bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT–YB1–MDR1 Signaling Pathway
Authors: Mo Dongliang , Fang Hongbo , Niu Kaifeng , Liu Jing , Wu Meng , Li Shiyou , Zhu Tienian , Aleskandarany Mohammed A. , Arora Arvind , Lobo Dileep N. , Madhusudan Srinivasan , Balajee Adayabalam S. , Chi Zhenfen , Zhao Yongliang 
Published: March 2016

Abstract
Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic and chemotherapeutic significance of RECQL4 in human gastric cancer, which has yet to be determined. We observed significant increases in RECQL4 mRNA or protein in &gt;70% of three independent sets of human gastric cancer specimens examined, relative to normal gastric tissues. Strikingly, high RECQL4 expression in primary tumors correlated well with poor survival and gastric cancer lines with high RECQL4 expression displayed increased resistance to cisplatin treatment. Mechanistic investigations revealed a novel role for RECQL4 in transcriptional regulation of the multidrug resistance gene MDR1, through a physical interaction with the transcription factor YB1. Notably, ectopic expression of RECQL4 in cisplatin-sensitive gastric cancer cells with low endogenous RECQL4 was sufficient to render them resistant to cisplatin, in a manner associated with YB1 elevation and MDR1 activation. Conversely, RECQL4 silencing in cisplatin-resistant gastric cancer cells with high endogenous RECQL4 suppressed YB1 phosphorylation, reduced MDR1 expression, and resensitized cells to cisplatin. In establishing RECQL4 as a critical mediator of cisplatin resistance in gastric cancer cells, our findings provide a therapeutic rationale to target RECQL4 or the downstream AKT–YB1–MDR1 axis to improve gastric cancer treatment. Cancer Res; 76(10); 3057–66. ©2016 AACR.
Integrative Analysis of DCE-MRI and Gene Expression Profiles in Construction of a Gene Classifier for Assessment of Hypoxia-Related Risk of Chemoradiotherapy Failure in Cervical Cancer
Authors: Fjeldbo Christina S. , Julin Cathinka H. , Lando Malin , Forsberg Malin F. , Aarnes Eva-Katrine , Alsner Jan , Kristensen Gunnar B. , Malinen Eirik , Lyng Heidi 
Published: March 2016

Abstract
Purpose: A 31-gene expression signature reflected in dynamic contrast enhanced (DCE)-MR images and correlated with hypoxia-related aggressiveness in cervical cancer was identified in previous work. We here aimed to construct a dichotomous classifier with key signature genes and a predefined classification threshold that separated cervical cancer patients into a more and less hypoxic group with different outcome to chemoradiotherapy.
Experimental Design: A training cohort of 42 patients and two independent cohorts of 108 and 131 patients were included. Gene expression data were generated from tumor biopsies by two Illumina array generations (WG-6, HT-12). Technical transfer of the classifier to a reverse transcription quantitative PCR (RT-qPCR) platform was performed for 74 patients. The amplitude ABrix in the Brix pharmacokinetic model was extracted from DCE-MR images of 64 patients and used as an indicator of hypoxia.
Results: Classifier candidates were constructed by integrative analysis of ABrix and gene expression profiles in the training cohort and evaluated by a leave-one-out cross-validation approach. On the basis of their ability to separate patients correctly according to hypoxia status, a 6-gene classifier was identified. The classifier separated the patients into two groups with different progression-free survival probability. The robustness of the classifier was demonstrated by successful validation of hypoxia association and prognostic value across cohorts, array generations, and assay platforms. The prognostic value was independent of existing clinical markers, regardless of clinical endpoints.
Conclusions: A robust DCE-MRI–associated gene classifier has been constructed that may be used to achieve an early indication of patients' risk of hypoxia-related chemoradiotherapy failure. Clin Cancer Res; 22(16); 4067–76. ©2016 AACR.
Chaperonin Containing TCP-1 Protein Level in Breast Cancer Cells Predicts Therapeutic Application of a Cytotoxic Peptide
Authors: Bassiouni Rania , Nemec Kathleen N. , Iketani Ashley , Flores Orielyz , Showalter Anne , Khaled Amr S. , Vishnubhotla Priya , Sprung Robert W. , Kaittanis Charalambos , Perez Jesus M. , Khaled Annette R. 
Published: March 2016

