bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender-related differences in MS: a study of conventional and nonconventional MRI measures
Authors: Antulov R , Weinstock-Guttman B , Cox JL , Hussein S , Durfee J , Caiola C , Dwyer MG , Bergsland N , Abdelrahman N , Stosic M , Hojnacki D , Munschauer FE , Miletic D , Zivadinov R 
Published: November 2008

Background Studies showed gender-associated differences in multiple sclerosis (MS) disease evolution and in the evolution of conventional magnetic resonance imaging (MRI) findings. Objective The aim of this study was to investigate gender differences according to a number of conventional and nonconventional MRI measures in patients with MS. Methods We examined 763 consecutive patients with MS [499 (19.2% men) relapsing-remitting (RR), 230 (24.8% men) secondary-progressive, and 34 (44.1% men) primary-progressive], 32 (21.9% men) patients with clinically isolated syndrome (CIS), and 101 (30.7% men) normal controls (NC). Patients were assessed using conventional and nonconventional MRI measures. Gender-related MRI differences were investigated using general linear model analysis, corrected for MS disease type. Results In the total MS group, male patients showed lower normalized peripheral gray matter (GM) ( P < 0.001) and normalized GM ( P = 0.011) volumes than female patients. Female patients presented lower normalized white matter (WM) volumes ( P = 0.011). These gender effects were not observed in NC. Male patients also showed more advanced central atrophy ( P = 0.022). In RRMS male patients, there was also a higher lateral ventricle volume ( P = 0.001). The GM-WM normalized ratio was lower for male patients with MS compared with male NC (0.97 vs. 1.09, P < 0.001) but not in patients with CIS compared with NC. Conclusions There were no significant gender-related differences regarding nonconventional MRI measures. GM and central atrophy are more advanced in male patients, whereas WM atrophy is more advanced in female patients. These gender-related MRI differences may be explained by the effect of sex hormones on brain damage and repair mechanisms.
RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis
Authors: Yan Ming , Ahn Eun-Young , Hiebert Scott W. , Zhang Dong-Er 
Published: November 2008

Abstract
The 8;21 translocation, which involves the gene encoding the RUNX family DNA-binding transcription factor AML1 (RUNX1) on chromosome 21 and the ETO (MTG8) gene on chromosome 8, generates AML1-ETO fusion proteins. Previous analyses have demonstrated that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. More recently, we have identified an alternatively spliced form of AML1-ETO, AML1-ETO9a, from t(8;21) acute myeloid leukemia (AML) patient samples. AML1-ETO9a lacks the C-terminal NHR3 and NHR4 domains of AML1-ETO and is highly leukemogenic in the mouse model. Here, we report that the AML1 DNA-binding domain and the ETO NHR2-dimerization domain, but not the ETO NHR1 domain, are critical for the induction of AML by AML1-ETO9a. A region between NHR1 and NHR2 affects latency of leukemogenesis. These results provide valuable insight into further analysis of the molecular mechanism of t(8;21) in leukemogenesis.
ExonMiner: Web service for analysis of GeneChip Exon array data
Authors: Numata Kazuyuki , Yoshida Ryo , Nagasaki Masao , Saito Ayumu , Imoto Seiya , Miyano Satoru 
Published: November 2008

Abstract

Background
Some splicing isoform-specific transcriptional regulations are related to disease. Therefore, detection of disease specific splice variations is the first step for finding disease specific transcriptional regulations. Affymetrix Human Exon 1.0 ST Array can measure exon-level expression profiles that are suitable to find differentially expressed exons in genome-wide scale. However, exon array produces massive datasets that are more than we can handle and analyze on personal computer.

Results
We have developed ExonMiner that is the first all-in-one web service for analysis of exon array data to detect transcripts that have significantly different splicing patterns in two cells, e.g. normal and cancer cells. ExonMiner can perform the following analyses: (1) data normalization, (2) statistical analysis based on two-way ANOVA, (3) finding transcripts with significantly different splice patterns, (4) efficient visualization based on heatmaps and barplots, and (5) meta-analysis to detect exon level biomarkers. We implemented ExonMiner on a supercomputer system in order to perform genome-wide analysis for more than 300,000 transcripts in exon array data, which has the potential to reveal the aberrant splice variations in cancer cells as exon level biomarkers.

