bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local Recurrence after Breast-Conserving Therapy in Relation to Gene Expression Patterns in a Large Series of Patients
Authors: Kreike Bas , Halfwerk Hans , Armstrong Nicola , Bult Peter , Foekens John A. , Veltkamp Sanne C. , Nuyten Dimitry S.A. , Bartelink Harry , van de Vijver Marc J. 
Published: May 2009

Abstract
Purpose: The majority of patients with early-stage breast cancer are treated with breast-conserving therapy (BCT). Several clinical risk factors are associated with local recurrence (LR) after BCT but are unable to explain all instances of LR after BCT. Here, gene expression microarrays are used to identify novel risk factors for LR after BCT.
Experimental Design: Gene expression profiles of 56 primary invasive breast carcinomas from patients who developed a LR after BCT were compared with profiles of 109 tumors from patients who did not develop a LR after BCT. Both unsupervised and supervised methods of classification were used to separate patients into groups corresponding to disease outcome. In addition, for 15 patients, the gene expression profile in the recurrence was compared with that of the primary tumor.
Results: The two main clusters found by hierarchical cluster analysis of all 165 primary invasive breast carcinomas revealed no association with LR. Predefined gene sets (molecular subtypes and “chromosomal instability” signature) are associated with LR (P = 0.0002 and 0.003, respectively). Significant analysis of microarrays revealed an association between LR and cell proliferation, not captured by histologic grading. Class prediction analysis constructed a gene classifier, which was successfully validated, cross-platform, on an independent data set of 161 patients (log-rank P = 0.041). In multivariate analysis, young age was the only independent predictor of LR.
Conclusions: We have constructed and cross-platform validated a gene expression profile predictive for LR after BCT, which is characterized by genes involved in cell proliferation but not a surrogate for high histologic grade.
Serum Peptidome Profiling Revealed Platelet Factor 4 as a Potential Discriminating Peptide Associated with Pancreatic Cancer
Authors: Fiedler Georg Martin , Leichtle Alexander Benedikt , Kase Julia , Baumann Sven , Ceglarek Uta , Felix Klaus , Conrad Tim , Witzigmann Helmut , Weimann Arved , Schütte Christof , Hauss Johann , Büchler Markus , Thiery Joachim 
Published: May 2009

AbstractPurpose: Mass spectrometry–based serum peptidome profiling is a promising tool to identify novel disease-associated biomarkers, but is limited by preanalytic factors and the intricacies of complex data processing. Therefore, we investigated whether standardized sample protocols and new bioinformatic tools combined with external data validation improve the validity of peptidome profiling for the discovery of pancreatic cancer–associated serum markers.Experimental Design: For the discovery study, two sets of sera from patients with pancreatic cancer (n = 40) and healthy controls (n = 40) were obtained from two different clinical centers. For external data validation, we collected an independent set of samples from patients (n = 20) and healthy controls (n = 20). Magnetic beads with different surface functionalities were used for peptidome fractionation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Data evaluation was carried out by comparing two different bioinformatic strategies. Following proteome database search, the matching candidate peptide was verified by MALDI-TOF MS after specific antibody-based immunoaffinity chromatography and independently confirmed by an ELISA assay.Results: Two significant peaks (m/z 3884; 5959) achieved a sensitivity of 86.3% and a specificity of 97.6% for the discrimination of patients and healthy controls in the external validation set. Adding peak m/z 3884 to conventional clinical tumor markers (CA 19-9 and CEA) improved sensitivity and specificity, as shown by receiver operator characteristics curve analysis (AUROCcombined = 1.00). Mass spectrometry–based m/z 3884 peak identification and following immunologic quantitation revealed platelet factor 4 as the corresponding peptide.Conclusions: MALDI-TOF MS-based serum peptidome profiling allowed the discovery and validation of platelet factor 4 as a new discriminating marker in pancreatic cancer.
Estrogen Receptor Subtype– and Promoter-Specific Modulation of Aryl Hydrocarbon Receptor–Dependent Transcription
Authors: Wihlén Björn , Ahmed Shaimaa , Inzunza José , Matthews Jason 
Published: May 2009

