bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Mode I Periodic Parallel Cracks-Tip Stress Field in an Infinite Orthotropic Plate
Authors: Zhao Wenbin , Yu Lujuan , Zhang Xuexia , Xie Hailing , Hu Zhixin
Published: December 2013

The mechanical behavior near crack tip for periodic parallel cracks in an orthotropic composite plate subjected to the uniformly distributed load within the cracks surface is studied. The mechanical problem is turned into the boundary value problem of partial differential equation. By using the periodicity of the hyperbolic function in the complex domain and constructing proper Westergaard stress function, the periodicity of parallel cracks can be removed. Using the complex variable function method and the undetermined coefficients method, the boundary value problem of partial differential equation can be solved with the help of boundary conditions. The analytic expressions for stress intensity factor, stress, and displacement near the crack tip of periodical parallel cracks are obtained. When the vertical distance of cracks tends to infinity, the stress intensity factor degenerates into a single central crack situation. The stress intensity factor around the crack tip of periodic parallel cracks in an orthotropic composite plate depends on the shape factor. The interaction happens between the cracks. Finally, a numerical analysis of the stress and displacement changed with the polar angle is done.
Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model
Authors: Lee Hahn-Ey , Lee Sun Hee , Baek Minki , Choi Hwang , Park Kwanjin
Published: December 2013

Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing 1×109/mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats (n=20), with saline substituted in a control group (n=10). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children.
Implementation of High Performance Microstepping Driver Using FPGA with the Aim of Realizing Accurate Control on a Linear Motion System
Authors: Alidoust Aghdam Farid , Saeidi Haghi Siamak
Published: December 2013

This paper presents an FPGA-based microstepping driver which drives a linear motion system with a smooth and precise way. Proposed driver built on a Spartan3 FPGA (XC3S400 core) development board from Xilinx. Implementation of driver realized by an FPGA and using Verilog hardware description language in the Xilinx ISE environment. The driver’s control behavior can be adapted just by altering Verilog scripts. In addition, a linear motion system developed (with 4 mm movement per motor revolution) and coupled it to the stepper motor. The performance of the driver is tested by measuring the distance traveled on linear motion system. The experimental results verified using hardware-in-loop Matlab and Xilinx cosimulation method. This driver accomplishes a firm and accurate control and is responsive.
A Highly Thermostable Xylanase fromStenotrophomonas maltophilia: Purification and Partial Characterization
Authors: Raj Abhay , Kumar Sharad , Singh Sudheer Kumar
Published: December 2013

Seven xylanolytic bacterial strains were isolated from saw-dust dump soil. The bacterial strain X6 was selected on the basis of the highest xylanase activity with no cellulase contamination. It was identified asStenotrophomonas maltophiliaby biochemical tests and 16S rRNA gene sequencing approach. Xylanase production studies byS. maltophiliaon different commercial xylans and agro-industrial residues suggested that wheat bran was the best carbon source for xylanase production (26.4 ± 0.6 IU/mL). The studies with inorganic and organic nitrogen sources suggested yeast extract as the best support for xylanase production (25 ± 0.6 IU/mL). Maximum xylanase production was observed at initial medium pH = 8.0 (23.8 ± 0.4 IU/mL) with production at pH = 7.0 and pH = 9.0 being almost comparable. Xylanase produced byS. maltophiliawas purified to homogeneity using ammonium sulfate precipitation, gel filtration, and ion exchange chromatography. The final purification was 5.43-fold with recovery of 19.18%. The molecular weight of the purified xylanase protein was ~142 kDa. Both crude and purified xylanase had good stability at pH = 9.0 and 80°C with activity retention greater than 90% after 30 min incubation. The enzyme stability at high temperature and alkaline pH make it potentially effective for industrial applications.
The Autosomal Recessive Inheritance of Hereditary Gingival Fibromatosis
Authors: Majumder Poulami , Nair Vineet , Mukherjee Malancha , Ghosh Sujoy , Dey Subrata Kumar
Published: December 2013

Hereditary gingival fibromatosis (HGF) is a rare condition which is marked by enlargement of gingival tissue that covers teeth to various extents leading to aesthetic disfigurement. This study presents a case of a 28-year-old female patient and 18-year-old male who belong to the same family suffering from HGF with chief complaint of overgrowing swelling gingiva. The presence of enlarged gingiva with the same eruption was found in their other family members with no concomitant drug or medical history, and the occurrence of HGF has been found in one generation of this family which may indicate the autosomal recessive inheritance pattern of HGF. Hereditary gingival fibromatosis is an idiopathic condition as its etiology is unknown and it was found to recur in some cases even after surgical treatment. Both patients underwent thorough oral prophylaxis and later surgical therapy to correct the deformity.
Sleeping Schedule-Aware Local Broadcast in Wireless Sensor Networks
Authors: Hong Jue , Li Zhuo , Lu Dianjie , Lu Sanglu
Published: December 2013

