bluuebunny/crossref_metadata_2025_split huggingface dataset:
GMFilter and SXTestPlate: software tools for improving the SNPlex™ genotyping system
Authors: Teuber Markus , Wenz Michael H , Schreiber Stefan , Franke Andre 
Published: March 2009

Abstract

Background
Genotyping of single-nucleotide polymorphisms (SNPs) is a fundamental technology in modern genetics. The SNPlex™ mid-throughput genotyping system (Applied Biosystems, Foster City, CA, USA) enables the multiplexed genotyping of up to 48 SNPs simultaneously in a single DNA sample. The high level of automation and the large amount of data produced in a high-throughput laboratory require advanced software tools for quality control and workflow management.

Results
We have developed two programs, which address two main aspects of quality control in a SNPlex™ genotyping environment: GMFilter improves the analysis of SNPlex™ plates by removing wells with a low overall signal intensity. It enables scientists to automatically process the raw data in a standardized way before analyzing a plate with the proprietary GeneMapper software from Applied Biosystems. SXTestPlate examines the genotype concordance of a SNPlex™ test plate, which was typed with a control SNP set. This program allows for regular quality control checks of a SNPlex™ genotyping platform. It is compatible to other genotyping methods as well.

Conclusion
GMFilter and SXTestPlate provide a valuable tool set for laboratories engaged in genotyping based on the SNPlex™ system. The programs enhance the analysis of SNPlex™ plates with the GeneMapper software and enable scientists to evaluate the performance of their genotyping platform.
Global comparative transcriptome analysis of cartilage formation in vivo
Authors: Cameron Trevor L , Belluoccio Daniele , Farlie Peter G , Brachvogel Bent , Bateman John F 
Published: March 2009

Abstract

Background
During vertebrate embryogenesis the initial stages of bone formation by endochondral ossification involve the aggregation and proliferation of mesenchymal cells into condensations. Continued growth of the condensations and differentiation of the mesenchymal cells into chondrocytes results in the formation of cartilage templates, or anlagen, which prefigure the shape of the future bones. The chondrocytes in the anlagen further differentiate by undergoing a complex sequence of maturation and hypertrophy, and are eventually replaced by mineralized bone. Regulation of the onset of chondrogenesis is incompletely understood, and would be informed by comprehensive analyses of in vivo gene expression.

Results
Tibial and fibular pre-condensed mesenchyme was microdissected from mouse hind limbs at 11.5 dpc, and the corresponding condensations at 12.5 dpc and cartilage anlagen at 13.5 dpc. Total RNA was isolated, and cRNA generated by linear amplification was interrogated using mouse whole genome microarrays. Differential expression was validated by quantitative PCR for Agc1, Bmp8a, Col2a1, Fgfr4, Foxa3, Gdf5, Klf2, Klf4, Lepre1, Ncad, Sox11, and Trpv4. Further, independent validation of the microarray data was achieved by in situ hybridization to analyse the expression of Lepre1, Pcdh8, Sox11, and Trpv4 from 11.5 dpc to 13.5 dpc during mouse hind limb development. We found significant differential expression of 931 genes during these early stages of chondrogenesis. Of these, 380 genes were down-regulated and 551 up-regulated. Our studies characterized the expression pattern of gene families previously associated with chondrogenesis, such as adhesion molecules, secreted signalling molecules, transcription factors, and extracellular matrix components. Gene ontology approaches identified 892 differentially expressed genes not previously identified during the initiation of chondrogenesis. These included several Bmp, Gdf, Wnt, Sox and Fox family members.

Conclusion
These data represent the first global gene expression profiling analysis of chondrogenic tissues during in vivo development. They identify genes for further study on their functional roles in chondrogenesis, and provide a comprehensive and important resource for future studies on cartilage development and disease.
Developmental and neurochemical features of cholinergic neurons in the murine cerebral cortex
Authors: Consonni Silvia , Leone Silvia , Becchetti Andrea , Amadeo Alida 
Published: March 2009

Abstract

Background
The existence and role of intrinsic cholinergic cells in the cerebral cortex is controversial, because of their variable localization and morphology in different mammalian species. We have applied choline acetyltransferase (ChAT) immunocytochemistry to study the distribution of cholinergic neurons in the murine cerebral cortex, in the adult and during postnatal development. For more precise neurochemical identification of these neurons, the possible colocalization of ChAT with different markers of cortical neuronal populations has been analyzed by confocal microscopy. This method was also used to verify the relationship between cholinergic cells and cortical microvessels.

