bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commercialized Multigene Predictors of Clinical Outcome for Breast Cancer
Authors: Ross Jeffrey S. , Hatzis Christos , Symmans W. Fraser , Pusztai Lajos , Hortobágyi Gabriel N. 
Published: May 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Assess the strengths and weaknesses of the four main techniques used to measure multiple gene expression using clinical breast cancer specimens.Compare the advantages and disadvantages of the oncotype DX™ and MammaPrint® multigene assays and compare the TAILORx and MINDACT clinical trials for the prediction of clinical outcome in breast cancer.Evaluate the costs versus benefits associated with the use of expensive multigene breast cancer predictors in the management of breast cancer.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
In the past 5 years, a number of commercialized multigene prognostic and predictive tests have entered the complex and expanding landscape of breast cancer companion diagnostics. These tests have used a variety of formats ranging from the familiar slide-based assays of immunohistochemistry and fluorescence in situ hybridization to the nonmorphology-driven molecular platforms of quantitative multiplex real-time polymerase chain reaction and genomic microarray profiling. In this review, 14 multigene assays are evaluated as to their scientific validation, current clinical utility, regulatory approval status, and estimated cost–benefit ratio. Emphasis is placed on two tests: oncotype DX™ and MammaPrint®. Current evidence indicates that the oncotype DX™ test has the advantages of earlier commercial launch, wide acceptance for payment by third-party payors in the U.S., ease of use of formalin-fixed paraffin-embedded tissues, recent listing by the American Society of Clinical Oncology Breast Cancer Tumor Markers Update Committee as recommended for use, continuous scoring system algorithm, ability to serve as both a prognostic test and predictive test for certain hormonal and chemotherapeutic agents, demonstrated cost-effectiveness in one published study, and a high accrual rate for the prospective validation clinical trial (Trial Assigning Individualized Options for Treatment). The MammaPrint® assay has the advantages of a 510(k) clearance by the U.S. Food and Drug Administration, a larger gene number, which may enhance further utility, and a potentially wider patient eligibility, including lymph node–positive, estrogen receptor (ER)-negative, and younger patients being accrued into the prospective trial (Microarray in Node-Negative Disease May Avoid Chemotherapy). A number of other assays have specific predictive goals that are most often focused on the efficacy of tamoxifen in ER-positive patients, such as the two-gene ratio test and the cytochrome P450 CYP2D6 genotyping assay.
Relation Between the Level of American Indian and Alaska Native Diabetes Education Program Services and Quality-of-Care Indicators
Authors: Roubideaux Yvette , Noonan Carolyn , Goldberg Jack H. , Valdez S. Lorraine , Brown Tammy L. , Manson Spero M. , Acton Kelly 
Published: May 2008

Objectives. We examined the relation between the level of diabetes education program services in the Indian Health Service (IHS) and indicators of the quality of diabetes care to determine if more-comprehensive diabetes services were associated with better quality of diabetes care.Methods. In this cross-sectional study, we used the IHS Integrated Diabetes Education Recognition Program to rank program services into 1 of 3 levels of comprehensiveness, ranging from lowest (developmental) to highest (integrated). We compared quality-of-care indicators among programs of differing levels with the 2001 IHS Diabetes Care and Outcomes Audit. Quality indicators included patients having recommended yearly examinations, education, and laboratory tests and achieving recommended levels of intermediate outcomes of care.Results. Most of the 86 participating programs were classified at or below the developmental level; only 9 programs (11%) were ranked at higher levels. After adjusting for patient characteristics, program factors, and correlation of patients within programs, we associated programs that were more comprehensive with higher completion rates of yearly lipid and hemoglobin A1C tests (P < .05).Conclusions. System-wide improvements in diabetes education are associated with better diabetes care. The results can help inform the development of diabetes education programs.
Perceived Discrimination and Mortality in a Population-Based Study of Older Adults
Authors: Barnes Lisa L. , de Leon Carlos F. Mendes , Lewis Tené T. , Bienias Julia L. , Wilson Robert S. , Evans Denis A. 
Published: May 2008

