit Algorithm Based on Continuous Moving Least Square to Simulate Material Mixing in Friction Stir Welding Process
Authors: Timesli Abdelaziz , Braikat Bouazza , Lahmam Hassane , Zahrouni Hamid
Published: December 2013

An implicit iterative algorithm, based on the continuous moving least square (CMLS), is developed to simulate material mixing in Friction Stir Welding (FSW) process. Strong formulation is chosen for the modeling of the mechanical problem in Lagrangian framework to avoid the drawback of numerical integration. This algorithm is well adapted to large deformations in the mixing zone in the neighborhood of the welding tool. We limit ourselves to bidimensional viscoplastic problem to show the performance of the proposed implicit algorithm. The results show that the proposed algorithm can be employed to simulate FSW.
Efficient Cluster Head Selection Algorithm for MANET
Authors: Hussain Khalid , Abdullah Abdul Hanan , Iqbal Saleem , Awan Khalid M. , Ahsan Faraz
Published: December 2013

In mobile ad hoc network (MANET) cluster head selection is considered a gigantic challenge. In wireless sensor network LEACH protocol can be used to select cluster head on the bases of energy, but it is still a dispute in mobil ad hoc networks and especially when nodes are itinerant. In this paper we proposed an efficient cluster head selection algorithm (ECHSA), for selection of the cluster head efficiently in Mobile ad hoc networks. We evaluate our proposed algorithm through simulation in OMNet++ as well as on test bed; we experience the result according to our assumption. For further evaluation we also compare our proposed protocol with several other protocols like LEACH-C and consequences show perfection.
Effects of Exercise in the Treatment of Overweight and Obese Children and Adolescents: A Systematic Review of Meta-Analyses
Authors: Kelley George A. , Kelley Kristi S.
Published: December 2013

Purpose. Conduct a systematic review of previous meta-analyses addressing the effects of exercise in the treatment of overweight and obese children and adolescents.Methods. Previous meta-analyses of randomized controlled exercise trials that assessed adiposity in overweight and obese children and adolescents were included by searching nine electronic databases and cross-referencing from retrieved studies. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. The alpha level for statistical significance was set atP≤0.05.Results. Of the 308 studies reviewed, two aggregate data meta-analyses representing 14 and 17 studies and 481 and 701 boys and girls met all eligibility criteria. Methodological quality was 64% and 73%. For both studies, statistically significant reductions in percent body fat were observed (P=0.006andP<0.00001). The number-needed-to treat (NNT) was 4 and 3 with an estimated 24.5 and 31.5 million overweight and obese children in the world potentially benefitting, 2.8 and 3.6 million in the US. No other measures of adiposity (BMI-related measures, body weight, and central obesity) were statistically significant.Conclusions. Exercise is efficacious for reducing percent body fat in overweight and obese children and adolescents. Insufficient evidence exists to suggest that exercise reduces other measures of adiposity.
Electrochemical Investigation of Anthraquinone‐Based Chemodosimeter for Cu2+ Metal Ion
Authors: Yoon Yeo Woon , Kim Jong Seung , Kim Tae Hyun
Published: December 2013

The electrochemical properties of an anthraquinone‐containing Cu2+‐promoted desulfurization chemodosimeter (AQCD) in the presence of various metal ions were investigated by voltammetry. AQCD showed voltammetric changes toward divalent metal ions (M2+), which are similar to those of anthraquinone (AQ) and 1‐aminoanthraquinone (AQNH2) with the metal ions except Cu2+. This can be explained on the electrostatic interaction (AQCD‐M2+) and chemodosimetric reaction (AQCD‐Cu2+).
Online Detection of Abnormal Events in Video Streams
Authors: Wang Tian , Chen Jie , Snoussi Hichem
Published: December 2013

We propose an algorithm to handle the problem of detecting abnormal events, which is a challenging but important subject in video surveillance. The algorithm consists of an image descriptor and online nonlinear classification method. We introduce the covariance matrix of the optical flow and image intensity as a descriptor encoding moving information. The nonlinear online support vector machine (SVM) firstly learns a limited set of the training frames to provide a basic reference model then updates the model and detects abnormal events in the current frame. We finally apply the method to detect abnormal events on a benchmark video surveillance dataset to demonstrate the effectiveness of the proposed technique.
Investigation on the Electrical Conductivity of Transformer Oil‐Based AlN Nanofluid
Authors: Dong M. , Shen L. P. , Wang H. , Wang H. B. , Miao J.
Published: December 2013