Results
ChAT positive cells appeared at the end of the first postnatal week. Their density dramatically increased at the beginning of the second postnatal week, during which it remained higher than in perinatal and adult stages. In the adult neocortex, cholinergic neurons were particularly expressed in the somatosensory area, although their density was also significant in visual and auditory areas. ChAT positive cells tended to be scarce in other regions. They were mainly localized in the supragranular layers and displayed a fusiform/bipolar morphology.
The colocalization of ChAT with pyramidal neuron markers was negligible. On the other hand, more than half of the cholinergic neurons contained calretinin, but none of them expressed parvalbumin or calbindin. However, only a fraction of the ChAT positive cells during development and very few in adulthood turned out to be GABAergic, as judged from expression of GABA and its biosynthetic enzymes GAD67/65. Consistently, ChAT showed no localization with interneurons expressing green fluorescent protein under control of the GAD67 promoter in the adult neocortex. Finally, the cortical cholinergic cells often showed close association with the microvessel walls, as identified with the gliovascular marker aquaporin 4, supporting previous hypotheses on the role of cholinergic cells in modulating the cortical microcirculation.

Conclusion
Our results show that the development of the intracortical cholinergic system accompanies the cortical rearrangements during the second postnatal week, a crucial stage for the establishment of cortical cytoarchitecture and for synaptogenesis. Although intrinsic ChAT positive cells usually expressed calretinin, they displayed a variable GABAergic phenotype depending on marker and on cortical developmental stage.
Exploring the transcriptional landscape of plant circadian rhythms using genome tiling arrays
Authors: Hazen Samuel P , Naef Felix , Quisel Tom , Gendron Joshua M , Chen Huaming , Ecker Joseph R , Borevitz Justin O , Kay Steve A 
Published: March 2009

Abstract
Background
Organisms are able to anticipate changes in the daily environment with an internal oscillator know as the circadian clock. Transcription is an important mechanism in maintaining these oscillations. Here we explore, using whole genome tiling arrays, the extent of rhythmic expression patterns genome-wide, with an unbiased analysis of coding and noncoding regions of the Arabidopsis genome.

Results
As in previous studies, we detected a circadian rhythm for approximately 25% of the protein coding genes in the genome. With an unbiased interrogation of the genome, extensive rhythmic introns were detected predominantly in phase with adjacent rhythmic exons, creating a transcript that, if translated, would be expected to produce a truncated protein. In some cases, such as the MYB transcription factor AT2G20400, an intron was found to exhibit a circadian rhythm while the remainder of the transcript was otherwise arrhythmic. In addition to several known noncoding transcripts, including microRNA, trans-acting short interfering RNA, and small nucleolar RNA, greater than one thousand intergenic regions were detected as circadian clock regulated, many of which have no predicted function, either coding or noncoding. Nearly 7% of the protein coding genes produced rhythmic antisense transcripts, often for genes whose sense strand was not similarly rhythmic.

Conclusions
This study revealed widespread circadian clock regulation of the Arabidopsis genome extending well beyond the protein coding transcripts measured to date. This suggests a greater level of structural and temporal dynamics than previously known.
Widespread evidence for horizontal transfer of transposable elements across Drosophilagenomes
Authors: Bartolomé Carolina , Bello Xabier , Maside Xulio 
Published: March 2009

Abstract
Background
Horizontal transfer (HT) could play an important role in the long-term persistence of transposable elements (TEs) because it provides them with the possibility to avoid the checking effects of host-silencing mechanisms and natural selection, which would eventually drive their elimination from the genome. However, despite the increasing evidence for HT of TEs, its rate of occurrence among the TE pools of model eukaryotic organisms is still unknown.

Results
We have extracted and compared the nucleotide sequences of all potentially functional autonomous TEs present in the genomes of Drosophila melanogaster, D. simulans and D. yakuba - 1,436 insertions classified into 141 distinct families - and show that a large fraction of the families found in two or more species display levels of genetic divergence and within-species diversity that are significantly lower than expected by assuming copy-number equilibrium and vertical transmission, and consistent with a recent origin by HT. Long terminal repeat (LTR) retrotransposons form nearly 90% of the HT cases detected. HT footprints are also frequent among DNA transposons (40% of families compared) but rare among non-LTR retroelements (6%). Our results suggest a genomic rate of 0.04 HT events per family per million years between the three species studied, as well as significant variation between major classes of elements.

