bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copy Number Imbalances between Screen- and Symptom-Detected Breast Cancers and Impact on Disease-Free Survival
Authors: Brewster A.M. , Thompson P. , Sahin A.A. , Do K. , Edgerton M. , Murray J.L. , Tsavachidis S. , Zhou R. , Liu Y. , Zhang L. , Mills G. , Bondy M. 
Published: July 2011

AbstractScreening mammography results in the increased detection of indolent tumors. We hypothesized that screen- and symptom-detected tumors would show genotypic differences as copy number imbalances (CNI) that, in part, explain differences in the clinical behavior between screen- and symptom-detected breast tumors. We evaluated 850 women aged 40 and above diagnosed with stage I and II breast cancer at the University of Texas MD Anderson Cancer Center between 1985 and 2000 with information available on method of tumor detection (screen vs. symptoms). CNIs in screen- and symptom-detected tumors were identified using high-density molecular inversion probe arrays. Cox proportional modeling was used to estimate the effect of method of tumor detection on disease-free survival after adjusting for age, stage, and the CNIs. The majority of tumors were symptom detected (n = 603) compared with screen detected (n = 247). Copy number gains in chromosomes 2p, 3q, 8q, 11p, and 20q were associated with method of breast cancer detection (P &lt; 0.00001). We estimated that 32% and 63% of the survival advantage of screen detection was accounted for by age, stage, nuclear grade, and Ki67 in women aged 50 to 70 and aged 40 to 87, respectively. In each age category, an additional 20% of the survival advantage was accounted for by CNIs associated with method of detection. Specific CNIs differ between screen- and symptom-detected tumors and explain part of the survival advantage associated with screen-detected tumors. Measurement of tumor genotype has the potential to improve discrimination between indolent and aggressive screen-detected tumors and aids patient and physician decision making about use of surgical and adjuvant treatments. Cancer Prev Res; 4(10); 1609–16. ©2011 AACR.
Mesoscale Convective Complexes over Southern Africa
Authors: Blamey R. C. , Reason C. J. C. 
Published: July 2011

AbstractThe maximum spatial correlation technique (MASCOTTE) is an objective and automated method developed to simultaneously determine both the structural properties and evolution (tracking) of cloud shields of convective systems. Originally designed to monitor systems over the Amazon region, this method has now been adapted for subtropical southern Africa. In this paper, a detailed climatology of 70 mesoscale convective complexes (MCCs) that occurred during the austral summer months over southern Africa during the 1998–2006 period are presented. Most MCCs are clustered along the eastern regions of southern Africa, adjacent to the warm waters of the Mozambique Channel and Agulhas Current. A few infrequent systems are found to be developing in Namibia and Botswana. The systems are found to predominantly occur during the months of November–February, with maximum activity occurring in November and December. The transition from a more midlatitude-dominated circulation to a tropical circulation over the region during the late summer leads to an uncharacteristic equatorward migration of the MCC distribution then. The analysis also suggests that there is variability in MCC frequency on monthly and seasonal time scales. Although fewer in number (about nine per season) compared to MCC populations in other regions, the systems do tend to follow the nocturnal life cycle as documented elsewhere.
An Operation-Based Scheme for a Multiyear and Multipurpose Reservoir to Enhance Macroscale Hydrologic Models
Authors: Wu Yiping , Chen Ji 
Published: July 2011

Abstract
This paper develops an operation-based numerical scheme for simulating storage in and outflow from a multiyear and multipurpose reservoir at a daily time step in order to enhance the simulation capacity of macroscale land surface hydrologic models. In the new scheme, besides the purpose of flood control, three other operational purposes—hydropower generation, downstream water supply, and water impoundment—are considered, and accordingly three related decision-based parameters are introduced. The new scheme is then integrated into the Soil and Water Assessment Tool (SWAT), which is a macroscale hydrologic model. The observed water storage and outflow from a multiyear and multipurpose reservoir, the Xinfengjiang Reservoir in southern China, are used to examine the new scheme. Compared with two other reservoir operation schemes—namely, a modified existing reservoir operation scheme in SWAT (i.e., the target release scheme) and a multilinear regression scheme—the new scheme can give a consistently better simulation of the reservoir storage and outflow. Furthermore, through a sensitivity analysis, this study shows that the three decision-based parameters can represent the significance of each operational purpose in different periods and the new scheme can advance the flexibility and capability of the simulation of the reservoir storage and outflow.
Orientation and mobility training for partially-sighted older adults using an identification cane: a systematic review
Authors: Ballemans Judith , Kempen Gertrudis IJM , Zijlstra GA Rixt 
Published: July 2011