AbstractPurpose: Metastatic disease is a leading cause of death for patients with breast cancer, driving the need for new therapies. CT20p is a peptide previously discovered by our group that displays cancer-specific cytotoxicity. To design the optimal therapeutic use of the peptide, we identified the intracellular target of CT20p in breast cancer cells, correlating expression patterns of the target with susceptibility to CT20p.Experimental Design: Using polymeric nanoparticles to deliver CT20p, we assessed cytoskeletal changes, cell migration, adhesion, and viability in cells treated with the peptide. Protein pull-down experiments, coupled to mass spectrometry, enabled identification of the peptide's intracellular target. Biochemical and histologic techniques validated target identity in human cell lines and breast cancer tissue microarrays and revealed susceptibility patterns to CT20p.Results: Chaperonin containing TCP-1 (CCT) was identified as the intracellular target of CT20p. Cancer cells susceptible to CT20p had increased CCT, and overexpression of CCTβ, a subunit of the CCT complex, enhanced susceptibility to CT20p. Susceptible cells displayed reduced tubulin, a substrate of CCT, and inhibition of migration upon CT20p treatment. CCTβ levels were higher in invasive ductal carcinomas than in cancer adjacent tissues and increased with breast cancer stage. Decreased breast cancer patient survival correlated with genomic alternations in CCTβ and higher levels of the chaperone.Conclusions: Increased CCT protein in breast cancer cells underlies the cytotoxicity of CT20p. CCT is thus a potential target for therapeutic intervention and serves as a companion diagnostic to personalize the therapeutic use of CT20p for breast cancer treatment. Clin Cancer Res; 22(17); 4366–79. ©2016 AACR.
Power Transformer Incipient Faults Diagnosis Based on Dissolved Gas Analysis
Authors: E. Gouda Osama , M. Saleh Saber , El-hoshy Salah Hamdy 
Published: March 2016

Incipient fault diagnosis of a power transformer is greatly influenced by the condition assessment of its insulation system oil and/or paper insulation. Dissolved gas-in-oil analysis (DGA) is one of the most powerfull techniques for the detection of incipient fault condition within oil-immersed transformers. The transformer data has been analyzed using key gases, Doernenburg, Roger, IEC and Duval triangle techniques. This paper introduce a MATLAB program to help in unification DGA interpretation techniques to investigate the accuracy of these techniques in interpreting the transformer condition and to provide the best suggestion for the type of the fault within the transformer based on fault percentage. It proposes a proper maintenance action based on DGA results which is useful for planning an appropriate maintenance strategy to keep the power transformer in acceptable condition. The evaluation is carried out on DGA data obtained from 352 oil samples has been summarized into 46 samples that have been collected from a 38 different transformers of different rating and different life span.
Localization schemes in Underwater Sensor Network (UWSN): A Survey
Authors: Ahmed Mukhtiar , Salleh Mazleena 
Published: March 2016

<p>Underwater Wireless Sensor Networks (UWSNs) is much more attractive area for the researchers due to its versatile applications like tactical surveillance, assisted navigation, equipment monitoring, oceanography data collection, pollution monitoring, offshore exploration, disaster prevention and seismic monitoring. The researchers are also collecting the scientific data from underwater environment for observing mission. Due to the continuous node movement in underwater environment creates the majority of the problems for localization. Localization is one of the major issues in underwater environment. This survey paper focuses the different valuable localization schemes which focus the open issues and challenges for researchers. </p>
Electrical Vehicle Modeling and Backstepping Control
Authors: Mohammed Mekkaoui , Meguenni Kada Zemalache , Abdel Hafid Omari , Motefai Lotfi 
Published: March 2016

