bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8Ain a breast cancer cell line
Authors: Muggerud Aslaug Aamodt , Edgren Henrik , Wolf Maija , Kleivi Kristine , Dejeux Emelyne , Tost Jörg , Sørlie Therese , Kallioniemi Olli 
Published: May 2009

Abstract

Background
Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging.

Methods
We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations.

Results
This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. qRT-PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P = 0.006).

Conclusion
We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.
HA117 gene increased the multidrug resistance of K562 cells in vitro: an investigation to the function of a novel gene related to drug resistance
Authors: Guo Yuxia , Zheng Gaihuan , Jin Xianqing , Xu Youhua , Luo Qing , Liu Xiaomei , Zhao Zhenzhen , Chen Yong 
Published: May 2009

Abstract

Objective
A novel multi-drug resistance gene named as HA117 has been screened and cloned in multidrug resisitant leukemia cell lines in our previous research, but its function is still unknown. In this study, HA117 gene was investigated whether it could increase the drug resistance in chronic myelogenous myeloid leukemia cell line K562.

Methods
HA117 was cloned and adenovirus vectors were constructed with the HA117 gene (Adeasy-HA117). K562 cells were infected by Ad-HA117 to get the K562/Ad-HA117 cells with HA117 gene expression. The infection efficiency and the multiplicity of infection (MOI) were detected by fluorescence and flow cytometry. The expression of HA117 gene was detected by RT-PCR. The drug sensitivities of K562/Ad-HA117 cells were detected by Methyl Thiazolyl Tetrazolium (MTT) assay.

Results
Recombinant adenovirus vectors were constructed and a MOI of 100 is most suitable to infect K562 cells. The infected K562 cells demonstrated in vitro production of HA117 mRNA as measured by reverse-transcriptase polymerase chain reaction. There were no significant changes in K562/Ad-HA117 cells growth, while the drug sensitivities of K562/Ad-HA117 cells to Vincristine, Adriamycin, Etoposide, Daunorubicin, Mitomycin and Cyclophosphamide decreased 4.44, 7.18, 3.01, 9.53, 3.48 and 3.61 times than that of uninfected K562 cells, respectively (P < 0.05).

Conclusion
Expression of the novel gene HA117 could significantly increased the multi-drug resistance of K562 cells, which indicated that HA117 is a functionally relevant multidrug resistance gene.
Adherence to Long-Term Surveillance Mammography Among Women With Ductal Carcinoma In Situ Treated With Breast-Conserving Surgery
Authors: Nekhlyudov Larissa , Habel Laurel A. , Achacoso Ninah S. , Jung Inkyung , Haque Reina , Collins Laura C. , Schnitt Stuart J. , Quesenberry Charles P. , Fletcher Suzanne W. 
Published: May 2009

Purpose Breast-conserving surgery (BCS) is an effective treatment for ductal carcinoma in situ (DCIS) but women who undergo BCS remain at risk for recurrences. Whether mammographic surveillance after BCS occurs and by whom is not known. Methods We reviewed medical records of women diagnosed with DCIS between 1990 and 2001 and treated with BCS. Using descriptive statistics, generalized estimating, and logistic regression modeling, we examined the rates and predictors of surveillance mammography over a 10-year period after BCS. Results The cohort included 3,037 women observed for a median of 4.8 years (range, 0.5 to 15.7). Of the 2,676 women observed for at least 1 year after BCS, most (79%) had at least one surveillance mammogram during the first year of follow-up; 69% in year 5 and 61% in year 10. Among those observed for 5 years, surveillance mammograms were more likely among women age 60 to 69 years (odds ratio [OR], 1.72; 95% CI, 1.26 to 2.34), users of menopausal hormone therapy at diagnosis (OR, 1.26; 95% CI, 1.01 to 1.57) as well as those treated with adjuvant radiation (OR, 1.28; 95% CI, 1.08 to 1.53) and adjuvant radiation with tamoxifen (OR, 1.61; 95% CI, 1.13 to 2.30). Surveillance mammograms were less likely among obese women (OR, 0.70; 95% CI, 0.56 to 0.86). The findings were similar among women observed for 10 years. Only 34% and 15% of women observed for 5 and 10 years, respectively, had a surveillance mammogram during each year of follow-up. Conclusion Surveillance mammography after BCS among insured women with DCIS often did not occur yearly and declined over time after treatment. Patients and providers must remain vigilant about surveillance after BCS.
Poor Outcome for Children and Adolescents With Progressive Disease or Relapse of Lymphoblastic Lymphoma: A Report From the Berlin-Frankfurt-Muenster Group
Authors: Burkhardt Birgit , Reiter Alfred , Landmann Eva , Lang Peter , Lassay Lisa , Dickerhoff Roswitha , Lakomek Max , Henze Günter , von Stackelberg Arend 
Published: May 2009

