bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-Life Factors and Breast Cancer Risk in Hispanic Women: the Role of Adolescent Body Size
Authors: Sangaramoorthy Meera , Phipps Amanda I. , Horn-Ross Pamela L. , Koo Jocelyn , John Esther M. 
Published: December 2011

AbstractBackground: Adult body size has long been known to influence breast cancer risk, and there is now increasing evidence that childhood and adolescent body size may also play a role.Methods: We assessed the association with body size at ages 10, 15, and 20 years in 475 premenopausal and 775 postmenopausal Hispanic women who participated in a population-based case–control study of breast cancer conducted from 1995 to 2004 in the San Francisco Bay Area. We used unconditional logistic regression to estimate ORs and 95% CIs for the associations with self-reported relative weight compared with peers and body build at ages 10, 15, and 20 years.Results: In premenopausal women, we found inverse associations with relative weight compared with peers, with ORs of 0.63 (Ptrend = 0.05), 0.31 (Ptrend &lt; 0.01), and 0.44 (Ptrend = 0.02) for heavier versus lighter weight at ages 10, 15, and 20 years, respectively. These inverse associations were stronger in currently overweight women and U.S.-born women and did not differ significantly for case groups defined by estrogen receptor status. In postmenopausal women, not currently using hormone therapy, inverse associations with relative weight were limited to U.S.-born Hispanics.Conclusions: Large body size at a young age may have a long-lasting influence on breast cancer risk in premenopausal, and possibly postmenopausal, Hispanic women that is independent of current body mass index.Impact: These findings need to be weighed against adverse health effects associated with early-life obesity. Cancer Epidemiol Biomarkers Prev; 20(12); 2572–82. ©2011 AACR.
Opposing Effects of Runx2 and Estradiol on Breast Cancer Cell Proliferation: In Vitro Identification of Reciprocally Regulated Gene Signature Related to Clinical Letrozole Responsiveness
Authors: Chimge Nyam-Osor , Baniwal Sanjeev K. , Luo Jingqin , Coetzee Simon , Khalid Omar , Berman Benjamin P. , Tripathy Debu , Ellis Matthew J. , Frenkel Baruch 
Published: December 2011

Abstract
Purpose: To assess the clinical significance of the interaction between estrogen and Runx2 signaling, previously shown in vitro.
Experimental Design: MCF7/Rx2dox breast cancer cells were treated with estradiol and/or doxycycline to induce Runx2, and global gene expression was profiled to define genes regulated by estradiol, Runx2, or both. Anchorage-independent growth was assessed by soft-agar colony formation assays. Expression of gene sets defined using the MCF7/Rx2dox system was analyzed in pre- and on-treatment biopsies from hormone receptor–positive patients undergoing neoadjuvant letrozole treatment in two independent studies, and short-term changes in gene expression were correlated with tumor size reduction or Ki67 index at surgery.
Results: Reflecting its oncogenic property, estradiol strongly promoted soft-agar colony formation, whereas Runx2 blocked this process suggesting tumor suppressor property. Transcriptome analysis of MCF7/Rx2dox cells treated with estradiol and/or doxycycline showed reciprocal attenuation of Runx2 and estrogen signaling. Correspondingly in breast cancer tumors, expression of estradiol- and Runx2-regulated genes was inversely correlated, and letrozole increased expression of Runx2-stimulated genes, as defined in the MCF7/Rx2dox model. Of particular interest was a gene set upregulated by estradiol and downregulated by Runx2 in vitro; its short-term response to letrozole treatment associated with tumor size reduction and Ki67 index at surgery better than other estradiol-regulated gene sets.
Conclusion: This work provides clinical evidence for the importance of antagonism between Runx2 and E2 signaling in breast cancer. Likely sensing the tension between them, letrozole responsiveness of a genomic node, positively regulated by estradiol and negatively regulated by Runx2 in vitro, best correlated with the clinical efficacy of letrozole treatment. Clin Cancer Res; 18(3); 901–11. ©2011 AACR.
Therapeutic Mechanism and Efficacy of the Antibody–Drug Conjugate BAY 79-4620 Targeting Human Carbonic Anhydrase 9
Authors: Petrul Heike M. , Schatz Christoph A. , Kopitz Charlotte C. , Adnane Lila , McCabe Timothy J. , Trail Pamela , Ha Sha , Chang Yong S. , Voznesensky Andrei , Ranges Gerald , Tamburini Paul P. 
Published: December 2011

