bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2genetic heterogeneity in breast carcinoma
Authors: Öhlschlegel Christian , Zahel Katharina , Kradolfer Doris , Hell Margreth , Jochum Wolfram 
Published: October 2011

AimsTo determine the frequency ofHER2genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas withHER2genetic heterogeneity.Methods530 invasive breast carcinomas were retrospectively analysed forHER2genetic heterogeneity, and investigated for a potential association ofHER2genetic heterogeneity with otherHER2FISH findings, clinicopathological parameters, oestrogen/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score.ResultsThe overall frequency ofHER2genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas.HER2genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lackingHER2amplification, 16.1% showedHER2genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency ofHER2genetic heterogeneity was 41%, and was associated with the absence ofHER2gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate.ConclusionHER2genetic heterogeneity according to the ASCO/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas withHER2genetic heterogeneity have a negativeHER2amplification status, although they contain a significant number of tumour cells withHER2gene amplification. Single cell scoring of theHER2/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas withHER2genetic heterogeneity, because they lack specific clinicopathological characteristics.
Modelling the association of disability according to the WHO International Classification of Functioning, Disability and Health (ICF) with mortality in the British Women's Heart and Health Study
Authors: Dale Caroline , Prieto-Merino David , Kuper Hannah , Adamson Joy , Bowling Ann , Ebrahim Shah , Casas Juan P 
Published: October 2011

BackgroundThe WHO International Classification of Functioning, Disability and Health (ICF) is now the dominant model for exploring the social consequences of a health condition. This paper investigates the association of the different ICF disability domains with mortality.MethodsData are from the British Women Heart and Health Study, a large (n=4157) prospectively studied cohort of women randomly selected from 23 towns aged 64–83 years in 2003. Scores were calculated to describe the cumulative load of impairments, limitations and restrictions within each ICF domain. Cox proportional hazards regression was used to calculate mortality HRs per unit score increase within each ICF domain. Adjustments were made for age, town, living status, socioeconomic status, lifestyle behaviours and health conditions.ResultsEach ICF domain was associated with mortality after controlling for lifestyle factors and health conditions. However, only complex activities (HR=1.09, 95% CI 1.01 to 1.18) and participation (HR=1.10, 95% CI 1.04 to 1.16) were independent predictors of mortality following adjustment for all other disability domains and potential confounders.ConclusionsResults suggest that difficulties with complex activities or social participation could be used to identify and target women at high risk of dying. Interventions to facilitate complex activities or improve social participation may help to delay mortality in elderly women.
Autocrine Endothelin-3/Endothelin Receptor B Signaling Maintains Cellular and Molecular Properties of Glioblastoma Stem Cells
Authors: Liu Yue , Ye Fei , Yamada Kazunari , Tso Jonathan L. , Zhang Yibei , Nguyen David H. , Dong Qinghua , Soto Horacio , Choe Jinny , Dembo Anna , Wheeler Hayley , Eskin Ascia , Schmid Ingrid , Yong William H. , Mischel Paul S. , Cloughesy Timothy F. , Kornblum Harley I. , Nelson Stanley F. , Liau Linda M. , Tso Cho-Lea 
Published: October 2011

Abstract
Glioblastoma stem cells (GSC) express both radial glial cell and neural crest cell (NCC)-associated genes. We report that endothelin 3 (EDN3), an essential mitogen for NCC development and migration, is highly produced by GSCs. Serum-induced proliferative differentiation rapidly decreased EDN3 production and downregulated the expression of stemness-associated genes, and reciprocally, two glioblastoma markers, EDN1 and YKL-40 transcripts, were induced. Correspondingly, patient glioblastoma tissues express low levels of EDN3 mRNA and high levels of EDN1 and YKL-40 mRNA. Blocking EDN3/EDN receptor B (EDNRB) signaling by an EDNRB antagonist (BQ788), or EDN3 RNA interference (siRNA), leads to cell apoptosis and functional impairment of tumor sphere formation and cell spreading/migration in culture and loss of tumorigenic capacity in animals. Using exogenous EDN3 as the sole mitogen in culture does not support GSC propagation, but it can rescue GSCs from undergoing cell apoptosis. Molecular analysis by gene expression profiling revealed that most genes downregulated by EDN3/EDNRB blockade were those involved in cytoskeleton organization, pause of growth and differentiation, and DNA damage response, implicating the involvement of EDN3/EDNRB signaling in maintaining GSC migration, undifferentiation, and survival. These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence. Mol Cancer Res; 9(12); 1668–85. ©2011 AACR.
Venous and arterial thrombosis in dialysis patients
Authors: Ocak Gurbey , Vossen Carla , Rotmans Joris , Lijfering Willem , Rosendaal Frits , Parlevliet Karien , Krediet Ray , Boeschoten Els , Verduijn Marion , Dekker Friedo 
Published: October 2011

