bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects
Authors: Tay Lee , Leon Francisco , Vratsanos George , Raymond Ralph , Corbo Michael 
Published: April 2007

Abstract
The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes.
Soluble Fas ligand inhibits angiogenesis in rheumatoid arthritis
Authors: Kim Wan-Uk , Kwok Seung-Ki , Hong Kyung-Hee , Yoo Seung-Ah , Kong Jin-Sun , Choe Jongseon , Cho Chul-Soo 
Published: April 2007

AbstractThe characteristics of rheumatoid arthritis (RA) pathology include the infiltration of inflammatory leukocytes, the proliferation of synovial cells, and the presence of extensive angiogenesis, referred to as rheumatoid pannus. Fas ligand is critical to the homeostatic regulation of the immune response, but its role in the angiogenic process of RA remains to be defined. In this study, we investigated whether soluble Fas ligand (sFasL) induces synoviocyte apoptosis and regulates angiogenesis of endothelial cells in RA. The levels of sFasL were elevated in the synovial fluids of RA patients when compared to those of osteoarthritis (OA) patients, and they correlated inversely with vascular endothelial growth factor165(VEGF165) concentrations. sFasL, ranging from 10 to 100 ng/ml, induced the apoptosis of RA fibroblast-like synoviocytes (FLS)in vitro, and thereby decreased VEGF165production. In addition, sFasL inhibited VEGF165-induced migration and chemotaxis of endothelial cells to basal levels in a manner independent of the Fas-mediated cell death. sFasL dose-dependently suppressed the VEGF165-stimulated increase in pAkt expression in endothelial cells, which might be associated with its anti-migratory effect on endothelial cells. Moreover, sFasL strongly inhibited neovascularization in the Matrigel plugin vivo. Our data suggest that sFasL shows anti-angiogenic activity within RA joints not only by inducing apoptosis of VEGF165-producing cells but also by blocking VEGF165-induced migration of endothelial cells, independent of Fas-mediated apoptosis.
Identification of typical medullary breast carcinoma as a genomic sub-group of basal-like carcinomas, a heterogeneous new molecular entity
Authors: Vincent-Salomon Anne , Gruel Nadège , Lucchesi Carlo , MacGrogan Gaëtan , Dendale Remi , Sigal-Zafrani Brigitte , Longy Michel , Raynal Virginie , Pierron Gaëlle , de Mascarel Isabelle , Taris Corinne , Stoppa-Lyonnet Dominique , Pierga Jean-Yves , Salmon Rémy , Sastre-Garau Xavier , Fourquet Alain , Delattre Olivier , de Cremoux Patricia , Aurias Alain 
Published: April 2007

Abstract
Introduction
Typical medullary breast carcinoma (MBC) has recently been recognized to be part of the basal-like carcinoma spectrum, a feature in agreement with the high rate of TP53 mutations previously reported in MBCs. The present study was therefore designed to identify phenotypic and genetic alterations that distinguish MBCs from basal-like carcinomas (BLC).

Methods
Expression levels of estrogen receptor (ER), progesterone receptor (PR), ERBB2, TP53, cytokeratins (KRTs) 5/6, 14, 8/18, epidermal growth factor receptor and KIT, as well as TP53 gene sequence and high-density array comparative genomic hybridization (CGH) profiles, were assessed and compared in a series of 33 MBCs and 26 BLCs.

Results
All tumors were negative for ER, PR and ERBB2. KRTs 5/6 were more frequently expressed in MBCs (94%) than in BLCs (56%) (p = 0.0004). TP53 mutations were disclosed in 20/26 MBCs (77%) and 20/24 BLCs (83%). Array CGH analysis showed that a higher number of gains (95 regions) and losses (34 regions) was observed in MBCs than in BLCs (36 regions of gain; 13 regions of losses). In addition, gains of 1q and 8q, and losses of X were found to be common to the two groups, whereas gains of 10p (53% of the cases), 9p (30.8% of the cases) and 16q (25.8% of the cases), and losses of 4p (34.8% of the cases), and amplicons of 1q, 8p, 10p and 12p were the genetic alterations found to characterize MBC.