Aluminum‐nitride‐(AlN)‐transformer oil‐based nanofluid was prepared by dispersing AlN nanoparticles in transformer oil. The composition‐dependent electrical conductivity of AlN‐transformer oil nanofluid was investigated at different ambient temperatures. The results indicate the nonlinear dependences of the electrical conductivity on volumetric fraction and temperature. In comparison to the pure transformer oil, the electrical conductivity of nanofluid containing 0.5% AlN nanoparticles has increased by 1057 times at 60°C. By considering the electrophoresis of the AlN nanoparticles, a straightforward electrical conductivity model is established to modulate and understand the experiment results.
An Energy-Efficient and Scalable Secure Data Aggregation for Wireless Sensor Networks
Authors: Wang Taochun , Qin Xiaolin , Liu Liang
Published: December 2013

Due to the characteristics of resource-constrained and battery-powered sensors in wireless sensor networks (WSNs), energy consumption is always a major concern. Data aggregation is an essential technique to reduce the communication overhead and energy consumption. Since many applications require data privacy, we need to take security into consideration. In this paper, we propose an energy-efficient, secure, highly accurate, and scalable scheme for data aggregation (EESSDA). The main idea of EESSDA is that secure data aggregation is achieved by establishing secure channel and slicing technology. The EESSDA scheme does not need encryption and decryption operations during the data aggregation, which saves energy and obtain high accuracy of aggregation results. Meanwhile, in EESSDA scheme, the advanced deployment of shared information between nodes is not required, making the networks with good scalability. Our analysis and simulations show that EESSDA is of lower communication overhead, more efficiency and accuracy, and better privacy preservation and scalability than existing schemes.
Comparison of Two Creatinine-Based Equations for Predicting Decline in Renal Function in Type 2 Diabetic Patients with Nephropathy in a Korean Population
Authors: Lee Eun Young , Lee Young-Mi , Choi Kyu Hun , Lee Hyun Chul , Lee Byung-Wan , Kim Beom Seok
Published: December 2013

Aim.To compare two creatinine-based estimated glomerular filtration rate (eGFR) equations, the chronic kidney disease epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD), for predicting the risk of CKD progression in type 2 diabetic patients with nephropathy.Methods.A total of 707 type 2 diabetic patients with 24 hr urinary albumin excretion of more than 30 mg/day were retrospectively recruited and traced until doubling of baseline serum creatinine (SCr) levels was noted.Results.During the follow-up period (median, 2.4 years), the CKD-EPI equation reclassified 10.9% of all MDRD-estimated subjects: 9.1% to an earlier stage of CKD and 1.8% to a later stage of CKD. Overall, the prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was lowered from 54% to 51.6% by applying the CKD-EPI equation. On Cox-regression analysis, both equations exhibited significant associations with an increased risk for doubling of SCr. However, only the CKD-EPI equation maintained a significant hazard ratio for doubling of SCr in earlier-stage CKD (eGFR ≥ 45 mL/min/1.73 m2), when compared to stage 1 CKD (eGFR ≥ 90 mL/min/1.73 m2).Conclusion.In regard to CKD progression, these results suggest that the CKD-EPI equation might more accurately stratify earlier-stage CKD among type 2 diabetic patients with nephropathy than the MDRD study equation.
Predictive Role of ADA in Bronchoalveolar Lavage Fluid in Making the Diagnosis of Pulmonary Tuberculosis
Authors: Binesh Fariba , Halvani Abolhassan
Published: December 2013