Nowadays, the development of electric vehicles has become a general trend. Electrical vehicles have improved their performance, and have been made suitable for commercial and domestic use during the last decades. The proportional–integral–differential (PID) controller has been widely used in the industrial ﬁeld. It has a simple structure, and can be easily realized. The recursive backstepping design methodology is originally introduced inadaptive control theory to systematically construct the feedback control law, the parameter adaptation law and the associated Lyapunov function for a class of nonlinear systems satisfying certain structured properties. the backstepping control (BKC) is used to improve the robustness and real-time performance of the electrical vehicle system. Numerical simulation results show the effectiveness of this approach.
Nonlinear Servomotor in Single Pulse Simulation of Electrical Discharge Machining System Modeling
Authors: Lee Hassan , Yahya Azli , Khamis Nor Hisham , Samion Shahrullail 
Published: March 2016

<p>Electrical Discharge Machining, EDM is a nonconventional and high precision machining. EDM system is considered a combination of servo system and EDM process. The servo system precisely controls the gap between electrode and workpiece for the continuous electrical discharges occurrence. Machining performance and stability depend on the performance of servo system. The EDM servo system usually modeled as a linear system, which ignores the nonlinearities of the motor. An assumption that the nonlinearities are insignificant in EDM system model may leads to modeling errors and result in poor control performance. In this study, nonlinear EDM servo system model was presented and the dynamic response of the model was analyzed and compared with the linear model. Simulation result shows a slightly difference in system response and a controller used in linear model is less efficient for a nonlinear EDM servo system model. The results are very useful for control strategy and can contribute to a better machining performance and stability of EDM applications.</p>
The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia
Authors: Stiber Jonathan A. , Wu Jiao-Hui , Zhang Lisheng , Nepliouev Igor , Zhang Zhu-Shan , Bryson Victoria G. , Brian Leigh , Bentley Rex C. , Gordon-Weeks Phillip R. , Rosenberg Paul B. , Freedman Neil J. 
Published: March 2016

Objective—
Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfamily C TRP (TRPC) channels requires the scaffolding protein Homer 1, which associates with the actin-binding protein Drebrin. We found that SMC Drebrin expression is upregulated in atherosclerosis and in response to injury and investigated whether Drebrin inhibits SMC activation, either through regulation of TRP channel function via Homer or through a direct effect on the actin cytoskeleton.

Approach and Results—

Wild-type (WT) and congenic
Dbn
−/+
mice were subjected to wire-mediated carotid endothelial denudation. Subsequent neointimal hyperplasia was 2.4±0.3-fold greater in
Dbn
−/+
than in WT mice. Levels of globular actin were equivalent in
Dbn
−/+
and WT SMCs, but there was a 2.4±0.5-fold decrease in filamentous actin in
Dbn
−/+
SMCs compared with WT. Filamentous actin was restored to WT levels in
Dbn
−/+
SMCs by adenoviral-mediated rescue expression of Drebrin. Compared with WT SMCs,
Dbn
−/+
SMCs exhibited increased TRP channel activity in response to platelet-derived growth factor, increased migration assessed in Boyden chambers, and increased proliferation. Enhanced TRP channel activity and migration in
Dbn
−/+
SMCs were normalized to WT levels by rescue expression of not only WT Drebrin but also a mutant Drebrin isoform that binds actin but fails to bind Homer.

Conclusions—
Drebrin reduces SMC activation through its interaction with the actin cytoskeleton but independently of its interaction with Homer scaffolds.
New Prothrombin Mutation (Arg596Trp, Prothrombin Padua 2) Associated With Venous Thromboembolism
Authors: Bulato Cristiana , Radu Claudia Maria , Campello Elena , Gavasso Sabrina , Spiezia Luca , Tormene Daniela , Simioni Paolo 
Published: March 2016

Objective—
Two different prothrombin variants, p.Arg596Leu and p.Arg596Gln, conferring antithrombin resistance to patients with venous thromboembolism have been recently reported. Here, we describe a novel substitution affecting Arg596 of prothrombin molecule (Arginine596 to Tryptophan or p.Arg596Trp or Arg221aTrp in the chymotrypsinogen numbering system or prothrombin Padua 2) in 2 Italian families with venous thromboembolism.