Conclusions
The genome-wide patterns of sequence diversity of the active autonomous TEs in the genomes of D. melanogaster, D. simulans and D. yakuba suggest that one-third of the TE families originated by recent HT between these species. This result emphasizes the important role of horizontal transmission in the natural history of Drosophila TEs.
Phase III Study of Gemcitabine Plus Docetaxel Compared With Capecitabine Plus Docetaxel for Anthracycline-Pretreated Patients With Metastatic Breast Cancer
Authors: Chan Stephen , Romieu Gilles , Huober Jens , Delozier Thierry , Tubiana-Hulin Michele , Schneeweiss Andreas , Lluch Ana , Llombart Antonio , du Bois Andreas , Kreienberg Rolf , Mayordomo Jose Ignacio , Antón Antonio , Harrison Mark , Jones Alison , Carrasco Eva , Vaury A. Thareau , Frimodt-Moller Bente , Fumoleau Pierre 
Published: March 2009

Purpose Patients with metastatic breast cancer who are pretreated with anthracyclines frequently receive taxane-based combinations. This phase III study compared the efficacy and safety of gemcitabine-docetaxel (GD) with capecitabine-docetaxel (CD) in advanced breast cancer. Patients and Methods Patients were randomly assigned to GD (G 1,000 mg/m2 days 1 and 8; D 75 mg/m2 day 1) or CD (C 1,250 mg/m2 twice daily days 1 through 14; D 75 mg/m2 day 1) every 21 days. Comparison of progression-free survival (PFS) was the primary objective. Results Patient characteristics were balanced between arms (N = 305). Median PFS was 8.05 months (95% CI, 6.60 to 8.71) for GD and 7.98 (95% CI, 6.93 to 8.77) for CD (log-rank P = .121). Overall response rate (ORR) was 32% in both arms, and overall survival (OS) was not different between arms (P = .983). Time to treatment failure (TTF; defined as discontinuation, progressive disease, death as a result of any cause, or the start of a new anticancer therapy) was superior in the GD arm (P = .059). Hematologic toxicity was similar in both arms, except for grades 3 to 4 leukopenia (GD, 78%; CD, 66%; P = .025) and transfusions (GD, 17%; CD, 7%; P = .0051). Grades 3 to 4 diarrhea, mucositis, and hand-and-foot syndrome were significantly higher in the CD arm. Fewer patients in the GD arm discontinued because of drug-related adverse events (13% v 27% in CD; P = .002). Conclusion No difference was observed between GD and CD arms in PFS, ORR, and OS. TTF was longer in the GD arm. These findings, combined with a nonhematologic toxicity profile that favors GD over approved doses of CD, suggest that gemcitabine may be a better option than capecitabine in combination with docetaxel in this clinical setting.
DPC4 Gene Status of the Primary Carcinoma Correlates With Patterns of Failure in Patients With Pancreatic Cancer
Authors: Iacobuzio-Donahue Christine A. , Fu Baojin , Yachida Shinichi , Luo Mingde , Abe Hisashi , Henderson Clark M. , Vilardell Felip , Wang Zheng , Keller Jesse W. , Banerjee Priya , Herman Joseph M. , Cameron John L. , Yeo Charles J. , Halushka Marc K. , Eshleman James R. , Raben Marian , Klein Alison P. , Hruban Ralph H. , Hidalgo Manuel , Laheru Daniel 
Published: March 2009

Purpose Contrary to the extensive data accumulated regarding pancreatic carcinogenesis, the clinical and molecular features characteristic of advanced stage (stage III and IV) disease are unknown. A comprehensive study of pancreatic cancers from patients who have succumbed to their disease has the potential to greatly expand our understanding of the most lethal stage of this disease and identify novel areas for intervention. Materials and Methods Rapid autopsies were performed on 76 patients with documented pancreatic cancer. The histologic features of end stage disease were determined and correlated to the stage at initial diagnosis, patterns of failure (locally destructive v metastatic disease) and the status of the KRAS2, TP53, and DPC4 genes. Results At autopsy, 30% of patients died with locally destructive pancreatic cancer, and 70% died with widespread metastatic disease. These divergent patterns of failure found at autopsy (locally destructive v metastatic) were unrelated to clinical stage at initial presentation, treatment history, or histopathologic features. However, Dpc4 immunolabeling status of carcinoma tissues harvested at autopsy, a sensitive marker of DPC4 genetic status, was highly correlated with the presence of widespread metastasis but not with locally destructive tumors (P = .007). Conclusion Pancreatic cancers are represented by distinct genetic subtypes with significantly different patterns of failure. Determinations of DPC4 status at initial diagnosis may be of value in stratifying patients into treatment regimens related to local control versus systemic therapy.
Online Quality Control, Hyperfractionated Radiotherapy Alone and Reduced Boost Volume for Standard Risk Medulloblastoma: Long-Term Results of MSFOP 98
Authors: Carrie Christian , Grill Jacques , Figarella-Branger Dominique , Bernier Valerie , Padovani Laetitia , Habrand Jean Louis , Benhassel Mohamed , Mege Martine , Mahé Marc , Quetin Philippe , Maire Jean Philippe , Baron Marie Helene , Clavere Pierre , Chapet Sophie , Maingon Philippe , Alapetite Claire , Claude Line , Laprie Anne , Dussart Sophie 
Published: March 2009

