bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in Gene and Protein Expression and the Effects of Race/Ethnicity on Breast Cancer Subtypes
Authors: Chavez-MacGregor Mariana , Liu Shuying , De Melo-Gagliato Debora , Chen Huiqin , Do Kim-Anh , Pusztai Lajos , Fraser Symmans W. , Nair Lakshmy , Hortobagyi Gabriel N. , Mills Gordon B. , Meric-Bernstam Funda , Gonzalez-Angulo Ana M. 
Published: December 2013

Abstract
Background: Differences in gene or protein expression patterns between breast cancers according to race/ethnicity and cancer subtype.
Methods: Transcriptional profiling was performed using Affymetrix HG-U133A platform in 376 patients and reverse phase protein array analysis (RPPA) was done for 177 proteins in 255 patients from a separate cohort. Unsupervised clustering was conducted, as well as supervised comparison by race and tumor subtype. Standard statistical methods, BRB-Array tools, and Ingenuity Pathways software packages were used to analyze the data.
Results: Median age was 50 years in both the cohorts. In the RPPA cohort, 54.5% of the tumors were hormone receptor–positive (HR-positive), 20.7% HER2-positive, and 24.71% triple-negative (TNBC). One hundred and forty-seven (57.6%), 47 (18.43%), and 46 (18.1%) of the patients were White, Hispanic, and Black, respectively. Unsupervised hierarchical clustering of the protein expression data showed no distinct clusters by race (P values were 0.492, 0.489, and 0.494 for the HR-positive, HER2-positive, and TNBC tumors respectively). In the gene expression cohort, 54.2% of the tumors were HR-positive, 16.5% HER2-positive, and 29.3% TNBC. Two hundred and sixteen (57.5%), 111 (29.52%), and 32 (8.52%) patients were White, Hispanic, and Black, respectively. No probe set with a false discovery rate (FDR) of &lt;0.05 showed an association with race by breast cancer subtype; similar results were obtained using pathway and gene set enrichment analysis methods.
Conclusions: We did not detect a significant variation in RNA or protein expression comparing different race/ethnicity groups of women with breast cancer.
Impact: More research on the complex network of factors that result in outcomes differences among race/ethnicities is needed. Cancer Epidemiol Biomarkers Prev; 23(2); 316–23. ©2013 AACR.
BET Bromodomain Inhibition ofMYC-Amplified Medulloblastoma
Authors: Bandopadhayay Pratiti , Bergthold Guillaume , Nguyen Brian , Schubert Simone , Gholamin Sharareh , Tang Yujie , Bolin Sara , Schumacher Steven E. , Zeid Rhamy , Masoud Sabran , Yu Furong , Vue Nujsaubnusi , Gibson William J. , Paolella Brenton R. , Mitra Siddhartha S. , Cheshier Samuel H. , Qi Jun , Liu Kun-Wei , Wechsler-Reya Robert , Weiss William A. , Swartling Fredrik J. , Kieran Mark W. , Bradner James E. , Beroukhim Rameen , Cho Yoon-Jae 
Published: December 2013