Approach and Results—
Prothrombin Padua 2 has been characterized either in plasma of carriers or using Arg596Trp recombinant prothrombin. Routine coagulation tests, thrombin generation, and antithrombin resistance tests were performed, as well as measurement of the levels of thrombin–antithrombin complexes. All carriers were heterozygotes and presented with a mild reduction of the prothrombin activity. Thrombin generation in carriers showed only a markedly prolonged decay. This finding was confirmed in plasma reconstituted with Arg596Trp recombinant prothrombin mimicking a homozygous condition, which showed longer decay and higher endogenous thrombin potential in thrombin generation than wild-type recombinant prothrombin reconstituted plasma. Patient’s plasma as well as Arg596Trp recombinant prothrombin showed a clear thrombin resistance to antithrombin inactivation. These findings were supported by the assessment of thrombin–antithrombin complexes formation, which was strongly reduced for Arg596Trp recombinant prothrombin as compared with wild-type recombinant prothrombin. In a series of 400 unrelated consecutive patients with venous thromboembolism, 2 carriers of prothrombin Padua 2 were found (estimated prevalence of 0.5%).

Conclusions—
Our study showed that prothrombin Padua 2 induces antithrombin resistance and is associated with an increased risk of venous thromboembolism. Codon 596 (CGG) of prothrombin is a hot spot for mutations, which constitute a new and relatively frequent cause of inherited thrombophilia.
Regulation of Caveolin-1 Expression Determines Early Brain Edema After Experimental Focal Cerebral Ischemia
Authors: Choi Kang-Ho , Kim Hyung-Seok , Park Man-Seok , Kim Joon-Tae , Kim Ja-Hae , Cho Kyung-Ah , Lee Min-Cheol , Lee Hong-Joon , Cho Ki-Hyun 
Published: March 2016

Background and Purpose—
Most patients with cerebral infarction die of brain edema because of the breakdown of the blood–brain barrier (BBB) in ischemic tissue. Caveolins (a group of proteins) are key modulators of vascular permeability; however, a direct role of caveolin-1 (Cav-1) in the regulation of BBB permeability during ischemic injury has yet to be identified.

Methods—
Cav-1 expression was measured by immunoblotting after photothrombotic ischemia. A direct functional role of Cav-1 in cerebral edema and BBB permeability during cerebral ischemia was investigated by genetic manipulation (gene disruption and re-expression) of Cav-1 protein expression in mice.

Results—

There was a significant correlation between the extent of BBB disruption and the Cav-1 expression. In Cav-1–deficient (Cav-1
−/−
) mice, the extent of BBB disruption after cerebral ischemia was increased compared with wild-type (Cav-1
+/+
) mice, whereas the increase in cerebral edema volume was ameliorated by lentiviral-mediated re-expression of Cav-1. Furthermore, Cav-1
−/−
mice had significantly higher degradation of tight junction proteins and proteolytic activity of matrix metalloproteinase than Cav-1
+/+
mice. Conversely, re-expression of Cav-1 in Cav-1
−/−
mice restored tight junction protein expression and reduced matrix metalloproteinase proteolytic activity.

Conclusions—
These results indicate that Cav-1 is a critical determinant of BBB permeability. Strategies for regulating Cav-1 represent a novel therapeutic approach to controlling BBB disruption and subsequent neurological deterioration during cerebral ischemia.
The first case of natural spontaneous triploidy in the family Bombinatoridae
Authors: Litvinchuk Spartak N. , Rosanov Juriy M. 
Published: March 2016

A triploid specimen of the diploid anuran species Bombina orientalis was identified by means of DNA flow cytometry. The finding is interpreted as a case of natural spontaneous autotriploidy. The incidence of triploidy was 1.8% per species (n = 55) and 11.1% per sample (n = 9).
A survey of Lab Tests Online-UK users: a key resource for patients to empower and help them understand their laboratory test results
Authors: Leyland Rebecca , Freedman Danielle B 
Published: March 2016