Conclusion
ExonMiner is well suited for analysis of exon array data and does not require any installation of software except for internet browsers. What all users need to do is to access the ExonMiner URL http://ae.hgc.jp/exonminer. Users can analyze full dataset of exon array data within hours by high-level statistical analysis with sound theoretical basis that finds aberrant splice variants as biomarkers.
CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes
Authors: Hestand Matthew S , van Galen Michiel , Villerius Michel P , van Ommen Gert-Jan B , den Dunnen Johan T , 't Hoen Peter AC 
Published: November 2008

AbstractBackgroundThe identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments.ResultsWe have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACRdatabase that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool.ConclusionThe program CORE_TF is accessible in a user friendly web interface athttp://www.LGTC.nl/CORE_TF. It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites.
PlantPAN: Plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups
Authors: Chang Wen-Chi , Lee Tzong-Yi , Huang Hsien-Da , Huang His-Yuan , Pan Rong-Long 
Published: November 2008

Abstract

Background
The elucidation of transcriptional regulation in plant genes is important area of research for plant scientists, following the mapping of various plant genomes, such as A. thaliana, O. sativa and Z. mays. A variety of bioinformatic servers or databases of plant promoters have been established, although most have been focused only on annotating transcription factor binding sites in a single gene and have neglected some important regulatory elements (tandem repeats and CpG/CpNpG islands) in promoter regions. Additionally, the combinatorial interaction of transcription factors (TFs) is important in regulating the gene group that is associated with the same expression pattern. Therefore, a tool for detecting the co-regulation of transcription factors in a group of gene promoters is required.

Results
This study develops a database-assisted system, PlantPAN (Plant Promoter Analysis Navigator), for recognizing combinatorial cis-regulatory elements with a distance constraint in sets of plant genes. The system collects the plant transcription factor binding profiles from PLACE, TRANSFAC (public release 7.0), AGRIS, and JASPER databases and allows users to input a group of gene IDs or promoter sequences, enabling the co-occurrence of combinatorial transcription factor binding sites (TFBSs) within a defined distance (20 bp to 200 bp) to be identified. Furthermore, the new resource enables other regulatory features in a plant promoter, such as CpG/CpNpG islands and tandem repeats, to be displayed. The regulatory elements in the conserved regions of the promoters across homologous genes are detected and presented.

Conclusion
In addition to providing a user-friendly input/output interface, PlantPAN has numerous advantages in the analysis of a plant promoter. Several case studies have established the effectiveness of PlantPAN. This novel analytical resource is now freely available at http://PlantPAN.mbc.nctu.edu.tw.
Frequency and predictors of miliary tuberculosis in patients with miliary pulmonary nodules in South Korea: A retrospective cohort study
Authors: Jin Sang-Man , Lee Hyun Ju , Park Eun-Ah , Lee Ho Yun , Lee Sang-Min , Yang Seok-Chul , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Shim Young-Soo , Yim Jae-Joon 
Published: November 2008

Abstract

Background
Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules.

Methods
We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea.

Results
We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age ≤30 years, HIV infection, corticosteroid use, bronchogenic spread of lesions, and ground-glass opacities occupying >25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB.

Conclusion
Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.
Gene expression profile of cervical and skin tissues from human papillomavirus type 16 E6 transgenic mice
Authors: Mendoza-Villanueva D , Diaz-Chavez J , Uribe-Figueroa L , Rangel-Escareão C , Hidalgo-Miranda A , March-Mifsut S , Jimenez-Sanchez G , Lambert PF , Gariglio P 
Published: November 2008

AbstractBackgroundAlthough K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. These findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues.MethodsWe evaluated the expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with nontransgenic. To identify differentially expressed genes a linear model was implemented using R and the LIMMA package. Two criteria were used to select the set of relevant genes. First a set of genes with a Log-odds ≥ 3 were selected. Then, a hierarchical search of genes was based on Log Fold Changes.ResultsMicroarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in the cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation of pro-apoptotic genes and genes related to the immune response. In the cervix of K14E6 transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways but did observe alterations in the expression of immune response genes. Pathways such as angiogenesis, cell junction and epidermis development, also were altered in their gene expression profiles in both tissues.ConclusionExpression of the HPV16 E6 oncoprotein in our model alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis, the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets.
Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status
Authors: Wei Zhong , Mengzhao Wang , Li Zhang , Longyun Li , Xiaotong Zhang 
Published: November 2008

Abstract

Background
This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.

