bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a national external quality assessment scheme for breast pathology in the UK
Authors: Ellis I O , Coleman D , Wells C , Kodikara S , Paish E M , Moss S , Al-sam S , Anderson N , Bobrow L , Buley I , Connolly C E , Dallimore N S , Hales S , Hanby A , Humphreys S , Knox F , Lowe J , Macartney J , Nash R , Parham D , Patnick J , Pinder S E , Quinn C M , Robertson A J , Shrimankar J , Walker R A , Winder R 
Published: January 2006

Background:This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology.Aims/Methods:The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using κ statistics.Results:Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high—this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit—this included histological grading; (3) where consistency could be improved but only by changing the system of classification—this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved—this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming.Conclusions:These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.
Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study
Authors: Fong P-Y , Xue W-C , Ngan H Y S , Chiu P-M , Chan K Y K , Tsao S W , Cheung A N Y 
Published: January 2006

Background:Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified.Aims:To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis.Methods:cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed.Results:Downregulation of caspase 10 in choriocarcinoma was detected by both Atlas™ human cDNA expression array and Atlas™ human 1.2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p  =  0.035) and chorioarcinoma (p  =  0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p < 0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p  =  0.02 and p  =  0.04, respectively) and M30 (p < 0.001 and p  =  0.003, respectively) approaches.Conclusions:These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.
Immunohistochemical assessment of hepatitis C virus antigen in cholestatic hepatitis after liver transplantation
Authors: Fenwick F , Bassendine M F , Agarwal K , Bevitt D , Pumeechockchai W , Burt A D , Toms G L 
Published: January 2006

Background:Patients with common variable immunodeficiency may exhibit rapidly progressive hepatitis when infected with hepatitis C virus (HCV), leading to cirrhosis and liver failure. Liver transplantation in these patients may result in a cholestatic form of HCV reinfection with exceptionally high virus loads.Aims:To report an immunohistochemical investigation of the pretransplant and post-transplant liver of one such patient.Methods/Results:On immunohistochemical staining of frozen sections with anti-HCV core monoclonal antibody or fluorescein labelled human polyclonal anti-HCV IgG, no HCV antigens were demonstrated in the native cirrhotic liver removed at transplant, despite a viral load of 106.4genomes/g. The transplanted liver, collected six weeks post-transplant, exhibited cholestatic recurrent hepatitis, had an HCV virus load of 1010genomes/g of liver, and revealed HCV antigen in the cytoplasm of most hepatocytes, with a pronounced periportal distribution. No virus antigen was demonstrable in other cell types. The core antigen was also detected in paraffin wax embedded, formaldehyde fixed tissue of this liver after high temperature antigen retrieval, but not in the native cirrhotic liver or a selection of HCV positive livers collected pretransplant from immunocompetent patients. Attempts to delineate the distribution of E1, NS3, and NS4 antigens were unsuccessful because monoclonal antibodies to these antigens produced “false positive” staining of foci of hepatocytes in the post-transplant livers of HCV seronegative patients with cholestasis.Conclusion:This case provided an opportunity to study the natural development of HCV during acute infection in the absence of an immune response, and may help to elucidate the pathogenesis of HCV recurrence in liver allografts.
Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case–control study
Authors: Massi D , Puig S , Franchi A , Malvehy J , Vidal-Sicart S , González-Cao M , Baroni G , Ketabchi S , Palou J , Santucci M 
Published: January 2006

