bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bias analysis to improve monitoring an HIV epidemic and its response: approach and application to a survey of female sex workers in Iran
Authors: Mirzazadeh Ali , Mansournia Mohammad-Ali , Nedjat Saharnaz , Navadeh Soodabeh , McFarland Willi , Haghdoost Ali Akbar , Mohammad Kazem 
Published: June 2013

BackgroundWe present probabilistic and Bayesian techniques to correct for bias in categorical and numerical measures and empirically apply them to a recent survey of female sex workers (FSW) conducted in Iran.MethodsWe used bias parameters from a previous validation study to correct estimates of behaviours reported by FSW. Monte-Carlo Sensitivity Analysis and Bayesian bias analysis produced point and simulation intervals (SI).ResultsThe apparent and corrected prevalence differed by a minimum of 1% for the number of ‘non-condom use sexual acts’ (36.8% vs 35.8%) to a maximum of 33% for ‘ever associated with a venue to sell sex’ (35.5% vs 68.0%). The negative predictive value of the questionnaire for ‘history of STI’ and ‘ever associated with a venue to sell sex’ was 36.3% (95% SI 4.2% to 69.1%) and 46.9% (95% SI 6.3% to 79.1%), respectively. Bias-adjusted numerical measures of behaviours increased by 0.1 year for ‘age at first sex act for money’ to 1.5 for ‘number of sexual contacts in last 7 days’.ConclusionsThe ‘true’ estimates of most behaviours are considerably higher than those reported and the related SIs are wider than conventional CIs. Our analysis indicates the need for and applicability of bias analysis in surveys, particularly in stigmatised settings.
Socioeconomic inequalities in oral health in different European welfare state regimes
Authors: Guarnizo-Herreño Carol C , Watt Richard G , Pikhart Hynek , Sheiham Aubrey , Tsakos Georgios 
Published: June 2013

BackgroundThere is very little information about the relationship between welfare regimes and oral health inequalities. We compared socioeconomic inequalities in adults’ oral health in five European welfare-state regimes: Scandinavian, Anglo-Saxon, Bismarckian, Southern and Eastern.MethodsUsing data from the oral health module of the Eurobarometer 72.3 survey, we assessed inequalities in two self-reported oral health measures: no functional dentition (less than 20 natural teeth) and edentulousness (no natural teeth). Occupational social class, education and subjective social status (SSS) were included as socioeconomic position indicators. We estimated age-standardised prevalence rates, ORs, the Relative Index of Inequality (RII) and the Slope Index of Inequality (SII).ResultsThe Scandinavian regime showed the lowest prevalence rates of the two oral health measures while the Eastern showed the highest. In all welfare regimes there was a general pattern of social gradients by occupational social class and education. Relative educational inequalities in no functional dentition were largest in the Scandinavian welfare regime (RII=3.81; 95% CI 2.68 to 5.42). The Scandinavian and Southern regimes showed the largest relative inequalities in edentulousness by occupation and education, respectively. There were larger absolute inequalities in no functional dentition in the Eastern regime by occupation (SII=42.16; 95% CI 31.42 to 52.89) and in the Southern by SSS (SII=27.92; 95% CI 17.36 to 38.47).ConclusionsOral health inequalities in adults exist in all welfare-state regimes, but contrary to what may be expected from theory, they are not smaller in the Scandinavian regime. Future work should examine the potential mechanisms linking welfare provision and oral health inequalities.
Successful correction of D‐lactic acid neurotoxicity (drunken lamb syndrome) by bolus administration of oral sodium bicarbonate
Authors: Angell J. W. , Jones G. L. , Voigt K. , Grove‐White D. H. 
Published: June 2013

Drunken lamb syndrome (DLS) has recently been described as lamb D‐lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically, each lamb had a metabolic acidosis characterised by D‐lactic acidosis and exhibited clinical signs including: not hyperthermic, no evidence of dehydration, demonstrating an ataxic gait tending to recumbency (DLS) and possibly somnolence. These lambs received 50 mmol of sodium bicarbonate as an 8.4 per cent solution given orally, together with parenteral long‐acting amoxicillin. All 18 cases made a full clinical recovery. This study demonstrates a novel effective treatment for a disease that is usually fatal, and also demonstrates a strong correlation between venous plasma bicarbonate concentrations and venous plasma D‐lactate concentrations (R2 =0.49).
N-TERM WIENER CHAOS APPROXIMATION RATES FOR ELLIPTIC PDEs WITH LOGNORMAL GAUSSIAN RANDOM INPUTS
Authors: HOANG VIET HA , SCHWAB CHRISTOPH 
Published: July 2013

