bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathway-Based Serum microRNA Profiling and Survival in Patients with Advanced Stage Non–Small Cell Lung Cancer
Authors: Wang Yan , Gu Jian , Roth Jack A. , Hildebrandt Michelle A.T. , Lippman Scott M. , Ye Yuanqing , Minna John D. , Wu Xifeng 
Published: June 2013

Abstract
This study was designed to identify TGF-β signaling pathway-related serum microRNAs (miRNA) as predictors of survival in advanced non–small cell lung cancer (NSCLC). Serum samples from 391 patients with advanced NSCLC were collected before treatment. Global miRNA microarray expression profiling based on sera from four patients with good survival (&gt;24 months) and four patients with poor survival (&lt;6 months) was used to identify 140 highly expressed serum miRNAs, among which 35 miRNAs had binding sites within the 3′-untranslated regions of a panel of 11 genes in the TGF-β signaling pathway and were assayed by quantitative RT-PCR for their associations with survival in a training (n = 192) and testing set (n = 191). Out of the 35 miRNAs, survival analysis using Cox regression model identified 17 miRNAs significantly associated with 2-year patient survival. MiR-16 exhibited the most statistically significant association: high expression of miR-16 was associated with a significantly better survival [adjusted hazard ratio (HR) = 0.4, 95% confidence interval (CI): 0.3–0.5]. A combined 17-miRNA risk score was created that was able to identify patients at the highest risk of death. Those with a high-risk score had a 2.5-fold increased risk of death compared with those with a low risk score (95% CI: 1.8–3.4; P = 1.1 × 10−7). This increase in risk of death was corresponding to a 7.8-month decrease in median survival time (P = 9.5 × 10−14). Our results suggest that serum miRNAs could serve as predictors of survival for advanced NSCLC. Cancer Res; 73(15); 4801–9. ©2013 AACR.
DDB2: A Novel Regulator of NF-κB and Breast Tumor Invasion
Authors: Ennen Marie , Klotz Rémi , Touche Nadège , Pinel Sophie , Barbieux Claire , Besancenot Vanessa , Brunner Emilie , Thiebaut Denise , Jung Alain C. , Ledrappier Sonia , Domenjoud Lionel , Abecassis Joseph , Plénat François , Grandemange Stéphanie , Becuwe Philippe 
Published: June 2013

Abstract
The DNA repair protein damaged DNA-binding 2 (DDB2) has been implicated in promoting cell-cycle progression by regulating gene expression. DDB2 is selectively overexpressed in breast tumor cells that are noninvasive, but not in those that are invasive. We found that its overexpression in invasive human breast tumor cells limited their motility and invasiveness in vitro and blocked their ability to colonize lungs in vivo, defining a new function for DDB2 in malignant progression. DDB2 overexpression attenuated the activity of NF-κB and the expression of its target matrix metalloprotease 9 (MMP9). Mechanistic investigations indicated that DDB2 decreased NF-κB activity by upregulating expression of IκBα by binding the proximal promoter of this gene. This effect was causally linked to invasive capacity. Indeed, knockdown of DDB2-induced IκBα gene expression restored NF-κB activity and MMP9 expression, along with the invasive properties of breast tumor cells overexpressing DDB2. Taken together, our findings enlighten understanding of how breast cancer cells progress to an invasive phenotype and underscore potential clinical interest in DDB2 as a prognostic marker or therapeutic target in this setting. Cancer Res; 73(16); 5040–52. ©2013 AACR.
Potassium Channel KCNA1 Modulates Oncogene-Induced Senescence and Transformation
Authors: Lallet-Daher Hélène , Wiel Clotilde , Gitenay Delphine , Navaratnam Naveenan , Augert Arnaud , Le Calvé Benjamin , Verbeke Stéphanie , Carling David , Aubert Sébastien , Vindrieux David , Bernard David 
Published: June 2013

