bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormone Therapy, Estrogen Metabolism, and Risk of Breast Cancer in the Women's Health Initiative Hormone Therapy Trial
Authors: Mackey Rachel H. , Fanelli Theresa J. , Modugno Francesmary , Cauley Jane A. , McTigue Kathleen M. , Brooks Maria Mori , Chlebowski Rowan T. , Manson JoAnn E. , Klug Thomas L. , Kip Kevin E. , Curb J. David , Kuller Lewis H. 
Published: November 2012

Abstract
Background: In the Women's Health Initiative Hormone Trials (WHI-HT), breast cancer risk was increased with estrogen plus progestin (E+P) but not with unopposed estrogen (E-alone). We hypothesized that E+P would preferentially metabolize to 16α-hydroxyestrone (16α-OHE1) rather than 2-hydroxyestrone (2-OHE1), and that breast cancer risk would be associated with baseline and 1 year changes in estrogen metabolites: positively for 16α-OHE1 levels and negatively for levels of 2-OHE-1 and the 2:16 ratio.
Methods: In a prospective case-control study nested in the WHI-HT, 845 confirmed breast cancer cases were matched to 1,690 controls by age and ethnicity. Using stored serum, 2-OHE1 and 16α-OHE1 levels were measured by enzyme immunoassay at baseline, and for those randomized to active treatment (n = 1,259), at 1 year.
Results: The 1-year increase in 16α-OHE1 was greater with E+P than E-alone (median 55.5 pg/mL vs. 43.5 pg/mL, P &lt; 0.001), but both increased 2-OHE1 by ∼300 pg/mL. Breast cancer risk was modestly associated with higher baseline levels of 2-OHE1 and the 2:16 ratio, and for estrogen receptor+/progesterone+ cases only, higher baseline 16α-OHE1 levels. For those randomized to active treatment, breast cancer risk was associated with greater increase in 2-OHE-1 and the 2:16 ratio, but associations were not significant.
Conclusions: Although E+P modestly increased 16α-OHE1 more than E-alone, increase in 16α-OHE1 was not associated with breast cancer.
Impact: Study results do not explain differences between the WHI E+P and WHI E-alone breast cancer results but metabolism of oral HT, which may explain smaller than expected increase in breast cancer compared with endogenous estrogens. Cancer Epidemiol Biomarkers Prev; 21(11); 2022–32. ©2012 AACR.
Maternal Use of Folic Acid and Other Supplements and Risk of Childhood Brain Tumors
Authors: Milne Elizabeth , Greenop Kathryn R. , Bower Carol , Miller Margaret , van Bockxmeer Frank M. , Scott Rodney J. , de Klerk Nicholas H. , Ashton Lesley J. , Gottardo Nicholas G. , Armstrong Bruce K. 
Published: November 2012

AbstractBackground: Interest in a possible protective effect of maternal vitamin use before or during pregnancy against childhood brain tumors (CBT) and other childhood cancers has grown over the past decade. Our Australian study of CBTs, conducted between 2005 and 2011, investigated whether maternal use folic acid and other supplements was protective.Methods: Case children were identified through the 10 Australian pediatric oncology centers and controls were recruited by national random digit dialing. Mothers of 327 cases and 867 control children provided information on supplement use before and during the index pregnancy, including brand name, dose, and timing. Data were analyzed using multivariable unconditional logistic regression.Results: The OR for any maternal use of folic acid, use of folic acid without iron or vitamins B6, B12, C, or A, and any vitamin use before pregnancy, were: 0.68 [95% confidence interval (CI), 0.46–1.00; 0.55 (95% CI, 0.32–0.93) and 0.68 (95% CI, 0.46–1.01), respectively. The ORs for use of these supplements during pregnancy were also below unity, but generally closer to the null than those for the prepregnancy period. There was some evidence of an inverse dose–response during each time period.Conclusions: These results suggest that folic acid supplements before and possibly during pregnancy may protect against CBT. Such associations are biologically plausible through established mechanisms.Impact: This study provides evidence of a specific protective effect of prenatal folic acid supplementation against the risk of CBT that is not attributable to the actions of the other micronutrients investigated. Cancer Epidemiol Biomarkers Prev; 21(11); 1933–41. ©2012 AACR.
Type II Diabetes Mellitus and the Incidence of Epithelial Ovarian Cancer in the Cancer Prevention Study-II Nutrition Cohort
Authors: Gapstur Susan M. , Patel Alpa V. , Diver W. Ryan , Hildebrand Janet S. , Gaudet Mia M. , Jacobs Eric J. , Campbell Peter T. 
Published: November 2012