We consider diffusion in a random medium modeled as diffusion equation with lognormal Gaussian diffusion coefficient. Sufficient conditions on the log permeability are provided in order for a weak solution to exist in certain Bochner–Lebesgue spaces with respect to a Gaussian measure. The stochastic problem is reformulated as an equivalent deterministic parametric problem on ℝℕ. It is shown that the weak solution can be represented as Wiener–Itô Polynomial Chaos series of Hermite Polynomials of a countable number of i.i.d standard Gaussian random variables taking values in ℝ1. We establish sufficient conditions on the random inputs for weighted sequence norms of the Wiener–Itô decomposition coefficients of the random solution to be p-summable for some 0 < p < 1. For random inputs with additional spatial regularity, stronger norms of the weighted coefficient sequence in the random solutions' Wiener–Itô decomposition are shown to be p-summable for the same value of 0 < p < 1. We prove rates of nonlinear, best N-term Wiener Polynomial Chaos approximations of the random field, as well as of Finite Element discretizations of these approximations from a dense, nested family V0 ⊂ V1 ⊂ V2 ⊂ ⋯ V of finite element spaces of continuous, piecewise linear Finite Elements.
Volcanoes of the Diamante cross-chain: evidence for a mid-crustal felsic magma body beneath the Southern Izu–Bonin–Mariana arc
Authors: Stern Robert J. , Tamura Yoshi , Ishizuka Osamu , Shukano Hiroshi , Bloomer Sherman H. , Embley Robert W. , Leybourne Matthew , Kawabata Hiroshi , Nunokawa Akiko , Nichols Alexander R. L. , Kohut Edward , Pujana Ignacio 
Published: June 2013

Abstract

Three submarine Diamante cross-chain volcanoes in the southern Mariana arc mark a magma-healed zone of along-arc (north–south) extension that allows either mafic mantle-derived basalts or felsic magmas from the middle of thickened arc crust to erupt. The largest volcano is East Diamante, with a well-developed (5×10 km) caldera that formed via violent felsic submarine eruptions beginning nearly 0.5 Ma. One or more of these eruptions also formed a giant submarine dune field extending 30 km to the NW of the volcano. Felsic igneous activity continues at least as recently as
c.
20 000 years ago, with emplacement of resurgent dacite domes, some hot enough to power the only black smoker hydrothermal system known in the Mariana arc. In contrast, felsic eruptions do not occur on the two volcanoes to the west, implying that the mid-crustal felsic zone does not underlie the thinner crust of the Mariana Trough back-arc basin. Diamante cross-chain lavas define a medium K suite; mafic lava phenocryst assemblages show arc-like associations of anorthite-rich plagioclase with Fe-rich olivine. Magmatic temperatures for a basaltic andesite and three dacites are
c.
1100 °C and
c.
800 °C, respectively, typical for cool, wet, subduction-related felsic magmas. Felsic magmas formed under low-P crustal conditions. The Diamante cross-chain is the southernmost of at least seven and perhaps eight Mariana arc volcanoes in a
c.
115 km long arc segment characterized by felsic eruptions. This is the ‘Anatahan Felsic Province’, which may have formed above a mid-crustal tonalite body that formed by fractionation or was re-melted when heated by
c.
1200 °C mafic, mantle-derived magmas. Across- and along-arc variations suggest that felsic eruptions and dome emplacement occurred when midcrustal tonalite was remobilized by intrusions of mafic magma, while north–south extension facilitated the development of conduits to the surface.

Supplementary material:

Detailed Hyperdolphin ROV dive tracks, Cook 7 dredge locations,
40
Ar/
39
Ar analytical data, analytical methods, major and selected trace element analyses of whole rock samples, and compositional data for minerals are available at
http://www.geolsoc.org.uk/SUP18611
Almost-correct specifications
Authors: Blackshear Sam , Lahiri Shuvendu K. 
Published: July 2013