Purpose Little is known about the outcome of pediatric patients with lymphoblastic lymphoma (LBL) who suffer from progressive disease or relapse. Patients and Methods We analyzed the pattern of LBL relapses after current non-Hodgkin's lymphoma Berlin-Frankfurt-Muenster (BFM) frontline therapy between April 1990 and March 2003. Relapse therapy was according to acute lymphoblastic leukemia (ALL) –Relapse-BFM protocols or ALL-BFM protocols for high-risk patients. Results Twenty-eight (11%) of 251 registered patients with precursor T-cell LBL (T-LBL) and six (8%) of 73 patients with precursor B-cell LBL (pB-LBL) suffered from relapse. Of the 28 patients with T-LBL, one died from infection during relapse chemotherapy, 18 failed to achieve stable remission and died from disease progression, and nine reached allogeneic stem-cell transplantation (SCT). Two of these nine patients who underwent SCT died from transplantation-associated toxicity, three died from disease progression, and four are still alive. These four patients are in second remission of their lymphoma for 48, 68, 125, and 131 months, respectively, after allogeneic SCT. One of the four patients developed colon adenocarcinoma 47 months after SCT. Of the six patients with pB-LBL who experienced relapse, one patient died as a result of toxicity of relapse chemotherapy, two died from disease progression after chemotherapy, and three received allogeneic SCT. Of these, two died from subsequent disease progression, and one is still alive 57 months after allogeneic SCT. Conclusion Using modern conventional therapy in the frontline treatment of LBL, 10% of patients suffer from progressive disease or relapse. Because of the extremely poor reinduction success, the salvage rate for these patients is poor, with only a 14% (SE = 6%) overall survival. Long-term survival was only achieved in those few patients who were able to undergo an allogeneic SCT.
Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer
Authors: Patel Jyoti D. , Hensing Thomas A. , Rademaker Alfred , Hart Eric M. , Blum Matthew G. , Milton Daniel T. , Bonomi Philip D. 
Published: May 2009

Purpose This study evaluated the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naive stage IIIB (effusion) or stage IV nonsquamous non–small-cell lung cancer (NSCLC). Patients and Methods Patients received pemetrexed 500 mg/m2, carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for six cycles. For patients with response or stable disease, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity. Results Fifty patients were enrolled and received treatment. The median follow-up was 13.0 months, and the median number of treatment cycles was seven (range, one to 51). Thirty patients (60%) completed ≥ six treatment cycles, and nine (18%) completed ≥ 18 treatment cycles. Among the 49 patients assessable for response, the objective response rate was 55% (95% CI, 41% to 69%). Median progression-free and overall survival rates were 7.8 months (95% CI, 5.2 to 11.5 months) and 14.1 months (95% CI, 10.8 to 19.6 months), respectively. Grade 3/4 hematologic toxicity was modest—anemia (6%; 0), neutropenia (4%; 0), and thrombocytopenia (0; 8%). Grade 3/4 nonhematologic toxicities were proteinuria (2%; 0), venous thrombosis (4%; 2%), arterial thrombosis (2%; 0), fatigue (8%; 0), infection (8%; 2%), nephrotoxicity (2%; 0), and diverticulitis (6%; 2%). There were no grade 3 or greater hemorrhagic events or hypertension cases. Conclusion This regimen, involving a maintenance component, was associated with acceptable toxicity and relatively long survival in patients with advanced nonsquamous NSCLC. These results justify a phase III comparison against the standard-of-care in this patient population.
The European Economic Constitution and the Constitutional Dimension of Private Law
Authors: Collins Hugh 
Published: May 2009

Abstract
Intervening in the debate about the future of the European Union and the need for a balanced economic constitution that will consolidate a distinctive European social model, the essay argues that private law shares constitutional qualities with other public law sources such as abstract declarations of social and political rights, and that the construction of European private law is a necessary ingredient of the project for establishing a European economic constitution. In making this argument, the essay examines the concept of an economic constitution, its relation to the idea of a private law society, and the criticisms that have been made of the existing European economic constitution that it is unbalanced.
Sexual Development in Lucilia cuprina (Diptera, Calliphoridae) Is Controlled by the Transformer Gene
Authors: Concha Carolina , Scott Maxwell J 
Published: May 2009