Conclusion
Our study has revealed that MBCs are part of the basal-like group and share common genomic alterations with BLCs, the most frequent being 1q and 8q gains and X losses; however, MBCs are a distinct entity within the basal-like spectrum, characterized by a higher rate of KRT 5/6 expression, a higher rate of gains and losses than BLCs, recurrent 10p, 9p and 16q gains, 4p losses, and 1q, 8p, 10p and 12p amplicons. Our results thus contribute to a better understanding of the heterogeneity in basal-like breast tumors and provide potential diagnostic tools.
N-terminal pro-brain natriuretic peptide as an early prognostic factor in cancer patients developing septic shock
Authors: Mokart Djamel , Sannini Antoine , Brun Jean-Paul , Faucher Marion , Blaise Didier , Blache Jean-Louis , Faucher Catherine 
Published: April 2007

Abstract
Introduction
The overall prognosis of critically ill patients with cancer has improved during the past decade. The aim of this study was to identify early prognostic factors of intensive care unit (ICU) mortality in patients with cancer.

Methods
We designed a prospective, consecutive, observational study over a one-year period. Fifty-one cancer patients with septic shock were enrolled.

Results
The ICU mortality rate was 51% (26 deaths). Among the 45 patients who benefited from transthoracic echocardiography evaluation, 17 showed right ventricular dysfunction, 18 showed left ventricular diastolic dysfunction, 18 showed left ventricular systolic dysfunction, and 11 did not show any cardiac dysfunction. During the first three days of ICU course, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly higher in patients presenting cardiac dysfunctions compared to patients without any cardiac dysfunction. Multivariate analysis discriminated early prognostic factors (within the first 24 hours after the septic shock diagnosis). ICU mortality was independently associated with NT-proBNP levels at day 2 (odds ratio, 1.2; 95% confidence interval, 1.004 to 1.32; p = 0.022). An NT-proBNP level of more than 6,624 pg/ml predicted ICU mortality with a sensitivity of 86%, a specificity of 77%, a positive predictive value of 79%, a negative predictive value of 85%, and an accuracy of 81%.

Conclusion
We observed that critically ill cancer patients with septic shock have an approximately 50% chance of survival to ICU discharge. NT-proBNP was independently associated with ICU mortality within the first 24 hours. NT-proBNP could be a useful tool for detecting high-risk cancer patients within the first 24 hours after septic shock diagnosis.
The influence of volume and intensive care unit organization on hospital mortality in patients admitted with severe sepsis: a retrospective multicentre cohort study
Authors: Peelen Linda , de Keizer Nicolette F , Peek Niels , Scheffer Gert Jan , van der Voort Peter HJ , de Jonge Evert 
Published: April 2007

Abstract
Introduction
The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis.

Methods
A retrospective cohort study was conducted using the database of the Dutch National Intensive Care Evaluation (NICE) registry. Analyses were based on consecutive patients admitted between 1 January 2003 and 30 June 2005 who fulfilled criteria for severe sepsis within the first 24 hours of admission. A 13-item questionnaire was sent to all 32 ICUs across The Netherlands that participated in the NICE registry within this period in order to obtain information on ICU organization and staffing. The association between in-hospital mortality and factors related to ICU organization was investigated using logistic regression analysis, combined with generalized estimation equations to account for potential correlations of outcomes within ICUs. Correction for patient-related factors took place by including Simplified Acute Physiology Score II, age, sex and number of dysfunctioning organ systems in the analyses.

Results
Analyses based on 4,605 patients from 28 ICUs (questionnaire response rate 90.6%) revealed that a higher annual volume of severe sepsis patients is associated with a lower in-hospital mortality (P = 0.029). The presence of a medium care unit (MCU) as a step-down facility with intermediate care is associated with a higher in-hospital mortality (P = 0.013). For other items regarding ICU organization, no independent significant relationships with in-hospital mortality were found.