Objective: This study aimed to provide an overview of the development, content, feasibility, and effectiveness of existing orientation and mobility training programmes in the use of the identification cane. Data sources: A systematic bibliographic database search in PubMed, PsychInfo, ERIC, CINAHL and the Cochrane Library was performed, in combination with the expert consultation (n = 42; orientation and mobility experts), and hand-searching of reference lists. Review methods: Selection criteria included a description of the development, the content, the feasibility, or the effectiveness of orientation and mobility training in the use of the identification cane. Two reviewers independently agreed on eligibility and methodological quality. A narrative/qualitative data analysis method was applied to extract data from obtained documents. Results: The sensitive database search and hand-searching of reference lists revealed 248 potentially relevant abstracts. None met the eligibility criteria. Expert consultation resulted in the inclusion of six documents in which the information presented on the orientation and mobility training in the use of the identification cane was incomplete and of low methodological quality. Conclusion: Our review of the literature showed a lack of well-described protocols and studies on orientation and mobility training in identification cane use.
Foot posture after stroke: frequency, nature and clinical significance
Authors: Forghany Saeed , Tyson Sarah , Nester Christopher , Preece Stephen , Jones Richard 
Published: July 2011

Objectives: Clinical convention suggests that foot posture and movements are adversely affected by stroke and cause walking difficulties but there is little objective data to support or refute these beliefs. This study explores static foot posture in people with stroke and their relationship to weakness and spasticity and walking limitations. Design: Cross-sectional survey. Setting: Stroke services and support groups of two acute hospitals. Subjects: Seventy-two stroke survivors with mobility limitations. Main measures: Foot Posture Index; Demographics; Motricity Index (weakness); modified Ashworth Scale (spasticity); Walking Handicap Scale (walking limitations). Results: About one-third of participants had abnormal foot posture on the weak side, which was associated with walking limitations. Most (70%) had a symmetrical foot posture with similar frequencies of supination (13%) and pronation (16%) abnormalities. There was no relationship between foot posture and weakness and spasticity; age was the only independent predictor of foot posture abnormalities. Conclusions: A minority of people with stroke had abnormal or asymmetrical foot posture and equal numbers suffered pronation and supination abnormalities; these findings challenge the beliefs that underpin the clinical management of stroke-related foot problems.
The Effect of Lace-up Ankle Braces on Injury Rates in High School Basketball Players
Authors: McGuine Timothy A. , Brooks Alison , Hetzel Scott 
Published: July 2011

Background: Ankle injuries are the most common injury in basketball players. However, no prospective studies have been performed to determine if wearing lace-up ankle braces will reduce the incidence of ankle injuries in high school athletes. Purpose: This trial was undertaken to determine if lace-up ankle braces reduce the incidence and severity of acute first-time and recurrent ankle injuries sustained by high school basketball players. Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 1460 male and female basketball players from 46 high schools were randomly assigned to a braced or control group. The braced group players wore lace-up ankle braces during the 2009-2010 basketball season. Athletic trainers recorded brace compliance, athlete exposures, and injuries. Cox proportional hazards models (adjusted for demographic covariates), accounting for intracluster correlation, were utilized to compare time to first acute ankle injury between groups. Injury severity (days lost) was tested with the Wilcoxon rank-sum test. Results: The rate of acute ankle injury (per 1000 exposures) was 0.47 in the braced group and 1.41 in the control group (Cox hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.20, 0.52; P < .001). The median severity of acute ankle injuries was similar ( P = .23) in the braced (6 days) and control group (7 days). For players with a previous ankle injury, the incidence of acute ankle injury was 0.83 in the braced group and 1.79 in the control group (Cox HR 0.39; 95% CI 0.17, 0.90; P = .028). For players who did not report a previous ankle injury, the incidence of acute ankle injury was 0.40 in the braced group and 1.35 in the control group (Cox HR 0.30; 95% CI 0.17, 0.52, P < .001). Conclusion: Use of lace-up ankle braces reduced the incidence but not the severity of acute ankle injuries in male and female high school basketball athletes both with and without a previous history of an ankle injury.
CD19-independent instruction of murine marginal zone B-cell development by constitutive Notch2 signaling
Authors: Hampel Franziska , Ehrenberg Stefanie , Hojer Caroline , Draeseke Anne , Marschall-Schröter Gabriele , Kühn Ralf , Mack Brigitte , Gires Olivier , Vahl Christoph J. , Schmidt-Supprian Marc , Strobl Lothar J. , Zimber-Strobl Ursula 
Published: July 2011