Abstract
Insects use an amazing variety of genetic systems to control sexual development. A Y-linked male determining gene (M) controls sex in the Australian sheep blowfly Lucilia cuprina, an important pest insect. In this study, we isolated the L. cuprina transformer (Lctra) and transformer2 (Lctra2) genes, which are potential targets of M. The LCTRA and LCTRA2 proteins are significantly more similar to homologs from tephritid insects than Drosophila. The Lctra transcript is alternatively spliced such that only females make a full-length protein and the presence of six TRA/TRA2 binding sites in the female first intron suggest that Lctra splicing is autoregulated as in tephritids. LCTRA is essential for female development as RNAi knockdown of Lctra mRNA leads to the development of male genitalia in XX adults. Analysis of Lctra expression during development shows that early and midstage male and female embryos express the female form of Lctra and males express only the male form by the first instar larval stage. Our results suggest that an autoregulatory loop sustains female development and that expression of M inhibits Lctra autoregulation, switching its splicing to the male form. The conservation of tra function and regulation in a Calliphorid insect shows that this sex determination system is not confined to Tephritidae. Isolation of these genes is an important step toward the development of a strain of L. cuprina suitable for a genetic control program.
The Genealogical Consequences of Fecundity Variance Polymorphism
Authors: Taylor Jesse E 
Published: May 2009

AbstractThe genealogical consequences of within-generation fecundity variance polymorphism are studied using coalescent processes structured by genetic backgrounds. I show that these processes have three distinctive features. The first is that the coalescent rates within backgrounds are not jointly proportional to the infinitesimal variance, but instead depend only on the frequencies and traits of genotypes containing each allele. Second, the coalescent processes at unlinked loci are correlated with the genealogy at the selected locus; i.e., fecundity variance polymorphism has a genomewide impact on genealogies. Third, in diploid models, there are infinitely many combinations of fecundity distributions that have the same diffusion approximation but distinct coalescent processes; i.e., in this class of models, ancestral processes and allele frequency dynamics are not in one-to-one correspondence. Similar properties are expected to hold in models that allow for heritable variation in other traits that affect the coalescent effective population size, such as sex ratio or fecundity and survival schedules.
Kernicterus in Preterm Infants
Authors: Okumura Akihisa , Kidokoro Hiroyuki , Shoji Hiromichi , Nakazawa Tomoyuki , Mimaki Masakazu , Fujii Katsunori , Oba Hiroshi , Shimizu Toshiaki 
Published: May 2009

OBJECTIVE. We sought to clarify the features of kernicterus in preterm infants.METHODS. The subjects of this study were 8 preterm infants with athetoid cerebral palsy whose gestational ages were ≤34 weeks. We retrospectively investigated clinical, laboratory, MRI, and brainstem auditory evoked potential (BAEP) findings.RESULTS. Gestational age was ≤26 weeks in 6 of the 8 infants, and birth weight was &lt;1000 g in 5 infants. Serious postnatal complications with systemic deterioration were observed in 3 infants. Total bilirubin levels were measured frequently in the majority of infants; peak values of &gt;15 mg/dL were observed in 3 infants. No infant showed neurologic symptoms characteristic of classical acute bilirubin encephalopathy during the neonatal period. Dystonic posture and abnormal muscle tone were first recognized within 6 months' corrected age in all patients. During infancy, MRI was performed in 7 infants. Abnormal high-intensity areas were observed in the bilateral globi pallidi in all 7 infants. However, MRI during the neonatal period or after 1 year's corrected age showed no abnormal findings. BAEP measurements were abnormal in 7 of the 8 infants.CONCLUSIONS. Preterm infants with athetotic cerebral palsy showed rather homogeneous features, similar to term infants with kernicterus, with marked hyperbilirubinemia. This combination of clinical, laboratory, neuroimaging, and neurophysiological data will contribute to the increased recognition of preterm infants with kernicterus.
Increased Serum Pentraxin 3 in Patients with Systemic Sclerosis
Authors: IWATA YOHEI , YOSHIZAKI AYUMI , OGAWA FUMIHIDE , KOMURA KAZUHIRO , HARA TOSHIHIDE , MUROI EIJI , TAKENAKA MOTOI , SHIMIZU KAZUHIRO , HASEGAWA MINORU , FUJIMOTO MANABU , TAKEHARA KAZUHIKO , SATO SHINICHI 
Published: May 2009