Broadcast is widely used in applications in wireless sensor networks (WSNs). In the last decade, the broadcast problem in WSNs has been well studied. However, few of existing broadcasting strategies have considered the scenarios with sleeping schedules, which have been emerging as a prevalent energy-saving method for WSNs. In WSNs with sleeping schedule, each node switches on and off periodically, rendering the broadcast problem more difficult. To handle the periodical sleep issue, we focus on designing effective sleeping schedule-aware broadcast algorithms. We practically propose SALB, a sleeping schedule-aware local broadcast algorithm. In SALB, a typical local algorithm for constructing connected dominating set is employed to form the broadcast backbone. To guarantee proper transmission of broadcast messages, a sleep-aware forwarding mechanism is implemented. Moreover, heuristic strategies are used to decrease the number of transmissions and the broadcast latency. Theoretical analysis shows that the number of transmissions for SALB is within 4(min(Δ,[Formula: see text]) ( c is constant) is constant) times of the optimal value. And the broadcast latency of SALB is within 4[Formula: see text] times of the optimal value (Δ is the maximum degree in the network, [Formula: see text] is the scheduling period length). The performance of SALB is evaluated via simulations.
Green Extraction: Enhanced Extraction Yield of Asiatic Acid from Centella asiatica (L.) Nanopowders
Authors: Borhan M. Z. , Ahmad R. , Rusop M. , Abdullah S.
Published: December 2013

Nanopowders of Centella asiatica (L.) were produced using planetary ball mill in order to investigate the differences of water extraction yield of asiatic acid as compared to micropowders of Centella asiatica. Effect of extraction time (20–60 min) on extraction yield of asiatic acid from Centella asiatica was examined. Results showed that water extraction of asiatic acid using Centella asiatica nanopowders exhibits was almost 50% higher extraction yield with 7.09 mg/g as compared to the micropowders of Centella asiatica. It was concluded that nanopowders contributed in enhancing water extraction yield of asiatic acid as compared to micropowders. Thereby utilizing nanopowders in water extraction could improve the extraction of asiatic acid via clean, eco-friendly, and less expensive process.
The Prognostic Value of Peripheral Artery Diseases in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Barbarash Olga L. , Zykov Mikhail V. , Pecherina Tamara B. , Kashtalap Vasily V. , Barbarash Leonid S. , Kutikhin Anton G.
Published: December 2013

Hypothesis. To evaluate the clinical and prognostic role of haemodynamically insignificant stenosis of the extracranial arteries (ECA) and lower extremity arteries (LEA) among patients with ST-segment elevation myocardial infarction (STEMI).Patients and Methods. The study sample consisted of 423 patients with STEMI who were consecutively admitted to the Kemerovo Cardiological Centre.Results. The prevalence of polyvascular diseases (PVD), as defined by an increased intima-media thickness (IMT) of the common carotid artery or by stenosis of the ECA or LEA, was 95%. Among patients with ECA or LEA, the case fatality rate of those with stenosis with occlusion of less than 30% of the vessel lumen was 5.7%, whereas the case fatality rate among patients with stenosis with occlusion of more than 30% of the vessel lumen was 15.1% (χ2=13.68,P=0.003). Using the GRACE score model, together with the determination of additional factors (congestive heart failure, PVD, prior stroke, and smoking status), we developed an improved model (KemScore) for death risk stratification for a 12-month period. The value of the AUC for our model (KemScore) was 0.83 (95% CI = 0.76–0.90), which was significantly higher than the initial GRACE score value of 0.71 (95% CI = 0.63–0.79).
A New Method for Short Multivariate Fuzzy Time Series Based on Genetic Algorithm and Fuzzy Clustering
Authors: Selim Kamal S. , Elanany Gihan A.
Published: December 2013

Forecasting activities play an important role in our daily life. In recent years, fuzzy time series (FTS) methods were developed to deal with forecasting problems. FTS attracted researchers because of its ability to predict the future values in some critical situations where most standard forecasting models are doubtfully applicable or produce bad fittings. However, some critical issues in FTS are still open; these issues are often subjective and affect the accuracy of forecasting. In this paper, we focus on improving the accuracy of FTS forecasting methods. The new method integrates the fuzzy clustering and genetic algorithm with FTS to reduce subjectivity and improve its accuracy. In the new method, the genetic algorithm is responsible for selecting the proper model. Also, the fuzzy clustering algorithm is responsible for fuzzifying the historical data, based on its membership degrees to each cluster, and using these memberships to defuzzify the results. This method provides better forecasting accuracy when compared with other extant researches.
The Role of Thrombophilia in Pregnancy
Authors: Battinelli Elisabeth M. , Marshall Ariela , Connors Jean M.
Published: December 2013

Thrombotic disease is a major cause of peripartum morbidity and mortality worldwide. Development of thrombosis in pregnancy is multifactorial due to the physiologic changes of pregnancy—which induce a relative hypercoagulable state—as well as physical changes leading to increased stasis and also the effects of both the inherited and the acquired thrombophilias. In this review, we discuss the impact of each of these factors on the development of thrombosis as well as the evidence for the impact of pregnancy-associated thrombosis on pregnancy outcome. We then discuss the use of both prophylactic and therapeutic anticoagulation during pregnancy and the puerperium. We review the indications and dosing recommendations for administration of anticoagulation in a context of discussing the evidence including the lack of evidence and formal guidelines in this area. We briefly address the role of the new oral anticoagulants in pregnancy and conclude that significant further research in women with thrombophilias and pregnancy-associated thrombosis may help clarify the management of this condition in the future.
Peaked and Smooth Solitons forK*(4,1)Equation
Authors: Xie Yongan , Fu Hualiang , Tang Shengqiang
Published: December 2013