Objectives. We examined the relation of individual-level perceived discrimination to mortality in a biracial, population-based sample. Methods. Participants were 4154 older adults from the Chicago Health and Aging Project who underwent up to 2 interviews over 4.5 years. Perceived discrimination was measured at baseline, and vital status was obtained at each follow-up and verified through the National Death Index. Results. During follow-up, 1166 deaths occurred. Participants reporting more perceived discrimination had a higher relative risk of death (hazard ratio [HR]= 1.05; 95% confidence interval [CI]=1.01, 1.09). This association was independent of differences in negative affect or chronic illness and appeared to be stronger among Whites than among Blacks (Whites: HR=1.12; 95% CI=1.04, 1.20; Blacks: HR=1.03; 95% CI=0.99, 1.07). Secondary analyses revealed that the relation to mortality was related to discriminatory experiences of a more demeaning nature and that racial differences were no longer significant when the sample was restricted to respondents interviewed by someone of the same race. Conclusions. Perceived discrimination was associated with increased mortality risk in a general population of older adults. The results suggest that subjective experience of interpersonal mistreatment is toxic in old age. This study adds to a growing literature documenting discrimination as an important social determinant of health.
Gender and Race/Ethnicity Differences in Lead Dose Biomarkers
Authors: Theppeang Keson , Glass Thomas A. , Bandeen-Roche Karen , Todd Andrew C. , Rohde Charles A. , Schwartz Brian S. 
Published: May 2008

Objectives. We sought to identify predictors of lead concentrations in the blood, tibias, and patellae of older adults and to describe differences by gender, race/ethnicity, and other factors that can influence lead toxicokinetics and, thus modify health effects. Methods. Participants aged 50 to 70 years (N=1140) were randomly identified from selected neighborhoods in Baltimore, Maryland. We measured lead concentrations by anodic stripping voltammetry (in blood) and 109Cd-induced K-shell x-ray fluorescence (in bone). We used multiple linear regression to identify predictors of lead concentrations. Results. Mean (SD) lead concentrations in blood, tibias, and patellae were 3.5 (2.4) μg/dL, 18.9 (12.5) μg/g, and 6.8 (18.1) μg/g, respectively. Tibia concentrations were 29% higher in African Americans than in Whites (P < .01). We observed effect modification by race/ethnicity on the association of gender and physical activity to blood lead concentrations and by gender on the association of age to tibia lead concentrations. Patella lead concentrations differed by gender; apolipoprotein E genotype modified this relation. Conclusions. African Americans evidenced a prominent disparity in lifetime lead dose. Women may be at higher risk of release of lead from bone and consequent health effects because of increased bone demineralization with aging.
Temporal Trends in Self-Reported Functional Limitations and Physical Disability Among the Community-Dwelling Elderly Population: The Framingham Heart Study
Authors: Murabito Joanne M. , Pencina Michael J. , Zhu Lei , Kelly-Hayes Margaret , Shrader Peter , D’Agostino Ralph B. 
Published: May 2008

Objectives. We sought to determine change in the prevalence of functional limitations and physical disability among the community-dwelling elderly population across 3 decades. Methods. We studied original participants of the Framingham Heart Study, aged 79 to 88 years, at examination 15 (1977–1979; 177 women, 103 men), examination 20 (1988–1990; 159 women, 98 men) and examination 25 (1997–1999; 174 women, 119 men). Self-reported functional limitation was defined using the Nagi scale, and physical disability was defined using the Rosow-Breslau and Katz scales. Results. Functional limitations declined across examinations from 74.6% to 60.5% to 37.9% (P < .001) among women and from 54.2% to 37.8% to 27.8% (P<.001) among men. Physical disability declined from 74.5% to 48.5% to 34.6% (P < .001) among women and 42.3% to 33.3% to 22.8% (P = .009) among men. Among women, improvements in functional limitations (P = .05) were greater from examination 20 to 25, whereas for physical disability (P=.02), improvements were greater from examination 15 to 20. Improvements in function were constant across the 3 examinations in men. Conclusions. Among community-dwelling elders, the prevalence of functional limitations and physical disability declined significantly in both women and men from the 1970s to the 1990s. This may in part be due to improvements in technological devices used to maintain independence. Further work is needed to identify the underlining causes of the decline so preventative measures can be established that promote independence for the elderly population.
Differential Roles of Cardiomyocyte and Macrophage Peroxisome Proliferator–Activated Receptor γ in Cardiac Fibrosis
Authors: Caglayan Evren , Stauber Bradley , Collins Alan R. , Lyon Christopher J. , Yin Fen , Liu Joey , Rosenkranz Stephan , Erdmann Erland , Peterson Leif E. , Ross Robert S. , Tangirala Rajendra K. , Hsueh Willa A. 
Published: May 2008