Abstract
Background: Despite consistent associations of type II diabetes mellitus with hormonally related cancers such as breast and endometrium, the relation between type II diabetes mellitus and ovarian cancer risk is unclear.
Methods: Associations of type II diabetes mellitus status, duration, and insulin use with epithelial ovarian cancer overall, and with serous and nonserous histologic subtypes were examined in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of U.S. men and women predominantly aged 50 years and older. Between 1992 and 2007, 524 incident epithelial ovarian cancer cases were identified among 63,440 postmenopausal women. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were computed using extended Cox regression to update diabetes status and bilateral oophorectomy status during follow-up.
Results: Type II diabetes mellitus status (RR = 1.05; 95% CI, 0.75–1.46) and duration were not associated with epithelial ovarian cancer risk. Although not statistically significantly different (Pdifference = 0.39), the RR was higher for type II diabetes mellitus with insulin use (RR = 1.28; 95% CI, 0.74–2.24) than for type II diabetes mellitus without insulin use (RR = 0.96; 95% CI, 0.64–1.43). Diabetes seemed to be more strongly associated with nonserous (RR = 1.41; 95% CI, 0.70–2.85) than serous (RR = 0.71; 95% CI, 0.41–1.23) histologic subtypes.
Conclusions: Type II diabetes mellitus was not associated with risk of epithelial ovarian cancer, although higher risks with nonserous subtypes and among insulin users cannot be ruled out.
Impact: Larger studies are needed to clarify associations of type II diabetes mellitus with or without insulin use with risk of ovarian cancer overall and by histologic subtypes. Cancer Epidemiol Biomarkers Prev; 21(11); 2000–5. ©2012 AACR.
Genetic Ablation of the Tetraspanin CD151 Reduces Spontaneous Metastatic Spread of Prostate Cancer in the TRAMP Model
Authors: Copeland Ben T. , Bowman Matthew J. , Ashman Leonie K. 
Published: November 2012

Abstract
Tetraspanins are integral membrane proteins that associate with motility-related molecules such as integrins. Experimental studies have indicated that they may be important regulators of tumor invasion and metastasis, and high expression of the tetraspanin CD151 has been linked to poor prognosis in a number of cancers. Here, we show for the first time that genetic ablation of CD151 inhibits spontaneous metastasis in a transgenic mouse model of de novo tumorigenesis. To evaluate the effects of CD151 on de novo prostate cancer initiation and metastasis, a Cd151−/− (KO) murine model was crossed with the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. Mice were analyzed for initiation of prostate tumor by palpation and primary tumors were analyzed by immunohistochemistry. Liver and lungs were examined for incidence and size of spontaneous metastatic lesions by histopathology. Knocking-out Cd151 had no significant effect on prostate cancer initiation or on expression of markers of proliferation, apoptosis, or angiogenesis in primary tumors. However, it did significantly decrease metastasis in a site-specific fashion, notably to the lungs but not the liver. Thus, CD151 acts principally as promoter of metastasis in this model. Prostate cancer is the second highest cause of cancer-related deaths in men in most Western countries, with the majority of deaths attributed to late-stage metastatic disease. CD151 may prove to be a valuable prognostic marker for treatment stratification and is a possible antimetastatic target. Mol Cancer Res; 11(1); 95–105. ©2012 AACR.
The Madden–Julian Oscillation in ECHAM6 and the Introduction of an Objective MJO Metric
Authors: Crueger Traute , Stevens Bjorn , Brokopf Renate 
Published: November 2012

Abstract
This study presents a quantitative evaluation of the simulated Madden–Julian oscillation (MJO) in an ensemble of 42 experiments performed with ECHAM6 and previous ECHAM versions. The ECHAM6 experiments differ in their parameter settings, resolution, and whether the atmosphere is coupled to an ocean or not. The analysis concentrates on a few basic features of the MJO, namely, the signatures of convection/precipitation coupled with the circulation system and the eastward propagation strength of outgoing longwave radiation (OLR) and 850- and 200-hPa zonal winds within the MJO-related frequency–wavenumber range. It also examines whether precipitation and OLR show similar signatures in the MJO as simulated by ECHAM. The experiments reveal an MJO, however, to different degrees and in different aspects, so that a sound assessment requires a multivariate approach. In particular, the convective rainfall signatures are decoupled from the dynamic signature of the MJO in the simulations herein, which eventually leads to the introduction of a new MJO diagram and metric that incorporate OLR and the zonal winds in 850 and 200 hPa. The analysis here confirms the importance of the convection scheme: only with the Nordeng modifications to the Tiedtke scheme can realistic MJO features be simulated. High-resolution coupled experiments better represent the MJO as compared to low-resolution AMIP experiments. This is shown to follow from two more general findings, namely, that 1) air–sea interaction mainly increases the convective signature and 2) increased resolution enhances eastward propagation.
Interaction of Additive Noise and Nonlinear Dynamics in the Double-Gyre Wind-Driven Ocean Circulation
Authors: Sapsis Themistoklis P. , Dijkstra Henk A. 
Published: November 2012

Abstract
In this paper the authors study the interactions of additive noise and nonlinear dynamics in a quasigeostrophic model of the double-gyre wind-driven ocean circulation. The recently developed framework of dynamically orthogonal field theory is used to determine the statistics of the flows that arise through successive bifurcations of the system as the ratio of forcing to friction is increased. This study focuses on the understanding of the role of the spatial and temporal coherence of the noise in the wind stress forcing. When the wind stress noise is temporally white, the statistics of the stochastic double-gyre flow does not depend on the spatial structure and amplitude of the noise. This implies that a spatially inhomogeneous noise forcing in the wind stress field only has an effect on the dynamics of the flow when the noise is temporally colored. The latter kind of stochastic forcing may cause more complex or more coherent dynamics depending on its spatial correlation properties.
Transition and Equilibration of Neutral Atmospheric Boundary Layer Flow in One-Way Nested Large-Eddy Simulations Using the Weather Research and Forecasting Model
Authors: Mirocha Jeff , Kirkil Gokhan , Bou-Zeid Elie , Chow Fotini Katopodes , Kosović Branko 
Published: November 2012

Abstract
The Weather Research and Forecasting Model permits finescale large-eddy simulations (LES) to be nested within coarser simulations, an approach that can generate more accurate turbulence statistics and improve other aspects of simulated flows. However, errors are introduced into the finer domain from the nesting methodology. Comparing nested domain, flat-terrain simulations of the neutral atmospheric boundary layer with single-domain simulations using the same mesh, but instead using periodic lateral boundary conditions, reveals the errors contributed to the nested solution from the parent domain and nest interfaces. Comparison of velocity spectra shows good agreement among higher frequencies, but greater power predicted on the nested domain at lower frequencies. Profiles of mean wind speed show significant near-surface deficits near the inflow boundaries, but equilibrate to improved values with distance. Profiles of the vertical flux of x momentum show significant underprediction by the nested domain close to the surface and near the inlet boundaries. While these underpredictions of the stresses, which cause the near-surface velocity deficits, attenuate with distance within the nested domains, significant errors remain throughout. Profiles of the resolved turbulence kinetic energy show considerable deviations from their single-domain values throughout the nested domains. The authors examine the accuracy of these parameters and their sensitivities to the turbulence subfilter stress model, mesh resolution, and grid aspect ratio, and provide guidance to practitioners of nested LES.
Cyber Situation Awareness
Authors: Dutt Varun , Ahn Young-Suk , Gonzalez Cleotilde 
Published: November 2012

Objective: To determine the effects of an adversary’s behavior on the defender’s accurate and timely detection of network threats. Background: Cyber attacks cause major work disruption. It is important to understand how a defender’s behavior (experience and tolerance to threats), as well as adversarial behavior (attack strategy), might impact the detection of threats. In this article, we use cognitive modeling to make predictions regarding these factors. Method: Different model types representing a defender, based on Instance-Based Learning Theory (IBLT), faced different adversarial behaviors. A defender’s model was defined by experience of threats: threat-prone (90% threats and 10% nonthreats) and nonthreat-prone (10% threats and 90% nonthreats); and different tolerance levels to threats: risk-averse (model declares a cyber attack after perceiving one threat out of eight total) and risk-seeking (model declares a cyber attack after perceiving seven threats out of eight total). Adversarial behavior is simulated by considering different attack strategies: patient (threats occur late) and impatient (threats occur early). Results: For an impatient strategy, risk-averse models with threat-prone experiences show improved detection compared with risk-seeking models with nonthreat-prone experiences; however, the same is not true for a patient strategy. Conclusions: Based upon model predictions, a defender’s prior threat experiences and his or her tolerance to threats are likely to predict detection accuracy; but considering the nature of adversarial behavior is also important. Application: Decision-support tools that consider the role of a defender’s experience and tolerance to threats along with the nature of adversarial behavior are likely to improve a defender’s overall threat detection.
Using Virtual Reality to Assess User Experience
Authors: Rebelo Francisco , Noriega Paulo , Duarte Emília , Soares Marcelo 
Published: November 2012