Background:Cutaneous melanoma spreads preferentially through the lymphatic route and sentinel lymph node (SLN) status is regarded as the most important predictor of survival.Aims:To evaluate whether tumour lymphangiogenesis and the expression of vascular endothelial growth factor C (VEGF-C) is related to the risk of SLN metastasis and to clinical outcome in a case–control series of patients with melanoma.Methods:Forty five invasive melanoma specimens (15 cases and 30 matched controls) were investigated by immunostaining for the lymphatic endothelial marker D2-40 and for VEGF-C. Lymphangiogenesis was measured using computer assisted morphometric analysis.Results:Peritumorous lymphatic vessels were more numerous, had larger average size, and greater relative area than intratumorous lymphatics. The number and area of peritumorous and intratumorous lymphatics was significantly higher in melanomas associated with SLN metastasis than in non-metastatic melanomas. No significant difference in VEGF-C expression by neoplastic cells was shown between metastatic and non-metastatic melanomas. Using logistic regression analysis, intratumorous lymphatic vessel (LV) area was the most significant predictor of SLN metastasis (p = 0.04). Using multivariate analysis, peritumorous LV density was an independent variable affecting overall survival, whereas the intratumorous LV area approached significance (p = 0.07).Conclusions:This study provides evidence that the presence of high peritumorous and intratumorous lymphatic microvessel density is associated with SLN metastasis and shorter survival. The intratumorous lymphatic vessel area is the most significant factor predicting SLN metastasis. The tumour associated lymphatic network constitutes a potential criterion in the selection of high risk patients for complementary treatment and a new target for antimelanoma therapeutic strategies.
Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic analysis including primary and corresponding metastatic tumours
Authors: Kornprat P , Rehak P , Rüschoff J , Langner C 
Published: January 2006

Aims:The insulin-like growth factor (IGF) system has been implicated in tumour development and progression. This study was designed to analyse the expression of the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder cancer.Methods:IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in 57 gallbladder carcinomas and corresponding lymph node (n  =  11) and hepatic (n  =  7) metastases using a tissue microarray technique and correlated with tumour stage, grade, and patient outcome.Results:Cancer tissue allowing a reliable evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14 of the 55 primary tumours, in addition to six and three of the 17 metastases, respectively. No associations with tumour stage, grade, or prognosis were detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases. IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover, IGF-IR expression in less than 50% of cancer cells was an independent marker of poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence interval, 1.4 to 11.2; p  =  0.01).Conclusions:The expression of IGF-IR and its ligands provides evidence for the existence of an auto/paracrine loop of tumour cell stimulation in gallbladder cancer and makes this type of cancer a candidate for therapeutic strategies aimed at interfering with the IGF pathway. The recognition of IGF-IR as a new independent prognostic biomarker may help to identify patients who might benefit from adjuvant treatment.
Healing and the "Son of David": Matthew's Warrant
Authors: Baxter Wayne 
Published: January 2006

AbstractThis article examines Matthew's warrant for linking the christological title "Son of David" with Jesus' healing activity, arguing that the Evangelist based this connection on the Davidic Shepherd of Ezekiel 34. The study will seek to demonstrate this premise by sketching a composite of the Matthean "Son of David" and comparing this composite to Ezekiel's Davidic Shepherd, bringing to light the contextual, verbal and thematic links between Matthew's Son of David motif and Ezekiel 34, and by pointing out the inadequacies of other competing theories.
Future Changes in Biogenic Isoprene Emissions: How Might They Affect Regional and Global Atmospheric Chemistry?
Authors: Wiedinmyer Christine , Tie Xuexi , Guenther Alex , Neilson Ron , Granier Claire 
Published: January 2006

Abstract
Isoprene is emitted from vegetation to the atmosphere in significant quantities, and it plays an important role in the reactions that control tropospheric oxidant concentrations. As future climatic and land-cover changes occur, the spatial and temporal variations, as well as the magnitude of these biogenic isoprene emissions, are expected to change. This paper presents a study of the change in biogenic isoprene emissions that would result from both anthropogenic land-cover and climate-driven changes. Annual global isoprene emissions were estimated to be 522 Tg yr−1 under current climatological and land-cover conditions. When climate-driven land-cover changes are predicted, but climate does not change, total global emissions did not change significantly, although regional impacts were important. However, the use of future temperature and land-cover drivers to estimate isoprene emissions produced a global estimate of 889 Tg yr−1. Anthropogenic land-cover changes, such as urbanization and changes of natural vegetation to plantation forests, can also have substantial impacts on isoprene emissions (i.e., up to 717 Tg yr−1, a 37% increase, when land-cover changes but temperature remains at current-day values). The Model for Ozone and Related Tracers, version 2 (MOZART-2) was run with the different isoprene emission scenarios to simulate the potential changes in global atmospheric chemical composition. The simulated regional surface ozone concentrations changed as much as −9 to 55 ppbv under certain emission and climate scenarios. These results were used to evaluate changes in the ozone production chemistry under different emission scenarios. As expected, the impacts of changing isoprene emissions are regionally dependent, with large changes in China, the Amazon, and the United States.
Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol
Authors: Bateman ED , Fairall L , Lombardi DM , English R 
Published: January 2006