OBJECTIVE—Cardiac fibrosis is an important component of diabetic cardiomyopathy. Peroxisome proliferator–activated receptor γ (PPARγ) ligands repress proinflammatory gene expression, including that of osteopontin, a known contributor to the development of myocardial fibrosis. We thus investigated the hypothesis that PPARγ ligands could attenuate cardiac fibrosis.
RESEARCH DESIGN AND METHODS—Wild-type cardiomyocyte- and macrophage-specific PPARγ−/− mice were infused with angiotensin II (AngII) to promote cardiac fibrosis and treated with the PPARγ ligand pioglitazone to determine the roles of cardiomyocyte and macrophage PPARγ in cardiac fibrosis.
RESULTS—Cardiomyocyte-specific PPARγ−/− mice (cPPARγ−/−) developed spontaneous cardiac hypertrophy with increased ventricular osteopontin expression and macrophage content, which were exacerbated by AngII infusion. Pioglitazone attenuated AngII-induced fibrosis, macrophage accumulation, and osteopontin expression in both wild-type and cPPARγ−/− mice but induced hypertrophy in a PPARγ-dependent manner. We pursued two mechanisms to explain the antifibrotic cardiomyocyte-PPARγ–independent effects of pioglitazone: increased adiponectin expression and attenuation of proinflammatory macrophage activity. Adenovirus-expressed adiponectin had no effect on cardiac fibrosis and the PPARγ ligand pioglitazone did not attenuate AngII-induced cardiac fibrosis, osteopontin expression, or macrophage accumulation in monocyte-specific PPARγ−/− mice.
CONCLUSIONS—We arrived at the following conclusions: 1) both cardiomyocyte-specific PPARγ deficiency and activation promote cardiac hypertrophy, 2) both cardiomyocyte and monocyte PPARγ regulate cardiac macrophage infiltration, 3) inflammation is a key mediator of AngII-induced cardiac fibrosis, 4) macrophage PPARγ activation prevents myocardial macrophage accumulation, and 5) PPARγ ligands attenuate AngII-induced cardiac fibrosis by inhibiting myocardial macrophage infiltration. These observations have important implications for potential interventions to prevent cardiac fibrosis.
X-ray photoelectron spectroscopy and magnetism of Mn1−x
Alx alloys
Authors: Rednic Vasile , Rednic Lidia , Coldea Marin , Pop Viorel , Neumann Manfred , Pacurariu Roxana , Tunyagi Arthur 
Published: May 2008

Abstract
X-ray photoelectron spectroscopy (XPS), magnetization and magnetic susceptibility of Mn1−x
Alx (x = 0.0, 0.2, 0.4, 0.5, 0.6, 0.7) alloys are reported. X-ray diffraction measurements showed that all investigated samples have the same crystallographic structure as the parent compound (AuCu3-structure type). The alloys are disordered for x ≤ 0.5, but become almost crystallographically ordered for higher Al concentration. This change in the crystallographic order is reflected both in the magnetization and Curie temperature values. The exchange interaction is ferromagnetic between the pairs of the near-neighbour Mn-Ni and Ni-Ni magnetic moments and antiferromagnetic for Mn-Mn pairs. The last one is present only in the disordered alloys, which leads to smaller values of the magnetization of these alloys in comparison with the ordered ones. The Mn magnetic moment has the fully ordered value of 3.2 μB in all investigated alloys. The decrease of the Ni magnetic moment as the Al concentration increases may be explained by the hybridization of the Ni 3d and Al 3sp states, which leads to a partial filling of the Ni 3d band. The magnetic susceptibility measurements pointed out the existence of spin fluctuations on Ni sites.
Effect of L-carnitine against acute mitoxantrone toxicity in mice
Authors: Niang Mohamed , Tomšík Pavel , Mělka Milan , Stoklasová Alena , Cerman Jaroslav , Šišpera Ludìk 
Published: May 2008