Objective: The aim of this article is to discuss how user experience (UX) evaluation can benefit from the use of virtual reality (VR). Background: UX is usually evaluated in laboratory settings. However, considering that UX occurs as a consequence of the interaction between the product, the user, and the context of use, the assessment of UX can benefit from a more ecological test setting. VR provides the means to develop realistic-looking virtual environments with the advantage of allowing greater control of the experimental conditions while granting good ecological validity. Method: The methods used to evaluate UX, as well as their main limitations, are identified. The current VR equipment and its potential applications (as well as its limitations and drawbacks) to overcome some of the limitations in the assessment of UX are highlighted. Results: The relevance of VR for UX studies is discussed, and a VR-based framework for evaluating UX is presented. Conclusion: UX research may benefit from a VR-based methodology in the scopes of user research (e.g., assessment of users’ expectations derived from their lifestyles) and human–product interaction (e.g., assessment of users’ emotions since the first moment of contact with the product and then during the interaction). Application: This article provides knowledge to researchers and professionals engaged in the design of technological interfaces about the usefulness of VR in the evaluation of UX.
Antimicrobial and Analgesic Prescribing Patterns for Acute Otitis Externa, 2004‐2010
Authors: Collier Sarah A. , Hlavsa Michele C. , Piercefield Emily W. , Beach Michael J. 
Published: November 2012

ObjectiveAcute otitis externa (AOE) is a common but preventable ear condition. Clinical guidelines issued in 2006 recommended topical treatments for uncomplicated AOE, but systemic antimicrobials appear to be commonly prescribed. The objective of this analysis was to describe pre‐ and postguideline prescribing patterns by clinician specialty and antimicrobial type and assess trends over time.Study DesignRetrospective longitudinal analysis of a large insurance database.SettingOutpatient departments in the United States.MethodsInitial outpatient visits in 2004 to 2010 for AOE (excluding visits with complicating conditions) were extracted from an insurance database. Prescription drug claims were linked and categorized by clinician specialty and antimicrobial type.ResultsThe analysis included 907,261 initial outpatient visits. Use of systemic antimicrobials declined by 4.9% (95% confidence interval [CI], 4.1%, 5.7%) from 36.5% of initial visits in 2004 to 32.1% in 2010. Use of systemic antimicrobials varied by specialty. Systemic antimicrobials were prescribed in 47.1% of 2010 emergency department (ED) visits (−6.9% from 2004, 95% CI −12.3, −1.5), 25.9% of otolaryngologist visits (−1.6%, 95% CI −5.6, 2.4), and 20.4% of pediatrician visits (−6.6%, 95% CI −8.8, −4.4). Penicillins were prescribed most frequently (42.3% of systemic prescriptions in 2010), followed by cephalosporins (19.8%), erythromycin/macrolides (17.4%), and quinolones (11.1%). Opioids were prescribed in 26.4% of ED visits and 9% of outpatient visits.ConclusionsUse of systemic antimicrobials declined over time, but one‐third of 2010 visits resulted in systemic antimicrobials, despite exclusion of visits with complicating factors. Use of systemic antimicrobials varied by specialty. Further educational efforts and outreach to other specialties might be warranted.
Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes
Authors: Marsh Rebecca A. , Rao Kanchan , Satwani Prakash , Lehmberg Kai , Müller Ingo , Li Dandan , Kim Mi-Ok , Fischer Alain , Latour Sylvain , Sedlacek Petr , Barlogis Vincent , Hamamoto Kazuko , Kanegane Hirokazu , Milanovich Sam , Margolis David A. , Dimmock David , Casper James , Douglas Dorothea N. , Amrolia Persis J. , Veys Paul , Kumar Ashish R. , Jordan Michael B. , Bleesing Jack J. , Filipovich Alexandra H. 
Published: November 2012