Methods
From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.

Results
Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival(PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.

Conclusion
Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.
Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells
Authors: Stratford Anna L , Fry Christopher J , Desilets Curtis , Davies Alastair H , Cho Yong Y , Li Yvonne , Dong Zigang , Berquin Isabelle M , Roux Philippe P , Dunn Sandra E 
Published: November 2008

Abstract
Introduction
Basal-like breast cancers (BLBC) frequently overexpress the epidermal growth factor receptor (EGFR) and subsequently have high levels of signaling through the MAP kinase pathway, which is thought to contribute to their aggressive behavior. While we have previously reported the expression of Y-box binding protein-1 (YB-1) in 73% of BLBC, it is unclear whether it can be regulated by a component of the MAP kinase signaling pathway. Phosphorylation of YB-1 at the serine 102 residue is required for transcriptional activation of growth-enhancing genes, such as EGFR. Using Motifscan we identified p90 ribosomal S6 kinase (RSK) as a potential candidate for activating YB-1.

Methods
Inhibition of RSK1 and RSK2 was achieved using siRNA and the small molecule SL0101. RSK1, RSK2, activated RSK and kinase-dead RSK were expressed in HCC1937 cells. Kinase assays were performed to illustrate direct phosphorylation of YB-1 by RSK. The impact of inhibiting RSK on YB-1 function was measured by luciferase assays and chromatin immunoprecipitation.

Results
Using an in vitro kinase assay, RSK1 and RSK2 were shown to directly phosphorylate YB-1. Interestingly, they were more effective activators of YB-1 than AKT or another novel YB-1 kinase, PKCα. Phosphorylation of YB-1 (serine 102 residue) is blocked by inhibition of the MAP kinase pathway or by perturbing RSK1/RSK2 with siRNA or SL0101. In immortalized breast epithelial cells where RSK is active yet AKT is not, YB-1 is phosphorylated. Supporting this observation, RSK2-/- mouse embryo fibroblasts lose the ability to phosphorylate YB-1 in response to epidermal growth factor. This subsequently interfered with the ability of YB-1 to regulate the expression of EGFR. The RSK inhibitor SL0101 decreased the ability of YB-1 to bind the promoter, transactivate and ultimately reduce EGFR expression. In concordance with these results the expression of constitutively active RSK1 increased YB-1 phosphorylation, yet the kinase-dead RSK did not.

Conclusions
We therefore conclude that RSK1/RSK2 are novel activators of YB-1, able to phosphorylate the serine 102 residue. This provides a newly described mechanism whereby YB-1 is activated in breast cancer. This implicates the EGFR/RSK/YB-1 pathway as an important component of BLBC, providing an important opportunity for therapeutic intervention.
Using Median Regression to Obtain Adjusted Estimates of Central Tendency for Skewed Laboratory and Epidemiologic Data
Authors: McGreevy Katharine M , Lipsitz Stuart R , Linder Jeffrey A , Rimm Eric , Hoel David G 
Published: November 2008

Abstract
Background: Laboratory studies often involve analyses of highly skewed data for which means are not an adequate measure of central tendency because they are sensitive to outliers. Attempts to transform skewed data to symmetry are not always successful, and medians are better measures of central tendency for such skewed distributions. When medians are compared across groups, confounding can be an issue, so there is a need for adjusted medians.
Methods: We illustrate the use of quantile regression to obtain adjusted medians. The method is illustrated by use of skewed nutrient data obtained from black and white men attending a prostate cancer screening. For 3 nutrients, saturated fats, caffeine, and vitamin K, we obtained medians adjusted by age, body mass index, and calories for men in each race group.
Results: Quantile regression, linear regression, and log-normal regression produced substantially different adjusted estimates of central tendency for saturated fats, caffeine, and vitamin K.
Conclusions: Our method was useful for analysis of skewed and other nonnormally distributed continuous outcome data and for calculation of adjusted medians.
Quantification of 8 HIV-Protease Inhibitors and 2 Nonnucleoside Reverse Transcriptase Inhibitors by Ultra-Performance Liquid Chromatography with Diode Array Detection
Authors: Elens Laure , Veriter Sophie , Di Fazio Vincent , Vanbinst Roger , Boesmans Daniel , Wallemacq Pierre , Haufroid Vincent 
Published: November 2008