Abstract
Oncogene-induced senescence (OIS) constitutes a failsafe program that restricts tumor development. However, the mechanisms that link oncogenesis to senescence are not completely understood. We carried out a loss-of-function genetic screen that identified the potassium channel KCNA1 as a determinant of OIS escape that can license tumor growth. Oncogenic stress triggers an increase in KCNA1 expression and its relocation from the cytoplasm to the membrane. Mechanistically, this relocation is due to a loss of protein kinase A (PKA)-induced phosphorylation at residue S446 of KCNA1. Accordingly, sustaining PKA activity or expressing a KCNA1 phosphomimetic mutant maintained KCNA1 in the cytoplasm and caused escape from OIS. KCNA1 relocation to the membrane induced a change in membrane potential that invariably resulted in cellular senescence. Restoring KCNA1 expression in transformation-competent cells triggered variation in membrane potential and blocked RAS-induced transformation, and PKA activation suppressed both effects. Furthermore, KCNA1 expression was reduced in human cancers, and this decrease correlated with an increase in breast cancer aggressiveness. Taken together, our results identify a novel pathway that restricts oncogenesis through a potassium channel-dependent senescence pathway. Cancer Res; 73(16); 5253–65. ©2013 AACR.
mTOR Signaling Feedback Modulates Mammary Epithelial Differentiation and Restrains Invasion Downstream of PTEN Loss
Authors: Ghosh Susmita , Varela Lidenys , Sood Akshay , Park Ben Ho , Lotan Tamara L. 
Published: June 2013

Abstract
Oncogenic signaling pathways are tightly regulated by negative feedback circuits and relief of these circuits represents a common mechanism of tumor drug resistance. Although the significance of these feedback pathways for signal transduction is evident, their relevance for cellular differentiation and morphogenesis in a genetically defined context is unclear. In this study, we used isogenic benign mammary organotypic cultures to interrogate the role of mTOR-mediated negative feedback in the specific setting of PTEN inactivation. We found that mTOR signaling promoted basal-like differentiation and repressed nuclear hormone receptor expression after short-term PTEN loss in murine cell cultures analyzed ex vivo. Unexpectedly, we found that PTEN inactivation inhibited growth factor-induced epithelial invasion and that downstream mTOR-mediated signaling feedback was both necessary and sufficient for this effect. Mechanistically, using isogenic MCF10A cells with and without somatic PTEN deletion, we showed that mTOR inhibition promoted EGF-mediated epithelial invasion by derepressing upstream EGF receptor, SRC tyrosine kinase, and phosphoinositide 3-kinase signaling. In addition to offering new signal transduction insights, these results bring to light a number of important and potentially clinically relevant cellular consequences of mTOR inhibition in the specific context of PTEN loss, including modulation of hormone and growth factor responsiveness and promotion of epithelial invasion. Our findings prompt future investigations of the possibility that mTOR inhibitor therapy may not only be ineffective but even deleterious in tumors with PTEN loss. Cancer Res; 73(16); 5218–31. ©2013 AACR.
Impact of Surface Forcing on Southern Hemisphere Atmospheric Blocking in the Australia–New Zealand Sector
Authors: Ummenhofer Caroline C. , McIntosh Peter C. , Pook Michael J. , Risbey James S. 
Published: June 2013

Abstract
Characteristics of atmospheric blocking in the Southern Hemisphere (SH) are explored in atmospheric general circulation model (AGCM) simulations with the Community Atmosphere Model, version 3, with a particular focus on the Australia–New Zealand sector. Preferred locations of blocking in SH observations and the associated seasonal cycle are well represented in the AGCM simulations, but the observed magnitude of blocking is underestimated throughout the year, particularly in late winter and spring. This is related to overly zonal flow due to an enhanced meridional pressure gradient in the model, which results in a decreased amplitude of the longwave trough/ridge pattern. A range of AGCM sensitivity experiments explores the effect on SH blocking of tropical heating, midlatitude sea surface temperatures, and land–sea temperature gradients created over the Australian continent during austral winter. The combined effects of tropical heating and extratropical temperature gradients are further explored in a configuration that is favorable for blocking in the Australia–New Zealand sector with warm SST anomalies to the north of Australia, cold to the southwest of Australia, warm to the southeast, and cool Australian land temperatures. The blocking-favorable configuration indicates a significant strengthening of the subtropical jet and a reduction in midlatitude flow, which results from changes in the thermal wind. While these overall changes in mean climate, predominantly forced by the tropical heating, enhance blocking activity, the magnitude of atmospheric blocking compared to observations is still underestimated. The blocking-unfavorable configuration with surface forcing anomalies of opposite sign results in a weakening subtropical jet, enhanced midlatitude flow, and significantly reduced blocking.
Application of a Bayesian Classifier of Anomalous Propagation to Single-Polarization Radar Reflectivity Data
Authors: Peter Justin R. , Seed Alan , Steinle Peter J. 
Published: June 2013