Key PointsHigh mortality rates are observed in patients with XIAP deficiency treated with myeloablative conditioning regimens for hematopoietic cell transplantation.
Characterization of replication and conjugation of plasmid pWTY27 from a widely distributed Streptomyces species
Authors: Wang Tao , Chen Zhenhua , Cheng Qiuxiang , Zhou Min , Tian Xinli , Xie Pengfei , Zhong Li , Shen Meijuan , Qin Zhongjun 
Published: November 2012

Abstract

Background

Streptomyces species are widely distributed in natural habitats, such as soils, lakes, plants and some extreme environments. Replication loci of several Streptomyces theta-type plasmids have been reported, but are not characterized in details. Conjugation loci of some Streptomyces rolling-circle-type plasmids are identified and mechanism of conjugal transferring are described.

Results
We report the detection of a widely distributed Streptomyces strain Y27 and its indigenous plasmid pWTY27 from fourteen plants and four soil samples cross China by both culturing and nonculturing methods. The complete nucleotide sequence of pWTY27 consisted of 14,288 bp. A basic locus for plasmid replication comprised repAB genes and an adjacent iteron sequence, to a long inverted-repeat (ca. 105 bp) of which the RepA protein bound specifically in vitro, suggesting that RepA may recognize a second structure (e.g. a long stem-loop) of the iteron DNA. A plasmid containing the locus propagated in linear mode when the telomeres of a linear plasmid were attached, indicating a bi-directional replication mode for pWTY27. As for rolling-circle plasmids, a single traA gene and a clt sequence (covering 16 bp within traA and its adjacent 159 bp) on pWTY27 were required for plasmid transfer. TraA recognized and bound specifically to the two regions of the clt sequence, one containing all the four DC1 of 7 bp (TGACACC) and one DC2 (CCCGCCC) and most of IC1, and another covering two DC2 and part of IC1, suggesting formation of a high-ordered DNA-protein complex.

Conclusions
This work (i) isolates a widespread Streptomyces strain Y27 and sequences its indigenous theta-type plasmid pWTY27; (ii) identifies the replication and conjugation loci of pWTY27 and; (iii) characterizes the binding sequences of the RepA and TraA proteins.
Identification of genes involved in the ACC-mediated control of root cell elongation in Arabidopsis thaliana
Authors: Markakis Marios Nektarios , De Cnodder Tinne , Lewandowski Michal , Simon Damien , Boron Agnieszka , Balcerowicz Daria , Doubbo Thanaa , Taconnat Ludivine , Renou Jean-Pierre , Höfte Herman , Verbelen Jean-Pierre , Vissenberg Kris 
Published: November 2012

Abstract

Background
Along the root axis of Arabidopsis thaliana, cells pass through different developmental stages. In the apical meristem repeated cycles of division increase the numbers of cells. Upon leaving the meristem, these cells pass the transition zone where they are physiologically and mechanically prepared to undergo subsequent rapid elongation. During the process of elongation epidermal cells increase their length by 300% in a couple of hours. When elongation ceases, the cells acquire their final size, shape and functions (in the differentiation zone). Ethylene administered as its precursor 1-aminocyclopropane-1-carboxylic acid (ACC) is capable of inhibiting elongation in a concentration-dependent way. Using a microarray analysis, genes and/or processes involved in this elongation arrest are identified.

Results
Using a CATMA-microarray analysis performed on control and 3h ACC-treated roots, 240 differentially expressed genes were identified. Quantitative Real-Time RT-PCR analysis of the 10 most up and down regulated genes combined with literature search confirmed the accurateness of the analysis. This revealed that inhibition of cell elongation is, at least partly, caused by restricting the events that under normal growth conditions initiate elongation and by increasing the processes that normally stop cellular elongation at the end of the elongation/onset of differentiation zone.

Conclusions
ACC interferes with cell elongation in the Arabidopsis thaliana roots by inhibiting cells from entering the elongation process and by immediately stimulating the formation of cross-links in cell wall components, diminishing the remaining elongation capacity. From the analysis of the differentially expressed genes, it becomes clear that many genes identified in this response, are also involved in several other kind of stress responses. This suggests that many responses originate from individual elicitors, but that somewhere in the downstream signaling cascade, these are converged to a ’common pathway’. Furthermore, several potential keyplayers, such as transcription factors and auxin-responsive genes, were identified by the microarray analysis. They await further analysis to reveal their exact role in the control of cell elongation.