AbstractB cell–specific gene ablation of Notch2 results in the loss of the marginal zone (MZ) B-cell lineage. To analyze the effects of constitutive Notch2 signaling in B cells, we have generated a transgenic mouse strain that allows the conditional expression of a constitutively active, intracellular form of Notch2 (Notch2IC). Expression of Notch2IC at the earliest developmental stages of the B-cell lineage completely abolished B-cell generation and led to the development of ectopic T cells in the bone marrow (BM), showing that Notch2IC is acting redundantly with Notch1IC in driving ectopic T-cell differentiation. In B cells clearly committed to the B-cell lineage induction of Notch2IC drove all cells toward the MZ B-cell compartment at the expense of follicular B cells. Notch2IC-expressing B cells reflected the phenotype of wild-type MZ B cells for their localization in the MZ, the expression of characteristic surface markers, their enhanced proliferation after stimulation, and increased basal activity of Akt, Erk, and Jnk. Notch2IC-driven MZ B-cell generation in the spleen was achieved even in the absence of CD19. Our results implicate that a constitutive Notch2 signal in transitional type 1 B cells is sufficient to drive MZ B-cell differentiation.
Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia
Authors: Ouillette Peter , Collins Roxane , Shakhan Sajid , Li Jinghui , Peres Edward , Kujawski Lisa , Talpaz Moshe , Kaminski Mark , Li Cheng , Shedden Kerby , Malek Sami N. 
Published: July 2011

Abstract
Genomic aberrations are of predominant importance to the biology and clinical outcome of patients with chronic lymphocytic leukemia (CLL), and FISH-based genomic risk classifications are routinely used in clinical decision making in CLL. One of the known limitations of CLL FISH is the inability to comprehensively interrogate the CLL genome for genomic changes. In an effort at overcoming the existing limitations in CLL genome analysis, we have analyzed high-purity DNA isolated from FACS-sorted CD19+ cells and paired CD3+ or buccal cells from 255 patients with CLL for acquired genomic copy number aberrations (aCNAs) with the use of ultra-high-density Affymetrix SNP 6.0 arrays. Overall, ≥ 2 subchromosomal aCNAs were found in 39% (100 of 255) of all cases analyzed, whereas ≥ 3 subchromosomal aCNAs were detected in 20% (50 of 255) of cases. Subsequently, we have correlated genomic lesion loads (genomic complexity) with the clinical outcome measures time to first therapy and overall survival. With the use of multivariate analyses incorporating the most important prognostic factors in CLL together with SNP 6.0 array–based genomic lesion loads at various thresholds, we identify elevated CLL genomic complexity as an independent and powerful marker for the identification of patients with aggressive CLL and short survival.
A novel Fc-engineered monoclonal antibody to CD37 with enhanced ADCC and high proapoptotic activity for treatment of B-cell malignancies
Authors: Heider Karl-Heinz , Kiefer Kerstin , Zenz Thorsten , Volden Matthias , Stilgenbauer Stephan , Ostermann Elinborg , Baum Anke , Lamche Herbert , Küpcü Zaruhi , Jacobi Alexander , Müller Steffen , Hirt Ulrich , Adolf Günther R. , Borges Eric 
Published: July 2011

AbstractThe tetraspanin CD37 is widely expressed in B-cell malignancies and represents an attractive target for immunotherapy with mAbs. We have chimerized a high-affinity mouse Ab to CD37 and engineered the CH2 domain for improved binding to human Fcγ receptors. The resulting mAb 37.1 showed high intrinsic proapoptotic activity on malignant B cells accompanied by homotypic aggregation. Furthermore, the Ab-mediated high Ab-dependent cell-mediated cytotoxicity (ADCC) on lymphoma and primary CLL cells. mAb 37.1 strongly depleted normal B cells as well as spiked B-lymphoma cells in blood samples from healthy donors as well as malignant B cells in blood from CLL patients. In all assays, mAb 37.1 was superior to rituximab in terms of potency and maximal cell lysis. A single dose of mAb CD37.1 administered to human CD37-transgenic mice resulted in a reversible, dose-dependent reduction of peripheral B cells. In a Ramos mouse model of human B-cell lymphoma, administration of mAb 37.1 strongly suppressed tumor growth. Finally, a surrogate Fc-engineered Ab to macaque CD37, with in vitro proapoptotic and ADCC activities very similar to those of mAb 37.1, induced dose-dependent, reversible B-cell depletion in cynomolgus monkeys. In conclusion, the remarkable preclinical pharmacodynamic and antitumor effects of mAb 37.1 warrant clinical development for B-cell malignancies.
Mice deficient in LMAN1 exhibit FV and FVIII deficiencies and liver accumulation of α1-antitrypsin
Authors: Zhang Bin , Zheng Chunlei , Zhu Min , Tao Jiayi , Vasievich Matthew P. , Baines Andrea , Kim Jinoh , Schekman Randy , Kaufman Randal J. , Ginsburg David 
Published: July 2011