Abstract
A naïve Bayes classifier (NBC) was developed to distinguish precipitation echoes from anomalous propagation (anaprop). The NBC is an application of Bayes's theorem, which makes its classification decision based on the class with the maximum a posteriori probability. Several feature fields were input to the Bayes classifier: texture of reflectivity (TDBZ), a measure of the reflectivity fluctuations (SPIN), and vertical profile of reflectivity (VPDBZ). Prior conditional probability distribution functions (PDFs) of the feature fields were constructed from training sets for several meteorological scenarios and for anaprop. A Box–Cox transform was applied to transform these PDFs to approximate Gaussian distributions, which enabled efficient numerical computation as they could be specified completely by their mean and standard deviation. Combinations of the feature fields were tested on the training datasets to evaluate the best combination for discriminating anaprop and precipitation, which was found to be TDBZ and VPDBZ. The NBC was applied to a case of convective rain embedded in anaprop and found to be effective at distinguishing the echoes. Furthermore, despite having been trained with data from a single radar, the NBC was successful at distinguishing precipitation and anaprop from two nearby radars with differing wavelength and beamwidth characteristics. The NBC was extended to implement a strength of classification index that provides a metric to quantify the confidence with which data have been classified as precipitation and, consequently, a method to censor data for assimilation or quantitative precipitation estimation.
Automated Discrimination of Certain Brightness Fronts in RADARSAT-2 Images of the Ocean Surface
Authors: Jones Chris T. , Sikora Todd D. , Vachon Paris W. , Wolfe John , DeTracey Brendan 
Published: June 2013

Abstract
Automated classification of the signatures of atmospheric and oceanic processes in synthetic aperture radar (SAR) images of the ocean surface has been a difficult problem, partly because different processes can produce signatures that are very similar in appearance. For example, brightness fronts that are the signatures of horizontal wind shear caused by atmospheric processes that occur independently of properties of the ocean (WIN herein) often appear very similar to brightness fronts that are signatures of sea surface temperature (SST) fronts (SST herein). Using Moderate Resolution Imaging Spectroradiometer (MODIS)-derived SST for validation, 302 SAR SST and 193 SAR WIN signatures were collected from over 250 RADARSAT-2 images of the Gulf Stream region using a Canny edge detector. A vector consisting of textural and contextual features was extracted from each signature and used to train and test logistic regression, maximum likelihood, and binary tree classifiers. Following methods proven effective in the analysis of SAR images of sea ice, textural features included those computed from the gray-level co-occurrence matrix for regions along and astride each signature. Contextual features consisted of summaries of the wind vector field near each signature. Results indicate that signatures labeled SST can be automatically discriminated from signatures labeled WIN using the mean wind direction with respect to a brightness front with an accuracy of between 80% and 90%.
Evaluation of SSMIS Upper Atmosphere Sounding Channels for High-Altitude Data Assimilation
Authors: Hoppel Karl W. , Eckermann Stephen D. , Coy Lawrence , Nedoluha Gerald E. , Allen Douglas R. , Swadley Steven D. , Baker Nancy L. 
Published: June 2013

