bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease
Authors: Pokov Ilya , Kuliczkowski Wiktor , Chesebro James , Badimon Juan , Serebruany Victor 
Published: June 2008

SummaryThe objective was to describe the indices of platelet aggregation and activation in a large cohort of diabetic patients with coronary artery disease (CAD). Recently, a number of observations have indicated that patients with diabetes mellitus (DM) exhibit persistent platelet activation, and low response after antiplatelet therapy, although no randomized data exist. We sought to define the baseline platelet biomarkers, and the patterns of response to aspirin and clopidogrel therapy in DM versus non-diabetic patients. Secondary post-hoc analyses were made of platelet activity biomarkers in the dataset which consisted of patients with documented CAD (n=822), including those with DM (n=257). Patients with DM exhibited higher baseline platelet activity by adenosine diphosphate (ADP)- (p=0.0002), and collagen-induced (p=0.03) aggregometry; Ultegra- (p=0.0001), and PFA-100 (p=0.02) analyzers; and expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (p=0.01), glycoprotein (GP) IIb/IIIa antigen (p=0.001), and activity (p=0.02), vitronectin receptor (p=0.03), P selectin (p=0.02), and intact epitope of PAR-1 thrombin receptor (p=0.02). Antiplatelet response after clopidogrel in diabetics was impaired when compared with non-diabetics. In conclusion, diabetic patients exhibit high pretreatment platelet activity, and do not respond well to the available antiplatelet regimens when compared with similar patients without DM. The clinical implications of these findings are unknown but are potentially important. Considering worsened outcomes in this high-risk population, clinical trials in DM are urgently needed in order to define the optimal degree of platelet inhibition and suitability for more aggressive antiplatelet regimens.
An evaluation of methods for determining reference intervals for light transmission platelet aggregation tests on samples with normal or reduced platelet counts
Authors: Moffat Karen A. , Pai Menaka , Liu Yang , Seecharan Jodi , McKay Heather , Webert Kathryn E. , Cook Richard J. , Heddle Nancy M. , Hayward Catherine P. M. 
Published: June 2008

SummaryLight transmission platelet aggregation tests are important for diagnosing platelet function defects. However, uncertainties exist about the best procedures to determine aggregation reference intervals. We investigated methods for determining reference intervals for light transmission aggregation tests, using the % maximal aggregation values for prospectively collected data on healthy control samples. Reference intervals for samples tested at 250 x 109 platelets/l were determined by mean ± 2 standard deviations and non-parametric analyses. To establish reference intervals for tests on thrombocytopenic subjects, regression analyses were used to estimate 95% confidence limits for % maximal aggregation, according to sample platelet counts, using data for control samples diluted to match the platelet count of undiluted thrombocytopenic patient platelet-rich plasma samples. For samples tested at 250 x 109 platelets/l, non-parametric analyses described 95% of data for healthy control samples better than mean ± 2 standard deviations. For samples tested at lower counts, to match thrombocytopenic samples, the % maximal aggregation was influenced by platelet count and derived limits were wider at very low platelet counts for almost all agonists. With ristocetin, it proved feasible to test samples with very low platelet counts to exclude Bernard-Soulier syndrome and type 2B von Willebrand disease. Non-parametric analyses should be the preferred method to establish light transmission aggregation reference intervals for samples tested at normal platelet counts. The derived limits for thrombocytopenic samples provide guidance for evaluating thrombocytopenic platelet function disorders, including which agonists to test, based on the sample platelet count.
Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry
Authors: Ruíz-Giménez Nuria , Suárez Carmen , González Rocío , Nieto José , Todolí José , Samperiz Ángel , Monreal Manuel ,   and the RIETE Investigators
Published: June 2008

SummaryA score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1–4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval [CI]: 0.1–0.6), 2.6% (95% CI: 2.3–2.9), and 7.3% (95% CI: 5.6–9.3), respectively. The likelihood ratio test was:0.14 (95% CI:0.07–0.27) for patients at low risk;2.96 (95% CI:2.18–4.02) for those at high risk. In the validation sample the incidence of major bleeding was:0.1%,2.8%,and 6.2%,respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.
Aristotle on Natural Slavery
Authors: Heath Malcolm 
Published: June 2008

AbstractAristotle's claim that natural slaves do not possess autonomous rationality (Pol. 1.5, 1254b20-23) cannot plausibly be interpreted in an unrestricted sense, since this would conflict with what Aristotle knew about non-Greek societies. Aristotle's argument requires only a lack of autonomous practical rationality. An impairment of the capacity for integrated practical deliberation, resulting from an environmentally induced excess or deficiency in thumos (Pol. 7.7, 1327b18-31), would be sufficient to make natural slaves incapable of eudaimonia without being obtrusively implausible relative to what Aristotle is likely to have believed about non-Greeks. Since Aristotle seems to have believed that the existence of people who can be enslaved without injustice is a hypothetical necessity, if those capable of eudaimonia are to achieve it, the existence of natural slaves has implications for our understanding of Aristotle's natural teleology.
Attitudes of Parents and Physicians Toward Febrile Seizures
Authors: Yilmaz Deniz , Arhan Ebru , Yuksel Deniz , Özçelik Aysima , Senbil Nesrin , Serdaroglu Ayse , Gurer Y.K. Yavuz 
Published: June 2008