Conclusion
A larger annual volume of patients with severe sepsis admitted to Dutch ICUs is associated with lower in-hospital mortality in this patient group. The presence of a MCU as a step-down facility is associated with greater in-hospital mortality. No other significant associations between in-hospital mortality and factors related to ICU organization were found.
Minimally invasive cardiopulmonary bypass: does it really change the outcome?
Authors: Ranucci Marco , Isgrò Giuseppe 
Published: April 2007

Abstract
Introduction
Many innovative cardiopulmonary bypass (CPB) systems have recently been proposed by the industry. With few differences, they all share a philosophy based on priming volume reduction, closed circuit with separation of the surgical field suction, centrifugal pump, and biocompatible circuit and oxygenator. These minimally invasive CPB (MICPB) systems are intended to limit the deleterious effects of a conventional CPB. However, no evidence exists with respect to their effectiveness in improving the postoperative outcome in a large population of patients. This study aimed to verify the clinical impact of an MICPB in a large population of patients undergoing coronary artery revascularization.

Methods
We conducted a retrospective analysis of 1,663 patients treated with an MICPB. The control group (conventional CPB) was extracted from a series of 2,877 patients according to a propensity score analysis.

Results
Patients receiving an MICPB had a shorter intensive care unit (ICU) stay, had lower peak postoperative serum creatinine and bilirubin levels, and suffered less postoperative blood loss. Within a multivariable model, MICPB is independently associated with lower rates of atrial fibrillation (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.69 to 0.99) and ventricular arrhythmias (OR 0.45, 95% CI 0.28 to 0.73) and with higher rates of early discharge from the ICU (OR 1.31, 95% CI 1.06 to 1.6) and from the hospital (OR 1.46, 95% CI 1.18 to 1.8). Hospital mortality did not differ between groups.

Conclusion
MICPBs are associated with reduced morbidity. However, these results will need to be confirmed in a large, prospective, randomized, controlled trial.
Sense-antisense pairs in mammals: functional and evolutionary considerations
Authors: Galante Pedro AF , Vidal Daniel O , de Souza Jorge E , Camargo Anamaria A , de Souza Sandro J 
Published: April 2007

Abstract
Background
A significant number of genes in mammalian genomes are being found to have natural antisense transcripts (NATs). These sense-antisense (S-AS) pairs are believed to be involved in several cellular phenomena.

Results
Here, we generated a catalog of S-AS pairs occurring in the human and mouse genomes by analyzing different sources of expressed sequences available in the public domain plus 122 massively parallel signature sequencing (MPSS) libraries from a variety of human and mouse tissues. Using this dataset of almost 20,000 S-AS pairs in both genomes we investigated, in a computational and experimental way, several putative roles that have been assigned to NATs, including gene expression regulation. Furthermore, these global analyses allowed us to better dissect and propose new roles for NATs. Surprisingly, we found that a significant fraction of NATs are artifacts produced by genomic priming during cDNA library construction.

Conclusion
We propose an evolutionary and functional model in which alternative polyadenylation and retroposition account for the origin of a significant number of functional S-AS pairs in mammalian genomes.
Porcine transcriptome analysis based on 97 non-normalized cDNA libraries and assembly of 1,021,891 expressed sequence tags
Authors: Gorodkin Jan , Cirera Susanna , Hedegaard Jakob , Gilchrist Michael J , Panitz Frank , Jørgensen Claus , Scheibye-Knudsen Karsten , Arvin Troels , Lumholdt Steen , Sawera Milena , Green Trine , Nielsen Bente J , Havgaard Jakob H , Rosenkilde Carina , Wang Jun , Li Heng , Li Ruiqiang , Liu Bin , Hu Songnian , Dong Wei , Li Wei , Yu Jun , Wang Jian , Stærfeldt Hans-Henrik , Wernersson Rasmus , Madsen Lone B , Thomsen Bo , Hornshøj Henrik , Bujie Zhan , Wang Xuegang , Wang Xuefei , Bolund Lars , Brunak Søren , Yang Huanming , Bendixen Christian , Fredholm Merete 
Published: April 2007