Current diagnostic tests for tuberculosis (TB) are time-consuming. The aim of this study was to evaluate the diagnostic usefulness of ADA in bronchoalveolar lavage fluid in patients with pulmonary TB. A cross-sectional study was performed in Yazd, Iran, between 2009 and 2010. Patients suspected of pulmonary TB with negative sputum smear for AFB were included in the study. Mean ADA levels in BAL fluids were measured and compared between study groups. Sixty-three patients were enrolled in the study among which 15 cases had pulmonary TB, 33 had pulmonary diseases other than TB, and 15 subjects with normal bronchoscopy results were considered as controls. Mean ADA levels in BAL fluid were4.13±2.55,2.42±1.06, and1.93±0.88, respectively. This rate was significantly higher in the pulmonary TB group compared to the other two groups (P=0.001). Using ROC curve with a cut-off value of 3.5 IU/L, the highest sensitivity (57%) and specificity (84%) were obtained in diagnosis of TB. The results showed that although ADA activity in BAL fluid of pulmonary TB patients was higher than those seen in other diseases, a negative test does not rule out pulmonary TB.
A Slicing Tree Representation and QCP-Model-Based Heuristic Algorithm for the Unequal-Area Block Facility Layout Problem
Authors: Chang Mei-Shiang , Ku Ting-Chen
Published: December 2013

The facility layout problem is a typical combinational optimization problem. In this research, a slicing tree representation and a quadratically constrained program model are combined with harmony search to develop a heuristic method for solving the unequal-area block layout problem. Because of characteristics of slicing tree structure, we propose a regional structure of harmony memory to memorize facility layout solutions and two kinds of harmony improvisation to enhance global search ability of the proposed heuristic method. The proposed harmony search based heuristic is tested on 10 well-known unequal-area facility layout problems from the literature. The results are compared with the previously best-known solutions obtained by genetic algorithm, tabu search, and ant system as well as exact methods. For problems O7, O9, vC10Ra, M11*, and Nug12, new best solutions are found. For other problems, the proposed approach can find solutions that are very similar to previous best-known solutions.
Analysis of a Single Hemodialysis on Phosphate Removal of the Internal Fistula Patients by Mathematical and Statistical Methods
Authors: Yu Qiyao , Bai Yaling , Zhang Junxia , Cui Liwen , Zhang Huiran , Xu Jinsheng , Gao Chao
Published: December 2013

Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide challenge in hemodialysis patients. In china, the number of dialysis patients is growing but few data are available about their bone disorders. In the current study, we aimed to evaluate the effect of clinical factors on the serum phosphorus clearance in the 80 maintenance hemodialysis (MHD) patients. Six clinical factors were identified for their association with the serum phosphorus clearance using the analysis of Spearman’s single linear correlation, including predialysis serum phosphate level, CRR, membrane surface area of the dialyzer, effective blood flow rate, the blood chamber volume, and hematocrit. In an overall multivariate analysis, pre-P, CRR, membrane SA, and Qb were identified as independent risk factors associated with the serum phosphorus clearance. In conclusion, HD could effectively clear serum phosphorus. The analysis of CRR might help to estimate serum phosphorus reduction ratio.
Error Correction for Laser Tracking System Using Dynamic Weighting Model
Authors: Liu W. L. , Wang Zhankui , Wang Shibo , Li Xiaoyang
Published: December 2013

Laser tracking system (LTS) has been widely used in energy industries to meet increasingly high accuracy requirements. However, its measuring accuracy is highly affected by the dynamic uncertainty errors of LTS, and also the current range and angle measurements of LTS are mainly weighted statically, obtaining the dynamic weighting model which is essential for LTS to improve the measuring accuracy. In this paper, a dynamic weighting model that describes not only the dynamic uncertainty but also the geometric variations of LTS is developed, which can be adjusted to the weighting factors of dynamic parameters according to the range observations relative to the angle observations. Intensive experimental studies are conducted to check validity of the theoretical results. The results show that the measuring accuracy of LTS has been increased 2 times after using this technique for correction.
Multifocal Epithelial Hyperplasia of Oral Cavity Expressing HPV 16 Gene: A Rare Entity
Authors: Prabhat M. P. V. , Raja Lakshmi Chintamaneni , Sai Madhavi N. , Bhavana Sujana Mulk , Sarat Gummadapu , Ramamohan Kodali
Published: December 2013

Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus. Usually HPV involves either cutaneous or mucosal surfaces, whereas concomitant mucocutaneous involvement is extremely rare. We report such a unique case of multifocal epithelial hyperplasia involving multiple sites of oral cavity along with skin lesions in a 65-year-old female. We also discuss the probable multifactorial etiology and variable clinical presentations of the lesions, including evidence of HPV 16 expression, as detected by polymerase chain reaction. The present report illustrates the need for careful examination and prompt diagnosis of the disease, as it might be associated with high risk genotypes such as HPV 16 and 18.
Selection of Construction Methods: A Knowledge‐Based Approach
Authors: Ferrada Ximena , Serpell Alfredo , Skibniewski Miroslaw
Published: December 2013