Abstract
Upper atmosphere sounding (UAS) channels of the Special Sensor Microwave Imager/Sounder (SSMIS) were assimilated using a high-altitude version of the Navy Global Environmental Model (NAVGEM) in order to investigate their potential for operational forecasting from the surface to the mesospause. UAS radiances were assimilated into NAVGEM using the new Community Radiative Transfer Model (CRTM) that accounts for Zeeman line splitting by geomagnetic fields. UAS radiance data from April 2010 to March 2011 are shown to be in good agreement with coincident temperature measurements from the Sounding of the Atmosphere Using Broadband Emission Radiometry (SABER) instrument that were used to simulate UAS brightness temperatures. Four NAVGEM experiments were performed during July 2010 that assimilated (i) no mesospheric observations, (ii) UAS data only, (iii) SABER and Microwave Limb Sounder (MLS) mesospheric temperatures only, and (iv) SABER, MLS, and UAS data. Zonal mean temperatures and observation − forecast differences for the UAS-only and SABER+MLS experiments are similar throughout most of the mesosphere, and show large improvements over the experiment assimilating no mesospheric observations, proving that assimilation of UAS radiances can provide a reliable large-scale constraint throughout the mesosphere for operational, high-altitude analysis. This is confirmed by comparison of solar migrating tides and the quasi-two-day wave in the mesospheric analyses. The UAS-only experiment produces realistic tidal and two-day wave amplitudes in the summer mesosphere in agreement with the experiments assimilating MLS and SABER observations, whereas the experiment with no mesospheric observations produces excessively strong mesospheric winds and two-day wave amplitudes.
Computational cloning of drug target genes of a parasitic nematode, Oesophagostomum dentatum
Authors: Romine Nathan M , Martin Richard J , Beetham Jeffrey K 
Published: June 2013

Abstract

Background
Gene identification and sequence determination are critical requirements for many biological, genomic, and bioinformatic studies. With the advent of next generation sequencing (NGS) technologies, such determinations are predominantly accomplished in silico for organisms for which the genome is known or for which there exists substantial gene sequence information. Without detailed genomic/gene information, in silico sequence determination is not straightforward, and full coding sequence determination typically involves time- and labor-intensive PCR-based amplification and cloning methods.

Results
An improved method was developed with which to determine full length gene coding sequences in silico using de novo assembly of RNA-Seq data. The scheme improves upon initial contigs through contig-to-gene identification by BLAST nearest–neighbor comparison, and through single-contig refinement by iterative-binning and -assembly of reads. Application of the iterative method produced the gene identification and full coding sequence for 9 of 12 genes and improved the sequence of 3 of the 12 genes targeted by benzimidazole, macrocyclic lactone, and nicotinic agonist classes of anthelminthic drugs in the swine nodular parasite Oesophagostomum dentatum. The approach improved upon the initial optimized assembly with Velvet that only identified full coding sequences for 2 genes.

Conclusions
Our reiterative methodology represents a simplified pipeline with which to determine longer gene sequences in silico from next generation sequence data for any nematode for which detailed genetic/gene information is lacking. The method significantly improved upon an initial Velvet assembly of RNA-Seq data that yielded only 2 full length sequences. The identified coding sequences for the 11 target genes enables further future examinations including: (i) the use of recombinant target protein in functional assays seeking a better understanding of the mechanism of drug resistance, and (ii) seeking comparative genomic and transcriptomic assessments between parasite isolates that exhibit varied drug sensitivities.
High-throughput sequencing of methylated cytosine enriched by modification-dependent restriction endonuclease MspJI
Authors: Huang Xiaojun , Lu Hanlin , Wang Jun-Wen , Xu Liqin , Liu Siyang , Sun Jihua , Gao Fei 
Published: June 2013

Abstract

Background
As a well-known epigenomic modification, DNA methylation is found to be common in plants and plays an important role in many biological processes. Relying on the unique feature of methylation-dependent digestion, the family of methylation-requiring restriction-like endonuclease, such as MspJI and its homologs, was suggested for a potential usage in methylation detection.

Results
In this study, we combine MspJI digestion and electrophoretic band selection with next generation high-throughput sequencing technology to detect 5-methylcytosines in Arabidopsis genome. By developing a bioinformatics workflow to attribute the CNNR sites recognized by MspJI to the reference genome, we fulfilled the systematic assessment of this method.

Conclusions
According to the assessment, here we provide the method for generating a detailed map of plant methylome that could be feasible, reliable and economical in methylation investigation.
Risk factors for subclinical atherosclerosis in HIV-infected patients under and over 40 years: a case–control study
Authors: Albuquerque Valéria Maria Gonçalves , Zírpoli Josefina Claudia , de Barros Miranda-Filho Demócrito , Albuquerque Maria de Fátima Pessoa Militão , Montarroyos Ulisses Ramos , de Alencar Ximenes Ricardo Arraes , Lacerda Heloísa Ramos 
Published: June 2013

Abstract

Background
Cardiovascular diseases (CVD) are a major cause of death in people with AIDS. Factors contributing to atherosclerosis include traditional risk factors, antiretrovirals and inflammatory factors related to HIV infection. This study set out to compare risk factors associated with subclinical atherosclerosis in individuals under and over 40 years of age.