Abstract
Background
Knowledge of the structure of gene expression is essential for mammalian transcriptomics research. We analyzed a collection of more than one million porcine expressed sequence tags (ESTs), of which two-thirds were generated in the Sino-Danish Pig Genome Project and one-third are from public databases. The Sino-Danish ESTs were generated from one normalized and 97 non-normalized cDNA libraries representing 35 different tissues and three developmental stages.

Results
Using the Distiller package, the ESTs were assembled to roughly 48,000 contigs and 73,000 singletons, of which approximately 25% have a high confidence match to UniProt. Approximately 6,000 new porcine gene clusters were identified. Expression analysis based on the non-normalized libraries resulted in the following findings. The distribution of cluster sizes is scaling invariant. Brain and testes are among the tissues with the greatest number of different expressed genes, whereas tissues with more specialized function, such as developing liver, have fewer expressed genes. There are at least 65 high confidence housekeeping gene candidates and 876 cDNA library-specific gene candidates. We identified differential expression of genes between different tissues, in particular brain/spinal cord, and found patterns of correlation between genes that share expression in pairs of libraries. Finally, there was remarkable agreement in expression between specialized tissues according to Gene Ontology categories.

Conclusion
This EST collection, the largest to date in pig, represents an essential resource for annotation, comparative genomics, assembly of the pig genome sequence, and further porcine transcription studies.
Assembly of the Candida albicans genome into sixteen supercontigs aligned on the eight chromosomes
Authors: van het Hoog Marco , Rast Timothy J , Martchenko Mikhail , Grindle Suzanne , Dignard Daniel , Hogues Hervé , Cuomo Christine , Berriman Matthew , Scherer Stewart , Magee BB , Whiteway Malcolm , Chibana Hiroji , Nantel André , Magee PT 
Published: April 2007

Abstract
Background
The 10.9× genomic sequence of Candida albicans, the most important human fungal pathogen, was published in 2004. Assembly 19 consisted of 412 supercontigs, of which 266 were a haploid set, since this fungus is diploid and contains an extensive degree of heterozygosity but lacks a complete sexual cycle. However, sequences of specific chromosomes were not determined.

Results
Supercontigs from Assembly 19 (183, representing 98.4% of the sequence) were assigned to individual chromosomes purified by pulse-field gel electrophoresis and hybridized to DNA microarrays. Nine Assembly 19 supercontigs were found to contain markers from two different chromosomes. Assembly 21 contains the sequence of each of the eight chromosomes and was determined using a synteny analysis with preliminary versions of the Candida dubliniensis genome assembly, bioinformatics, a sequence tagged site (STS) map of overlapping fosmid clones, and an optical map. The orientation and order of the contigs on each chromosome, repeat regions too large to be covered by a sequence run, such as the ribosomal DNA cluster and the major repeat sequence, and telomere placement were determined using the STS map. Sequence gaps were closed by PCR and sequencing of the products. The overall assembly was compared to an optical map; this identified some misassembled contigs and gave a size estimate for each chromosome.

Conclusion
Assembly 21 reveals an ancient chromosome fusion, a number of small internal duplications followed by inversions, and a subtelomeric arrangement, including a new gene family, the TLO genes. Correlations of position with relatedness of gene families imply a novel method of dispersion. The sequence of the individual chromosomes of C. albicans raises interesting biological questions about gene family creation and dispersion, subtelomere organization, and chromosome evolution.
Comparative genomics using Fugu reveals insights into regulatory subfunctionalization
Authors: Woolfe Adam , Elgar Greg 
Published: April 2007

Abstract
Background
A major mechanism for the preservation of gene duplicates in the genome is thought to be mediated via loss or modification of cis-regulatory subfunctions between paralogs following duplication (a process known as regulatory subfunctionalization). Despite a number of gene expression studies that support this mechanism, no comprehensive analysis of regulatory subfunctionalization has been undertaken at the level of the distal cis-regulatory modules involved. We have exploited fish-mammal genomic alignments to identify and compare more than 800 conserved non-coding elements (CNEs) that associate with genes that have undergone fish-specific duplication and retention.