Background Lab Tests Online-UK celebrated its 10th anniversary in 2014 and to mark the occasion the first comprehensive survey of website users was undertaken. Methods A pop-up box with a link to Survey Monkey was used to offer website users the chance to participate in the survey, which was live from 4 March 2014 to 11 April 2014. Results Six hundred and sixty-one participants started the questionnaire and 338 completed all of the demographic questions. Although the website is designed and aimed at patients and the public, a significant number of respondents were health-care professionals (47%). The majority of survey participants found the Lab Tests Online-UK website via a search engine and were visiting the site for themselves. The majority of participants found what they were looking for on the website and found the information very easy or fairly easy to understand. The patient respondents were keen to see their laboratory test results (87%), but the majority did not have access (60%) at the time of the survey. Conclusions This survey provides good evidence that the Lab Tests Online-UK website is a useful resource for patients and health-care professionals alike. It comes at a poignant time as the release of results direct to patients starts with access to their medical records. The Lab Tests Online-UK website has a key role in enabling patients to understand their lab test results, and therefore empowering them to take an interest and engage in their own healthcare.
A multicenter, randomized, placebo-controlled study to evaluate the efficacy and safety of Varithena® (polidocanol endovenous microfoam 1%) for symptomatic, visible varicose veins with saphenofemoral junction incompetence
Authors: Gibson Kathleen , Kabnick Lowell 
Published: March 2016

Objectives A randomized, placebo-controlled, multicenter study was conducted to evaluate the safety and efficacy of polidocanol endovenous microfoam (1%, Varithena® [polidocanol injectable foam], BTG International Ltd.). Methods Patients (n = 77) with symptomatic, visible varicose veins were randomized to treatment with either Varithena 1% or placebo. Results Varithena provided greater mean changes from Baseline in patient-reported assessments of symptoms (e.g., heaviness, achiness, swelling, throbbing, itching [HASTI®] score 30.7 points vs 16.7 points, p = 0.0009, primary endpoint; and modified Venous Insufficiency Epidemiological and Economic Study-Quality-of-Life/Symptoms [m-VEINES-QOL/Sym; p < 0.001]), physician-assessed VCSS, and physician- and patient-assessed appearance compared with placebo. The HASTI score correlated highly with the modified-VEINES-QOL/Sym and Chronic Venous Insufficiency Questionnaire-2 scores (r = 0.7 to > 0.9, p ≤ 0.001). Adverse events included contusion, incision-site hematoma, and limb discomfort. Venous thrombus adverse events were reported as mild and generally resolved without sequelae. Conclusions Varithena provided significantly greater symptom relief and improvement in leg appearance compared with placebo. Adverse events were generally mild and transient. ( www.clinicaltrials.gov [NCT00758420]).
Prediction of the response of ocular adnexal lymphoma to chemotherapy using combined pretreatment dynamic contrast-enhanced and diffusion-weighted MRI
Authors: Guo Pengde , Liu Zhaohui , Yan Fei , Wang Jingwen , Wei Liqiang , Lv Han , Wang Zhenchang , Xian Junfang 
Published: March 2016

Background There are no established biomarkers predictive of the efficacy of treatment for ocular adnexal lymphoma (OAL). Purpose To evaluate the effectiveness of pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the response of OAL to chemotherapy. Material and Methods Twenty-one patients, who were pathologically diagnosed with OAL, were retrospectively analyzed. According to the National Comprehensive Cancer Network (NCCN) response evaluation criteria for non-Hodgkin’s lymphoma, patients were divided into responders (n = 14) and non-responders (n = 7). The volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (Ve), and apparent diffusion coefficient (ADC) were computed. Two independent-sample tests were applied for statistical analysis. For significantly different parameters, receiver-operator characteristics curve analysis was performed. Results The Ktrans value (min−1), Kep value (min−1), and ADC value (10−3 mm2/s) were 0.76 ± 0.36 vs. 0.47 ± 0.18 (mean ± SD), 4.43 ± 1.29 vs. 3.14 ± 1.37, and 0.51 ± 0.12 vs. 0.66 ± 0.15, respectively, in the responders and non-responders groups. Significant differences were found between the two groups regarding these parameters ( P < 0.05). However, no significant difference was observed in Ve (min−1) between the groups ( P > 0.05). Ktrans, Kep, and ADC had a moderately predictive sensitivity or specificity. When Ktrans and ADC or the three parameters were combined, a considerably higher sensitivity (85.7%) and specificity (85.7%) with a significant discriminative accuracy (area under the curve = 0.929; P = 0.002) was found. Conclusion Ktrans, Kep, and ADC could potentially predict OAL response to chemotherapy. A combination of these DWI and DCE-MRI quantitative parameters might increase sensitivity and specificity.