AbstractPurpose: MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma.Experimental Design: We evaluated the effects of genetic and pharmacologic inhibition of BET bromodomains on proliferation, cell cycle, and apoptosis in established and newly generated patient- and genetically engineered mouse model (GEMM)-derived medulloblastoma cell lines and xenografts that harbored amplifications of MYC or MYCN. We also assessed the effect of JQ1 on MYC expression and global MYC-associated transcriptional activity. We assessed the in vivo efficacy of JQ1 in orthotopic xenografts established in immunocompromised mice.Results: Treatment of MYC-amplified medulloblastoma cells with JQ1 decreased cell viability associated with arrest at G1 and apoptosis. We observed downregulation of MYC expression and confirmed the inhibition of MYC-associated transcriptional targets. The exogenous expression of MYC from a retroviral promoter reduced the effect of JQ1 on cell viability, suggesting that attenuated levels of MYC contribute to the functional effects of JQ1. JQ1 significantly prolonged the survival of orthotopic xenograft models of MYC-amplified medulloblastoma (P &lt; 0.001). Xenografts harvested from mice after five doses of JQ1 had reduced the expression of MYC mRNA and a reduced proliferative index.Conclusion: JQ1 suppresses MYC expression and MYC-associated transcriptional activity in medulloblastomas, resulting in an overall decrease in medulloblastoma cell viability. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYC-amplified medulloblastoma. Clin Cancer Res; 20(4); 912–25. ©2013 AACR.
Pharmacodynamic and Antineoplastic Activity of BI 836845, a Fully Human IGF Ligand-Neutralizing Antibody, and Mechanistic Rationale for Combination with Rapamycin
Authors: Friedbichler Katrin , Hofmann Marco H. , Kroez Monika , Ostermann Elinborg , Lamche Herbert R. , Koessl Christian , Borges Eric , Pollak Michael N. , Adolf Günther , Adam Paul J. 
Published: December 2013

Abstract
Insulin-like growth factor (IGF) signaling is thought to play a role in the development and progression of multiple cancer types. To date, therapeutic strategies aimed at disrupting IGF signaling have largely focused on antibodies that target the IGF-I receptor (IGF-IR). Here, we describe the pharmacologic profile of BI 836845, a fully human monoclonal antibody that utilizes an alternative approach to IGF signaling inhibition by selectively neutralizing the bioactivity of IGF ligands. Biochemical analyses of BI 836845 demonstrated high affinity to human IGF-I and IGF-II, resulting in effective inhibition of IGF-induced activation of both IGF-IR and IR-A in vitro. Cross-reactivity to rodent IGFs has enabled rigorous assessment of the pharmacologic activity of BI 836845 in preclinical models. Pharmacodynamic studies in rats showed potent reduction of serum IGF bioactivity in the absence of metabolic adverse effects, leading to growth inhibition as evidenced by reduced body weight gain and tail length. Moreover, BI 836845 reduced the proliferation of human cell lines derived from different cancer types and enhanced the antitumor efficacy of rapamycin by blocking a rapamycin-induced increase in upstream signaling in vitro as well as in human tumor xenograft models in nude mice. Our data suggest that BI 836845 represents a potentially more effective and tolerable approach to the inhibition of IGF signaling compared with agents that target the IGF-I receptor directly, with potential for rational combinations with other targeted agents in clinical studies. Mol Cancer Ther; 13(2); 399–409. ©2013 AACR.
ROS1 and ALK Fusions in Colorectal Cancer, with Evidence of Intratumoral Heterogeneity for Molecular Drivers
Authors: Aisner Dara L. , Nguyen Teresa T. , Paskulin Diego D. , Le Anh T. , Haney Jerry , Schulte Nathan , Chionh Fiona , Hardingham Jenny , Mariadason John , Tebbutt Niall , Doebele Robert C. , Weickhardt Andrew J. , Varella-Garcia Marileila 
Published: December 2013

Abstract
Activated anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinases, through gene fusions, have been found in lung adenocarcinomas and are highly sensitive to selective kinase inhibitors. This study aimed at identifying the presence of these rearrangements in human colorectal adenocarcinoma specimens using a 4-target, 4-color break-apart FISH assay to simultaneously determine the genomic status of ALK and ROS1. Among the clinical colorectal cancer specimens analyzed, rearrangement-positive cases for both ALK and ROS1 were observed. The fusion partner for ALK was identified as EML4 and the fusion partner for one of the ROS1-positive cases was SLC34A2, the partner for the other ROS1-positive case remains to be identified. A small fraction of specimens presented duplicated or clustered copies of native ALK and ROS1. In addition, rearrangements were detected in samples that also harbored KRAS and BRAF mutations in two of the three cases. Interestingly, the ALK-positive specimen displayed marked intratumoral heterogeneity and rearrangement was also identified in regions of high-grade dysplasia. Despite the additional oncogenic events and tumor heterogeneity observed, elucidation of the first cases of ROS1 rearrangements and confirmation of ALK rearrangements support further evaluation of these genomic fusions as potential therapeutic targets in colorectal cancer.
Implications: ROS1 and ALK fusions occur in colorectal cancer and may have substantial impact in therapy selection. Mol Cancer Res; 12(1); 111–8. ©2013 AACR.
Anmerkungen zu einigen Papyruskommentaren zu Pindar
Authors: Benelli Luca 
Published: December 2013