Objectives Although febrile seizures are common in children, attitudes may change among parents. The management of a child may differ depending on the specialty of the attending physician. This study was carried out to analyze attitudes of Turkish parents and physicians toward febrile seizures. Material and Methods 308 children with febrile seizure who were admitted to the Department of Pediatric Neurology at Dr Sami Ulus Children's Hospital and Gazi University in Turkey between January 2006 and March 2007 were enrolled. Results Prior to seizure, approximately half of the parents took appropriate steps in reducing fever. The data also showed that there was a wide variation of treatment practice depending on the specialty of the attending physician. Discussion Educational level and economic status are important variables affecting attitudes of parents toward fever and febrile seizure. The management of the child with a febrile seizure differs even within the same specialty in Turkish physicians.
Targeting a single mismatched minor histocompatibility antigen with tumor-restricted expression eradicates human solid tumors
Authors: Hambach Lothar , Vermeij Marcel , Buser Andreas , Aghai Zohara , van der Kwast Theodorus , Goulmy Els 
Published: June 2008

AbstractRegressions of metastatic solid tumors after allogeneic human leukocyte antigen (HLA)–matched stem cell transplantation (SCT) are often associated with detrimental graft-versus-host disease (GVHD). The graft-versus-host reaction of the HLA-matched donor is directed mainly against the multiple mismatched minor histocompatibility antigens (mHags) of the patient. mHags are strong HLA-restricted alloantigens with differential tissue distribution. Ubiquitously expressed mHags are the prime in situ targets of GVHD. The mHag HA-1 is hematopoiesis restricted, but displays additionally an aberrant expression on solid tumors. Thus, HA-1 might be an excellent target to boost the anti–solid tumor effect of allogeneic SCT without inducing severe GVHD. Here, we show that cytotoxic T lymphocytes (CTLs) solely targeting the human mHag HA-1 are capable of eradicating 3-dimensional human solid tumors in a highly mHag-specific manner in vitro, accompanied by interferon-γ release. In vivo, HA-1–specific CTLs distribute systemically and prevent human breast cancer metastases in immunodeficient mice. Moreover, HA-1–specific CTLs infiltrate and inhibit the progression of fully established metastases. Our study provides the first proof for the efficacy of a clinically applicable concept to exploit single mismatched mHags with hematopoiesis- and solid tumor–restricted expression for boosting the anti–solid tumor effect of allogeneic SCT.
Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP
Authors: Rimsza Lisa M. , LeBlanc Michael L. , Unger Joseph M. , Miller Thomas P. , Grogan Thomas M. , Persky Daniel O. , Martel Ralph R. , Sabalos Constantine M. , Seligmann Bruce , Braziel Rita M. , Campo Elias , Rosenwald Andreas , Connors Joseph M. , Sehn Laurie H. , Johnson Nathalie , Gascoyne Randy D. 
Published: June 2008

AbstractGene expression profiling (GEP) on frozen tissues has identified genes predicting outcome in patients with diffuse large B-cell lymphoma (DLBCL). Confirmation of results in current patients is limited by availability of frozen samples and addition of monoclonal antibodies to treatment regimens. We used a quantitative nuclease protection assay (qNPA) to analyze formalin-fixed, paraffin-embedded tissue blocks for 36 previously identified genes (N = 209, 93 chemotherapy; 116 rituximab + chemotherapy). By qNPA, 208 cases were successfully analyzed (99.5%). In addition, 15 of 36 and 11 of 36 genes, representing each functional group previously identified by GEP, were associated with survival (P < .05) in the 2 treatment groups, respectively. In addition, 30 of 36 hazard ratios of death trended in the same direction versus the original studies. Multivariate and variable cut-off point analysis identified low levels of HLA-DRB (< 20%) and high levels of MYC (> 80%) as independent indicators of survival, together distinguishing cases with the worst prognosis. Our results solve a clinical research problem by demonstrating that prognostic genes can be meaningfully quantified using qNPA technology on formalin-fixed, paraffin-embedded tissues; previous GEP findings in DLBCL are relevant with current treatments; and 2 genes, representing immune escape and proliferation, are the common features of the most aggressive DLBCL.
A single nucleotide polymorphism at chromosome 2q21.3 (LCT −13910C>T) associates with clinical outcome after allogeneic hematopoietic stem cell transplantation
Authors: Hauser Hanns , Zach Otto , Krieger Otto , Kasparu Hedwig , Koenig Josef , Girschikofsky Michael , Oberbauer Rainer , Lutz Dieter 
Published: June 2008

