bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer
Authors: Wyatt Alexander W , Mo Fan , Wang Kendric , McConeghy Brian , Brahmbhatt Sonal , Jong Lina , Mitchell Devon M , Johnston Rebecca L , Haegert Anne , Li Estelle , Liew Janet , Yeung Jake , Shrestha Raunak , Lapuk Anna V , McPherson Andrew , Shukin Robert , Bell Robert H , Anderson Shawn , Bishop Jennifer , Hurtado-Coll Antonio , Xiao Hong , Chinnaiyan Arul M , Mehra Rohit , Lin Dong , Wang Yuzhuo , Fazli Ladan , Gleave Martin E , Volik Stanislav V , Collins Colin C 
Published: August 2014

Abstract
Background
Genomic analyses of hundreds of prostate tumors have defined a diverse landscape of mutations and genome rearrangements, but the transcriptomic effect of this complexity is less well understood, particularly at the individual tumor level. We selected a cohort of 25 high-risk prostate tumors, representing the lethal phenotype, and applied deep RNA-sequencing and matched whole genome sequencing, followed by detailed molecular characterization.

Results
Ten tumors were exposed to neo-adjuvant hormone therapy and expressed marked evidence of therapy response in all except one extreme case, which demonstrated early resistance via apparent neuroendocrine transdifferentiation. We observe high inter-tumor heterogeneity, including unique sets of outlier transcripts in each tumor. Interestingly, outlier expression converged on druggable cellular pathways associated with cell cycle progression, translational control or immune regulation, suggesting distinct contemporary pathway affinity and a mechanism of tumor stratification. We characterize hundreds of novel fusion transcripts, including a high frequency of ETS fusions associated with complex genome rearrangements and the disruption of tumor suppressors. Remarkably, several tumors express unique but potentially-oncogenic non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression. Finally, one ETS-negative tumor has a striking tandem duplication genotype which appears to be highly aggressive and present at low recurrence in ETS-negative prostate cancer, suggestive of a novel molecular subtype.

Conclusions
The multitude of rare genomic and transcriptomic events detected in a high-risk tumor cohort offer novel opportunities for personalized oncology and their convergence on key pathways and functions has broad implications for precision medicine.
Evaluation of solvent effect on the extraction of phenolic compounds and antioxidant capacities from the berries: application of principal component analysis
Authors: Boeing Joana Schuelter , Barizão Érica Oliveira , e Silva Beatriz Costa , Montanher Paula Fernandes , de Cinque Almeida Vitor , Visentainer Jesuí Vergilio 
Published: August 2014

AbstractBackgroundThis study evaluated the effect of the solvent on the extraction of antioxidant compounds from black mulberry (Morus nigra), blackberry (Rubus ulmifolius) and strawberry (Fragariaxananassa). Different extracts of each berry were evaluated from the determination of total phenolic content, anthocyanin content and antioxidant capacity, and data were applied to the principal component analysis (PCA) to gain an overview of the effect of the solvent in extraction method.ResultsFor all the berries analyzed, acetone/water (70/30, v/v) solvent mixture was more efficient solvent in the extracting of phenolic compounds, and methanol/water/acetic acid (70/29.5/0.5, v/v/v) showed the best values for anthocyanin content. Mixtures of ethanol/water (50/50, v/v), acetone water/acetic acid (70/29.5/0.5, v/v/v) and acetone/water (50/50, v/v) presented the highest antioxidant capacities for black mulberries, blackberries and strawberries, respectively.ConclusionAntioxidants extractions are extremely affected by the solvent combination used. In addition, the obtained extracts with the organic solvent-water mixtures were distinguished from the extracts obtained with pure organic solvents, through the PCA analysis.
Treatment patterns in psoriatic arthritis patients newly initiated on oral nonbiologic or biologic disease-modifying antirheumatic drugs
Authors: Zhang Huabin F , Gauthier Geneviève , Hiscock Robert , Curtis Jeffrey R 
Published: August 2014

Abstract
Introduction
This study aimed to describe treatment changes (discontinuation, switching, and therapy add-on) following the initiation of biologic or nonbiologic oral disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA) patients.