Abstract
This article will discuss, in two separate parts, two different ancient commentaries on Pindar. The first, P. Berol. 13875, may be an abbreviated version of an original commentary of Didymos: the words πελε- / κυφ̣[ό]ρ̣αν ἵππον (P. Berol. 13875 ll. 9-10 = Pi. Fr. Dub. 339a M.) represent a fragment of Simonides, not of Pindar. The source of Schol. in Pi. N. 4.3/5 may be an abbreviated version of Theon’s commentary on Pindar. In the second part of the article, some passages of the P. Oxy. 2451 A Fr. 2, the second commentary, will be discussed. Pi. I. 3 and 4 are two different victory odes. Thematic similarities or repetitions of individual words between the end of a poem and beginning of the following poem can also be found in the corpus of other lyric poets, especially in Sappho. Only with the order of the manuscripts do the similarities and repetitions between the end of Pi. I. 3 and the beginning of Pi. I. 4 become clear: this may have been the intention of the original Alexandrian editors.
Evaluation of AIRS Cloud-Thermodynamic-Phase Determination with CALIPSO
Authors: Jin Hongchun , Nasiri Shaima L. 
Published: December 2013

AbstractAtmospheric Infrared Sounder (AIRS) infrared-based cloud-thermodynamic-phase retrievals are evaluated using the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) cloud thermodynamic phase. The AIRS cloud phase is derived from spectral information contained within the 8–12-μm window, and CALIPSO provides coincident pixel-scale observations of cloud phase using the depolarization capability of the 532-nm channel. Comparisons are performed between the AIRS and CALIPSO cloud-phase observations for single-layer (48.5% of all clouds), heterogeneous-layer (45.9%), and multilayered (5.6%) clouds. The AIRS ice phase is in agreement with CALIPSO for more than 90% of coincident observations globally, with the largest discrepancies found in high latitudes and multilayered clouds. AIRS water phase generally follows CALIPSO spatial patterns, but the frequency is lower by about a factor of 2. The ice and water phases of AIRS both show misclassifications about 1% of the time when compared with CALIPSO. Not all clouds demonstrate strong phase signatures in the AIRS spectrum, which leads AIRS to classify unknown phase to around 10% of CALIPSO’s ice clouds and 60% of CALIPSO’s water clouds. This study shows that the algorithm is capable of detecting ice clouds within the AIRS field of view and can be used as the first step in further retrievals of ice-cloud optical thickness and effective particle size.
Generalized Split-Explicit Runge–Kutta Methods for the Compressible Euler Equations
Authors: Knoth Oswald , Wensch Joerg 
Published: December 2013

Abstract
The compressible Euler equations exhibit wave phenomena on different scales. A suitable spatial discretization results in partitioned ordinary differential equations where fast and slow modes are present. Generalized split-explicit methods for the time integration of these problems are presented. The methods combine explicit Runge–Kutta methods for the slow modes and with a free choice integrator for the fast modes. Order conditions for these methods are discussed.
Construction principles to develop methods with enlarged stability area are presented. Among the generalized class several new methods are developed and compared to the well-established three-stage low-storage Runge–Kutta method (RK3). The new methods allow a 4 times larger macro step size. They require a smaller integration interval for the fast modes. Further, these methods satisfy the order conditions for order three even for nonlinear equations. Numerical tests on more complex problems than the model equation confirm the enhanced stability properties of these methods.
Primary care physicians’ and psychiatrists’ willingness to refer to religious mental health providers
Authors: Lawrence Ryan E , Rasinski Kenneth A , Yoon John D , Curlin Farr A 
Published: December 2013