SummaryWhether the risk of both venous and arterial thrombosis is increased in dialysis patients as compared to the general population is unknown. In addition, it is unknown which subgroups are at highest risk. Fur-thermore, it is unknown whether having a history of venous thrombosis or arterial thrombosis prior to dialysis treatment increases mortality risk. A total of 455 dialysis patients were followed for objectively verified symptomatic thrombotic events between January 1997 and June 2009. The incidence rates in dialysis patients as compared to the general population was 5.6-fold (95% CI 3.1–8.9) increased for venous thrombosis, 11.9-fold (95% CI 9.3–14.9) increased for myocardial infarction, and 8.4-fold (95% CI 5.7–11.5) increased for ischaemic stroke. The combination of haemodialysis, lowest tertile of albumin, history of venous thrombosis, and malignancy was associated with subsequent venous thrombosis. Increased age, renal vascular disease, diabetes, high cholesterol levels, history of venous thrombosis, and history of arterial thrombosis were associated with subsequent arterial thrombosis. The all-cause mortality risk was 1.9-fold (95% CI 1.1–3.3) increased for patients with a history of venous thrombosis and 1.9-fold (95% CI 1.4–2.6) increased for patients with a history of arterial thrombosis. A potential limitation of this study was that in some risk categories as-sociations with venous thrombosis did not reach statistical significance due to small numbers. In conclusion, dialysis patients have clearly elev-ated risks of venous thrombosis and arterial thrombosis and occurrence of venous thrombosis or arterial thrombosis prior to the start of dialysis is associated with an increased mortality risk.
Costs associated with outpatient, emergency room and inpatient care for migraine in the USA
Authors: Insinga Ralph P , Ng-Mak Daisy S , Hanson Mary E 
Published: October 2011

Background: Data on the average US costs of an outpatient visit, emergency room (ER) visit or hospitalization for migraine are scant, with the most recent available values based on healthcare charges reported from 1994 data. Methods: We estimated healthcare costs associated with outpatient and ER visits and inpatient hospitalizations related to migraine retrospectively obtained from the 2007 Medstat MarketScan Commercial Claims & Encounters database. Tabulated costs reflected payments from insurers, patients and other sources. All costs were adjusted to 2010 US dollars. Results: The estimated mean cost (95% CI) for migraine-related care per outpatient visit ( N = 680,946) was $139.88 ($139.35–140.41); per ER visit ( N = 88,128) was $775.09 ($768.10–782.09); and per inpatient hospitalization ( N = 5516) was $7317.07 ($7134.96–7499.17). The most frequently coded procedures at outpatient and ER visits were subcutaneous or intra-muscular injection, and for hospitalizations was computed tomography. Estimated annual US healthcare costs in 2010 for migraine associated with: outpatient visits were $3.2 billion, ER visits were $700 million, and inpatient hospitalizations were $375 million. Conclusions: Direct healthcare costs associated with patient visits and hospitalizations for migraine headaches have increased since previously published estimates. Further research is needed to understand the current overall healthcare cost burden per patient and within the US population.
New Suture Method for Radial Tears of the Meniscus
Authors: Matsubara Hirokazu , Okazaki Ken , Izawa Toshiaki , Tashiro Yasutaka , Matsuda Shuichi , Nishimura Takuya , Nakanishi Yoshitaka , Kawamura Hideya , Iwamoto Yukihide 
Published: October 2011