Abstract
Carbonic anhydrase IX (CAIX) is a cell surface glycoprotein that is expressed in many different tumors and yet restricted in normal tissues to the gastrointestinal tract. It is upregulated by hypoxia and correlates with tumor grade and poor survival in several tumor indications. Monoclonal antibodies (mAb) with single digit nanomolar binding affinity for CAIX were derived by panning with the recombinant ectodomain of CAIX against the MorphoSys HUCAL Gold library of human Fabs. Highest affinity Fabs were converted to full-length IgGs and subjected to further characterization based upon their avidity and selectivity for CAIX, their capacity to undergo internalization in CAIX-expressing cell lines, and their selective localization to CAIX-positive human xenografted tumors when administered to mice as fluorescent conjugates. Through this selection process, the 3ee9 mAb was identified, which upon conjugation to monomethyl auristatin E through a self-immolative enzyme-cleavable linker yielded the potent and selective CAIX antibody–drug conjugate CAIX-ADC (BAY 79-4620). In preclinical human xenograft models in mice representing several tumor indications, BAY 79-4620 showed potent antitumor efficacy and in some models showed partial and complete tumor shrinkage even following a single dose. The mechanism of action was shown by histology to involve the sequelae of events typical of antitubulin agents. Efficacy in murine preclinical models correlated semiquantitatively, with CAIX expression levels as determined by immunohistochemistry and ELISA. These preclinical data collectively support the development of BAY 79-4620 for the treatment of cancer patients with CAIX overexpressing tumors. Mol Cancer Ther; 11(2); 340–9. ©2011 AACR.
Apolipoprotein B Secretion Is Regulated by Hepatic Triglyceride, and Not Insulin, in a Model of Increased Hepatic Insulin Signaling
Authors: Moon Byoung C. , Hernandez-Ono Antonio , Stiles Bangyan , Wu Hong , Ginsberg Henry N. 
Published: December 2011

Objective—

States of insulin resistance, hyperinsulinemia, and hepatic steatosis are associated with increased secretion of triglycerides (TG) and apolipoprotein B (apoB), even though insulin targets apoB for degradation. We used hepatic-specific “phosphatase and tensin homologue deleted on chromosome 10” (
Pten
) knockout (h
Pten
-ko) mice, with increased hepatic insulin signaling, to determine the relative roles of insulin signaling and hepatic TG in regulating apoB secretion.

Methods and Results—

TG and apoB secretion was elevated in h
Pten
-ko mice. When hepatic TG was reduced by inhibition of diacylglycerol acyltransferase 1/diacylglycerol acyltransferase 2 or sterol regulatory element-binding protein-1c, both TG secretion and apoB secretion fell without changes in hepatic insulin signaling. Acute reconstitution of h
Pten
reduced hepatic TG content, and both TG and apoB secretion fell within 4 days despite decreased hepatic insulin signaling. Acute depletion of hepatic
Pten
by adenoviral introduction of Cre into
Pten
floxed mice caused steatosis within 4 days, and secretion of both TG and apoB increased despite increased hepatic insulin signaling. Even when steatosis after acute Pten depletion was prevented by pretreatment with SREBP-1c antisense oligonucleotides, apoB secretion was not reduced after 4 days. Ex vivo results were in primary hepatocytes were similar.

Conclusion—
Either hepatic TG is the dominant regulator of apoB secretion or any inhibitory effects of hepatic insulin signaling on apoB secretion is very short-lived.
Investigating the Role of the Coronary Vasculature in the Mechanisms of Defibrillation
Authors: Bishop Martin J. , Plank Gernot , Vigmond Edward 
Published: December 2011

Background—
The direct role of coronary vessels in defibrillation, although hypothesized to be important, remains to be elucidated. We investigated how vessel-induced virtual electrode polarizations assist reentry termination.