Methods
Adult patients with ≥2 PsA diagnoses from physician office visits, initiated on a biologic or nonbiologic oral DMARD, were selected from the Truven Health Analytics MarketScan® Research Database (2005 to 2009). Patients were required to have continuous insurance coverage ≥6 months prior to and ≥12 months post index date (first prescription fill date). Treatment discontinuation, treatment switch, and therapy add-on were captured over the 1 year period following the index date. Treatment changes were described separately for patients initiated on nonbiologic and biologic DMARDs.

Results
A total of 1,698 and 3,263 patients were initiated on an oral nonbiologic DMARD and biologic DMARD respectively. For patients initiated on nonbiologic DMARDs, 69% had ≥1 therapy change over the 12 month study period (median time 85 days). Among patients who had a therapy change, 83% discontinued, 29% switched therapy (64% switched to a biologic DMARD), and 25% had a therapy add-on (76% added-on with a biologic DMARD). For patients initiated on a biologic DMARD, 46% had ≥1 therapy change (median time 110 days). Among patients who had a therapy change, 100% discontinued, 25% switched therapy (92% switched to another biologic DMARD), and 7% had a therapy add-on with a nonbiologic DMARD.

Conclusion
This study suggests that PsA patients newly initiated on a nonbiologic/biologic DMARD do not remain on the index treatment for a long period of time. A better understanding of factors related to these early treatment changes in PsA patients is needed.
Clinical value of whole-body PET/CT in patients with active rheumatic diseases
Authors: Yamashita Hiroyuki , Kubota Kazuo , Mimori Akio 
Published: August 2014

AbstractAdvanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of 18 F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia rheumatica, adult-onset Still's disease, relapsing polychondritis, immunoglobulin G4-related disease, large-vessel vasculitis, Wegener's granulomatosis, polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.
Application of insect songs in monitoring population density level of Locusta migratoria migratoria (Orthoptera: Acrididae)
Authors: Wang Yinliang , Huang Qiuchen , Zhang Xue , Ren Bingzhong 
Published: August 2014

AbstractBackgroundThe locustsLocusta migratoria migratoria(Orthoptera: Acrididae) is the most destructive agricultural pests worldwide, the population and distribution ofL. migratoria migratoriagrowing rapidly in recent years. It is crucial to find a green, economical way to monitor this insect's population for effective control tactics. In this study, acoustic samples were recorded and analyzed under three different density levels of Asian migratory locustL. migratoria migratoria.ResultsThe results showed that the songs ofL. migratoria migratoriahad a very stable acoustic feature in time domains; then, we used duration of pulse as a tool for identifying and counting the numbers of pulse to classify the population size. After removing the background noises, an automatic density classification and monitoring system was established based on the backpropagation (BP) neural network. The field sample test showed that the accuracy of the density level recognition reached 96.67%.ConclusionsThe results indicated that the calling songs of insects could be an effective character to distinguish population density level of locust plagues, and it could be potentially used as a green and environmental protection solution in monitoring the dynamics of locust plagues and other acoustic agriculture pests.
Childhood family income, adolescent violent criminality and substance misuse: quasi-experimental total population study
Authors: Sariaslan Amir , Larsson Henrik , D'Onofrio Brian , Långström Niklas , Lichtenstein Paul 
Published: August 2014

BackgroundLow socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned.AimsTo investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors.MethodNationwide Swedish quasi-experimental, family-based study following cohorts born 1989–1993 (ntotal = 526 167, ncousins = 262 267, nsiblings = 216 424) between the ages of 15 and 21 years.ResultsChildren of parents in the lowest income quintile experienced a seven-fold increased hazard rate (HR) of being convicted of violent criminality compared with peers in the highest quintile (HR = 6.78, 95% CI 6.23–7.38). This association was entirely accounted for by unobserved familial risk factors (HR = 0.95, 95% CI 0.44–2.03). Similar pattern of effects was found for substance misuse.ConclusionsThere were no associations between childhood family income and subsequent violent criminality and substance misuse once we had adjusted for unobserved familial risk factors.
White matter integrity and late-life depression in community-dwelling individuals: diffusion tensor imaging study using tract-based spatial statistics
Authors: Reppermund Simone , Zhuang Lin , Wen Wei , Slavin Melissa J. , Trollor Julian N. , Brodaty Henry , Sachdev Perminder S. 
Published: August 2014