Background: Repair of complete radial meniscal tears is a key to restoring the mechanical integrity necessary to maintain hoop tension in the meniscus. The primary stability of the meniscal repair is one of the most important factors for meniscal healing, but the biomechanical structural properties of different repair techniques for complete radial meniscal tears remain unknown. Hypothesis: Our novel cross-suture technique with suturing oblique to the collagen fibrils of the meniscus will yield better fixation than the standard double horizontal suture technique with suturing parallel to the collagen fibrils in the meniscus. Study Design: Controlled laboratory study. Methods: Biomechanical investigation was performed on 40 fresh human menisci (2 groups of 20 menisci each) from patients who underwent total knee arthroplasty. In the cross-suture technique group (group A), the sutures crossed over 5 mm from the tear and 5 mm and 10 mm from the rim. In the double horizontal suture technique group (group B), the sutures were parallel and had the same attachment points as group A. The specimens were cyclically loaded 500 times between 5 and 30 N and then loaded to failure after completion of the cyclic load testing. Results: Compared with the double horizontal suture group, the cross-suture group had a significantly higher ultimate failure load (78.96 ± 19.27 N vs 68.16 ± 12.92 N; P < .05), significantly greater stiffness (8.01 ± 1.54 N/mm vs 6.46 ± 1.12 N/mm; P < .05), and significantly lower displacement (5.74 ± 1.84 mm vs 8.56 ± 2.39 mm; P < .05) after a 500–cycle loading protocol. Conclusion: Our cross-suture technique significantly improved the structural properties of the repaired complete radial meniscal tears. Clinical Relevance: The cross-suture technique for repair of radial meniscal tears provides high stability and could be a promising solution in young and in active patients.
Persistency of neutralizing antibodies depends on titer and interferon-beta preparation
Authors: Hegen Harald , Schleiser Manuel , Gneiss Claudia , Di Pauli Franziska , Ehling Rainer , Kuenz Bettina , Lutterotti Andreas , Berger Thomas , Deisenhammer Florian 
Published: October 2011

Background: Neutralizing antibodies (NAbs) affect the efficacy of interferon-beta (IFNβ) treatment in multiple sclerosis (MS) patients, particularly if NAbs persist. Persistency depends on NAb titers, which differ between IFNβ preparations. Objective: This study evaluated IFNβ preparation-specific NAb cut-off titers during early treatment for prediction of NAb persistency. Methods: Patients who had at least one NAb test between 12 and 30 months (baseline) as well as after more than 48 months (follow-up) on IFNβ treatment were included in this longitudinal study. Results: At baseline 1064 patients had a NAb test. Of those, 203 had a follow-up test. In the follow-up group 23.2% of patients were NAb positive during baseline. NAb frequency significantly decreased by 40.7% in the IFNβ-1a and by 60% in the IFNβ-1b group at follow-up after a mean time of 75.4 months on treatment, and median NAb titers decreased significantly in both groups. During baseline, NAb titers of >258 neutralizing units (NU) had a sensitivity of 81.3% and a specificity of 90.9% in the IFNβ-1a group, whereas titers of >460 NU had a sensitivity of 100% and a specificity of 91.7% in the IFNβ-1b group to predict persistency at follow-up. When these cut-off titers are applied, 10.2% of all treated patients developed persistent NAbs. Conclusion: IFNβ preparation-specific NAb cut-off titers for prediction of NAb persistency, which may be useful in individual treatment decision making, are provided.
Conserved and non-conserved enhancers direct tissue specific transcription in ancient germ layer specific developmental control genes
Authors: Chatterjee Sumantra , Bourque Guillaume , Lufkin Thomas 
Published: October 2011

Abstract

Background
Identifying DNA sequences (enhancers) that direct the precise spatial and temporal expression of developmental control genes remains a significant challenge in the annotation of vertebrate genomes. Locating these sequences, which in many cases lie at a great distance from the transcription start site, has been a major obstacle in deciphering gene regulation. Coupling of comparative genomics with functional validation to locate such regulatory elements has been a successful method in locating many such regulatory elements. But most of these studies looked either at a single gene only or the whole genome without focusing on any particular process. The pressing need is to integrate the tools of comparative genomics with knowledge of developmental biology to validate enhancers for developmental transcription factors in greater detail

Results
Our results show that near four different genes (nkx3.2, pax9, otx1b and foxa2) in zebrafish, only 20-30% of highly conserved DNA sequences can act as developmental enhancers irrespective of the tissue the gene expresses in. We find that some genes also have multiple conserved enhancers expressing in the same tissue at the same or different time points in development. We also located non-conserved enhancers for two of the genes (pax9 and otx1b). Our modified Bacterial artificial chromosome (BACs) studies for these 4 genes revealed that many of these enhancers work in a synergistic fashion, which cannot be captured by individual DNA constructs and are not conserved at the sequence level. Our detailed biochemical and transgenic analysis revealed Foxa1 binds to the otx1b non-conserved enhancer to direct its activity in forebrain and otic vesicle of zebrafish at 24 hpf.