Abstract
Various experiments were performed in our laboratory to define a possible role for carnitine derivatives in mitoxantrone (MX) therapy. We report here the results of the effect of L-carnitine (LCAR) on the lethal toxicity of MX in mice. MX was administered intravenously at doses of 7, 9, 11, 13, 15 or 17 mg kg−1 either alone or in combination with LCAR at a single intravenous dose of 200 mg kg−1. The dependence of the probability of death on various doses was evaluated for the MX-LCAR combination compared to MX alone. From these experiments, the following lethal dose fifty (LD50) values were calculated: LD50 for MX alone was 15.2 mg kg−1, whereas in combination with LCAR it increases to 21.8 mg kg−1. The relative toxicity given as the ratio of the LD50 of both MX alone and the combination of MX-LCAR was 69.7%. The results of our experiments unequivocally show the effect of LCAR on acute toxic doses of MX.
Temperament, ADHD and peer relations among schoolchildren: the mediating role of school bullying
Authors: Bacchini Dario , Affuso Gaetana , Trotta Teresa 
Published: May 2008

AbstractThe goal of the study is to investigate the link between temperament, attention‐deficit hyperactivity disorder (ADHD) symptoms, social preference, bullying and victimization. The study sample consisted of 195 children attending the fourth and fifth grade (age 8–10), their mothers and their teachers. A multiinformant approach was used: mothers were interviewed about the temperament of their children; teachers were asked about ADHD symptoms; children responded to a peer nominations inventory designed to investigate their roles as bullies and/or victims and their social preferences (liked and disliked peers). A Structural Equation Model multigroup analysis (males and females) was used to test the relationships among variables hypothesized by the authors. The analysis showed that temperamental variables have a direct relation to ADHD symptoms, that ADHD has a direct relation to bullying behavior in males and to victimization in females and that bullies and victims are less well accepted than peers who belong to neither category. ADHD has only an indirect relation to social preference through the mediating role of school bullying. Aggr. Behav. 34:447–459, 2008. © 2008 Wiley‐Liss, Inc.
Natural and anthropogenic determinants of genetic structure in the largest remaining population of the endangered golden‐brown mouse lemur, Microcebus ravelobensis
Authors: Radespiel Ute , Rakotondravony Romule , Chikhi Lounès 
Published: May 2008

AbstractGenetic differentiation between natural populations is best understood as a result of both natural and anthropogenic factors. Genetic studies on large populations still living under relatively undisturbed conditions are extremely valuable to disentangle these influences. The effect of three natural (geographic distance, landscape, dispersal) factors and two anthropogenic factors (road, savannah) on gene flow was analyzed in the largest remaining forest region in the range of the endangered golden‐brown mouse lemur in Madagascar. A total of 187 individuals from 12 sites were sampled and genotyped at eight polymorphic microsatellite loci. All sites exhibited similar levels of genetic variation. The level of genetic differentiation was low to moderate with pairwise FST values ranging from −0.002 to 0.12, but most were significant and all sites exhibited high self‐assignment rates. A spatial autocorrelation analysis was performed at two geographic scales revealing a pattern of isolation‐by‐distance and suggesting that no clear differences exist between male and female local dispersal. Two Bayesian approaches revealed that a stretch of savannah represented a significant barrier to movement, whereas the influence of the road on gene flow was less clear. Finally, we found that landscape characteristics, in particular altitude, play a role in the functional connectivity of the sites. The study underlines the importance of studies in relatively undisturbed conditions for the interpretation of population genetics data in fragmented environments. The results are discussed in terms of their conservation relevance for forest‐dwelling animals such as most primate species. Am. J. Primatol. 70:860–870, 2008. © 2008 Wiley‐Liss, Inc.
Das Leben als ein nanoskaliges Phänomen
Authors: Mann Stephen 
Published: May 2008