Abstract
In this study, we examined the role of estrogen receptors (ER) in aryl hydrocarbon receptor (AHR)–dependent transactivation. Chromatin immunoprecipitation assays showed that AHR agonists differentially induced recruitment of ERα to the AHR target genes CYP1A1 and CYP1B1. Cotreatment with 17β-estradiol significantly increased β-naphthoflavone (BNF)– and 2,3,7,8-tetrachlorodibenzo-p-dioxin–induced recruitment of ERα to CYP1A1, whereas 3,3′-diindolylmethane induced promoter occupancy of ERα at CYP1A1 that was unaffected by cotreatment with 17β-estradiol. Cyclical recruitment of AHR and ERα to CYP1A1 was only observed in cells treated with BNF. Stable and subtype-specific knockdown of ERα or ERβ using shRNA showed that suppression of ERα significantly reduced, whereas knockdown of ERβ significantly enhanced, AHR agonist–induced Cyp1a1 expression in HC11 mouse mammary epithelial cells. AHR agonist–induced Cyp1b1 expression was reduced by ERβ knockdown but unaffected by ERα knockdown. The siRNA-mediated knockdown of ERα in MCF-7 human breast cancer cells did not affect 2,3,7,8-tetrachlorodibenzo-p-dioxin–dependent regulation of CYP1A1 and CYP1B1 mRNA expression. In agreement with our in vitro findings in the HC11 cells, ERα knockout mice exhibit reduced BNF-dependent induction of Cyp1a1 mRNA. These results establish ligand- and promoter-specific influences on the cyclical recruitment patterns for AHR and show ER species-, subtype-, and promoter-specific modulation of AHR-dependent transcription. (Mol Cancer Res 2009;7(6):977–86)
Development of Dietary Phytochemical Chemopreventive Agents: Biomarkers and Choice of Dose for Early Clinical Trials
Authors: Scott Edwina N. , Gescher Andreas J. , Steward William P. , Brown Karen 
Published: May 2009

AbstractIn view of safety concerns surrounding the use of pharmaceuticals such as nonsteroidal anti-inflammatory drugs and tamoxifen as cancer chemopreventive agents, potentially innocuous phytochemicals derived from the diet are considered attractive alternatives. However, results from cancer chemoprevention trials of dietary agents have been disappointing to date, as promising activities observed in rodent models and cells in vitro have not translated into clinical success. This may be partly due to the development process for these agents, which is complex for a number of reasons; the definitive end point, inhibition of carcinogenesis, requires large numbers of individuals followed-up over many years. Furthermore, whereas biomarkers are frequently used as surrogate efficacy end points to expedite the process, biomarker assessment and validation has proven difficult because dietary agents exert multiple actions with an unknown hierarchy of biological importance. These factors have made determining the dose for clinical investigation extremely challenging, and at present, there are no defined strategies for rationally identifying the most appropriate doses. In this commentary, the complexities involved in the development of dietary chemoprevention agents are discussed, and a tentative route towards selection of the optimal clinical dose is proposed. The approach highlights the need to conduct long-term preclinical studies with realistic concentrations that are achievable in human tissues and the importance of efficacy biomarkers that are intrinsically linked to the key mechanisms of action. A more logical design of studies should increase the likelihood that the encouraging preclinical results observed for many phytochemicals translate into tangible clinical benefit.
Resolution Dependence of the Tropopause Inversion Layer in an Idealized Model for Upper-Tropospheric Anticyclones
Authors: Müller Andreas , Wirth Volkmar 
Published: May 2009

Abstract
This note investigates the dependence of the extratropical tropopause inversion layer (TIL) on numerical resolution in an idealized modeling framework. Axisymmetric upper-tropospheric anticyclones are constructed by specifying potential vorticity (PV) and solving the nonlinear PV-inversion problem. The PV distribution has a smooth but near-discontinuous change of PV across the tropopause in a transition zone with vertical depth δ. For fixed δ the strength of the TIL changes with changing resolution until the transition zone is resolved by a fairly large number of grid points. The quality-controlled numerical solutions are used to study the behavior for δ → 0. This limit can lead to very strong TILs, but no indications for divergent behavior were found.
Drought-Induced Warming in the Continental United States under Different SST Regimes
Authors: Koster Randal D. , Wang Hailan , Schubert Siegfried D. , Suarez Max J. , Mahanama Sarith 
Published: May 2009