The appropriate selection of construction methods to be used during the execution of a construction project is a major determinant of high productivity, but sometimes this selection process is performed without the care and the systematic approach that it deserves, bringing negative consequences. This paper proposes a knowledge management approach that will enable the intelligent use of corporate experience and information and help to improve the selection of construction methods for a project. Then a knowledge‐based system to support this decision‐making process is proposed and described. To define and design the system, semistructured interviews were conducted within three construction companies with the purpose of studying the way that the method’ selection process is carried out in practice and the knowledge associated with it. A prototype of a Construction Methods Knowledge System (CMKS) was developed and then validated with construction industry professionals. As a conclusion, the CMKS was perceived as a valuable tool for construction methods’ selection, by helping companies to generate a corporate memory on this issue, reducing the reliance on individual knowledge and also the subjectivity of the decision‐making process. The described benefits as provided by the system favor a better performance of construction projects.
Partial Recovery of Audiological, Vestibular, and Radiological Findings following Spontaneous Intralabyrinthine Haemorrhage
Authors: Pézier Thomas , Baráth Krisztina , Hegemann Stefan
Published: December 2013

The diagnosis, work-up, and treatment of sudden sensorineural hearing loss and sudden vestibular loss vary widely between units. With the increasing access to both magnetic resonance imaging and objective vestibular testing, our understanding of the various aetiologies at hand is increasing. Despite this, the therapeutic options are limited and without a particularly strong evidence base. We present a rare, yet increasingly diagnosed, case of intralabyrinthine haemorrhage (ILH) together with radiological, audiological, and vestibular test results. Of note, this occurred spontaneously and has shown partial recovery in all the mentioned modalities.
The Role of Epiretinal Membrane on Treatment of Neovascular Age‐Related Macular Degeneration with Intravitreal Bevacizumab
Authors: Alkin Zeynep , Ozkaya Abdullah , Osmanbasoglu Ozen Ayranci , Agca Alper , Karakucuk Yalcin , Yazici Ahmet Taylan , Demirok Ahmet
Published: December 2013

Purpose. To determine the effect of epiretinal membranes (ERM) on the treatment response and the number of intravitreal bevacizumab injections (IVB) in patients with neovascular age‐related macular degeneration (nAMD). Methods. A retrospective chart review was performed on 63 eyes of 63 patients. The patients were divided into AMD group (n = 35) and AMD/ERM group (n = 28). Best corrected visual acuity (BCVA) and central retinal thickness (CRT), as well as the number of injections, were evaluated. Results. There was a significant improvement in BCVA at 3 months for the AMD and AMD/ERM groups (P = 0.02, P = 0.03, resp.). At 6, 12, and 18 months, BCVA did not change significantly in either of the groups compared to baseline (P > 0.05 for all). At 3, 6, 12, and 24 months, the AMD group had an improvement in BCVA (logMAR) of 0.09, 0.06, 0.06, and 0.03 versus 0.08, 0.07, 0.05, and 0.03 for the AMD/ERM group (P = 0.29, P = 0.88, P = 0.74, P = 0.85, resp.). A significant decrease in CRT occurred in both groups for all time points (P < 0.001 for all). The change in CRT was not statistically different between the two groups at all time points (P > 0.05 for all). The mean number of injections over 24 months was 8.8 in the AMD group and 9.2 in the AMD/ERM group (P = 0.76). Conclusion. During 24 months, visual and anatomical outcomes of IVB in nAMD patients were comparable with those in nAMD patients with ERM with similar injection numbers.
Current Evidence and Insights about Genetics in Thoracic Aorta Disease
Authors: Bisleri Gianluigi , Bagozzi Lorenzo , Muneretto Claudio
Published: December 2013

Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys‐Dietz, and Ehler‐Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve.
Developing a STEP-Compliant Multiagent on an Interoperable and Integrated CAD/CAM Platform
Authors: Mokhtar Alireza , Fatahi Valilai Omid
Published: December 2013