This paper is contributed to explore all possible single peak solutions for theK*(4,1)equationut=uxu2+2α(uuxxx+2uxuxx). Our procedure shows that theK*(4,1)equation either has peakon, cuspon, and smooth soliton solutions when sitting on a nonzero constant pedestallimξ→±∞u=A≠0or possesses compacton solutions only whenlimξ→±∞u=A=0. We present a new smooth soliton solution in an explicit form. Mathematical analysis and numeric graphs are provided for those soliton solutions of theK*(4,1)equation.
A Compact Size 4–19.1 GHz Heart Shape UWB Antenna with Triangular Patches
Authors: Isik Gokmen , Topaloglu Serkan
Published: December 2013

An ultrawideband antenna is designed, simulated, and realized. To overcome the narrow bandwidth characteristics of basic patch antennas, the structure of the radiation pattern is optimized by the aid of elliptical and rectangular patches. Also triangular patches are applied to the antenna edge in order to enhance the VSWR and gain properties. A typical VSWR of 1.5 (less than 2 in the whole frequency range) and a typical gain of 2 dBi (mainly above 1 dBi in the whole frequency range) are observed. The simulations present that the designed antenna has a bandwidth ratio of ~5 : 1 within the frequency range of 4–19.1 GHz with compact dimensions of 25 × 26 mm2. It is fabricated on a 0.5 mm thick, RO3035 substrate. The input impedance, gain, and radiation characteristics of the antenna are also presented. With these properties, it is verified that, with its novel shape, the proposed antenna can be used for various UWB applications.
Risk of Mortality (including Sudden Cardiac Death) and Major Cardiovascular Events in Users of Olanzapine and Other Antipsychotics: A Study with the General Practice Research Database
Authors: Jones Meghan E. , Campbell Giedra , Patel Deven , Brunner Elizabeth , Shatapathy Chetan C. , Murray-Thomas Tarita , van Staa Tjeerd P. , Motsko Stephen
Published: December 2013

Objective. Assess risk of cardiac events and mortality among users of olanzapine and other antipsychotics relative to nonusers.Methods. The General Practice Research Database was used to identify cohorts of antipsychotic users and nonusers with psychiatric illness. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA).Results. 183,392 antipsychotic users (including 20,954 olanzapine users) and 193,920 psychiatric nonusers were identified. There was a significantly higher rate of cardiac mortality (adjusted RR [aRR]: 1.53, CI, 1.12–2.09) in olanzapine users relative to psychiatric nonusers, consistent with findings for both atypical and typical antipsychotics. Relative to psychiatric nonusers, no increased risk of all-cause mortality was observed among olanzapine users (aRR: 1.04, CI, 0.93–1.17), but elevated all-cause mortality risk was observed when compared to all antipsychotic users (aRR: 1.75, CI, 1.64–1.87). There was no increased risk of CHD or VA among olanzapine users relative to psychiatric nonusers, consistent with findings for atypical but not typical antipsychotics. SCD cases were uncommon.Conclusions. Use of antipsychotic agents was associated with increased risk of all-cause and cardiac mortality. Patients treated with olanzapine were found to be at increased risk of cardiac mortality versus psychiatric nonusers.
Utilization of Oncotype DX in an Inner City Population: Race or Place?
Authors: Guth Amber A. , Fineberg Susan , Fei Kezhen , Franco Rebeca , Bickell Nina A.
Published: December 2013

Oncotype DX, a 21-gene-array analysis, can guide chemotherapy treatment decisions for women with ER+ tumors. Of 225 ER+ women participating in a patient assistance trial, 23% underwent Oncotype DX testing: 31% of whites, 21% of blacks, and 14% of Hispanics (P=0.04) were tested. Only 3 white women were treated at municipal hospitals and none was tested. 3% of women treated in municipal hospital as compared to 30% treated at tertiary referral centers were tested (P=0.001). Within tertiary referral centers, there was no racial difference in testing: 32% of whites, 29% of blacks, and 19% of Hispanics (P=0.25). Multivariate analysis (model c-statistic = 0.76;P<0.0001) revealed that women who underwent testing were more likely to have stage 1B (RR=1.70; 95% CI: 1.45–1.85) and to be treated after 2007 (RR=1.34; 95% CI: 1.01–1.65) and less likely to be treated at a municipal hospital (RR=0.20; 95% CI: 0.04–0.94). Women treated at municipal hospitals were less likely to undergo testing resulting in a misleading racial disparity that is driven by site of care. As Oncotype DX can reduce overuse of chemotherapy, it is imperative to expand testing to those who could benefit from yet experience underuse of this test, namely, women treated at safety net hospitals. This trial is registered withNCT00233077.
Securing Communication via Transmission of Artificial Noise by Both Sides: Bipolar-Beamforming Optimization
Authors: Zhou Yongkai , Zhu Yan , Li Fangbiao , Imm Zachary , Yin Xinxing , Xue Zhi
Published: December 2013