Background: Recent decades have witnessed some integration of mental health care and religious resources. Aim: We measured primary care physicians’ (PCPs) and psychiatrists’ knowledge of religious mental health-care providers, and their willingness to refer there. Methods: A national survey of PCPs and psychiatrists was conducted, using vignettes of depressed and anxious patients. Vignettes included Christian or Jewish patients, who regularly or rarely attended services. We asked whether physicians knew of local religious mental health providers, and whether they would refer patients there. Results: In all, 896/1427 PCPs and 312/487 psychiatrists responded. Half of PCPs (34.1%–44.1%) and psychiatrists (51.4%–56.3%) knew Christian providers; fewer PCPs (8.5%–9.9%) and psychiatrists (15.8%–19.6%) knew Jewish providers. Predictors included the following: patients were Christian (odds ratio (OR) = 2.2–2.9 for PCPs, 2.3–2.4 for psychiatrists), respondents were Christian (OR = 2.1–9.3 for PCPs) and respondents frequently attend services (OR = 3.5–7.0 for PCPs). Two-thirds of PCPs (63.3%–64%) and psychiatrists (48.8%–52.6%) would refer to religious providers. Predictors included the following: patients regularly attend services OR = 1.2 for PCPs, 1.6 for Psychiatrists, depression vignette only), respondents were Christian (OR = 2.8–18.1 for PCPs, 2.3–9.2 for psychiatrists) and respondents frequently attend services (OR = 5.1–6.3 for PCPs). Conclusion: Many physicians would refer patients to religious mental health providers. However, less religious PCPs are less knowledgeable about local religious providers.
Central site monitoring: Results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection
Authors: Lindblad Anne S , Manukyan Zorayr , Purohit-Sheth Tejashri , Gensler Gary , Okwesili Paul , Meeker-O’Connell Ann , Ball Leslie , Marler John R 
Published: December 2013

Background Site monitoring and source document verification account for 15%‒30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. Purpose To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. Methods An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA’s Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as ‘High Concern’, ‘Moderate Concern’, ‘Mild Concern’, or ‘No Concern’. Results The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were identified during inspection. Of the six sites for which OSI reviewed inspections and found no deviations, the central process flagged four at the lowest level of concern, one at a moderate level, and one was not flagged. Limitations Central data monitoring during the conduct of a trial while data checking was in progress was not evaluated. Conclusion Systematic central monitoring of clinical trial data can identify problems at the same trials and sites identified during FDA site inspections. Central data monitoring in conjunction with an overall monitoring process that adapts to identify risks as a trial progresses has the potential to reduce the frequency of site visits while increasing data integrity and decreasing trial costs compared to processes that are dependent primarily on source documentation.
Are the pituitary gonadotrophins determinants of complete molar pregnancy? An investigation using the method of least squares
Authors: Graham Iain H 
Published: December 2013

Objective To look for a relationship between the maternal age-specific incidence of complete molar pregnancy and the age-specific mid-follicular levels of circulating follicle stimulating hormone and luteinizing hormone. Design Calculation of correlation coefficients between the incidence of complete mole and the circulating levels of follicle stimulating hormone and luteinizing hormone using the method of least squares. Setting England and Wales. Participants All mothers between 23 and 49 years delivering in England and Wales between 2000 and 2009 inclusive and a sample of women between 23 and 49 years from Sheffield (1987). Main outcome measures The bivariate correlation coefficients between the incidence of complete mole and the mid-follicular plasma levels of the pituitary gonadotrophins. Results Exponential correlation between the incidence of complete mole and mid-follicular plasma follicle stimulating hormone, r = 0.965, r2 = 0.932. Linear correlation between the incidence of complete mole and mid-follicular plasma luteinizing hormone, r = 0.972, r2 = 0.944. Multivariate exponential regression between the incidence of complete mole and the combination of follicle stimulating and luteinizing hormones. This does not improve the prediction of the incidence of complete mole and it shows that luteinizing hormone is not a significant predictor of the incidence of complete mole in the presence of follicle stimulating hormone. Conclusions There is a strong positive exponential correlation between the maternal age-specific incidence of complete mole in England and Wales and the age-related mid-follicular levels of follicle stimulating hormone in a sample of English women.
Activated mouse eosinophils protect against lethal respiratory virus infection
Authors: Percopo Caroline M. , Dyer Kimberly D. , Ochkur Sergei I. , Luo Janice L. , Fischer Elizabeth R. , Lee James J. , Lee Nancy A. , Domachowske Joseph B. , Rosenberg Helene F. 
Published: December 2013