Methods and Results—
A highly anatomically detailed rabbit ventricular slice bidomain computer model was constructed from 25-μm magnetic resonance data, faithfully representing both structural and electric properties of blood vessels. For comparison, an equivalent simplified model with intramural cavities filled in was also built. Following fibrillation induction, 6 initial states were selected, and biphasic shocks (5–70 V) were applied using a realistic implanted cardioverter-defibrillator electrode configuration. A fundamental mechanism of biphasic defibrillation was uncovered in both models, involving successive break excitations (after each shock phase) emanating from opposing myocardial surfaces (in septum and left ventricle), which rapidly closed down excitable gaps. The presence of vessels accelerated this process, achieving more-rapid and successful defibrillation. Defibrillation failed in 5 cases (all because of initiation of new activity) compared with 8 with the simplified model (5/8 failures because of surviving activity). At stronger shocks, virtual electrodes formed around vessels, rapidly activating intramural tissue because of break excitations, assisting the main defibrillation mechanism, and eliminating all activity <15 ms of shock end in 60% of successful shocks (36% in simplified model). Subsequent analysis identified that only vessels >200 μm in diameter participated through this mechanism. Consequently, wavefronts could survive intramurally in the simplified model, leading to reentry and shock failure.

Conclusions—
We provide new insight into defibrillation mechanisms by showing how intramural blood vessels facilitate more-effective elimination of existing wavefronts, rapid closing down of excitable gaps, and successful defibrillation and give guidance toward the required resolution of cardiac imaging and model generation endeavors for mechanistic defibrillation analysis.
Estimating and Reporting on the Quality of Inpatient Stroke Care by Veterans Health Administration Medical Centers
Authors: Arling Greg , Reeves Mathew , Ross Joseph , Williams Linda S. , Keyhani Salomeh , Chumbler Neale , Phipps Michael S. , Roumie Christianne , Myers Laura J. , Salanitro Amanda H. , Ordin Diana L. , Myers Jennifer , Bravata Dawn M. 
Published: December 2011

Background—
Reporting of quality indicators (QIs) in Veterans Health Administration Medical Centers is complicated by estimation error caused by small numbers of eligible patients per facility. We applied multilevel modeling and empirical Bayes (EB) estimation in addressing this issue in performance reporting of stroke care quality in the Medical Centers.

Methods and Results—
We studied a retrospective cohort of 3812 veterans admitted to 106 Medical Centers with ischemic stroke during fiscal year 2007. The median number of study patients per facility was 34 (range, 12–105). Inpatient stroke care quality was measured with 13 evidence-based QIs. Eligible patients could either pass or fail each indicator. Multilevel modeling of a patient's pass/fail on individual QIs was used to produce facility-level EB-estimated QI pass rates and confidence intervals. The EB estimation reduced interfacility variation in QI rates. Small facilities and those with exceptionally high or low rates were most affected. We recommended 8 of the 13 QIs for performance reporting: dysphagia screening, National Institutes of Health Stroke Scale documentation, early ambulation, fall risk assessment, pressure ulcer risk assessment, Functional Independence Measure documentation, lipid management, and deep vein thrombosis prophylaxis. These QIs displayed sufficient variation across facilities, had room for improvement, and identified sites with performance that was significantly above or below the population average. The remaining 5 QIs were not recommended because of too few eligible patients or high pass rates with little variation.

Conclusions—
Considerations of statistical uncertainty should inform the choice of QIs and their application to performance reporting.
Clopidogrel Use and Early Outcomes Among Older Patients Receiving a Drug-Eluting Coronary Artery Stent
Authors: Roth Gregory A. , Morden Nancy E. , Zhou Weiping , Malenka David J. , Skinner Jonathan 
Published: December 2011

Background—
Clopidogrel use after drug-eluting stent (DES) coronary artery implantation is essential for the prevention of early in-stent thrombosis, but clopidogrel use among older DES recipients has not been widely studied. We sought to identify characteristics associated with failure to fill a clopidogrel prescription and to examine the relationship between a clopidogrel prescription fill and hospitalization for acute myocardial infarction (AMI) or death.

Methods and Results—
This study was a retrospective analysis of administrative data (20% sample) of 15 996 Medicare Part D enrollees who received a DES in 2006 to 2007. We modeled the adjusted probability and odds of clopidogrel prescription fill within 7 and 90 days of discharge and its association with AMI hospitalization or death. Of the study sample, 19.7% did not fill a clopidogrel prescription within 7 days of discharge, falling to 13.3% by day 90. The adjusted probability of filling a clopidogrel prescription within 7 or 90 days of discharge was lower for patients with dementia (20.2% less likely; 95% CI, 10.4%–30.1%), depression (10.7% less likely; 95% CI, 6.9%–14.5%), age >84 years compared to age 65 to 69 years (10.6% less likely; 95% CI, 8.6%–12.7%), black race (6.6% less likely; 95% CI, 4.2%–9.0%), intermediate levels of medication cost share (5.2% less likely; 95% CI, 2.9%–7.6%), and female sex (3.3% less likely; 95% CI, 2.1%–4.5%). It was higher for patients initially hospitalized for an AMI (12.5% more likely; 95% CI, 11.3%–13.6%). Failure to fill a clopidogrel prescription within 7 days of discharge was associated with a higher adjusted odds ratio of death during days 8 to 90 (2.44; 95% CI, 1.76–3.38) but was not associated with an increased risk of hospitalization for AMI.

Conclusions—
One in 5 patients failed to fill a prescription for clopidogrel at 7 days after DES placement, and 1 in 7 failed to do so by 3 months. Individual characteristics available at the time of hospital discharge were associated with a clopidogrel prescription fill. Those characteristics most strongly associated with nonadherence, including age >84 years, not having an AMI, depression, and dementia, may guide clinicians and health systems seeking to target this high-risk population and improve health outcomes after percutaneous coronary intervention.
Clinical Implications of Electrocardiographic Left Ventricular Strain and Hypertrophy in Asymptomatic Patients With Aortic Stenosis
Authors: Greve Anders M. , Boman Kurt , Gohlke-Baerwolf Christa , Kesäniemi Y. Antero , Nienaber Christoph , Ray Simon , Egstrup Kenneth , Rossebø Anne B. , Devereux Richard B. , Køber Lars , Willenheimer Ronnie , Wachtell Kristian 
Published: December 2011

Background—
The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described.

Methods and Results—

Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V
4
through V
6
) and LVH, assessed by Sokolow-Lyon voltage criteria (R
V5–6
+S
V1
≥35 mV) and Cornell voltage-duration criteria {[RaVL+S
V3
+(6 mV in women)]×QRS duration ≥2440 mV · ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3±0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4–6.8;
P
=0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0–16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3–3.1; both
P
=0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3–4.9;
P
=0.008).

Conclusions—
ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00092677.
Racial Differences in Parents’ Perceptions of Factors Important for Children to Live Well With Diabetes
Authors: Lipman Terri H. , Murphy Kathryn M. , Kumanyika Shiriki K. , Ratcliffe Sarah J. , Jawad Abbas F. , Ginsburg Kenneth R. 
Published: December 2011

Purpose The purpose of this study is to learn how to serve families with children with diabetes in a more culturally effective manner by exploring and more fully understanding differences in how white and African American families ranked factors they perceived as important to living well with diabetes. Methods This is a secondary analysis of a survey derived from qualitative and quantitative data. A total of 799 parents (84.1% white, 12.3% African American) completed the mailed survey. Respondents were asked to rate how much of a difference each of 30 survey items makes in a child and family who are living well with diabetes, which were placed in rank order by race. Items were combined into clinically relevant categories, and mean ratings for each category were calculated. Regression analyses were used to test for racial differences between items and within categories. Results The racial groups expressed many similar views; however, 2 major themes emerged reflecting racial differences in the prioritization of factors affecting the well-being of children with diabetes. First, African American families ascribed greater importance to social supports. Second, African Americans expressed a preference for interventions that target the whole family versus the individual child, whereas whites tended to prefer child-centered interventions. Conclusion There is a paucity of research on the goals and priorities of pediatric diabetes care from the perspective of parents from diverse racial backgrounds. Asking families about the type of care they prefer may help to improve the design and delivery of services in a culturally competent, effective manner.
‘The Blaydon Races’: lads and lasses, song tradition, and the evolution of an anthem
Authors: Hermeston Rod 
Published: December 2011