The paper considers the secure transmission in a wireless environment in which both the transmitter (Alice) and the legitimate receiver (Bob) send artificial noise (AN) to interfere with the eavesdropper (Eve). Optimal design is analyzed in detail for this AN-by-both-side model to deal with Eve’s stochastic channel condition and random spatial distribution. Bipolar-beamforming is first proposed to jointly design Alice and Bob’s transmitting signals. By optimally assigning the transmitting antenna for Bob and allocating the power ratio between Alice’s information and the AN signal, maximum secrecy capacity can be achieved. Simulation is done to illustrate the process of bipolar-beamforming optimization. Results show that the AN-by-both-side model has good secrecy performance on both average and extreme conditions as Eve approaches Alice or Bob.
Uroperitoneum after Caesarean Section
Authors: Nikolaos Antonakopoulos , Nikolaos Kyritsis , Dimitrios Vlachos , Georgios Vlachos
Published: December 2013

Intraoperative injuries of the bladder and the attendant vesicouterine and vesicovaginal fistulas formation are reported as rare events, but the rapid increase in the number of caesarean sections has contributed to the emergence of these complications. Early recognition of these complications makes them much easier to deal with, while simple measures intraoperatively can ensure that these complications will not escape attention. We present our rare case of uroperitoneum after cesarean section, the way of diagnosis and treatment, and due to this incident we review in detail the existing literature on the topic.
Exchange Rate Determination and Forecasting: Can the Microstructure Approach Rescue Us from the Exchange Rate Disparity?
Authors: Zhang Guangfeng , Zhang Qiong , Majeed Muhammad Tariq
Published: December 2013

Using two measures of private information and high-frequency transaction data from the leading interdealer electronic broking system Reuters D2000-2, we examine the association between exchange rate return and contemporaneous order flow and the predictability power of lagged order flow on the future exchange rate return. Our empirical analysis demonstrates that at high frequency (5, 10, 15, 20, 25, and 30 min) there exists strong positive association between exchange rate returns and contemporaneous order flow. However, the results indicate weak predictability of order flow on the future exchange rate return.
Robust Tracking Control for Rendezvous in Near-Circular Orbits
Authors: Wan Neng , Liu Ming , Karimi Hamid Reza
Published: December 2013

This paper investigates a robust guaranteed cost tracking control problem for thrust-limited spacecraft rendezvous in near-circular orbits. Relative motion model is established based on the two-body problem with noncircularity of the target orbit described as a parameter uncertainty. A guaranteed cost tracking controller with input saturation is designed via a linear matrix inequality (LMI) method, and sufficient conditions for the existence of the robust tracking controller are derived, which is more concise and less conservative compared with the previous works. Numerical examples are provided for both time-invariant and time-variant reference signals to illustrate the effectiveness of the proposed control scheme when applied to the terminal rendezvous and other astronautic missions with scheduled states signal.
Smartphone Medical Applications for Women’s Health: What Is the Evidence-Base and Feedback?
Authors: Derbyshire Emma , Dancey Darren
Published: December 2013

Background. Smartphone medical applications have a major role to play in women’s health with their roles being very broad, ranging from improving health behaviours to undertaking personalised tests.Objective(s). Using Medline, Web of Knowledge, and the PRISMA guidelines 15 randomized controlled trials (RCTs) were identified, with mobile interventions being tested on 1603 females, in relation to key aspects of health. Using a similar systematic approach an iPhone database search identified 47 applications (apps) developed to improve women’s health.Findings. Ten RCTs used text messaging or app interventions to support weight loss, with significant improvements being observed in eight studies. For other aspects of women’s health RCTs are needed to determine possible health benefits. iPhone store data analysis identified that a substantial number of women’s health apps did not have star ratings or feedback comments (68 and 49 per cent, resp.), raising concerns about their validity.Conclusion. Peer-review systems, supporting statements of evidence, or certification standards would be beneficial in maintaining the quality and credibility of future health-focused apps. Patient groups should also ideally be involved in the development and testing of mobile medical apps.
Astragalus Polysaccharide Suppresses Skeletal Muscle Myostatin Expression in Diabetes: Involvement of ROS-ERK and NF-κB Pathways
Authors: Liu Min , Qin Jian , Hao Yarong , Liu Min , Luo Jun , Luo Tao , Wei Lei
Published: December 2013