Abstract
The U.S. Climate Variability and Predictability (U.S. CLIVAR) Drought Working Group (DWG) recently performed a series of experiments in which a number of AGCMs were forced with different leading patterns of global SST variability. These experiments provide a unique opportunity to examine how different SST regimes affect temperature over the continental United States. Herein, the focus is on a particular aspect of June–August (JJA) near-surface air temperature: the temperature during relatively dry years for a given SST regime. For most of the models participating in the DWG experiments, a cold Pacific produces greater warming in the central United States during relatively dry years than a warm Pacific does for the following two separate reasons: (i) the cold Pacific leads on average, across all years, to drier conditions, and (ii) the particular evaporation regime induced by the cold Pacific enhances the impact of evaporation feedback on temperature, that is, the sensitivity of temperature to within-climate variations in moisture availability. These results are supported, to a large extent, by the observational record.
Calibrating 2-m Temperature of Limited-Area Ensemble Forecasts Using High-Resolution Analysis
Authors: Kann Alexander , Wittmann Christoph , Wang Yong , Ma Xulin 
Published: May 2009

Abstract
Although the quality of numerical ensemble prediction systems (EPS) has greatly improved during the last few years, these systems still show systematic deficiencies. Specifically, they are underdispersive and lack both reliability and sharpness. A variety of statistical postprocessing methods allows for improving direct model output. Since 2007, Aire Limitée Adaptation Dynamique Développement International Limited Area Ensemble Forecasting (ALADIN-LAEF) has been in operation at the Central Institute for Meteorology and Geodynamics (ZAMG), and its 2-m temperature model output subject to calibration. This work follows the approach of nonhomogeneous Gaussian regression (NGR) that addresses a statistical correction of the first and second moment (mean bias and dispersion) for Gaussian-distributed continuous variables. It is based on the multiple linear regression technique and provides a predictive probability density function (PDF) in terms of a normal distribution. Fitting the regression coefficients, a minimum continuous ranked probability score (CRPS) estimation has been chosen instead of the more traditional maximum likelihood technique. The use of high-resolution analysis data on a 1 km × 1 km grid as training data improves the forecast skill in terms of CRPS by about 35%, especially on the local scale. The percentage of outliers decreases significantly without loss of sharpness. Sensitivity studies confirm that about half of the total improvement can be attributed to the effect of a bias correction. The training length plays a minor role, at least for the chosen verification period. A rescaling of the predictive PDF is important in order to obtain sharp forecasts, especially in the short range. Applying the same method to the global ensemble from the European Centre for Medium-Range Weather Forecasts (ECMWF) gives improvements of similar magnitude. However, the calibrated 2-m temperature of ALADIN-LAEF still remains slightly better than the 2-m temperature from calibrated ECMWF-EPS, which leads to the conclusion that statistical downscaling of EPS cannot replace dynamical downscaling. Finally, an advanced version of NGR, the so-called NGR-TD, which uses time-weighted averaging within minimum CRPS estimation, is able to yield a further improvement of about 5% in terms of the CRPS.
The Impact of Horizontal Grid Spacing on the Microphysical and Kinematic Structures of Strong Tropical Cyclones Simulated with the WRF-ARW Model
Authors: Fierro Alexandre O. , Rogers Robert F. , Marks Frank D. , Nolan David S. 
Published: May 2009

Abstract
Using the Advanced Weather Research and Forecasting numerical model, the impact of horizontal grid spacing on the microphysical and kinematic structure of a numerically simulated tropical cyclone (TC), and their relationship to storm intensity was investigated with a set of five numerical simulations using input data for the case of Hurricane Rita (2005). The horizontal grid spacing of the parent domain was systematically changed such that the horizontal grid spacing of the inner nest varied from 1 to 5 km by an increment of 1 km, this while keeping geographical dimensions of the domains identical.
Within this small range of horizontal grid spacing, the morphology of the simulated storms and the evolution of the kinematic and microphysics field showed noteworthy differences. As grid spacing increased, the model produced a wider, more tilted eyewall, a larger radius of maximum winds, and higher-amplitude, low wavenumber eyewall asymmetries. The coarser-resolution simulations also produced larger volume, areal coverage, and mass flux of updraft speeds ≥5 m s−1; larger volumes of condensate and ice-phase particles aloft; larger boundary layer kinetic energy; and a stronger secondary circulation. While the contribution of updrafts ≥5 m s−1 to the total updraft mass flux varied little between the five cases, the contribution of downdrafts ≤−2 m s−1 to the total downdraft mass flux was by far the largest in the finest-resolution simulation.
Despite these structural differences, all of the simulations produced storms of similar intensity, as measured by peak 10-m wind speed and minimum surface pressure, suggesting that features in the higher-resolution simulations that tend to weaken TCs (i.e., smaller area of high surface fluxes and weaker total updraft mass flux) compensate for features that favor TC intensity (i.e., smaller-amplitude eyewall asymmetries and larger radial gradients). This raises the possibility that resolution increases in this range may not be as important as other model features (e.g., physical parameterization and initial condition improvements) for improving TC intensity forecasts.
An Anatomical and Biomechanical Comparison of Anteromedial and Anterolateral Approaches for Tibial Tunnel of Posterior Cruciate Ligament Reconstruction: Evaluation of the Widening Effect of the Anterolateral Approach
Authors: Ahn Jin Hwan , Bae Ji Hoon , Lee Yong Seuk , Choi Kuiwon , Bae Tae Soo , Wang Joon Ho 
Published: May 2009