Abstract
A single nucleotide polymorphism (SNP) responsible for lactase persistence (LCT −13910C>T) changes intestinal microflora. Considering the influence of bacterial microflora on various immune effects, we tested DNA from 111 recipients/donors and analyzed whether this SNP interferes with survival and the incidence of acute graft-versus-host disease (aGVHD) after allogeneic hematopoetic stem cell tranplantations (HSCT). Median overall survival (OS) was significantly longer when donors had a CC genotype (not reached after 133 vs 11.1 months, P = .004). Multivariate analysis identified a donor T allele (hazard ratio 2.63, 95% confidence interval 1.29-5.33, P = .008) as independent risk factor for death. Surprisingly, recipient genotypes did not influence outcome and there were no differences regarding aGVHD. Transplantation-related mortality (TRM), relapse and pneumonia were significantly less frequent in patients with CC donors. These findings add to the growing list of non-HLA polymorphisms with impact on outcome after allogeneic HSCT.
Semantic role labeling for protein transport predicates
Authors: Bethard Steven , Lu Zhiyong , Martin James H , Hunter Lawrence 
Published: June 2008

Abstract

Background
Automatic semantic role labeling (SRL) is a natural language processing (NLP) technique that maps sentences to semantic representations. This technique has been widely studied in the recent years, but mostly with data in newswire domains. Here, we report on a SRL model for identifying the semantic roles of biomedical predicates describing protein transport in GeneRIFs – manually curated sentences focusing on gene functions. To avoid the computational cost of syntactic parsing, and because the boundaries of our protein transport roles often did not match up with syntactic phrase boundaries, we approached this problem with a word-chunking paradigm and trained support vector machine classifiers to classify words as being at the beginning, inside or outside of a protein transport role.

Results
We collected a set of 837 GeneRIFs describing movements of proteins between cellular components, whose predicates were annotated for the semantic roles AGENT, PATIENT, ORIGIN and DESTINATION. We trained these models with the features of previous word-chunking models, features adapted from phrase-chunking models, and features derived from an analysis of our data. Our models were able to label protein transport semantic roles with 87.6% precision and 79.0% recall when using manually annotated protein boundaries, and 87.0% precision and 74.5% recall when using automatically identified ones.

Conclusion
We successfully adapted the word-chunking classification paradigm to semantic role labeling, applying it to a new domain with predicates completely absent from any previous studies. By combining the traditional word and phrasal role labeling features with biomedical features like protein boundaries and MEDPOST part of speech tags, we were able to address the challenges posed by the new domain data and subsequently build robust models that achieved F-measures as high as 83.1. This system for extracting protein transport information from GeneRIFs performs well even with proteins identified automatically, and is therefore more robust than the rule-based methods previously used to extract protein transport roles.
Microarray analysis of ncRNA expression patterns in Caenorhabditis elegans after RNAi against snoRNA associated proteins
Authors: Aftab Muhammad Nauman , He Housheng , Skogerbø Geir , Chen Runsheng 
Published: June 2008

Abstract

Background
Short non-coding RNAs (ncRNAs) perform their cellular functions in ribonucleoprotein (RNP) complexes, which are also essential for maintaining the stability of the ncRNAs. Depletion of individual protein components of non-coding ribonucleoprotein (ncRNP) particles by RNA interference (RNAi) may therefore affect expression levels of the corresponding ncRNA, and depletion of candidate associated proteins may constitute an alternative strategy when investigating ncRNA-protein interactions and ncRNA functions. Therefore, we carried out a pilot study in which the effects of RNAi against protein components of small nucleolar RNPs (snoRNPs) in Caenorhabditis elegans were observed on an ncRNA microarray.

Results
RNAi against individual C. elegans protein components of snoRNPs produced strongly reduced mRNA levels and distinct phenotypes for all targeted proteins. For each type of snoRNP, individual depletion of at least three of the four protein components produced significant (P ≦ 1.2 × 10-5) reductions in the expression levels of the corresponding small nucleolar RNAs (snoRNAs), whereas the expression levels of other ncRNAs were largely unaffected. The effects of depletion of individual proteins were in accordance with snoRNP structure analyses obtained in other species for all but two of the eight targeted proteins. Variations in snoRNA size, sequence and secondary structure characteristics were not systematically reflected in the affinity for individual protein component of snoRNPs. The data supported the classification of nearly all annotated snoRNAs and suggested the presence of several novel snoRNAs among unclassified short ncRNA transcripts. A number of transcripts containing canonical Sm binding element sequences (Sm Y RNAs) also showed reduced expression after depletion of protein components of C/D box snoRNPs, whereas the expression of some stem-bulge RNAs (sbRNAs) was increased after depletion of the same proteins.