AbstractBackgroundTo compare the efficacy and safety of budesonide/formoterol (Symbicort®) with formoterol (Oxis®) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting β2-agonist therapy.MethodsIn a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV140% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 μg), were randomized to receive either budesonide/formoterol (320/9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 μg]) or formoterol (9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 μg]). The primary efficacy variable was the average FEV1from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured.ResultsFEV1increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated.ConclusionBudesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting β2-agonist.
A proposed metric for assessing the measurement quality of individual microarrays
Authors: Kim Kyoungmi , Page Grier P , Beasley T Mark , Barnes Stephen , Scheirer Katherine E , Allison David B 
Published: January 2006

Abstract

Background
High-density microarray technology is increasingly applied to study gene expression levels on a large scale. Microarray experiments rely on several critical steps that may introduce error and uncertainty in analyses. These steps include mRNA sample extraction, amplification and labeling, hybridization, and scanning. In some cases this may be manifested as systematic spatial variation on the surface of microarray in which expression measurements within an individual array may vary as a function of geographic position on the array surface.

Results
We hypothesized that an index of the degree of spatiality of gene expression measurements associated with their physical geographic locations on an array could indicate the summary of the physical reliability of the microarray. We introduced a novel way to formulate this index using a statistical analysis tool. Our approach regressed gene expression intensity measurements on a polynomial response surface of the microarray's Cartesian coordinates. We demonstrated this method using a fixed model and presented results from real and simulated datasets.

Conclusion
We demonstrated the potential of such a quantitative metric for assessing the reliability of individual arrays. Moreover, we showed that this procedure can be incorporated into laboratory practice as a means to set quality control specifications and as a tool to determine whether an array has sufficient quality to be retained in terms of spatial correlation of gene expression measurements.
MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in Metazoa
Authors: Catalano Domenico , Licciulli Flavio , Turi Antonio , Grillo Giorgio , Saccone Cecilia , D'Elia Domenica 
Published: January 2006

Abstract

Background
Mitochondria are sub-cellular organelles that have a central role in energy production and in other metabolic pathways of all eukaryotic respiring cells. In the last few years, with more and more genomes being sequenced, a huge amount of data has been generated providing an unprecedented opportunity to use the comparative analysis approach in studies of evolution and functional genomics with the aim of shedding light on molecular mechanisms regulating mitochondrial biogenesis and metabolism.
In this context, the problem of the optimal extraction of representative datasets of genomic and proteomic data assumes a crucial importance. Specialised resources for nuclear-encoded mitochondria-related proteins already exist; however, no mitochondrial database is currently available with the same features of MitoRes, which is an update of the MitoNuc database extensively modified in its structure, data sources and graphical interface. It contains data on nuclear-encoded mitochondria-related products for any metazoan species for which this type of data is available and also provides comprehensive sequence datasets (gene, transcript and protein) as well as useful tools for their extraction and export.

Description
MitoRes http://www2.ba.itb.cnr.it/MitoRes/ consolidates information from publicly external sources and automatically annotates them into a relational database. Additionally, it also clusters proteins on the basis of their sequence similarity and interconnects them with genomic data. The search engine and sequence management tools allow the query/retrieval of the database content and the extraction and export of sequences (gene, transcript, protein) and related sub-sequences (intron, exon, UTR, CDS, signal peptide and gene flanking regions) ready to be used for in silico analysis.

Conclusion
The tool we describe here has been developed to support lab scientists and bioinformaticians alike in the characterization of molecular features and evolution of mitochondrial targeting sequences. The way it provides for the retrieval and extraction of sequences allows the user to overcome the obstacles encountered in the integrative use of different bioinformatic resources and the completeness of the sequence collection allows intra- and interspecies comparison at different biological levels (gene, transcript and protein).
A reinforced merging methodology for mapping unique peptide motifs in members of protein families
Authors: Chang Hao-Teng , Pai Tun-Wen , Fan Tan-chi , Su Bo-Han , Wu Pei-Chih , Tang Chuan-Yi , Chang Chun-Tien , Liu Shi-Hwei , Chang Margaret Dah-Tsyr 
Published: January 2006

AbstractBackgroundMembers of a protein family often have highly conserved sequences; most of these sequences carry identical biological functions and possess similar three-dimensional (3-D) structures. However, enzymes with high sequence identity may acquire differential functions other than the common catalytic ability. It is probable that each of their variable regions consists of a unique peptide motif (UPM), which selectively interacts with other cellular proteins, rendering additional biological activities. The ability to identify and localize such UPMs is paramount in recognizing the characteristic role of each member of a protein family.ResultsWe have developed a reinforced merging algorithm (RMA) with which non-gapped UPMs were identified in a variety of query protein sequences including members of human ribonuclease A (RNaseA), epidermal growth factor receptor (EGFR), matrix metalloproteinase (MMP), and Sma-and-Mad related protein families (Smad). The UPMs generally occupy specific positions in the resolved 3-D structures, especially the loop regions on the structural surfaces. These motifs coincide with the recognition sites for antibodies, as the epitopes of four monoclonal antibodies and two polyclonal antibodies were shown to overlap with the UPMs. Most of the UPMs were found to correlate well with the potential antigenic regions predicted by PROTEAN. Furthermore, an accuracy of 70% can be achieved in terms of mapping a UPM to an epitope.ConclusionOur study provides a bioinformatic approach for searching and predicting potential epitopes and interacting motifs that distinguish different members of a protein family.
Molecular phylogenetics and comparative modeling of HEN1, a methyltransferase involved in plant microRNA biogenesis
Authors: Tkaczuk Karolina L , Obarska Agnieszka , Bujnicki Janusz M 
Published: January 2006

Abstract

Background
Recently, HEN1 protein from Arabidopsis thaliana was discovered as an essential enzyme in plant microRNA (miRNA) biogenesis. HEN1 transfers a methyl group from S-adenosylmethionine to the 2'-OH or 3'-OH group of the last nucleotide of miRNA/miRNA* duplexes produced by the nuclease Dicer. Previously it was found that HEN1 possesses a Rossmann-fold methyltransferase (RFM) domain and a long N-terminal extension including a putative double-stranded RNA-binding motif (DSRM). However, little is known about the details of the structure and the mechanism of action of this enzyme, and about its phylogenetic origin.

Results
Extensive database searches were carried out to identify orthologs and close paralogs of HEN1. Based on the multiple sequence alignment a phylogenetic tree of the HEN1 family was constructed. The fold-recognition approach was used to identify related methyltransferases with experimentally solved structures and to guide the homology modeling of the HEN1 catalytic domain. Additionally, we identified a La-like predicted RNA binding domain located C-terminally to the DSRM domain and a domain with a peptide prolyl cis/trans isomerase (PPIase) fold, but without the conserved PPIase active site, located N-terminally to the catalytic domain.

Conclusion
The bioinformatics analysis revealed that the catalytic domain of HEN1 is not closely related to any known RNA:2'-OH methyltransferases (e.g. to the RrmJ/fibrillarin superfamily), but rather to small-molecule methyltransferases. The structural model was used as a platform to identify the putative active site and substrate-binding residues of HEN and to propose its mechanism of action.