Practical implementation of a STEP-based architecture to provide a fully integrated and interoperable platform of data exchange has always been an intriguing issue. A variety of CAD/CAM environments are struggling to embed and support STEP standard and its protocols in order to seamlessly operate within global data exchange. However, apparent paucity of efficient and reliable structure for data communication, manipulation, and restoration has remarkably hindered the desired progress. In this paper, taking these shortcomings into account, a practical architecture is introduced and STEP-based agents are implemented and installed on the platform. Moreover, feature recognition, interaction, and machining precedence as crucial issues of CAD/CAM research have been considered in developing the interoperable platform. Seamless integration and interaction of CAD/CAM modules are provided in the proposed system. The prototype is finally verified and discussed through a case study.
Targeting a Glioblastoma Cancer Stem-Cell Population Defined by EGF Receptor Variant III
Authors: Emlet David R. , Gupta Puja , Holgado-Madruga Marina , Del Vecchio Catherine A. , Mitra Siddhartha S. , Han Shuang-Yin , Li Gordon , Jensen Kristin C. , Vogel Hannes , Xu Linda Wei , Skirboll Stephen S. , Wong Albert J.
Published: December 2013

The relationship between mutated proteins and the cancer stem-cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGF receptor (EGFR) variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here, we show that EGFRvIII is highly coexpressed with CD133 and that EGFRvIII+/CD133+ defines the population of cancer stem cells (CSC) with the highest degree of self-renewal and tumor-initiating ability. EGFRvIII+ cells are associated with other stem/progenitor markers, whereas markers of differentiation are found in EGFRvIII− cells. EGFRvIII expression is lost in standard cell culture, but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII+/CD133+ coexpression, self-renewal, and tumor initiating abilities. Elimination of the EGFRvIII+/CD133+ population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC-specific expression and be used to specifically target this population. Cancer Res; 74(4); 1238–49. ©2013 AACR.
Tumor-Derived GM-CSF Promotes Inflammatory Colon Carcinogenesis via Stimulating Epithelial Release of VEGF
Authors: Wang Yi , Han Gencheng , Wang Ke , Liu Guijun , Wang Renxi , Xiao He , Li Xinying , Hou Chunmei , Shen Beifen , Guo Renfeng , Li Yan , Chen Guojiang
Published: December 2013

Chronic inflammation is a major driving force for the development of colitis-associated cancer (CAC). Elevated production of granulocyte macrophage colony-stimulating factor (GM-CSF) has been observed in mucosa of patients with inflammatory bowel disease. Its actions in the progression from colitis to cancer, however, remain poorly understood. Herein, we demonstrated that colonic epithelial cells (CEC) were a major cellular source of GM-CSF and its production was significantly augmented when CAC model was established by administration of azoxymethane and dextran sulfate sodium. Furthermore, we showed that GM-CSF was a driver for VEGF release by CEC in autocrine and/or paracrine manners through the extracellular signal-regulated kinase (ERK)-dependent pathway. Blocking GM-CSF activity in vivo significantly decreased epithelial release of VEGF, thereby abrogating CAC formation. In vitro treatment of transformed CEC with recombinant GM-CSF dramatically augmented its invasive potentials, largely in VEGF-dependent fashion. Furthermore, commensal microbiota-derived lipopolysaccharides were identified as a trigger for GM-CSF expression in CEC, as antibiotics treatment or Toll-like receptor 4 ablation considerably impaired its epithelial expression. Overall, these findings may have important implications for the understanding of mechanisms underlying CAC pathogenesis and the therapeutic potentials of regimens targeting GM-CSF or VEGF in clinic. Cancer Res; 74(3); 716–26. ©2013 AACR.
CRR9/CLPTM1L Regulates Cell Survival Signaling and Is Required for Ras Transformation and Lung Tumorigenesis
Authors: James Michael A. , Vikis Haris G. , Tate Everett , Rymaszewski Amy L. , You Ming
Published: December 2013