Abstract
Background: Most HPLC-UV methods for therapeutic drug monitoring of anti-HIV drugs have long run times, which reduce their applicability for high-throughput analysis. We developed an ultra-performance liquid chromatography (UPLC)–diode array detection method for the simultaneous quantification of the HIV-protease inhibitors (PIs) amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir (TPV), and the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine.
Methods: Solid-phase extraction of 1 mL plasma was performed with Waters HLB cartridges. After 3 wash steps, we eluted the drugs with methanol, evaporated the alcohol, and reconstituted the residue with 50 μL methanol. We injected a 4-μL volume into the UPLC system (Waters ACQUITY UPLC BEH C8 column maintained at 60 °C) and used a linear gradient of 50 mmol/L ammonium acetate and 50 mmol/L formic acid in water versus acetonitrile to achieve chromatographic separation of the drugs and internal standard (A-86093). Three wavelengths (215, 240, and 260 nm) were monitored.
Results: All drugs were eluted within 15 min. Calibration curves with concentrations of 0.025–10 mg/L (1.875–75 mg/L for TPV) showed coefficients of determination (r2) between 0.993 and 0.999. The lower limits of quantification were well below the trough concentrations reported in the literature. Inter- and intraassay CVs and the deviations between the nominal and measured concentrations were &lt;15%. The method was validated by successful participation in an international interlaboratory QC program.
Conclusions: This method allows fast and simultaneous quantification of all commercially available PIs and NNRTIs for therapeutic drug monitoring.
Only Large Reductions in Concentrations of Natriuretic Peptides (BNP and NT-proBNP) Are Associated with Improved Outcome in Ambulatory Patients with Chronic Heart Failure
Authors: Miller Wayne L , Hartman Karen A , Grill Diane E , Burnett John C , Jaffe Allan S 
Published: November 2008

Abstract
Background: Concentrations of B-type natriuretic peptides (BNPs), including N-terminal pro-B-type natriuretic peptide (NT-proBNP), can be used to estimate prognosis in chronic heart failure. Large biologic variability, however, limits the usefulness of serial measurements in individual patients. As a result, the magnitude of change in peptide concentrations that is clinically meaningful remains to be established.
Methods: We studied 172 New York Heart Association class III–IV outpatients. Primary endpoints were death/transplantation or heart failure hospitalization. The magnitude of peptide changes was categorized as no change (&lt;20% increase or decrease from enrollment), ≥20% to ≤80% increase or decrease; and &gt;80% increase or decrease. Changes were also assessed using cutpoints (500 ng/L for BNP and 1000 ng/L for NT-proBNP).
Results: Fifty-two patients died or received transplants during the course of the study. Risk reduction for heart failure hospitalization was demonstrated only for BNP decreases of &gt;80% from enrollment [hazard ratio (HR) 0.318, P = 0.0315]. BNP increases from less than to more than the prespecified cutpoint of 500 ng/L were associated with increased mortality risk (HR 2.101, P = 0.0069), whereas decreases from more than to less than the cutpoint did not reduce risk. NT-proBNP decreases from more than to less than the cutpoint of 1000 ng/L were associated with reduced risk of death/transplantation (HR 0.119, P = 0.0354).
Conclusions: BNP increases from less than to more than the cutpoint were associated with increased risk of events, whereas further increases did not add to risk. In contrast, only substantial natriuretic peptide decreases (&gt;80%) reduced risk. These data suggest that only robust decreases in natriuretic peptide concentrations should be targeted to reduce mortality and heart failure-related hospitalizations.