Results
Using the abundance of duplicated genes within the Fugu genome, we selected seven pairs of teleost-specific paralogs involved in early vertebrate development, each containing clusters of CNEs in their vicinity. CNEs present around each Fugu duplicated gene were identified using multiple alignments of orthologous regions between single-copy mammalian orthologs (representing the ancestral locus) and each fish duplicated region in turn. Comparative analysis reveals a pattern of element retention and loss between paralogs indicative of subfunctionalization, the extent of which differs between duplicate pairs. In addition to complete loss of specific regulatory elements, a number of CNEs have been retained in both regions but may be responsible for more subtle levels of subfunctionalization through sequence divergence.

Conclusion
Comparative analysis of conserved elements between duplicated genes provides a powerful approach for studying regulatory subfunctionalization at the level of the regulatory elements involved.
The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss
Authors: Miller David J , Hemmrich Georg , Ball Eldon E , Hayward David C , Khalturin Konstantin , Funayama Noriko , Agata Kiyokazu , Bosch Thomas CG 
Published: April 2007

Abstract
Background
Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest - it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora.

Results
To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR pathway is present in representatives of the basal cnidarian class Anthozoa, but neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-κB could be identified in the anthozoan Hydra. Moreover, the detection of complement C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests that a prototypic complement effector pathway may exist in anthozoans, but not in hydrozoans. Together with data for several other gene families, this implies that Hydra may have undergone substantial secondary gene loss during evolution. Such losses are not confined to Hydra, however, and at least one MAC/PF gene appears to have been lost from Nematostella.

Conclusion
Consideration of these patterns of gene distribution underscores the likely significance of gene loss during animal evolution whilst indicating ancient origins for many components of the vertebrate innate immune system.
On the functions of the h subunit of eukaryotic initiation factor 3 in late stages of translation initiation
Authors: Kim Byung-Hoon , Cai Xue , Vaughn Justin N , von Arnim Albrecht G 
Published: April 2007

Abstract
Background
The eukaryotic translation initiation factor 3 (eIF3) has multiple roles during the initiation of translation of cytoplasmic mRNAs. How individual subunits of eIF3 contribute to the translation of specific mRNAs remains poorly understood, however. This is true in particular for those subunits that are not conserved in budding yeast, such as eIF3h.

Results
Working with stable reporter transgenes in Arabidopsis thaliana mutants, it was demonstrated that the h subunit of eIF3 contributes to the efficient translation initiation of mRNAs harboring upstream open reading frames (uORFs) in their 5' leader sequence. uORFs, which can function as devices for translational regulation, are present in over 30% of Arabidopsis mRNAs, and are enriched among mRNAs for transcriptional regulators and protein modifying enzymes. Microarray comparisons of polysome loading in wild-type and eif3h mutant seedlings revealed that eIF3h generally helps to maintain efficient polysome loading of mRNAs harboring multiple uORFs. In addition, however, eIF3h also boosted the polysome loading of mRNAs with long leaders or coding sequences. Moreover, the relative polysome loading of certain functional groups of mRNAs, including ribosomal proteins, was actually increased in the eif3h mutant, suggesting that regulons of translational control can be revealed by mutations in generic translation initiation factors.

Conclusion
The intact eIF3h protein contributes to efficient translation initiation on 5' leader sequences harboring multiple uORFs, although mRNA features independent of uORFs are also implicated.