Purpose To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance. Patients and Methods Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Société Française d'Oncologie Pédiatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales. Results After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, −1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline. Conclusion HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.
Health Care System and Socioeconomic Factors Associated With Variance in Use of Sentinel Lymph Node Biopsy for Melanoma in the United States
Authors: Bilimoria Karl Y. , Balch Charles M. , Wayne Jeffrey D. , Chang David C. , Palis Bryan E. , Dy Sydney M. , Lange Julie R. 
Published: March 2009

Purpose Guidelines recommend sentinel lymph node biopsy (SLNB) for patients with clinical stage IB/II melanomas, but not clinical stage IA melanoma. This study examines factors associated with SLNB use for clinically node-negative melanoma. Methods Patients diagnosed with clinically node-negative invasive melanoma in 2004 and 2005 were identified from the National Cancer Data Base. Regression models were developed to assess the association of clinicopathologic (sex, age, race/ethnicity, comorbidities, T stage), socioeconomic (insurance status, educational level, income), and hospital (hospital type, geographic area) factors with SLNB use. Results A total of 16,598 patients were identified: 8,073 patients with clinical stage IA and 8,525 patients with clinical stage IB/II melanoma. For clinical stage IB/II melanoma, SLNB use was reported in 48.7% of patients. Patients with clinical stage IB/II melanoma were less likely to undergo SLNB if they were older than 75 years; had T1b tumors, no tumor ulceration, or head/neck or truncal lesions; were covered by Medicaid or Medicare; or lived in the Northeast, South, or West census regions. SLNB use was reported in 13.3% of patients with clinical stage IA melanoma and was more likely in patients who were younger than 56 years or lived in the Mountain or Pacific census regions. Patients treated at National Comprehensive Cancer Network–or National Cancer Institute–designated hospitals were most likely to undergo SLNB in adherence with national consensus guidelines. Conclusion SLNB use was associated with clinicopathologic factors but also with health system factors, including type of insurance, geographic area, and hospital type. These findings have implications for provider education and health policy.
Consolidation Therapy With Low-Dose Thalidomide and Prednisolone Prolongs the Survival of Multiple Myeloma Patients Undergoing a Single Autologous Stem-Cell Transplantation Procedure
Authors: Spencer Andrew , Prince H. Miles , Roberts Andrew W. , Prosser Ian W. , Bradstock Kenneth F. , Coyle Luke , Gill Devinder S. , Horvath Noemi , Reynolds John , Kennedy Nola 
Published: March 2009

Purpose Thalidomide is effective in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). However, the role of thalidomide in the post-autologous stem cell transplantation (ASCT) context remains unclear. This study assessed whether the addition of thalidomide consolidation following ASCT would improve the durability of responses achieved and overall survival. Patients and Methods Between January 2002 and March 2005, 269 patients with newly diagnosed MM who achieved disease stabilization or better with conventional induction chemotherapy received a single high-dose melphalan conditioned ASCT. Post-ASCT, 129 patients were randomly assigned to receive indefinite prednisolone maintenance therapy (control group) and 114 to receive the same in addition to 12 months of thalidomide consolidation (thalidomide group). The primary study end points were progression-free survival (PFS) and overall survival (OS). The secondary end point was tolerability. Results After a median follow-up of 3 years, the postrandomization 3-year PFS rates were 42% and 23% (P < .001; hazard ratio [HR], 0.5; 95% CI, 0.35 to 0.71) and the OS rates were 86% and 75% (P = .004; HR, 0.41; 95% CI, 0.22 to 0.76) in the thalidomide and control groups, respectively. There was no difference in survival between groups 12 months after disease progression (79% v 77%; P = .237). Neurological toxicities were more common in the thalidomide arm but there were no differences between arms for thromboembolic events. Conclusion Consolidation therapy with 12 months of thalidomide combined with prednisolone prolongs survival when used after a single high-dose therapy supported ASCT in patients with newly diagnosed MM. Furthermore, thalidomide consolidation therapy did not adversely impact on survival in the subsequent salvage setting.
Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas
Authors: Maurel Joan , López-Pousa Antonio , de las Peñas Ramón , Fra Joaquín , Martín Javier , Cruz Josefina , Casado Antonio , Poveda Andrés , Martínez-Trufero Javier , Balañá Carmen , Gómez María Auxiliadora , Cubedo Ricardo , Gallego Oscar , Rubio-Viqueira Belen , Rubió Jordi , Andrés Raquel , Sevilla Isabel , de la Cruz Juan Jose , del Muro Xavier García , Buesa Jose María 
Published: March 2009

Purpose To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. Patients and Methods Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m2 per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m2 delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). Results Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). Conclusion Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.