Conclusion
Our results clearly indicate that high level of functional conservation of genes is not necessarily associated with sequence conservation of its regulatory elements. Moreover certain non conserved DNA elements might have role in gene regulation. The need is to bring together multiple approaches to bear upon individual genes to decipher all its regulatory elements.
Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy
Authors: Keam Bhumsuk , Im Seock-Ah , Koh Youngil , Han Sae-Won , Oh Do-Youn , Cho Nariya , Kim Jee Hyun , Han Wonshik , Kang Keon Wook , Moon Woo Kyung , Kim Tae-You , Park In Ae , Noh Dong-Young , Chung June-Key , Bang Yung-Jue 
Published: October 2011

Abstract

Background
This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy.

Methods
Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response.

Results
The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008).

Conclusions
The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype.

Trial Registration
ClinicalTrials.gov: NCT01396655
The impact of aging on memory T cell phenotype and function in the human bone marrow
Authors: Herndler-Brandstetter Dietmar , Landgraf Katja , Tzankov Alexandar , Jenewein Brigitte , Brunauer Regina , Laschober Gerhard T , Parson Walther , Kloss Frank , Gassner Robert , Lepperdinger Günter , Grubeck-Loebenstein Beatrix 
Published: October 2011

ABSTRACTRecently, the BM has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4+ and CD8+ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of naïve and an increase in TEM cells. In contrast to the PB, a highly activated CD8+CD28– T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation, and differentiation of CD8+ T cells in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8+CD28– T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4+ and CD8+ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8+CD28– T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.
Prevalence of anxiety and its correlates among older adults in Latin America, India and China: cross-cultural study
Authors: Prina A. Matthew , Ferri Cleusa P. , Guerra Mariella , Brayne Carol , Prince Martin 
Published: October 2011

BackgroundAnxiety is a common mental disorder among older people who live in the Western world, yet little is known about its prevalence in low- and middle-income countries.AimsWe investigated the prevalence of anxiety and its correlates among older adults in low- and middle-income countries with diverse cultures.MethodCross-sectional surveys of all residents aged 65 or over (n = 15 021) in 11 catchment sites in 7 countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru) were carried out as part of the 10/66 collaboration. Anxiety was measured by using the Geriatric Mental State Examination (GMS) and the Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) diagnostic algorithm.ResultsThe age- and gender-standardised prevalence of anxiety varied greatly across sites, ranging from 0.1% (95% CI 0.0–0.3) in rural China to 9.6% (95% CI 6.2–13.1) in urban Peru. Urban centres had higher estimates of anxiety than their rural counterparts with adjusted (age, gender and site) odds ratios of 2.9 (95% CI 1.7–5.3). Age, gender, socioeconomic status and comorbid physical illnesses were all associated with a GMS/AGECAT diagnosis of anxiety, and so was disability (World Health Organization Disability Assessment Schedule II).ConclusionsAnxiety is common in Latin America. Estimates from this region are similar to the ones from high-income European countries found in the literature. As demographic change will occur more rapidly in these countries, further research exploring the mental health of older people in developing areas is vital, with the inclusion of other specific anxiety disorders, along with evidence for strategies for supporting those with these disorders.
“Asi Lo Paresçe Por Su Aspeto”: Physiognomy and the Construction of Difference in Colonial Bogotá
Authors: Rappaport Joanne 
Published: October 2011

Abstract
My objective in this article is to examine the relationship between perception and classification in the sixteenth- and seventeenth-century Andes, focusing in particular on the Nuevo Reino de Granada (today, Colombia). During the first century of colonization, the visual identification of members of ethnoracial categories — indios, mestizos, mulattos, negros, and Spaniards — transformed over time and space in the Atlantic context. I argue in this article that we may be confining ourselves to a conceptual straitjacket if we limit our interpretation of terms like “indio” or “mulato” to their ethnic or racial dimensions as part of a self-enclosed system of classification, because such usages were embedded in broader schemes of perception and categorization that both antedated the Spanish invasion of the Americas and continued to be employed on the Iberian Peninsula. In particular, ethnoracial categories interacted in a complex relationship with the ways that observers reacted to the physiognomy of the individuals who bore these labels, so that the fluidity of classification can be seen as deriving in part from the interpretation of visual cues.