Objective. The antidiabetes drug astragalus polysaccharide (APS) is capable of increasing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth factor myostatin plays an important role in regulating insulin signaling and insulin resistance. We hypothesized that regulation of skeletal muscle myostatin expression may be involved in the improvement of insulin sensitivity by APS.Methods. APS was administered to 13-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the saturated acid palmitate-induced insulin resistance and myostatin expression in C2C12 cells.Results. APS treatment ameliorated hyperglycemia, hyperlipidemia, and insulin resistance and decreased the elevation of myostatin expression and malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired glucose uptake, overproduction of ROS, activation of extracellular regulated protein kinases (ERK), and NF-κB were partially restored by APS treatment. The protective effects of APS were mimicked by ERK and NF-κB inhibitors, respectively.Conclusion. Our study demonstrates elevated myostatin expression in skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed to palmitate. APS is capable of improving insulin sensitivity and decreasing myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-κB pathway.
Prognostic Significance of Immunohistochemical Phenotypes in Patients Treated for High-Grade Cervical Intraepithelial Neoplasia
Authors: Origoni Massimo , Parma Marta , Dell'Antonio Giacomo , Gelardi Chiara , Stefani Chiara , Salvatore Stefano , Candiani Massimo
Published: December 2013

Strong evidence exists that the host’s immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (P≤0.0001). These data reinforce the evidence of the relevance of the host’s immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates.
Phytochemical and Antibacterial Investigations of the Extracts and Fractions from the Stem Bark of Hymenaea stigonocarpa Mart. ex Hayne and Effect on Ultrastructure of Staphylococcus aureus Induced by Hydroalcoholic Extract
Authors: Dimech Gustavo Santiago , Soares Luiz Alberto Lira , Ferreira Magda Assunção , de Oliveira Anne Gabrielle Vasconcelos , Carvalho Maria da Conceição , Ximenes Eulália Azevedo
Published: December 2013

The aim of this study was to investigate the antimicrobial activity of different extracts and fractions obtained from Hymenaea stigonocarpa stem barks. The cyclohexanic, ethyl acetate, ethanol, aqueous, and hydroalcoholic extracts were obtained by maceration. The hydroalcoholic extract was partitioned, which resulted in the ethyl acetate and aqueous fractions. All extracts and fractions were subjected to phytochemical screening and evaluation of total phenol and tannin contents. An HPLC‐DAD and ultrastructural alterations analysis were performed. Terpenes and coumarins were detected in the cyclohexanic extract. Flavonoids and condensed tannins were present in the other extracts and fractions. The extracts with the highest contents of tannins, ethanol (EE), hydroalcoholic (HE), and aqueous fraction (AF) showed also the highest antimicrobial activity. The MIC values ranged from 64 to 526 µg/mL. The chromatographic fingerprints suggest the presence of astilbin and other flavonoids in EE and HE. Presence of the thick cell wall, undulating outer layer, abnormal septa, and leakage of the cytoplasmic contents and absence of cell wall and cell lyses were the main alterations observed on Staphylococcus aureus ATCC 33591 after treatment with the Hymenaea stigonocarpa hydroalcoholic extract. The presence of phenolic compounds like flavonoids and tannins is possibly the reason for the antimicrobial activity.
Three-Dimensional Piezothermoelastic Stress of a Finite Functionally Graded Cylindrical Shell with Piezoelectric Layer
Authors: Kang Yong-gang , Wang Zhong-qi , Xie Gongnan
Published: December 2013

Three-dimensional piezothermoelastic solutions for a finite functionally graded cylindrical shell with piezoelectric layer are carried out in this paper. The cylindrical shell is simply supported at four end edges and is subjected to axisymmetric thermomechanical loads. The piezoelectric layers are polarized along radial direction as a sensor. The material properties are assumed to be temperature independent and radially dependent but are assumed to be homogeneous in each layer; the variables are expanded in Fourier series to satisfy the boundary conditions and multilayer approach is used. Numerical results of mullite/molybdenum functionally graded cylindrical shell are presented; the temperature change, stresses, electric potential, and electric displacement distributions are given and briefly discussed.
Small Bowel Hamartoma: A Huge Diverticulum of Small Bowel
Authors: Ebdewi Hamdi , Eltweri Amar M. , Salama Yahya , Gorgees Neshtman , Naidu Leena , Bowrey David J.
Published: December 2013

A-20-year old male, with no significant medical history, presented with clinical features mimicking a perforated acute appendicitis. Because of features of peritonitis, a laparotomy was performed which showed a segment of small bowel with multiple large diverticula and mesenteric cysts. A segmental small bowel resection was performed. The patient made an uneventful recovery from surgery. Histology revealed features of a small bowel hamartoma.
Pneumomediastinum, Subcutaneous Emphysema, and Tracheal Tear in the Early Postoperative Period of Spinal Surgery in a Paraplegic Achondroplastic Dwarf
Authors: Kahraman Sinan , Enercan Meriç , Demirhan Özkan , Şengül Türker , Dalar Levent , Hamzaoğlu Azmi
Published: December 2013

Achondroplasia was first described in 1878 and is the most common form of human skeletal dysplasia. Spinal manifestations include thoracolumbar kyphosis, foramen magnum, and spinal stenosis. Progressive kyphosis can result in spinal cord compression and paraplegia due to the reduced size of spinal canal. The deficits are typically progressive, presenting as an insidious onset of paresthesia, followed by the inability to walk and then by urinary incontinence. Paraplegia can be the result of direct pressure on the cord by bone or the injury to the anterior spinal vessels by a protruding bone. Surgical treatment consists of posterior instrumentation, fusion with total wide laminectomy at stenosis levels, and anterior interbody support. Pedicle screws are preferred for spinal instrumentation because wires and hooks may induce spinal cord injury due to the narrow spinal canal. Pedicle lengths are significantly shorter, and 20–25 mm long screws are appropriate for lower thoracic and lumbar pedicles in adult achondroplastic There is no information about the appropriate length of screws for the upper thoracic pedicles. Tracheal injury due to inappropriate pedicle screw length is a rare complication. We report an extremely rare case of tracheal tear due to posterior instrumentation and its management in the early postoperative period.
Nutlin-3a Efficacy in Sarcoma Predicted by Transcriptomic and Epigenetic Profiling
Authors: Pishas Kathleen I. , Neuhaus Susan J. , Clayer Mark T. , Schreiber Andreas W. , Lawrence David M. , Perugini Michelle , Whitfield Robert J. , Farshid Gelareh , Manavis Jim , Chryssidis Steve , Mayo Bronwen J. , Haycox Rebecca C. , Ho Kristen , Brown Michael P. , D'Andrea Richard J. , Evdokiou Andreas , Thomas David M. , Desai Jayesh , Callen David F. , Neilsen Paul M.
Published: December 2013

Nutlin-3a is a small-molecule antagonist of p53/MDM2 that is being explored as a treatment for sarcoma. In this study, we examined the molecular mechanisms underlying the sensitivity of sarcomas to Nutlin-3a. In an ex vivo tissue explant system, we found that TP53 pathway alterations (TP53 status, MDM2/MDM4 genomic amplification/mRNA overexpression, MDM2 SNP309, and TP53 SNP72) did not confer apoptotic or cytostatic responses in sarcoma tissue biopsies (n = 24). Unexpectedly, MDM2 status did not predict Nutlin-3a sensitivity. RNA sequencing revealed that the global transcriptomic profiles of these sarcomas provided a more robust prediction of apoptotic responses to Nutlin-3a. Expression profiling revealed a subset of TP53 target genes that were transactivated specifically in sarcomas that were highly sensitive to Nutlin-3a. Of these target genes, the GADD45A promoter region was shown to be hypermethylated in 82% of wild-type TP53 sarcomas that did not respond to Nutlin-3a, thereby providing mechanistic insight into the innate ability of sarcomas to resist apoptotic death following Nutlin-3a treatment. Collectively, our findings argue that the existing benchmark biomarker for MDM2 antagonist efficacy (MDM2 amplification) should not be used to predict outcome but rather global gene expression profiles and epigenetic status of sarcomas dictate their sensitivity to p53/MDM2 antagonists. Cancer Res; 74(3); 921–31. ©2013 AACR.
Colonization of the Human Gut by E. coli and Colorectal Cancer Risk
Authors: Bonnet Mathilde , Buc Emmanuel , Sauvanet Pierre , Darcha Claude , Dubois Damien , Pereira Bruno , Déchelotte Pierre , Bonnet Richard , Pezet Denis , Darfeuille-Michaud Arlette
Published: December 2013

Purpose: The intestinal microbiota is potentially involved in the development of colorectal carcinoma via various mechanisms. Escherichia coli are commensal bacteria of the human gut microbiota, but some pathogenic strains have acquired the ability to induce chronic inflammation and/or produce toxins, such as cyclomodulin, which could participate in the carcinogenesis process. Here, we analyzed the E. coli population associated with mucosa of patients with colon cancer in relation to clinicopathologic characteristics. We assessed carcinogenic properties of a colon cancer–associated E. coli strain in multiple intestinal neoplasia (Min) mice.

Experimental design: Mucosa-associated or internalized E. coli were quantified and characterized from tumors and mucosa of patients with colon cancer and the healthy mucosa of diverticulosis controls. Min mice were inoculated with a colon cancer–associated E. coli strain (11G5). The number of colonic polyps was evaluated at 7 weeks after infection.

Results: An increased level of mucosa-associated and internalized E. coli was observed in the tumors compared with normal tissue. A relationship between poor prognostic factors for colon cancer (tumor–node–metastasis stage) and colonization of mucosa by E. coli was observed. Pathogenic cyclomodulin-positive E. coli strains were more prevalent on mucosa of patients with stages III/IV than those with stage I colon cancer. Proliferative index and E. coli colonization level of the mucosa distant from the tumor significantly correlated. Min mice infected with the E. coli strain 11G5 displayed a marked increase in the number of visible colonic polyps compared with controls.

Conclusion: These findings support that pathogenic E. coli could be a cofactor in pathogenesis of colorectal cancer. Clin Cancer Res; 20(4); 859–67. ©2013 AACR.
DNA Methyltransferase Inhibition Reverses Epigenetically Embedded Phenotypes in Lung Cancer Preferentially Affecting Polycomb Target Genes
Authors: Hascher Antje , Haase Ann-Kristin , Hebestreit Katja , Rohde Christian , Klein Hans-Ulrich , Rius Maria , Jungen Dominik , Witten Anika , Stoll Monika , Schulze Isabell , Ogawa Seishi , Wiewrodt Rainer , Tickenbrock Lara , Berdel Wolfgang E. , Dugas Martin , Thoennissen Nils H. , Müller-Tidow Carsten
Published: December 2013

Purpose: Cancer cell phenotypes are partially determined by epigenetic specifications, such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations.

Experimental Design: An in vivo selection approach was used to generate highly aggressive non–small cell lung cancer (NSCLC) cell lines (A549 and HTB56) followed by genome-wide DNA methylation analysis. Furthermore, the therapeutic effects of the epigenetic agent azacytidine on DNA methylation patterns and the in vivo phenotypes were explored.

Results: Widespread changes of DNA methylation were observed during development of highly aggressive cell lines. Up to 2.5% of the CpG-rich region was differentially methylated as identified by reduced representation bisulfite sequencing compared with the less aggressive parental cell lines. DNA methyltransferase inhibition by azacytidine reversed the prometastatic phenotype; this was highly associated with the preferential loss of DNA methylation at sites that were hypermethylated during the in vivo selection. Of note, polycomb (PRC2) binding sites were particularly affected by DNA methylation changes after azacytidine exposure that persisted over time.

Conclusions: We could show that metastatic capability of NSCLC is closely associated with DNA methylome alterations. Because inhibition of DNA methyltransferase reversed metastasis-prone phenotype, epigenetic modulation seems to be a potential therapeutic approach to prevent metastasis formation. Clin Cancer Res; 20(4); 814–26. ©2013 AACR.
Mesothelin Overexpression Is a Marker of Tumor Aggressiveness and Is Associated with Reduced Recurrence-Free and Overall Survival in Early-Stage Lung Adenocarcinoma
Authors: Kachala Stefan S. , Bograd Adam J. , Villena-Vargas Jonathan , Suzuki Kei , Servais Elliot L. , Kadota Kyuichi , Chou Joanne , Sima Camelia S. , Vertes Eva , Rusch Valerie W. , Travis William D. , Sadelain Michel , Adusumilli Prasad S.
Published: December 2013

Purpose: In an effort to identify molecular markers of tumor aggressiveness and therapeutic targets in lung adenocarcinoma (ADC), we investigated the expression of mesothelin (MSLN) in lung ADC, as well as its biologic and clinical relevance.

Experimental Design: In a training and validation set of patients with early-stage (I–III) lung ADC (n = 1,209), a tissue microarray consisting of tumors and normal lung tissue was used to examine the association between MSLN expression and recurrence-free survival (RFS) and overall survival (OS). The influence of MSLN overexpression on lung ADC was investigated in vitro and in vivo by use of clinically relevant orthotopic and metastatic xenogeneic and syngeneic mouse models.

Results: MSLN was expressed in 69% of lung ADC tumors, with one in five patients strongly expressing MSLN and no expression in normal lung tissue. Increased MSLN expression was associated with reduced OS [HR = 1.78; 95% confidence interval (CI), 1.26–2.50; P < 0.01] and RFS (HR = 1.67; 95% CI, 1.21–2.27; P < 0.01) in multivariate analyses, even after adjustment for currently known markers of tumor aggressiveness in lung ADC: male sex, smoking history, increasing stage, morphologic pattern, visceral pleural invasion, lymphatic or vascular invasion, and mutation status. In vitro, lung ADC cells overexpressing MSLN demonstrated increased cell proliferation, migration, and invasion; in vivo, mice with MSLN(+) tumors demonstrated decreased survival (P = 0.001).

Conclusions: MSLN expression in patients with early-stage lung ADC is associated with increased risk of recurrence and reduced OS, indicating that MSLN expression is a molecular marker of tumor aggressiveness and a potential target for therapy. Clin Cancer Res; 20(4); 1020–8. ©2013 AACR.
NEDD9 Regulates 3D Migratory Activity Independent of the Rac1 Morphology Switch in Glioma and Neuroblastoma
Authors: Zhong Jessie , Bach Cuc T. , Shum Michael S.Y. , O'Neill Geraldine M.
Published: December 2013

Metastasizing tumor cells must transmigrate the dense extracellular matrix that surrounds most organs. The use of three-dimensional (3D) collagen gels has revealed that many cancer cells can switch between different modes of invasion that are characterized by distinct morphologies (e.g., rounded vs. elongated). The adhesion protein NEDD9 has the potential to regulate the switch between elongated and rounded morphologies; therefore, its role was interrogated in the invasion switch of glioblastoma and neuroblastoma tumors that similarly derive from populations of neural crest cells. Interestingly, siRNA-mediated depletion of NEDD9 failed to induce cell rounding in glioma or neuroblastoma cells, contrasting the effects that have been described in other tumor model systems. Given that Rac1 GTPase has been suggested to mediate the switch between elongated and rounded invasion, the functionality of the Rac1 morphology switch was evaluated in the glioma and neuroblastoma cells. Using both dominant-negative Rac1 and Rac1-specific siRNA, the presence of this morphologic switch was confirmed in the neuroblastoma, but not in the glioma cells. However, in the absence of a morphologic change following NEDD9 depletion, a significant decrease in the cellular migration rate was observed. Thus, the data reveal that NEDD9 can regulate 3D migration speed independent of the Rac1 morphology switch.

Implications: NEDD9 targeting is therapeutically viable as it does not stimulate adaptive changes in glioma and neuroblastoma invasion. Mol Cancer Res; 12(2); 264–73. ©2013 AACR.
Prenatal Prediction of Surgical Approach for Coarctation of the Aorta Repair
Authors: Gómez-Montes Enery , Herraiz Ignacio , Mendoza Alberto , Escribano David , Martínez-Moratalla Valcárcel José Manuel , Galindo Alberto
Published: December 2013

Objective: To evaluate the capacity of fetal echocardiography for predicting the more likely surgical approach in newborns with coarctation of the aorta (CoAo) (left thoracotomy vs. median sternotomy). Material and Methods: We selected all cases of suspected CoAo prenatally diagnosed in 2003-2012 (n = 95). 49/95 were considered at high-risk and 46/95 at low-risk of CoAo, and 38/49 and 7/46 were postnatally confirmed, respectively. We firstly evaluated in 40 cases of CoAo surgically repaired (24 thoracotomy, 16 sternotomy) whether there were differences in fetal echocardiographic parameters between both groups. Secondly, we assessed the performance of these parameters for predicting the surgical approach in fetuses at high risk of CoAo. Results: Sternotomy approach was associated with higher rate of postoperative complications and longer hospital stay compared with thoracotomy (81.3 vs. 41.7%, p = 0.014; 30.5 vs. 15.4 days, p = 0.0004, respectively). The Z-score of the aortic isthmus, measured in the sagittal plane, was significantly smaller in the sternotomy group. In fetuses at high-risk of having CoAo a cut-off value of the isthmus Z-score ≤ -2.5 had sensitivity of 78% and specificity of 82% for predicting sternotomy approach, with 9% false positive cases in which CoAo was not confirmed. Discussion: The surgical approach for CoAo repair may be prenatally predicted by means of the Z-score of aortic isthmus, measured in the sagittal plane.
Primary Retroperitoneal Müllerian Adenocarcinoma: A Case Report and Literature Review
Authors: Spinelli Claudio , Strambi Silvia , Tartaglia Dario , Di Franco Gregorio , Pucci V. , Faviana Pinuccia , Lencioni Monica
Published: December 2013

Primary retroperitoneal müllerian adenocarcinoma (PRMA) is an extremely rare clinical entity. We report the case of a 54-year-old woman who presented with a mass in the right lower retroperitoneum, identified during an ultrasound exam. Computed tomography confirmed a retroperitoneal mass measuring 11 cm. The patient underwent laparotomy and the mass was completely excised. The histopathological exam revealed PRMA.
Clinical Implications of Referral Bias in the Diagnostic Performance of Exercise Testing for Coronary Artery Disease
Authors: Ladapo Joseph A. , Blecker Saul , Elashoff Michael R. , Federspiel Jerome J. , Vieira Dorice L. , Sharma Gaurav , Monane Mark , Rosenberg Steven , Phelps Charles E. , Douglas Pamela S.
Published: December 2013

Background

Exercise testing with echocardiography or myocardial perfusion imaging is widely used to risk‐stratify patients with suspected coronary artery disease. However, reports of diagnostic performance rarely adjust for referral bias, and this practice may adversely influence patient care. Therefore, we evaluated the potential impact of referral bias on diagnostic effectiveness and clinical decision‐making.

Methods and Results

Searching PubMed and
EMBASE
(1990–2012), 2 investigators independently evaluated eligibility and abstracted data on study characteristics and referral patterns. Diagnostic performance reported in 4 previously published meta‐analyses of exercise echocardiography and myocardial perfusion imaging was adjusted using pooled referral rates and Bayesian methods. Twenty‐one studies reported referral patterns in 49 006 patients (mean age 60.7 years, 39.6% women, and 0.8% prior history of myocardial infarction). Catheterization referral rates after normal and abnormal exercise tests were 4.0% (95%
CI
, 2.9% to 5.0%) and 42.5% (36.2% to 48.9%), respectively, with odds ratio for referral after an abnormal test of 14.6 (10.7 to 19.9). After adjustment for referral, exercise echocardiography sensitivity fell from 84% (80% to 89%) to 34% (27% to 41%), and specificity rose from 77% (69% to 86%) to 99% (99% to 100%). Similarly, exercise myocardial perfusion imaging sensitivity fell from 85% (81% to 88%) to 38% (31% to 44%), and specificity rose from 69% (61% to 78%) to 99% (99% to 100%). Summary receiver operating curve analysis demonstrated only modest changes in overall discriminatory power but adjusting for referral increased positive‐predictive value and reduced negative‐predictive value.

Conclusions

Exercise echocardiography and myocardial perfusion imaging are considerably less sensitive and more specific for coronary artery disease after adjustment for referral. Given these findings, future work should assess the comparative ability of these and other tests to rule‐in versus rule‐out coronary artery disease.