Methods
Case–control study with 697 HIV/AIDS individuals without HAART or who remain on their first antiretroviral regimen. Of the total, 351 individuals under 40 years and 346 over 40 years were analyzed separately. Subclinical atherosclerosis was assessed by carotid intima-media thickness, using B-mode ultrasound. Multivariate logistic regression was performed to find predictors of subclinical atherosclerosis in the entire group. Subsequent analysis excluded patients with major risk factors for CVD. Magnitudes of associations were expressed by odds ratio (OR) statistical significance, using a 95% confidence interval and p-value <0.05.

Results
In the <40 years group subclinical atherosclerosis was associated with male gender (OR: 2.77, 95% CI: 1.43–5.34), nonwhite race (OR: 3.01, 95% CI: 1.23-6.53), obesity (OR: 5.13, 95% CI: 1.79–14.7) and metabolic syndrome (OR: 3.30, 95% CI: 1.44–7.58). In the group ≥40 years predictors of subclinical atherosclerosis were overweight and obesity (OR = 2.53, 95% CI, 0.85–7.54), current CD4 ≥350 cells/mL (OR: 2.81, 95% CI: 1.22–6.47) and NNRTI use ≥ 5 years (OR: 2.65, 95% CI: 1.10-6.37) or PI use >5 years (OR: 1.81, 95% CI: 0.38-8.59). In the multivariate model excluding patients with major risk factors for CVD, age, male sex and nonwhite race were associated with subclinical atherosclerosis in the <40 y group, while in the ≥40 y group, age, HIV viral load >10,000 copies and the use of NNRTI (OR: 7.60, 95% CI: 1.61-35.8) or PI ≥5 years (OR: 3.62, 95% CI: 0.48-26.8) were associated with subclinical atherosclerosis.

Conclusions
In young people the fight against obesity and metabolic syndrome is the main aim in the prevention of CVD. In individuals aged ≥40 y, the prevention of obesity is also of great importance. Moreover, the effects of uncontrolled viremia and the prolonged use of HAART appear to be more harmful in the older group.
Association between genomic recurrence risk and well-being among breast cancer patients
Authors: Retèl Valesca P , Groothuis-Oudshoorn Catharina GM , Aaronson Neil K , Brewer Noel T , Rutgers Emiel JT , van Harten Wim H 
Published: June 2013

Abstract

Background
Gene expression profiling (GEP) is increasingly used in the rapidly evolving field of personalized medicine. We sought to evaluate the association between GEP-assessed of breast cancer recurrence risk and patients’ well-being.

Methods
Participants were Dutch women from 10 hospitals being treated for early stage breast cancer who were enrolled in the MINDACT trial (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). As part of the trial, they received a disease recurrence risk estimate based on a 70-gene signature and on standard clinical criteria as scored via a modified version of Adjuvant! Online. \Women completed a questionnaire 6–8 weeks after surgery and after their decision regarding adjuvant chemotherapy. The questionnaire assessed perceived understanding, knowledge, risk perception, satisfaction, distress, cancer worry and health-related quality of life (HRQoL), 6–8 weeks after surgery and decision regarding adjuvant chemotherapy.

Results
Women (n = 347, response rate 62%) reported high satisfaction with and a good understanding of the GEP information they received. Women with low risk estimates from both the standard and genomic tests reported the lowest distress levels. Distress was higher predominately among patients who had received high genomic risk estimates, who did not receive genomic risk estimates, or who received conflicting estimates based on genomic and clinical criteria. Cancer worry was highest for patients with higher risk perceptions and lower satisfaction. Patients with concordant high-risk profiles and those for whom such profiles were not available reported lower quality of life.

Conclusion
Patients were generally satisfied with the information they received about recurrence risk based on genomic testing. Some types of genomic test results were associated with greater distress levels, but not with cancer worry or HRQoL.

Trial registration
ISRCTN: ISRCTN18543567