Background An anterolateral approach to the tibial tunnel of posterior cruciate ligament reconstruction is used to reduce the sharpness of the graft-tunnel angle, the so-called killer turn effect. However, with the anterolateral approach, the tunnel might be widened into an ovoid shape because of the small angle between the tunnel and the anterolateral cortex. Hypothesis The fixation strength of the posterior cruciate ligament graft in the tibial tunnel will be weaker in the anterolateral approach compared with the anteromedial approach. Study Design Controlled laboratory study. Methods Twenty paired cadaveric tibias were used. Tibial tunnels were made using following approaches: an anteromedial approach for 10 tibias and an anterolateral approach for 10 tibias. The anterior cortex-tunnel angle and the diameter of the tunnel entrance were measured by 2-dimensional computed tomographic scans. After fixation of the Achilles tendon allograft with a biodegradable screw, the maximal strength of the graft at failure was measured using a materials testing machine. Results The mean cortex-tunnel angle was 47.5° ± 9.3° in the anteromedial approach group and 28.3° ± 7.4° in the anterolateral approach group. The mean long diameter of the tunnels in the anteromedial approach group was 10.6 ± 1.0 mm and in the anterolateral approach group it was 14.0 ± 1.5 mm. These two parameters showed statistically significant differences between the 2 groups (P < .01). The mean maximum load at failure for the anteromedial approach group was 385.4 ± 139.7 N, and for the anterolateral approach group it was 225.1 ± 144.1 N. This difference was statistically significant (P = .021). Conclusion The anterolateral approach resulted in a tunnel with a wider entrance, a more acute cortex-tunnel angle, and a lower maximal load at failure compared with tunnels created using the anteromedial approach. Clinical Relevance The use of additional fixation methods, such as post ties or ligament washers and screws, should be considered when using an anterolateral approach for tibial tunnel of posterior cruciate ligament reconstruction.
In-vivo evidence for stable neuroaxonal damage in the brain of patients with benign multiple sclerosis
Authors: Benedetti B , Rovaris M , Rocca MA , Caputo D , Zaffaroni M , Capra R , Bertolotto A , Martinelli V , Comi G , Filippi M 
Published: May 2009

Objective The term benign multiple sclerosis (BMS) is referred to patients who have a mild or absent disability several years after disease clinical onset. Axonal damage can be measured in vivo using proton MR spectroscopy (1H-MRS). In this study, we quantified the severity of “global” axonal damage in BMS and early relapsing–remitting (RR) MS patients, using whole brain N-acetylaspartate (WBNAA) 1H-MRS, to better elucidate the structural correlates of a non-disabling disease evolution. Methods WBNAA concentration was measured in 37 patients with BMS (mean disease duration 22.3 years) and 17 patients with early RRMS (mean disease duration 4.0 years), using an unlocalized 1H-MRS sequence. Dual echo and T1-weighted scans were also obtained to measure T2-hyperintense lesion volume (TLV) and normalized brain volume (NBV). Results TLV was higher in BMS (mean TLV = 13.1 mL) than in early RRMS patients (mean TLV = 7.2 mL) ( P = 0.018), whereas neither NBV (mean NBV: 1491.0 mL in BMS vs 1520.3 mL in RRMS) nor WBNAA concentration (mean WBNAA: 10.5 mmol in BMS vs 11.4 mmol in RRMS) significantly differed between the two groups. In MS patients, no correlation was found between WBNAA concentration and Expanded Disability Status Scale (EDSS), TLV and NBV. Conclusions The similar WBNAA concentrations seen in BMS and early RRMS patients fit with the notion that a non-disabling long-term evolution of MS may be due, at least in part, to non-progression of pathology. Such a condition seems to be independent from MRI-visible lesions burden.
The utility of the Necessity—Concerns Framework in explaining treatment non-adherence in four chronic illness groups in Italy
Authors: Tibaldi Giuseppe , Clatworthy Jane , Torchio Elisabetta , Argentero Piergiorgio , Munizza Carmine , Horne Rob 
Published: May 2009