The transmembrane protein CLPTM1L is overexpressed in non–small cell lung cancer, where it protects tumor cells from genotoxic apoptosis. Here, we show that RNA interference-mediated blockade of CLPTM1L inhibits K-Ras–induced lung tumorigenesis. CLPTM1L expression was required in vitro for morphologic transformation by H-RasV12 or K-RasV12, anchorage-independent growth, and survival of anoikis of lung tumor cells. Mechanistic investigations indicated that CLPTM1L interacts with phosphoinositide 3-kinase and is essential for Ras-induced AKT phosphorylation. Furthermore that the anti-apoptotic protein Bcl-xL is regulated by CLPTM1L independently of AKT activation. Constitutive activation of AKT or Bcl-xL rescued the transformed phenotype in CLPTM1L-depleted cells. The CLPTM1L gene lies within a cancer susceptibility locus at chromosome 5p15.33 defined by genome-wide association studies. The risk genotype at the CLPTM1L locus was associated with high expression of CLPTM1L in normal lung tissue, suggesting that cis-regulation of CLPTM1L may contribute to lung cancer risk. Taken together, our results establish a protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization. Cancer Res; 74(4); 1116–27. ©2013 AACR.
Cyclin E1 Deregulation Occurs Early in Secretory Cell Transformation to Promote Formation of Fallopian Tube–Derived High-Grade Serous Ovarian Cancers
Authors: Karst Alison M. , Jones Paul M. , Vena Natalie , Ligon Azra H. , Liu Joyce F. , Hirsch Michelle S. , Etemadmoghadam Dariush , Bowtell David D.L. , Drapkin Ronny
Published: December 2013

The fallopian tube is now generally considered the dominant site of origin for high-grade serous ovarian carcinoma. However, the molecular pathogenesis of fallopian tube-derived serous carcinomas is poorly understood and there are few experimental studies examining the transformation of human fallopian tube cells. Prompted by recent genomic analyses that identified cyclin E1 (CCNE1) gene amplification as a candidate oncogenic driver in high-grade serous ovarian carcinoma, we evaluated the functional role of cyclin E1 in serous carcinogenesis. Cyclin E1 was expressed in early- and late-stage human tumor samples. In primary human fallopian tube secretory epithelial cells, cyclin E1 expression imparted malignant characteristics to untransformed cells if p53 was compromised, promoting an accumulation of DNA damage and altered transcription of DNA damage response genes related to DNA replication stress. Together, our findings corroborate the hypothesis that cyclin E1 dysregulation acts to drive malignant transformation in fallopian tube secretory cells that are the site of origin of high-grade serous ovarian carcinomas. Cancer Res; 74(4); 1141–52. ©2013 AACR.
Myocardial Expression Level of Neural Cell Adhesion Molecule Correlates With Reduced Left Ventricular Function in Human Cardiomyopathy
Authors: Nagao Kazuya , Sowa Naoya , Inoue Katsumi , Tokunaga Motoko , Fukuchi Kohei , Uchiyama Koji , Ito Haruyasu , Hayashi Fujio , Makita Toshinori , Inada Tsukasa , Tanaka Masaru , Kimura Takeshi , Ono Koh
Published: December 2013

Background—

Recently, we screened for cardiac genes induced by metabolic stress and identified neural cell adhesion molecule (NCAM) as a candidate. This study aimed to clarify the expression pattern of NCAM in human cardiomyopathy.

Methods and Results—

A total of 64 cardiac tissue samples of patients with dilated cardiomyopathy were dichotomized according to the immunohistochemically determined signal intensity of NCAM staining (NCAM-high and NCAM-low groups). Clinical and hemodynamic data of the patients were compared between the 2 groups. Fibrosis area, left ventricular end-diastolic volume index, and left ventricular diastolic pressure were greater in the NCAM-high group (22.8% versus 11.6%,
P
<0.05; 130.3±57.6 versus 104.8±31.7 mL/m
2
,
P
<0.05; 14.3±8.0 versus 8.8±4.7 mm Hg,
P
<0.005; respectively). Incidence of cardiac death and admission for worsening heart failure was higher in the NCAM-high group during a follow-up of 6.3 years (log-rank
P
<0.05). Another 18 tissue samples were analyzed to determine the relationships between expression level of NCAM and major metabolic genes as well as hemodynamic parameters. The mRNA level of NCAM correlated with the serum (
r
=0.58;
P
=0.01) and mRNA levels (
r
=0.61;
P
=0.008) of brain-derived natriuretic peptides. It was also correlated with the mRNA levels of proliferator-activated receptor-γ coactivator-1 α (
r
=0.69;
P
=0.002) and the nuclear respiratory factor 1 (
r
=0.74;
P
<0.001).