Modular assertion checkers are plagued with false alarms due to the need for precise environment specifications (preconditions and callee postconditions). Even the fully precise checkers report assertion failures under the most demonic environments allowed by unconstrained or partial specifications. The inability to preclude overly adversarial environments makes such checkers less attractive to developers and severely limits the adoption of such tools in the development cycle.
In this work, we propose a parameterized framework for prioritizing the assertion failures reported by a modular verifier, with the goal of suppressing warnings from overly demonic environments. We formalize it almost-correct specifications as the minimal weakening of an angelic specification (over a set of predicates) that precludes any dead code intraprocedurally. Our work is inspired by and generalizes some aspects of semantic inconsistency detection. Our formulation allows us to lift this idea to a general class of warnings. We have developed a prototype acspec, which we use to explore a few instantiations of the framework and report preliminary findings on a diverse set of C benchmarks.
Critical Tumor Suppressor Function Mediated by Epithelial Mig-6 in Endometrial Cancer
Authors: Kim Tae Hoon , Lee Dong-Kee , Cho Sung-Nam , Orvis Grant D. , Behringer Richard R. , Lydon John P. , Ku Bon Jeong , McCampbell Adrienne S. , Broaddus Russell R. , Jeong Jae-Wook 
Published: June 2013

Abstract
Endometrial cancer is preceded by endometrial hyperplasia, unopposed estrogen exposure, and genetic alterations, but the precise causes of endometrial cancer remain uncertain. Mig-6, mainly known as a negative regulator of the EGF receptor, is an important mediator of progesterone signaling in the uterus, where it mediates tumor suppression by modulating endometrial stromal–epithelial communications. In this study, we investigated the function of Mig-6 in the uterine epithelium using a tissue-specific gene knockout strategy, in which floxed Mig-6 (Mig-6f/f) mice were crossed to Wnt7a-Cre mice (Wnt7acre+Mig-6f/f). Wnt7acre+Mig-6f/f mice developed endometrial hyperplasia and estrogen-dependent endometrial cancer, exhibiting increased proliferation in epithelial cells as well as apoptosis in subepithelial stromal cells. We documented increased expression of NOTCH1 and BIRC3 in epithelial cells of Wnt7acre+Mig-6f/f mice and decreased expression of the progesterone receptor (PR) in stromal cells. Progesterone therapy controls endometrial growth and prevents endometrial cancer, but the effectiveness of progesterone as a treatment for women with endometrial cancer is less clear. We noted that the hyperplasic phenotype of Wnt7acre+Mig-6f/f mice was prevented by progesterone treatment, whereas this treatment had no effect in PRcre/+Mig-6f/f mice where Mig-6 was deleted in both the epithelial and stromal compartments of the uterus. In contrast, activation of progesterone signaling in the stroma regulated proliferation and apoptosis in the epithelium via suppression of ERα signaling. In summary, our results establish that epithelial Mig-6 functions as a critical tumor suppressor that mediates the ability of progesterone to prevent the development of endometrial cancer. Cancer Res; 73(16); 5090–9. ©2013 AACR.
AC1MMYR2, an Inhibitor of Dicer-Mediated Biogenesis of Oncomir miR-21, Reverses Epithelial–Mesenchymal Transition and Suppresses Tumor Growth and Progression
Authors: Shi Zhendong , Zhang Junxia , Qian Xiaomin , Han Lei , Zhang Kailiang , Chen Luyue , Liu Jilong , Ren Yu , Yang Ming , Zhang Anling , Pu Peiyu , Kang Chunsheng 
Published: June 2013

Abstract
The extensive involvement of miRNAs in cancer pathobiology has opened avenues for drug development based on oncomir inhibition. Dicer is the core enzyme in miRNA processing that cleaves the terminal loop of precursor microRNAs (pre-miRNAs) to generate mature miRNA duplexes. Using the three-dimensional structure of the Dicer binding site on the pre-miR-21 oncomir, we conducted an in silico high-throughput screen for small molecules that block miR-21 maturation. By this method, we identified a specific small-molecule inhibitor of miR-21, termed AC1MMYR2, which blocked the ability of Dicer to process pre-miR-21 to mature miR-21. AC1MMYR2 upregulated expression of PTEN, PDCD4, and RECK and reversed epithelial–mesenchymal transition via the induction of E-cadherin expression and the downregulation of mesenchymal markers, thereby suppressing proliferation, survival, and invasion in glioblastoma, breast cancer, and gastric cancer cells. As a single agent in vivo, AC1MMYR2 repressed tumor growth, invasiveness, and metastasis, increasing overall host survival with no observable tissue cytotoxicity in orthotopic models. Our results offer a novel, high-throughput method to screen for small-molecule inhibitors of miRNA maturation, presenting AC1MMYR2 as a broadly useful candidate antitumor drug. Cancer Res; 73(17); 5519–31. ©2013 AACR.
PPARδ Induces Estrogen Receptor-Positive Mammary Neoplasia through an Inflammatory and Metabolic Phenotype Linked to mTOR Activation
Authors: Yuan Hongyan , Lu Jin , Xiao Junfeng , Upadhyay Geeta , Umans Rachel , Kallakury Bhaskar , Yin Yuhzi , Fant Michael E. , Kopelovich Levy , Glazer Robert I. 
Published: June 2013