AbstractDer Nanometerbereich oder Nanobereich ist mehr als nur das Verbindungsstück zwischen der molekularen und makroskopischen Welt – es ist der spezifische Bereich, in dem chemische Information erfasst, verarbeitet und übertragen wird. In diesem Aufsatz betrachten wir die lebende Zelle als ein in sich geschlossenes, selbstregulierendes, komplexes chemisches System, das seine Arbeit vornehmlich im Nanometerbereich verrichtet, und wir schlagen vor, dass genau diese Beschränkung auf die Nanoskala für die Entstehung und die Erhaltung von zellulärem Leben in seiner Minimalform entscheidend ist. Wir behandeln zentrale Aspekte von Struktur und Funktion des zellmembranären und zellinternen Stoffwechsels, die mit dem Aufbau molekularer Komponenten zu globulären Nanoobjekten (integralen Membranproteinen, Enzymen, Rezeptoren usw.) und höher geordneten Architekturen wie Mikrotubuli, Ribosomen und molekularen Motoren einhergehen. Zukünftige Entwicklungen in den Nanowissenschaften könnten die Grundlage für die Erschaffung von künstlichem Leben liefern.
Designing index of void structure and tensile properties in wet‐spun polyacrylonitrile (PAN) fiber. I. Effect of dope polymer or nonsolvent concentration
Authors: Arbab S. , Noorpanah P. , Mohammadi N. , Soleimani M. 
Published: May 2008

AbstractAn index Xη−1 with numerator calculated solely from solubility parameters and denominator measured by on‐line viscosity of the fiber precursor in coagulation medium was defined as an indicator of the fiber structure and tensile properties. The Xη−1 values of wet‐spun and wound polyacrylonitrile fibers from their dimethylformamide solutions with different polymer concentrations (series A) or nonsolvent concentrations in 10 vol % polymer solutions (series B) into water with draw ratio of one were determined and compared with the corresponding fiber structure and tensile properties. The Xη−1 value of about 0.8 × 106 s−1 led to finger‐like structure with overall fiber porosity of 82 vol %. By reducing Xη−1 through dope polymer concentration enhancement to 20 vol %, overall fiber porosity decreased to 62 vol % via substitution of some micrometer voids with dense polymer ligament. Accordingly, strong fiber modulus and elongation at break enhancement were observed due to structural defect reduction and cohesive energy density increment. On the other hand, dope nonsolvent concentration increment from 0 to 5 vol % at 10 vol % polymer concentration showed minute overall fiber porosity decrement via Xη−1 increment through micrometer void substitution with nanometer ones (nuclei). Therefore, mild fiber modulus and elongation at break improvements were detected due to defect size reduction which magnifies mechanical properties improvements. Curve fitting of the Wang's second order modulus‐porosity correlation to the as‐spun fibers modulus‐porosity data verified the solid–liquid phase separation through nuclei growth‐resistance as the main governing morphological evolution mechanism. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Ethics in the rheumatology literature: A systematic review
Authors: Caplan Liron , Hoffecker Lilian , Prochazka Allan V. 
Published: May 2008

AbstractObjectiveTo address the perception that ethical issues are underrepresented in the rheumatology literature, a systematic review was conducted using multiple databases to identify articles that addressed ethical and rheumatologic issues.MethodsA rheumatologist, research librarian, and clinician‐ethicist designed queries for 4 electronic and ethics databases, searching for articles with content that was relevant to rheumatology/rheumatic diseases and that primarily focused on ethics. Based upon the Beauchamp and Childress framework, the retrieved articles were classified according to their ethical content, and the proportions addressing each Beauchamp and Childress ethical principle were analyzed using Cochran's Q statistic. Correlations between the appearance of discussions involving each of the 4 ethical principles were determined via chi‐square analysis.ResultsThe total number of manuscripts in the rheumatologic literature with an ethical focus was 104 out of an estimated library of >400,000 rheumatologically oriented manuscripts (0.026%). Very few manuscripts consisted of original research studies. Nonmaleficence (66%) was the most common theme, whereas justice represented the least frequently addressed ethical issue (12%). The differences in the proportions of each ethical principle reached statistical significance (Q = 73.8,P< 0.0001). Only 8 articles addressed >2 ethical principles. Discussion touching on autonomy and nonmaleficence frequently appeared in the same article (Pearson's χ2= 14.9,P< 0.001).ConclusionDespite the frequency of ethical issues while caring for patients, few reports within the rheumatic disease literature have focused on ethical issues. Further work should ascertain the degree to which the literature addresses the ethical questions in rheumatology.