Conclusions—

Expression of NCAM was associated with worsening hemodynamic parameters and major metabolic genes. Together with our previous findings, these data support the involvement of NCAM in left ventricular remodeling, revealing new insights into the pathophysiology of heart failure.
Factors Associated With the Prevalence of Hypertension in the Southeastern United States
Authors: Sampson Uchechukwu K.A. , Edwards Todd L. , Jahangir Eiman , Munro Heather , Wariboko Minaba , Wassef Mariam G. , Fazio Sergio , Mensah George A. , Kabagambe Edmond K. , Blot William J. , Lipworth Loren
Published: December 2013

Background—

Lifestyle and socioeconomic status have been implicated in the prevalence of hypertension; thus, we evaluated factors associated with hypertension in a cohort of blacks and whites with similar socioeconomic status characteristics.

Methods and Results—

We evaluated the prevalence and factors associated with self-reported hypertension (SR-HTN) and ascertained hypertension (A-HTN) among 69 211 participants in the Southern Community Cohort Study. Multivariable logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with hypertension. The prevalence of SR-HTN was 57% overall. Body mass index was associated with SR-HTN in all race-sex groups, with the OR rising to 4.03 (95% CI, 3.74–4.33) for morbidly obese participants (body mass index, >40 kg/m
2
). Blacks were more likely to have SR-HTN than whites (OR, 1.84; 95% CI, 1.75–1.93), and the association with black race was more pronounced among women (OR, 2.08; 95% CI, 1.95–2.21) than men (OR, 1.47; 95% CI, 1.36–1.60). Similar findings were noted in the analysis of A-HTN. Among those with SR-HTN and A-HTN who reported use of an antihypertensive agent, 94% were on at least one of the major classes of antihypertensive agents, but only 44% were on ≥2 classes and only 29% were on a diuretic. The odds of both uncontrolled hypertension (SR-HTN and A-HTN) and unreported hypertension (no SR-HTN and A-HTN) were twice as high among blacks as whites (OR, 2.13; 95% CI, 1.68–2.69; and OR, 1.99; 95% CI, 1.59–2.48, respectively).

Conclusions—

Despite socioeconomic status similarities, we observed suboptimal use of antihypertensives in this cohort and racial differences in the prevalence of uncontrolled and unreported hypertension, which merit further investigation.
Lung Natural Killer Cells Play a Major Counter-Regulatory Role in Pulmonary Vascular Hyperpermeability After Myocardial Infarction
Authors: Yan Xiaoxiang , Hegab Ahmed E. , Endo Jin , Anzai Atsushi , Matsuhashi Tomohiro , Katsumata Yoshinori , Ito Kentaro , Yamamoto Tsunehisa , Betsuyaku Tomoko , Shinmura Ken , Shen Weifeng , Vivier Eric , Fukuda Keiichi , Sano Motoaki
Published: December 2013

Rationale
:

Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs.

Objective
:

We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction.

Methods and Results
:

Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ–positive cell populations were unchanged, whereas IL-10–positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell–depleted mice rescued the respiratory phenotype. IL-1β–mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice.

Conclusions
:

This study is the first to identify a critical role for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after myocardial infarction.
Aggregate Risk of Cardiovascular Disease Among Adolescents Perinatally Infected With the Human Immunodeficiency Virus
Authors: Patel Kunjal , Wang Jiajia , Jacobson Denise L. , Lipshultz Steven E. , Landy David C. , Geffner Mitchell E. , DiMeglio Linda A. , Seage George R. , Williams Paige L. , Van Dyke Russell B. , Siberry George K. , Shearer William T. , Young Luciana , Scott Gwendolyn B. , Wilkinson James D. , Fisher Stacy D. , Starc Thomas J. , Miller Tracie L.
Published: December 2013

Background—

Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy.

Methods and Results—

Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period.