In this article I examine the evolution of the Tyneside song, ‘The Blaydon Races’, into a local anthem, with a focus on the contribution of the plurals lads and lasses to this status. I consider the obstacles to the dialect song becoming an anthem, in particular its origins in non-respectable 19th-century music hall. Existing scholarship on 19th-century dialect song or poetry often sees such material as enhancing solidarity at the levels of class or region (Beal, 2000; Wales, 2002, 2006). Influenced by the work of Coupland (2006) and Eckert (2005), however, I posit a more fluid conception of identity within popular entertainment spaces, which may operate alongside, contribute to, or undermine categories such as class or region. I use an electronic corpus of 19th-century Tyneside song to investigate the collocation of lads in particular with Tyneside, and its role in fostering local patriotism. I also consider the pragmatic function of lads as a term of address or apostrophe to sporting heroes in song. I then examine the terms of address lads and lasses within the already intimate context of shared music hall song choruses, recalling, nevertheless, the controversies surrounding the institution. This function of lads in the chorus of ‘The Blaydon Races’, and the cultural ‘resonance’ of references to ‘lads an’ lasses’ are seen potentially to enhance solidarity from the outset. However, increasingly with locally patriotic functions, they can enhance group bonding within evolving contexts of shared singing – within the later music hall, among troops in both World Wars, and among Newcastle United football supporters.
Gene polymorphisms of angiotensin-converting enzyme and angiotensin II Type 1 receptor among chronic kidney disease patients in a Chinese population
Authors: Su Sui-Lung , Lu Kuo-Cheng , Lin Yuh-Feng , Hsu Yu-Juei , Lee Pong-Ying , Yang Hsin-Yi , Kao Sen-Yeong 
Published: December 2011

Chronic kidney disease (CKD) is highly prevalent in Taiwan and an increasing number of patients are affected, with a high risk of progression to end-stage renal disease and huge medical expenses. It has been predicted that the presence of hypertension increases with decreasing renal function due to a decrease in sodium excretion and activation of the renin–angiotensin system (RAS). The aim of this study was to investigate the influence of genetic variants of the RAS gene on CKD. We performed a case control association study and genotyped 135 CKD patients and 270 healthy controls among Han Chinese in Taiwan. All subjects were genotyped for angiotensinogen ( AGT-M235T, T174M, A-20C), angiotensin-I converting enzyme ( ACE-A2350G) and angiotensin II type 1 receptor ( AGTR1-A1166C, C573T, C-521T) polymorphisms of RAS genes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Significant associations were observed in ACE-A2350G and AGTR1-C573T polymorphism between CKD patients and controls. In regard to ACE-A2350G, compared with the AA genotype the GG genotype protected against CKD (adjusted odds ratio [OR] = 0.34; p = 0.01). In regard to AGTR1-C573T, the CT genotype was a risk for CKD compared with the CC genotype (adjusted OR = 1.82; p = 0.03). We conclude that ACE-A2350G and AGTR1-C573T polymorphisms are likely candidate determinants of CKD.
The Treatment of Relapsed Refractory Chronic Lymphocytic Leukemia
Authors: Brown Jennifer R. 
Published: December 2011

AbstractDespite the widespread use of highly effective chemoimmunotherapy (CIT), fludarabine-refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical problem associated with poor overall survival (OS). The traditional definition, which includes those patients with no response or relapse within 6 months of fludarabine, is evolving with the recognition that even patients with longer remissions of up to several years after CIT have poor subsequent treatment response and survival. Approved therapeutic options for these patients remain limited, and the goal of therapy for physically fit patients is often to achieve adequate cytoreduction to proceed to allogeneic stem cell transplantation (alloSCT). Fortunately, several novel targeted therapeutics in clinical trials hold promise of significant benefit for this patient population. This review discusses the activity of available and novel therapeutics in fludarabine-refractory or fludarabine-resistant CLL as well as recently updated data on alloSCT in CLL.