Abstract
The peroxisome proliferator-activated receptor-δ (PPARδ) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes are potential risk factors for the ability of PPARδ agonists to promote tumorigenesis in the mammary gland. In this study, we describe a new transgenic mouse model in which activation of PPARδ in the mammary epithelium by endogenous or synthetic ligands resulted in progressive histopathologic changes that culminated in the appearance of estrogen receptor- and progesterone receptor-positive and ErbB2-negative infiltrating ductal carcinomas. Multiparous mice presented with mammary carcinomas after a latency of 12 months, and administration of the PPARδ ligand GW501516 reduced tumor latency to 5 months. Histopathologic changes occurred concurrently with an increase in an inflammatory, invasive, metabolic, and proliferative gene signature, including expression of the trophoblast gene, Plac1, beginning 1 week after GW501516 treatment, and remained elevated throughout tumorigenesis. The appearance of malignant changes correlated with a pronounced increase in phosphatidylcholine and lysophosphatidic acid metabolites, which coincided with activation of Akt and mTOR signaling that were attenuated by treatment with the mTOR inhibitor everolimus. Our findings are the first to show a direct role of PPARδ in the pathogenesis of mammary tumorigenesis, and suggest a rationale for therapeutic approaches to prevent and treat this disease. Cancer Res; 73(14); 4349–61. ©2013 AACR.
Targeting ERBB Receptors Shifts Their Partners and Triggers Persistent ERK Signaling through a Novel ERBB/EFNB1 Complex
Authors: Vermeer Paola D. , Colbert Paul L. , Wieking Bryant G. , Vermeer Daniel W. , Lee John H. 
Published: June 2013

Abstract
Most squamous cell carcinomas of the head and neck (HNSCC) overexpress ERBB1/EGFR, but EGF receptor (EGFR)-targeted therapies have yielded disappointing clinical results in treatment of this cancer. Here, we describe a novel interaction between EGFR and the ligand EphrinB1 (EFNB1), and we show that EFNB1 phosphorylation and downstream signaling persists in the presence of cetuximab. Mechanistically, cetuximab drives a shift in EGFR dimerization partners within the signaling complex, suggesting that targeted drugs may trigger partner rearrangements that allow persistent pathway activation. EFNB1 attenuation slowed tumor growth and increased survival in a murine model of HNSCC, suggesting a substantial contribution of EFNB1 signaling to HNSCC development. Together, our findings suggest that EFNB1 is part of the EGFR signaling complex and may mediate drug resistance in HNSCC as well as other solid tumors. Cancer Res; 73(18); 5787–97. ©2013 AACR.
Clinical Significance and Prognostic Value of microRNA Expression Signatures in Hepatocellular Carcinoma
Authors: Wei Rongrong , Huang Guo-Liang , Zhang Mei-Yin , Li Bin-Kui , Zhang Hui-Zhong , Shi Ming , Chen Xiao-Qian , Huang Long , Zhou Qing-Ming , Jia Wei-Hua , Zheng X.F. Steven , Yuan Yun-Fei , Wang Hui-Yun 
Published: June 2013

Abstract
Purpose: MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.
Experimental Design: Patients with hepatocellular carcinoma, undergoing hepatectomy were randomly divided into training set (60 patients) and test set (50 patients). Other 56 patients were used as an independent cohort. The miRNA expression levels were detected by microarray and verified by quantitative real-time reverse transcription-PCR (qRT-PCR).
Results: A 30-miRNA signature consisting of 10 downregulated and 20 upregulated miRNAs was established for distinguishing hepatocellular carcinoma from noncancerous liver tissues in the training set with 99.2% accuracy. The classification accuracies of this signature were 97% and 90% in the test set and independent cohort, respectively. The expression level of four miRNAs in the 30-miRNA signature was verified by qRT-PCR in the training set. Twenty miRNAs were then selected to construct prognostic signature in the training set. Of the 20 miRNAs, six were risk factors and 14 were protective factors. A formula based on the 20 miRNAs was built to compute prognostic index. Kaplan–Meier analysis showed that patients with a higher prognostic index had a significantly lower survival than those with a low index. This was verified in the test and independent sets. Multivariate analysis indicated that the 20-miRNA signature was an independent prognostic predictor.
Conclusions: The 30- and 20-miRNA signatures identified in this study should provide new molecular approaches for diagnosis and prognosis of patients with hepatocellular carcinoma and clues for elucidating molecular mechanism of hepatocarcinogenesis. Clin Cancer Res; 19(17); 4780–91. ©2013 AACR.
Vemurafenib Synergizes with Nutlin-3 to Deplete Survivin and Suppresses Melanoma Viability and Tumor Growth
Authors: Ji Zhenyu , Kumar Raj , Taylor Michael , Rajadurai Anpuchchelvi , Marzuka-Alcalá Alexander , Chen Y. Erin , Njauw Ching-Ni Jenny , Flaherty Keith , Jönsson Göran , Tsao Hensin 
Published: June 2013