Conclusions—

A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.
Macrophage Migration Inhibitory Factor Deletion Exacerbates Pressure Overload–Induced Cardiac Hypertrophy Through Mitigating Autophagy
Authors: Xu Xihui , Hua Yinan , Nair Sreejayan , Bucala Richard , Ren Jun
Published: December 2013

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) has been shown to be cardioprotective under various pathological conditions. However, the underlying mechanisms still remain elusive. In this study, we revealed that MIF deficiency overtly exacerbated abdominal aorta constriction–induced cardiac hypertrophy and contractile anomalies. MIF deficiency interrupted myocardial autophagy in hypertrophied hearts. Rapamycin administration mitigated the exacerbated hypertrophic responses in MIF
−/−
mice. Using the phenylephrine-induced hypertrophy in vitro model in H9C2 myoblasts, we confirmed that MIF governed the activation of AMP-activated protein kinase–mammalian target of rapamycin–autophagy cascade. Confocal microscopic examination demonstrated that MIF depletion prevented phenylephrine-induced mitophagy in H9C2 myoblasts. Myocardial Parkin, an E3 ubiquitin ligase and a marker for mitophagy, was significantly upregulated after sustained pressure overload, the effect of which was prevented by MIF knockout. Furthermore, our data exhibited that levels of MIF, AMP-activated protein kinase activation, and autophagy were elevated concurrently in human failing hearts. These data indicate that endogenous MIF regulates the mammalian target of rapamycin signaling to activate autophagy to preserve cardiac geometry and protect against hypertrophic responses.
Caffeine Intake Improves Fructose-Induced Hypertension and Insulin Resistance by Enhancing Central Insulin Signaling
Authors: Yeh Tung-Chen , Liu Chun-Peng , Cheng Wen-Han , Chen Bo-Rong , Lu Pei-Jung , Cheng Pei-Wen , Ho Wen-Yu , Sun Gwo-Ching , Liou Jau-Cheng , Tseng Ching-Jiunn
Published: December 2013

Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1
S307
) and reversed Akt
S473
and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production of superoxide and expression of receptor of advanced glycation end product in the NTS. These results suggest that caffeine may enhance insulin receptor substrate 1-phosphatidylinositol 3-kinase-Akt-neuronal nitric oxide synthase signaling to decrease blood pressure by abolishing superoxide production in the NTS.
Altered Inflammatory Response Is Associated With an Impaired Autonomic Input to the Bone Marrow in the Spontaneously Hypertensive Rat
Authors: Zubcevic Jasenka , Jun Joo Yun , Kim Seungbum , Perez Pablo D. , Afzal Aqeela , Shan Zhiying , Li Wencheng , Santisteban Monica M. , Yuan Wei , Febo Marcelo , Mocco Jay , Feng Yumei , Scott Edward , Baekey David M. , Raizada Mohan K.
Published: December 2013

Autonomic nervous system dysfunction, exaggerated inflammation, and impaired vascular repair are all hallmarks of hypertension. Considering that bone marrow (BM) is a major source of the inflammatory cells (ICs) and endothelial progenitor cells (EPCs), we hypothesized that impaired BM–autonomic nervous system interaction contributes to dysfunctional BM activity in hypertension. In the spontaneously hypertensive rat (SHR), we observed a >30% increase in BM and blood ICs (CD4.8
+
) and a >50% decrease in EPCs (CD90
+
.CD4.5.8
–
) when compared with the normotensive Wistar–Kyoto rat. Increased tyrosine hydroxylase (70%) and norepinephrine (160%) and decreased choline acetyl transferase (30%) and acetylcholine esterase (55%) indicated imbalanced autonomic nervous system in SHR BM. In Wistar–Kyoto rat, night time–associated elevation in sympathetic nerve activity (50%) and BM norepinephrine (41%) was associated with increased ICs (50%) and decreased EPCs (350%) although BM sympathetic denervation decreased ICs (25%) and increased EPCs (40%). In contrast, these effects were blunted in SHR, possibly because of chronic downregulation of BM adrenergic receptor α2a (by 50%–80%) and β2 (30%–45%). Application of norepinephrine resulted in increased BM IC activation/release, which was prevented by preadministration of acetylcholine. Electrophysiological recordings of femoral sympathetic nerve activity showed a more robust femoral sympathetic nerve activity in SHR when compared with Wistar–Kyoto rat, peaking earlier in the respiratory cycle, indicative of increased sympathetic tone. Finally, manganese-enhanced MRI demonstrated that presympathetic neuronal activation in SHR was associated with an accelerated retrograde transport of the green fluorescent protein–labeled pseudorabies virus from the BM. These observations demonstrate that a dysfunctional BM autonomic nervous system is associated with imbalanced EPCs and ICs in hypertension.