BackgroundLate-life depression has been associated with white matter changes in studies using the regions of interest approach.AimsTo investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling individuals using diffusion tensor imaging with tract-based spatial statistics.MethodThe sample comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression.ResultsIndividuals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up.ConclusionsReduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.
Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo
Authors: Vlaming Hanneke , van Welsem Tibor , de Graaf Erik L , Ontoso David , Altelaar AF Maarten , San‐Segundo Pedro A , Heck Albert JR , van Leeuwen Fred 
Published: August 2014

AbstractHistone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 and H3K4 methylation from a proximal as well as a more distal site, but only if in a correct orientation. This plasticity indicates that the exact location of the attachment site, the native ubiquitin‐lysine linkage and ubiquitination cycles are not critical for trans‐histone crosstalk in vivo. The flexibility in crosstalk also indicates that other ubiquitination events may promote H3 methylation.
Age-Specific Changes in Intrinsic Breast Cancer Subtypes: A Focus on Older Women
Authors: Jenkins Emily O. , Deal Allison M. , Anders Carey K. , Prat Aleix , Perou Charles M. , Carey Lisa A. , Muss Hyman B. 
Published: August 2014

Abstract

Purpose.
Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age.

Patients and Methods.
Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like. The association of age and subtype with recurrence-free survival (RFS), overall survival, and disease-specific survival (DSS) was assessed.

Results.
The incidence of luminal (A, B, and A+B) tumors increased with age (p &lt; .01, p &lt; .0001, and p &lt; .0001, respectively), whereas the percentage of basal-like tumors decreased (p &lt; .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS.

Conclusion.
More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome.
Determining Ground Penetrating Radar Amplitude Thresholds for the Corrosion State of Reinforced Concrete Bridge Decks
Authors: Martino Nicole , Maser Ken , Birken Ralf , Wang Ming 
Published: August 2014

The most expensive part to maintain throughout the lifespan of a reinforced concrete bridge is the deck, largely because rehabilitation occurs after degradation is visible on a surface. However, the mechanisms that are the cause of deterioration, such as reinforcing bar corrosion, are initiated long before damage is detected via visual inspection. If rebar corrosion can be detected in its early stages, before severe deterioration has resulted, maintenance costs can be significantly reduced and the life cycle extended. Recent studies have shown that ground penetrating radar (GPR) rebar reflection amplitude attenuation correlates with active corrosion in reinforced concrete bridge decks. A significant advantage of GPR over other non-destructive evaluation (NDE) methods is its ability to be operated at highway speeds so that traffic is not disrupted. However, a well-defined GPR amplitude threshold allowing the operator to distinguish non-corroded from corroded areas of the deck has yet to be established. Because reinforcing steel corrosion is the most predominant cause of bridge deck deterioration, this research seeks to quantify the thresholds relating GPR signal amplitudes and rebar corrosion. One bridge deck removed from service, seventeen artificially corroded slabs, and one in-service bridge deck were analyzed using GPR and half-cell potential (HCP), which measures the amount of active corrosion and is currently considered the standard NDE method. A significant correlation between these two methods was found for each case. To systematically determine a threshold for the GPR so that deteriorated areas of the deck can be identified, receiver operating characteristic (ROC) curves were utilized. With an accuracy of over 87% for each scenario, this method clearly demonstrates the use of GPR for distinguishing corrosion in bridge decks.
Comparison of Reduced and Conventional Two-Phase Flash Calculations
Authors: Gorucu S.E.. E. , Johns R.T.. T. 
Published: August 2014