Abstract
Purpose: For patients with advanced melanoma, primary and secondary resistance to selective BRAF inhibition remains one of the most critically compelling challenges. One rationale argues that novel biologically informed strategies are needed to maximally cripple melanoma cells up front before compensatory mechanisms emerge. As p53 is uncommonly mutated in melanoma, restoration of its function represents an attractive adjunct to selective BRAF inhibition.
Experimental Design: Thirty-seven BRAF(V600E)-mutated melanoma lines were subjected to synergy studies in vitro using a combination of vemurafenib and nutlin-3 (Nt-3). In addition, cellular responses and in vivo efficacy were also determined. We also analyzed changes in the levels of canonical apoptotic/survival factors in response to vemurafenib.
Results: Dual targeting of BRAF(V600E) and Hdm2 with vemurafenib and Nt-3, respectively, synergistically induced apoptosis and suppressed melanoma viability in vitro and tumor growth in vivo. Suppression of p53 in melanoma cells abrogated Nt-3′s effects fully and vemurafenib's effects partially. A survey of canonical survival factors revealed that both vemurafenib and Nt-3 independently attenuated levels of the antiapoptotic protein, survivin. Genetic depletion of survivin reproduces the cytotoxic effects of the combination strategy.
Conclusion: These results show preclinical feasibility for overcoming primary vemurafenib resistance by restoring p53 function. Moreover, it identifies survivin as one downstream mediator of the observed synergism and a potential secondary target. Clin Cancer Res; 19(16); 4383–91. ©2013 AACR.
Towards Sustained Silencing of HER2/neu in Cancer By Epigenetic Editing
Authors: Falahi Fahimeh , Huisman Christian , Kazemier Hinke G. , van der Vlies Pieter , Kok Klaas , Hospers Geke A.P. , Rots Marianne G. 
Published: June 2013

Abstract
The human epidermal growth factor receptor-2 (HER2/neu/ERBB2) is overexpressed in several cancer types. Although therapies targeting the HER2/neu protein result in inhibition of cell proliferation, the anticancer effect might be further optimized by limiting HER2/neu expression at the DNA level. Towards this aim, epigenetic editing was performed to suppress HER2/neu expression by inducing epigenetic silencing marks on the HER2/neu promoter.HER2/neu expression and HER2/neu promoter epigenetic modification status were determined in a panel of ovarian and breast cancer cell lines. HER2/neu-overexpressing cancer cells were transduced to express a zinc finger protein (ZFP), targeting the HER2/neugene, fused to histone methyltransferases (G9a, SUV39-H1)/super KRAB domain (SKD). Epigenetic assessment of the HER2/neu promoter showed that HER2/neu-ZFP fused to G9a efficiently induced the intended silencing histone methylation mark (H3K9me2). Importantly, H3K9me2 induction was associated with a dramatic downregulation of HER2/neu expression in HER2/neu- overexpressing cells. Downregulation by SKD, traditionally considered transient in nature, was associated with removal of the histone acetylation mark (H3ac). The downregulation of HER2/neu by induced H3K9 methylation and/or reduced H3 acetylation was sufficient to effectively inhibit cellular metabolic activity and clonogenicity. Furthermore, genome-wide analysis indicated preferential binding of the ZFP to its target sequence. These results not only show that H3K9 methylation can be induced but also that this epigenetic mark was instructive in promoting downregulation of HER2/neu expression.
Implications: Epigenetic editing provides a novel (synergistic) approach to modulate expression of oncogenes. Mol Cancer Res; 11(9); 1029–39. ©2013 AACR.