Objective.To determine serum concentrations of pentraxin 3 (PTX3) and its clinical associations in patients with systemic sclerosis (SSc).Methods.Serum PTX3 levels from 45 patients with diffuse cutaneous SSc (dSSc), 46 with limited cutaneous SSc (lSSc), and 20 healthy controls were examined by ELISA. PTX3 expression in the sclerotic skin from SSc patients was evaluated immunohistochemically. Normal and SSc fibroblasts were cultured and PTX3 levels in the culture medium were also examined by ELISA.Results.Serum PTX3 levels were elevated in patients with SSc relative to controls. PTX3 levels in dSSc patients were significantly higher than in controls and lSSc patients. PTX3 expression in the sclerotic skin from SSc patients was more intense relative to normal skin. Elevation of serum PTX3 levels was associated with more frequent presence of pulmonary fibrosis, cardiac disease, and pitting scar/ulcer and increased serum immunoglobulin levels and erythrocyte sedimentation rates. PTX3 levels correlated positively with modified Rodnan total skin thickness score, and negatively with percentage vital capacity and percentage DLCO in patients with SSc. PTX3 levels also correlated positively with serum levels of 8-isoprostane, a marker of oxidative stress, and hyaluronan, recently identified as an endogenous ligand for Toll-like receptors. PTX3 production from cultured SSc fibroblasts was increased by stimulation with hyaluronan.ConclusionThese results suggest that elevated serum PTX3 levels are associated with the disease severity of SSc.
Gonadal Hormones in Men with Rheumatoid Arthritis — From Onset Through 2 Years
Authors: TENGSTRAND BIRGITTA , CARLSTRÖM KJELL , HAFSTRÖM INGIÄLD 
Published: May 2009

Objective.To evaluate changes over a 2-year course in the hypothalamic-pituitary-gonadal (HPG) axis in men with early rheumatoid arthritis (RA) from start of treatment with disease modifying antirheumatic drugs.Methods.Forty-one men with early RA and with joint symptoms less than 1 year were studied. Mean age at inclusion was 53 years and mean disease duration 6 months. They were followed prospectively for 2 years for disease activity [Disease Activity Score 28 (DAS28)], physical impairment (Health Assessment Questionnaire), total serum testosterone, non-sex hormone-binding globulin-bound testosterone, and luteinizing hormone (LH). A group of 131 healthy, medicine-free men served as controls for baseline hormone concentrations.Results.The men with RA already had mean testosterone levels lower than controls early in the disease course. Patients older than 50 years also had significantly lower LH levels compared with controls, consistent with mild hypogonadotropic hypogonadism. In patients who responded to treatment at the 2-year followup the testosterone levels increased significantly. A decrease in DAS28 during the 2 years correlated significantly with increased testosterone levels (rs = −0.46, p = 0.006). LH levels were low and stable and did not correlate with disease activity.Conclusion.In early RA, current inflammation seemed to affect the HPG axis, mainly at the gonadal rather than the hypothalamic-pituitary level. Prospective studies are indicated to determine if low HPG activity may be a cause rather than a consequence of a chronic inflammatory state.
Osteoarthritis Measurement in Routine Rheumatology Outpatient Practice (OMIRROP) in Australia: A Survey of Practice Style, Instrument Use, Responder Criteria, and State-Attainment Criteria
Authors: BELLAMY ELIZABETH , WILSON CECILIA , BELLAMY NICHOLAS 
Published: May 2009

Objective.The purpose of the 2007 Osteoarthritis Measurement in Routine Rheumatology Outpatient Practice survey was to describe practice styles, instrument usage, and perceptions of responder criteria and state-attainment criteria in osteoarthritis (OA) management in routine clinical rheumatology practice.Methods.A 16-item questionnaire (65 subcomponents) was developed, pretested, revised, formatted, and mailed to rheumatologists residing in Australia. Responses were obtained from 136 rheumatologists (response rate 58%).Results.Approximately half the Australian respondents did not follow up their patients with hip and knee OA and two-thirds did not follow up their patients with hand OA. Health status measures (HSM) were infrequently used, even by those respondents who followed their patients with OA longitudinally, and the scores from those HSM that were used, were rarely if ever formally recorded. Respondents rated the following 6 requirements of a measure for use in clinical practice as very important: validity, reliability, responsiveness, simplicity, quick completion, and easy scoring. One-fifth to one-quarter of respondents indicated they did not know quantitatively what constituted a clinically important improvement, or a health state acceptable to patients with OA. The majority of the remainder selected values not closely aligned with published values in the peer review literature.Conclusion.While simply describing the health status of the patient is interesting, the more strategic applications are in benchmarking, and using the data to inform shared decision-making and therapeutic goal-setting. The OMIRROP survey suggests that further investigation of interpretation issues are essential, before evaluating the role of quantitative measurement in routine OA clinical practice.
The Gap Between Practice and Guidelines in the Choice of First-line Disease Modifying Antirheumatic Drug in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort
Authors: BENHAMOU MATHILDE , RINCHEVAL NATHALIE , ROY CARINE , FOLTZ VIOLAINE , ROZENBERG SYLVIE , SIBILIA JEAN , SCHAEVERBEKE THIERRY , BOURGEOIS PIERRE , RAVAUD PHILIPPE , FAUTREL BRUNO 
Published: May 2009

Objective.To compare rheumatologists’ prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines.Method.ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. “Definite” and “probable” RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients’ usual rheumatologists to investigate the reasons for their nonconformity with guidelines.Results.In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist.Conclusion.There is a substantial gap between CPG and rheumatologists’ daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA.