bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of bioequivalent radiation dose on survival of patients with limited-stage small-cell lung cancer
Authors: Xia Bing , Chen Gui-Yuan , Cai Xu-Wei , Zhao Jian-Dong , Yang Huan-Jun , Fan Min , Zhao Kuai-Le , Fu Xiao-Long 
Published: May 2011

Abstract

Background
To investigate the biological radiation dose-response for patients of limited-stage small-cell lung cancer (LS-SCLC) treated with high radiation dose.

Methods
Two hundred and five patients of LS-SCLC treated with sequential chemotherapy and thoracic radiotherapy with involved-field between 1997 and 2006 were reviewed retrospectively. Biologically effective dose (BED) was calculated for dose homogenization and was corrected with the factor of overall radiation time. Patients were divided into low BED group (n = 70) and high BED group (n = 135) with a cut-off of BED 57 Gy (equivalent to 60 Gy in 30 fractions over 40 days). Outcomes of the two groups were compared.

Results
Median follow-up was 20.7 months for all analyzable patients and 50.8 months for surviving patients. Considering all patients, median survival was 22.9 months (95% confidence interval, 20.6-25.2 months); 2- and 5-year survival rates were 47.2% and 22.3%, respectively. Patients in high BED group had a significantly better local control (p = 0.024), progression-free survival (p = 0.006) and overall survival (p = 0.005), with a trend toward improved distant-metastasis free survival (p = 0.196). Multivariable Cox regression demonstrated that age (p = 0.003), KPS (p = 0.009), weight loss (p = 0.023), and BED (p = 0.004) were significant predictors of overall survival.

Conclusions
Our data showed that a high BED was significantly associated with favourable outcomes in the Chinese LS-SCLC population, indicating that a positive BED-response relationship still existed even in a relatively high radiation dose range.
A transcriptional analysis of carotenoid, chlorophyll and plastidial isoprenoid biosynthesis genes during development and osmotic stress responses in Arabidopsis thaliana
Authors: Meier Stuart , Tzfadia Oren , Vallabhaneni Ratnakar , Gehring Chris , Wurtzel Eleanore T 
Published: May 2011

Abstract

Background
The carotenoids are pure isoprenoids that are essential components of the photosynthetic apparatus and are coordinately synthesized with chlorophylls in chloroplasts. However, little is known about the mechanisms that regulate carotenoid biosynthesis or the mechanisms that coordinate this synthesis with that of chlorophylls and other plastidial synthesized isoprenoid-derived compounds, including quinones, gibberellic acid and abscisic acid. Here, a comprehensive transcriptional analysis of individual carotenoid and isoprenoid-related biosynthesis pathway genes was performed in order to elucidate the role of transcriptional regulation in the coordinated synthesis of these compounds and to identify regulatory components that may mediate this process in Arabidopsis thaliana.

Results
A global microarray expression correlation analysis revealed that the phytoene synthase gene, which encodes the first dedicated and rate-limiting enzyme of carotenogenesis, is highly co-expressed with many photosynthesis-related genes including many isoprenoid-related biosynthesis pathway genes. Chemical and mutant analysis revealed that induction of the co-expressed genes following germination was dependent on gibberellic acid and brassinosteroids (BR) but was inhibited by abscisic acid (ABA). Mutant analyses further revealed that expression of many of the genes is suppressed in dark grown plants by Phytochrome Interacting transcription Factors (PIFs) and activated by photoactivated phytochromes, which in turn degrade PIFs and mediate a coordinated induction of the genes. The promoters of PSY and the co-expressed genes were found to contain an enrichment in putative BR-auxin response elements and G-boxes, which bind PIFs, further supporting a role for BRs and PIFs in regulating expression of the genes. In osmotically stressed root tissue, transcription of Calvin cycle, methylerythritol 4-phosphate pathway and carotenoid biosynthesis genes is induced and uncoupled from that of chlorophyll biosynthesis genes in a manner that is consistent with the increased synthesis of carotenoid precursors for ABA biosynthesis. In all tissues examined, induction of β-carotene hydroxylase transcript levels are linked to an increased demand for ABA.

Conclusions
This analysis provides compelling evidence to suggest that coordinated transcriptional regulation of isoprenoid-related biosynthesis pathway genes plays a major role in coordinating the synthesis of functionally related chloroplast localized isoprenoid-derived compounds.
Local apoptosis promotes collagen production by monocyte-derived cells in transforming growth factor β1-induced lung fibrosis
Authors: Peng Xueyan , Mathai Susan K , Murray Lynne A , Russell Thomas , Reilkoff Ronald , Chen Qingsheng , Gulati Mridu , Elias Jack A , Bucala Richard , Gan Ye , Herzog Erica L 
Published: May 2011

AbstractBackgroundCollagen-containing leukocytes (CD45+Col-I+) accumulate in diseased and fibrotic tissues. However, the precise identity of these cells and whether injury is required for their recruitment remain unknown. Using a murine model of pulmonary fibrosis in which an inducible, bioactive form of the human transforming growth factor (TGF)-β1 gene is targeted to the lung, we characterized the cell surface phenotype of collagen-containing CD45+cells in the lung and tested the hypothesis that apoptotic cell death responses are essential to the accumulation of CD45+Col-I+cells.ResultsOur studies demonstrate that CD45+Col-I+cells appearing in the TGF-β1-exposed murine lung express markers of the monocyte lineage. Inhibition of apoptosis via pharmacological caspase blockade led to a significant reduction in CD45+Col-I+cells, which appear to accumulate independently of alternatively activated macrophages. There are also increased levels of apoptosis and greater numbers of CD45+Col-I+in the lung tissue of patients with two distinct forms of fibrotic lung disease, idiopathic pulmonary fibrosis and connective tissue disease-related interstitial lung disease, when compared to lung from healthy normal controls. These findings are accompanied by an increase in collagen production in cultured monocytes obtained from subjects with fibrotic lung disease. Treatment of these cultured cells with the caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD/fmk) reduces both apoptosis and collagen production in all subjects.ConclusionsInterventions that prevent collagen production by monocytes via modulation of caspase activation and of apoptosis may be ameliorative in monocyte-associated, TGF-β1-driven processes such as pulmonary fibrosis.
Prevalence of metabolic syndrome in bus and truck drivers in Kashan, Iran
Authors: Saberi Hamid R , Moravveji Ali R , Fakharian Esmaeil , kashani Masoud Motalebi , Dehdashti Ali R 
Published: May 2011

Abstract

Background
Bus and truck drivers are apparently more involved in metabolic syndrome and its complications due to their working conditions. The related impacts are not only harmful for driver's health, but also may endanger others. The present research was carried out to determine the prevalence of metabolic syndrome among bus and truck drivers in Kashan, a city in Iran.

Materials
In 2007, 429 bus and truck male drivers were enrolled to this cross sectional study to examine the metabolic syndrome using ATPIII criteria. Statistical tests including Chi-Square test, T-student test and Pearson's correlation coefficient were used to analyze the data.

Results
Prevalence of metabolic syndrome in subjects was 35.9%. Hypertension and diabetes were seen in 42.9% and 7% of the drivers respectively. Body mass index (BMI) in 41% of the drivers within the range of 25-30 was considered overweight and 23% of them were found to be obese. High triglyceride (53.4%) and low HDL-C levels (48.7%) were more common than other components of metabolic syndrome. A significant positive correlation was seen between BMI, diabetes, high blood pressure and metabolic syndrome (p < 0.001); but there was no positive correlation between metabolic syndrome and smoking (p < 0.06).

Conclusion
High prevalence of metabolic syndrome and other relevant risk factors for coronary heart diseases (CHD) were detected among the drivers. Based on these findings, it is recommended to consider training programs, establish pertinent health regulations, and focus on the metabolic syndrome complications in high risk group to improve and maintain their quality of life and to promote their public health.
Pandemic influenza A (H1N1v) infection in pediatric population: a multicenter study in a North-East area of Italy
Authors: Da Dalt Liviana , Chillemi Chiara , Cavicchiolo Maria Elena , Bressan Silvia , Calistri Arianna , Palù Giorgio , Perilongo Giorgio 
Published: May 2011

Abstract

Background -
Data on clinical presentation, morbidity and mortality of 2009 pandemic influenza virus (H1N1v) in paediatric population are still emerging; most of the data so far available came from selected cohorts of children admitted to tertiary care paediatric hospitals.

Methods -
An observational study involving all the 19 Divisions of Paediatrics of the Veneto Region was conducted with the aim of investigating into the demographic and clinical characteristics, the treatment, the outcome and the risk factors for disease severity of H1N1v infection occurring in children.

Results -
Two hundred children, median age of 4.15 years (range 0-15) were enrolled from the last week of October till the first week of January 2010 for an overall hospitalization rate of 23/100.000. At least one underlying medical condition was found in 44% of patients. Fever and cough were the most frequent symptoms (93% and 65% respectively). 11 patients (6%) were admitted to a PICU and 5 (2.5%) required mechanical ventilation. Antiviral therapy was administered in 103 patients (51.5%) Death occurred in 2 patients (1%); both had severe prior medical conditions. Pre-existing neurologic diseases (OR 7.82; 95%CI: 1.15-53.34), the presence of hypoxemia (OR 10.47; 95%CI: 2.12-51.70) and anemia (Haemoglobin < 10 g/dL) (OR 14.15; 95%CI: 2.36-84.64) were risk factor for Intensive Care Unit admission.

Conclusions -
This observational study in a given area of North-East Italy confirms the rather favourable prognosis of children with influenza A H1N1 (2009). Pre-existing conditions, and which is new, significant anemia, are risk factors for a complicated course.
How orthogonal are the OBO Foundry ontologies?
Authors: Ghazvinian Amir , Noy Natalya F , Musen Mark A 
Published: May 2011

Abstract
Background
Ontologies in biomedicine facilitate information integration, data exchange, search and query of biomedical data, and other critical knowledge-intensive tasks. The OBO Foundry is a collaborative effort to establish a set of principles for ontology development with the eventual goal of creating a set of interoperable reference ontologies in the domain of biomedicine. One of the key requirements to achieve this goal is to ensure that ontology developers reuse term definitions that others have already created rather than create their own definitions, thereby making the ontologies orthogonal.

Methods
We used a simple lexical algorithm to analyze the extent to which the set of OBO Foundry candidate ontologies identified from September 2009 to September 2010 conforms to this vision. Specifically, we analyzed (1) the level of explicit term reuse in this set of ontologies, (2) the level of overlap, where two ontologies define similar terms independently, and (3) how the levels of reuse and overlap changed during the course of this year.

Results
We found that 30% of the ontologies reuse terms from other Foundry candidates and 96% of the candidate ontologies contain terms that overlap with terms from the other ontologies. We found that while term reuse increased among the ontologies between September 2009 and September 2010, the level of overlap among the ontologies remained relatively constant. Additionally, we analyzed the six ontologies announced as OBO Foundry members on March 5, 2010, and identified that the level of overlap was extremely low, but, notably, so was the level of term reuse.

Conclusions
We have created a prototype web application that allows OBO Foundry ontology developers to see which classes from their ontologies overlap with classes from other ontologies in the OBO Foundry (http://obomap.bioontology.org). From our analysis, we conclude that while the OBO Foundry has made significant progress toward orthogonality during the period of this study through increased adoption of explicit term reuse, a large amount of overlap remains among these ontologies. Furthermore, the characteristics of the identified overlap, such as the terms it comprises and its distribution among the ontologies, indicate that the achieving orthogonality will be exceptionally difficult, if not impossible.
Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology
Authors: Özgür Arzucan , Xiang Zuoshuang , Radev Dragomir R , He Yongqun 
Published: May 2011

AbstractBackgroundInterferon-gamma (IFN-γ) is vital in vaccine-induced immune defense against bacterial and viral infections and tumor. Our recent study demonstrated the power of a literature-based discovery method in extraction and comparison of the IFN-γ and vaccine-mediated gene interaction networks. The Vaccine Ontology (VO) contains a hierarchy of vaccine names. It is hypothesized that the application of VO will enhance the prediction of IFN-γ and vaccine-mediated gene interaction network.ResultsIn this study, 186 specific vaccine names listed in the Vaccine Ontology (VO) and their semantic relations were used for possible improved retrieval of the IFN-γ and vaccine associated gene interactions. The application of VO allows discovery of 38 more genes and 60 more interactions. Comparison of different layers of IFN-γ networks and the example BCG vaccine-induced subnetwork led to generation of new hypotheses. By analyzing all discovered genes using centrality metrics, 32 genes were ranked high in the VO-based IFN-γ vaccine network using four centrality scores. Furthermore, 28 specific vaccines were found to be associated with these top 32 genes. These specific vaccine-gene associations were further used to generate a network of vaccine-vaccine associations. The BCG and LVS vaccines are found to be the most central vaccines in the vaccine-vaccine association network.ConclusionOur results demonstrate that the combined usages of biomedical ontologies and centrality-based literature mining are able to significantly facilitate discovery of gene interaction networks and gene-concept associations.AvailabilityVO is available at:http://www.violinet.org/vaccineontology; and the SVM edit kernel for gene interaction extraction is available at:http://www.violinet.org/ifngvonet/int_ext_svm.zip
Representation of research hypotheses
Authors: Soldatova Larisa N , Rzhetsky Andrey 
Published: May 2011

Abstract
Background
Hypotheses are now being automatically produced on an industrial scale by computers in biology, e.g. the annotation of a genome is essentially a large set of hypotheses generated by sequence similarity programs; and robot scientists enable the full automation of a scientific investigation, including generation and testing of research hypotheses.

Results
This paper proposes a logically defined way for recording automatically generated hypotheses in machine amenable way. The proposed formalism allows the description of complete hypotheses sets as specified input and output for scientific investigations. The formalism supports the decomposition of research hypotheses into more specialised hypotheses if that is required by an application. Hypotheses are represented in an operational way – it is possible to design an experiment to test them. The explicit formal description of research hypotheses promotes the explicit formal description of the results and conclusions of an investigation. The paper also proposes a framework for automated hypotheses generation. We demonstrate how the key components of the proposed framework are implemented in the Robot Scientist “Adam”.

Conclusions
A formal representation of automatically generated research hypotheses can help to improve the way humans produce, record, and validate research hypotheses.

Availability
http://www.aber.ac.uk/en/cs/research/cb/projects/robotscientist/results/
Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats
Authors: Glage Silke , Klinge Petra M , Miller Miles C , Wallrapp Christine , Geigle Peter , Hedrich Hans J , Brinker Thomas 
Published: May 2011

Abstract

Background
Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases. Encapsulated genetically engineered cells have been suggested as a means for sustained local delivery of such peptides to the brain. In our experiments, we studied human mesenchymal stem cells which were transfected to produce glucagon-like peptide-1 (GLP-1).

Methods
Cells were packed in a water-permeable mesh bag containing 400 polymeric microcapsules, each containing 3000 cells. The mesh bags were either transplanted into the subdural space, into the brain parenchyma or into the cerebral ventricles of the cat brain. Mesh bags were explanted after two weeks, and cell viability, as well as GLP-1 concentration in the cerebrospinal fluid (CSF), was measured.

Results
Viability of cells did not significantly differ between the three implantation sites. However, CSF concentration of GLP-1 was significantly elevated only after ventricular transplantation with a maximum concentration of 73 pM (binding constant = 70 pM).

Conclusions
This study showed that ventricular cell-based delivery of soluble factors has the capability to achieve concentrations in the CSF which may become pharmacologically active. Despite the controversy about the pharmacokinetic limitations of ventricular drug delivery, there might be a niche in this for encapsulated cell biodelivery of soluble, highly biologically-effective neuropeptides of low molecular weight like GLP-1.
Histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in SKG mice
Authors: Misaki Kenta , Morinobu Akio , Saegusa Jun , Kasagi Shimpei , Fujita Masaaki , Miyamoto Yoshiaki , Matsuki Fumichika , Kumagai Shunichi 
Published: May 2011

Abstract
Introduction
The purpose of this study was to elucidate the effects of histone deacetylase inhibition on the phenotype and function of dendritic cells and on arthritis in SKG mice.

Methods
Arthritis was induced in SKG mice by zymosan A injection. Trichostatin A, a histone deacetylase inhibitor, was administered and its effects on arthritis were evaluated by joint swelling and histological evaluation. Interleukin-17 production in lymph node cells was determined by an enzyme-linked immunosorbent assay (ELISA). Foxp3 expression in lymph node cells and the phenotypes of splenic dendritic cells were examined by fluorescence-activated cell sorting (FACS). Bone marrow-derived dendritic cells (BM-DC) were generated with granulocyte macrophage colony-stimulating factor. The effects of trichostatin A on cell surface molecules, cytokine production, indoleamine 2,3-dioxygenase (IDO) expression and T cell stimulatory capacity were examined by FACS, ELISA, quantitative real-time polymerase chain reaction and Western blot, and the allo-mixed lymphocyte reaction, respectively.

Results
Trichostatin A, when administered before the onset of arthritis, prevented SKG mice from getting arthritis. Trichostatin A treatment also showed therapeutic effects on arthritis in SKG mice, when it was administered after the onset of arthritis. Trichostatin A treatment reduced Th17 cells and induced regulatory T cells in lymph node, and also decreased co-stimulatory molecule expression on splenic dendritic cells in vivo. In vitro, trichostatin A markedly suppressed zymosan A-induced interleukin-12 and interleukin-6 production by BM-DC and up-regulated IDO expression at mRNA and protein levels. Trichostatin A-treated BM-DC also showed less T cell stimulatory capacity.

Conclusions
Histone deacetylase inhibition changes dendritic cells to a tolerogenic phenotype and ameliorates arthritis in SKG mice.
Technical Advance: Surface plasmon resonance-based analysis of CXCL12 binding using immobilized lentiviral particles
Authors: Vega Beatriz , Muñoz Laura Martínez , Holgado Borja L , Lucas Pilar , Rodríguez-Frade J M , Calle Ana , Rodríguez-Fernández J L , Lechuga Laura M , Rodríguez José F , Gutiérrez-Gallego Ricardo , Mellado Mario 
Published: May 2011

ABSTRACTUse of SPR-based biosensors is an established method for measuring molecular interactions. Their application to the study of GPCRs is nonetheless limited to detergent-solubilized receptors that can then be reconstituted into a lipid environment. Using the chemokine receptor CXCR4 and its specific ligand CXCL12, we outline here a highly reproducible biosensor method based on receptor presentation on the surface of lentiviral particles; the approach is simple and does not require the use of antibodies to achieve correct receptor orientation on the sensorchip surface. We measured the kinetic parameters of CXCR4/CXCL12 binding in a single step and in real time and evaluated the effect of GAG presentation of chemokines on this interaction. The data indicate that at low concentrations, soluble heparin modulates CXCR4/CXCL12 interaction and at high concentrations, abrogates binding. These observations suggest that in addition to their known role in modulating local chemokine availability, GAG affect the receptor/ligand interaction, although their influence on affinity parameters is very limited. The method will also be useful for quantifying these biomarkers in biological fluids and for the development of high-throughput screening for their antagonists.
Valproatev.lithium in the treatment of bipolar disorder in clinical practice: observational nationwide register-based cohort study
Authors: Kessing Lars Vedel , Hellmund Gunnar , Geddes John R. , Goodwin Guy M. , Andersen Per Kragh 
Published: May 2011

BackgroundValproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse.AimsTo compare the effect of valproatev.lithium for treatment of bipolar disorder in clinical practice.MethodAn observational cohort study with linkage of nationwide registers of all people with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed valproate or lithium in Denmark during a period from 1995 to 2006.ResultsA total of 4268 participants were included among whom 719 received valproate and 3549 received lithium subsequent to the diagnosis of bipolar disorder. The rate of switch/add on to the opposite drug (lithium or valproate), antidepressants, antipsychotics or anticonvulsants (other than valproate) was increased for valproate compared with lithium (hazard ratio (HR) = 1.86, 95% CI 1.59–2.16). The rate of psychiatric hospital admissions was increased for valproatev.lithium (HR = 1.33, 95% CI 1.18–1.48) and regardless of the type of episode leading to a hospital admission (depressive or manic/mixed). Similarly, for participants with a depressive index episode (HR = 1.87, 95% CI 1.40–2.48), a manic index episode (HR = 1.24, 95% CI 1.01–1.51) and a mixed index episode (HR = 1.44, 95% CI 1.04–2.01), the overall rate of hospital admissions was significantly increased for valproate compared with lithium.ConclusionsIn daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.