Key PointsEosinophils recruited to the airways in response to A fumigatus sensitization and challenge degranulate in response to virus infection. Activated eosinophils are antiviral and promote survival from an otherwise lethal respiratory virus infection.
A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites
Authors: Haque Jamil A. , McDonald Matthew G. , Kulman John D. , Rettie Allan E. 
Published: December 2013

Key PointsFactor IX glutamyl carboxylation in engineered HEK 293 cells recapitulates in vivo anticoagulant inhibition of vitamin K cycle activity. Warfarin metabolite structure-activity analysis on vitamin K cycle antagonism determines their contributions to in vivo anticoagulation.
Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK–positive anaplastic large-cell lymphoma
Authors: Damm-Welk Christine , Mussolin Lara , Zimmermann Martin , Pillon Marta , Klapper Wolfram , Oschlies Ilske , d’Amore Emanuele S. G. , Reiter Alfred , Woessmann Wilhelm , Rosolen Angelo 
Published: December 2013

Key PointsEarly MRD positivity in NPM-ALK–positive ALCL correlates with a very high relapse risk and inferior survival.
Generation of a human airway epithelium derived basal cell line with multipotent differentiation capacity
Authors: Walters Matthew S , Gomi Kazunori , Ashbridge Beth , Moore Malcolm A S , Arbelaez Vanessa , Heldrich Jonna , Ding Bi-Sen , Rafii Shahin , Staudt Michelle R , Crystal Ronald G 
Published: December 2013

AbstractBackgroundAs the multipotent progenitor population of the airway epithelium, human airway basal cells (BC) replenish the specialized differentiated cell populations of the mucociliated airway epithelium during physiological turnover and repair. Cultured primary BC divide a limited number of times before entering a state of replicative senescence, preventing the establishment of long-term replicating cultures of airway BC that maintain their original phenotype.MethodsTo generate an immortalized human airway BC cell line, primary human airway BC obtained by brushing the airway epithelium of healthy nonsmokers were infected with a retrovirus expressing human telomerase (hTERT). The resulting immortalized cell line was then characterized under non-differentiating and differentiating air-liquid interface (ALI) culture conditions using ELISA, TaqMan quantitative PCR, Western analysis, and immunofluorescent and immunohistochemical staining analysis for cell type specific markers. In addition, the ability of the cell line to respond to environmental stimuli under differentiating ALI culture was assessed.ResultsWe successfully generated an immortalized human airway BC cell line termed BCi-NS1 via expression of hTERT. A single cell derived clone from the parental BCi-NS1 cells, BCi-NS1.1, retains characteristics of the original primary cells for over 40 passages and demonstrates a multipotent differentiation capacity into secretory (MUC5AC, MUC5B), goblet (TFF3), Clara (CC10) and ciliated (DNAI1, FOXJ1) cells on ALI culture. The cells can respond to external stimuli such as IL-13, resulting in alteration of the normal differentiation process.ConclusionDevelopment of immortalized human airway BC that retain multipotent differentiation capacity over long-term culture should be useful in understanding the biology of BC, the response of BC to environmental stress, and as a target for assessment of pharmacologic agents.