Summary
Phase-equilibrium calculations become computationally intensive in compositional simulation as the number of components and phases increases. Reduced methods were developed to address this problem, where the binary-interaction-parameter (BIP) matrix is approximated either by spectral decomposition (SD), as performed by Hendriks and van Bergen (1992), or with the two-parameter BIP formula of Li and Johns (2006). Several authors have recently stated that the SD method—and by reference all reduced methods—is not as fast as previously reported in the literature. In this paper we present the first study that compares all eight reduced and conventional methods published to date by use of optimized code and compilers.
The results show that the SD method and its variants are not as fast as other reduced methods, and can be slower than the conventional approach when fewer than 10 components are used. These conclusions confirm the findings of recently published papers. The reason for the slow speed is the requirement that the code must allow for a variable number of eigenvalues. We show that the reduced method of Li and Johns (2006) and its variants, however, are faster because the number of reduced parameters is fixed to six, which is independent of the number of components. Speed up in flash calculations for their formula is achieved for all fluids studied when more than six components are used. For example, for 10-component fluids, a speed up of 2–3 in the computational time for Newton-Raphson (NR) iterations is obtained compared with the conventional method modeled after minimization of Gibbs energy. The reduced method modeled after the linearized approach of Nichita and Graciaa (2011), which uses the two-parameter BIP formula of Li and Johns (2006), is also demonstrated to have a significantly larger radius of convergence than other reduced and conventional methods for five fluids studied.
The Lifetime Cost of Diabetes and Its Implications for Diabetes Prevention
Authors: Zhuo Xiaohui , Zhang Ping , Barker Lawrence , Albright Ann , Thompson Theodore J. , Gregg Edward 
Published: August 2014

OBJECTIVE
To assess the cost implications of diabetes prevention, it is important to know the lifetime medical cost of people with diabetes relative to those without. We derived such estimates using data representative of the U.S. national population.

RESEARCH DESIGN AND METHODS
We aggregated annual medical expenditures from the age of diabetes diagnosis to death to determine lifetime medical expenditure. Annual medical expenditures were estimated by sex, age at diagnosis, and diabetes duration using data from 2006–2009 Medical Expenditure Panel Surveys, which were linked to data from 2005–2008 National Health Interview Surveys. We combined survival data from published studies with the estimated annual expenditures to calculate lifetime spending. We then compared lifetime spending for people with diabetes with that for those without diabetes. Future spending was discounted at 3% annually.

RESULTS
The discounted excess lifetime medical spending for people with diabetes was $124,600 ($211,400 if not discounted), $91,200 ($135,600), $53,800 ($70,200), and $35,900 ($43,900) when diagnosed with diabetes at ages 40, 50, 60, and 65 years, respectively. Younger age at diagnosis and female sex were associated with higher levels of lifetime excess medical spending attributed to diabetes.

CONCLUSIONS
Having diabetes is associated with substantially higher lifetime medical expenditures despite being associated with reduced life expectancy. If prevention costs can be kept sufficiently low, diabetes prevention may lead to a reduction in long-term medical costs.
Improved representation of East Antarctic surface mass balance in a regional atmospheric climate model
Authors: Van Wessem J.M. , Reijmer C.H. , Morlighem M. , Mouginot J. , Rignot E. , Medley B. , Joughin I. , Wouters B. , Depoorter M.A. , Bamber J.L. , Lenaerts J.T.M. , Van De Berg W.J. , Van Den Broeke M.R. , Van Meijgaard E. 
Published: August 2014

AbstractThis study evaluates the impact of a recent upgrade in the physics package of the regional atmospheric climate model RACMO2 on the simulated surface mass balance (SMB) of the Antarctic ice sheet. The modelled SMB increases, in particular over the grounded ice sheet of East Antarctica (+44 Gt a–1), with a small change in West Antarctica. This mainly results from an increase in precipitation, which is explained by changes in the cloud microphysics, including a new parameterization for ice cloud supersaturation, and changes in large-scale circulation patterns, which alter topographically forced precipitation. The spatial changes in SMB are evaluated using 3234 in situ SMB observations and ice-balance velocities, and the temporal variability using GRACE satellite retrievals. The in situ observations and balance velocities show a clear improvement of the spatial representation of the SMB in the interior of East Antarctica, which has become considerably wetter. No improvements are seen for West Antarctica and the coastal regions. A comparison of model SMB temporal variability with GRACE satellite retrievals shows no significant change in performance.