Conclusion
The study confirms observations made for other organisms, where reduced ncRNA levels after depletion of protein components of ncRNPs were noted, and shows that such reductions in expression levels occur across entire sets of ncRNA. Thereby, the study also demonstrates the feasibility of combining RNAi against candidate proteins with ncRNA microarray analysis to investigate ncRNA-protein interactions and hence ncRNA cellular functions.
The interplay of StyR and IHF regulates substrate-dependent induction and carbon catabolite repression of styrene catabolism genes in Pseudomonas fluorescens ST
Authors: Rampioni Giordano , Leoni Livia , Pietrangeli Biancamaria , Zennaro Elisabetta 
Published: June 2008

Abstract

Background
In Pseudomonas fluorescens ST, the promoter of the styrene catabolic operon, PstyA, is induced by styrene and is subject to catabolite repression. PstyA regulation relies on the StyS/StyR two-component system and on the IHF global regulator. The phosphorylated response regulator StyR (StyR-P) activates PstyA in inducing conditions when it binds to the high-affinity site STY2, located about -40 bp from the transcription start point. A cis-acting element upstream of STY2, named URE, contains a low-affinity StyR-P binding site (STY1), overlapping the IHF binding site. Deletion of the URE led to a decrease of promoter activity in inducing conditions and to a partial release of catabolite repression. This study was undertaken to assess the relative role played by IHF and StyR-P on the URE, and to clarify if PstyA catabolite repression could rely on the interplay of these regulators.

Results
StyR-P and IHF compete for binding to the URE region. PstyA full activity in inducing conditions is achieved when StyR-P and IHF bind to site STY2 and to the URE, respectively. Under catabolite repression conditions, StyR-P binds the STY1 site, replacing IHF at the URE region. StyR-P bound to both STY1 and STY2 sites oligomerizes, likely promoting the formation of a DNA loop that closes the promoter in a repressed conformation. We found that StyR and IHF protein levels did not change in catabolite repression conditions, implying that PstyA repression is achieved through an increase in the StyR-P/StyR ratio.

Conclusion
We propose a model according to which the activity of the PstyA promoter is determined by conformational changes. An open conformation is operative in inducing conditions when StyR-P is bound to STY2 site and IHF to the URE. Under catabolite repression conditions StyR-P cellular levels would increase, displacing IHF from the URE and closing the promoter in a repressed conformation. The balance between the open and the closed promoter conformation would determine a fine modulation of the promoter activity. Since StyR and IHF protein levels do not vary in the different conditions, the key-factor regulating PstyA catabolite repression is likely the kinase activity of the StyR-cognate sensor protein StyS.
The Natural History of Primary Hyperparathyroidism with or without Parathyroid Surgery after 15 Years
Authors: Rubin Mishaela R. , Bilezikian John P. , McMahon Donald J. , Jacobs Thomas , Shane Elizabeth , Siris Ethel , Udesky Julia , Silverberg Shonni J. 
Published: June 2008

Context: Primary hyperparathyroidism (PHPT) often presents without classical symptoms such as overt skeletal disease or nephrolithiasis. We previously reported that calciotropic indices and bone mineral density (BMD) are stable in untreated patients for up to a decade, whereas after parathyroidectomy, normalization of biochemistries and increases in BMD ensue.
Objective: The objective of the study was to provide additional insights in patients with and without surgery for up to 15 yr.
Design: The study had an observational design.
Setting: The setting was a referral center.
Patients: Patients included 116 patients (25 men, 91 women); 99 (85%) were asymptomatic.
Intervention: Fifty-nine patients (51%) underwent parathyroidectomy and 57 patients were followed up without surgery.
Main Outcome Measure: BMD was measured.
Results: Lumbar spine BMD remained stable for 15 yr. However, BMD started to fall at cortical sites even before 10 yr, ultimately decreasing by 10 ± 3% (mean ± sem; P &lt; 0.05) at the femoral neck, and 35 ± 5%; P &lt; 0.05 at the distal radius, in the few patients observed for 15 yr. Thirty-seven percent of asymptomatic patients showed disease progression (one or more new guidelines for surgery) at any time point over the 15 yr. Meeting surgical criteria at baseline did not predict who would have progressive disease. BMD increases in patients who underwent surgery were sustained for the entire 15 yr.
Conclusions: Parathyroidectomy led to normalization of biochemical indices and sustained increases in BMD. Without surgery, PHPT progressed in one third of individuals over 15 yr; meeting surgical criteria at the outset did not predict this progression. Cortical bone density decreased in the majority of subjects with additional observation time points and long-term follow-up. These results raise questions regarding how long patients with PHPT should be followed up without intervention.