Objective: To translate the Beliefs about Medicines Questionnaire (BMQ) into Italian and explore the utility of the Necessity—Concerns Framework in explaining treatment non-adherence in four chronic illness groups in Italy. Methods: 449 patients with chronic illness (depression, asthma, diabetes and cardiac disease) were approached at outpatient clinics in Turin and asked to complete Italian translations of the BMQ and the Medication Adherence Report Scale. Results: 427 patients consented to participate in the study. The BMQ demonstrated good internal consistency, with Cronbach's alphas of 0.78 (Necessity subscale) and 0.72 (Concerns subscale). Participants were divided into four attitudinal groups based on their responses to the BMQ: 59% Accepting (high Necessity, low Concerns), 29% ambivalent (high Necessity, high Concerns), 8% Indifferent (low Necessity, low Concerns) and 4% Skeptical (low Necessity, high Concerns). Those in the Accepting group reported the highest adherence to medication and those in the Skeptical group the lowest (p50.01). Discussion: The BMQ has been successfully translated and validated in Italian. This study provides support for the Necessity—Concerns Framework in explaining medication non-adherence in chronic illness. Interventions that address low perceived need for treatment and concerns about potential adverse effects of treatment are likely to facilitate optimal use of medicines.
The comparison of early and late outcome of direct and conventional stenting of patients with st elevation myocardial infarction
Authors: Tacoy Gulten , Yazici Guliz Erdem , Erden Murat , Timurkaynak Timur 
Published: May 2009

Background: The aim of this study was to compare direct and conventional stenting procedure in the subacute stable phase on short- and long-term results in patients with ST elevation myocardial infarction. Methods: Eighty-eight clinically stable ST-segment elevation myocardial infarction (STEMI) patients were enrolled into the study. The patients were classified as group I (direct stenting) and group II (conventional stenting — stenting after balloon dilatation). Baseline characteristics of patients were scanned from hospital records. Coronary angiograms before and after the revascularization procedure were evaluated with the quantitative coronary angiogram technique. Patients were followed for 5 years for clinical outcomes. The study population consisted of 58 patients (65%) in group I and 30 patients (35%) in group II. Mean ages were 55.8 ± 10.8 and 57.3 ± 9.8, respectively. Results: There were no significant differences between the two groups regarding clinical characteristics (hypertension, diabetes mellitus, family history of cardiovascular disease, smoking and dyslipidemia). The thrombus score was similar in both groups. Diameter stenosis was lower in group I (54.8 ± 12.7 versus 61.4 ± 12.6; p = 0.023) and TFC (Thrombolysis in Myocardial Infarction frame count) was higher in group II (30.7 ± 14.5 versus 40.8 ± 26.7; p = 0.02) before the percutaneous coronary intervention (PCI). Other quantitative angiographic parameters were not different. For all angiographic criteria, the difference between pre- and post-PCI parameters was significantly different in both groups. However, the change in TFC was higher within the group II compared to pre-PCI TFC rates. This difference was statistically significant ( p = 0.002). Procedural success was statistically different between groups (69% in group I, 43% in group II; p50.01). Immediate clinical and angiographic results were similar. At 5-year follow-up the incidence of major adverse cardiac events including death, angina pectoris and myocardial infarction were similar for direct stenting versus conventional angioplasty. Conclusions: Direct stenting is safe and feasible for the treatment in patients with STEMI at the subacute phase. Immediate clinic, angiographic and late clinical results are similar for direct stenting and conventional stenting following balloon angioplasty. Although conventional stenting improved TFC better than direct stenting, this did not translate to better clinical outcomes.