AbstractThe type 1-transmembrane protein LMAN1 (ERGIC-53) forms a complex with the soluble protein MCFD2 and cycles between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment (ERGIC). Mutations in either LMAN1 or MCFD2 cause the combined deficiency of factor V (FV) and factor VIII (FVIII; F5F8D), suggesting an ER-to-Golgi cargo receptor function for the LMAN1-MCFD2 complex. Here we report the analysis of LMAN1-deficient mice. Levels of plasma FV and FVIII, and platelet FV, are all reduced to ∼ 50% of wild-type in Lman1−/− mice, compared with the 5%-30% levels typically observed in human F5F8D patients. Despite previous reports identifying cathepsin C, cathepsin Z, and α1-antitrypsin as additional potential cargoes for LMAN1, no differences were observed between wild-type and Lman1−/− mice in the levels of cathepsin C and cathepsin Z in liver lysates or α1-antitrypsin levels in plasma. LMAN1 deficiency had no apparent effect on COPII-coated vesicle formation in an in vitro assay. However, the ER in Lman1−/− hepatocytes is slightly distended, with significant accumulation of α1-antitrypsin and GRP78. An unexpected, partially penetrant, perinatal lethality was observed for Lman1−/− mice, dependent on the specific inbred strain genetic background, suggesting a potential role for other, as yet unidentified LMAN1-dependent cargo proteins.
Angiogenesis gene expression in murine endothelial cells during post-pneumonectomy lung growth
Authors: Lin Miao , Chamoto Kenji , Gibney Barry C , Lee Grace S , Collings-Simpson Dinee , Houdek Jan , Konerding Moritz A , Tsuda Akira , Mentzer Steven J 
Published: July 2011

Abstract
Although blood vessel growth occurs readily in the systemic bronchial circulation, angiogenesis in the pulmonary circulation is rare. Compensatory lung growth after pneumonectomy is an experimental model with presumed alveolar capillary angiogenesis. To investigate the genes participating in murine neoalveolarization, we studied the expression of angiogenesis genes in lung endothelial cells. After left pneumonectomy, the remaining right lung was examined on days 3, 6, 14 and 21days after surgery and compared to both no surgery and sham thoracotomy controls. The lungs were enzymatically digested and CD31+ endothelial cells were isolated using flow cytometry cell sorting. The transcriptional profile of the CD31+ endothelial cells was assessed using quantitative real-time polymerase chain reaction (PCR) arrays. Focusing on 84 angiogenesis-associated genes, we identified 22 genes with greater than 4-fold regulation and significantly enhanced transcription (p <.05) within 21 days of pneumonectomy. Cluster analysis of the 22 genes indicated that changes in gene expression did not occur in a single phase, but in at least four waves of gene expression: a wave demonstrating decreased gene expression more than 3 days after pneumonectomy and 3 sequential waves of increased expression on days 6, 14, and 21 after pneumonectomy. These findings indicate that a network of gene interactions contributes to angiogenesis during compensatory lung growth.
Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level
Authors: Romá-Mateo Carlos , Moreno Daniel , Vernia Santiago , Rubio Teresa , Bridges Travis M , Gentry Matthew S , Sanz Pascual 
Published: July 2011

Abstract

Background
Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin.

Results
After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex.

Conclusions
We found that malin and laforin are not conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins.
Population-genetic comparison of the Sorbian isolate population in Germany with the German KORA population using genome-wide SNP arrays
Authors: Gross Arnd , Tönjes Anke , Kovacs Peter , Veeramah Krishna R , Ahnert Peter , Roshyara Nab R , Gieger Christian , Rueckert Ina-Maria , Loeffler Markus , Stoneking Mark , Wichmann Heinz-Erich , Novembre John , Stumvoll Michael , Scholz Markus 
Published: July 2011

Abstract

Background
The Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples.

Results
The degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies.
Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses.

Conclusions
Sorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable.
Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses.