bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Gibbs sampling strategy applied to the mapping of ambiguous short-sequence tags
Authors: Wang Jianrong , Huda Ahsan , Lunyak Victoria V. , Jordan I. King 
Published: September 2010

Abstract
Motivation: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is widely used in biological research. ChIP-seq experiments yield many ambiguous tags that can be mapped with equal probability to multiple genomic sites. Such ambiguous tags are typically eliminated from consideration resulting in a potential loss of important biological information.
Results: We have developed a Gibbs sampling-based algorithm for the genomic mapping of ambiguous sequence tags. Our algorithm relies on the local genomic tag context to guide the mapping of ambiguous tags. The Gibbs sampling procedure we use simultaneously maps ambiguous tags and updates the probabilities used to infer correct tag map positions. We show that our algorithm is able to correctly map more ambiguous tags than existing mapping methods. Our approach is also able to uncover mapped genomic sites from highly repetitive sequences that can not be detected based on unique tags alone, including transposable elements, segmental duplications and peri-centromeric regions. This mapping approach should prove to be useful for increasing biological knowledge on the too often neglected repetitive genomic regions.
Availability: http://esbg.gatech.edu/jordan/software/map
Contact: king.jordan@biology.gatech.edu
Supplementary Information: Supplementary data are available at Bioinformatics online.
SimiCon: a web tool for protein–ligand model comparison through calculation of equivalent atomic contacts
Authors: Rueda Manuel , Katritch Vsevolod , Raush Eugene , Abagyan Ruben 
Published: September 2010

Abstract
Summary: SimiCon is a web server designed for an automated identification of equivalent protein–ligand atomic contacts in different conformational models of a complex. The contacts are computed with internal coordinate mechanics (ICM) software with respect to molecular symmetry and the results are shown in the browser as text, tables and interactive 3D graphics. The web server can be executed remotely without a browser to allow users to automate multiple calculations.
Availability: SimiCon is freely available at http://abagyan.ucsd.edu/SimiCon
Contact: rabagyan@ucsd.edu
RAPID detection of gene–gene interactions in genome-wide association studies
Authors: Brinza Dumitru , Schultz Matthew , Tesler Glenn , Bafna Vineet 
Published: September 2010

Abstract
Motivation: In complex disorders, independently evolving locus pairs might interact to confer disease susceptibility, with only a modest effect at each locus. With genome-wide association studies on large cohorts, testing all pairs for interaction confers a heavy computational burden, and a loss of power due to large Bonferroni-like corrections. Correspondingly, limiting the tests to pairs that show marginal effect at either locus, also has reduced power. Here, we describe an algorithm that discovers interacting locus pairs without explicitly testing all pairs, or requiring a marginal effect at each locus. The central idea is a mathematical transformation that maps ‘statistical correlation between locus pairs’ to ‘distance between two points in a Euclidean space’. This enables the use of geometric properties to identify proximal points (correlated locus pairs), without testing each pair explicitly. For large datasets (∼106 SNPs), this reduces the number of tests from 1012 to 106, significantly reducing the computational burden, without loss of power. The speed of the test allows for correction using permutation-based tests. The algorithm is encoded in a tool called Rapid (RApid Pair IDentification) for identifying paired interactions in case–control GWAS.
Results: We validated Rapid with extensive tests on simulated and real datasets. On simulated models of interaction, Rapid easily identified pairs with small marginal effects. On the benchmark disease, datasets from The Wellcome Trust Case Control Consortium, Rapid ran in about 1 CPU-hour per dataset, and identified many significant interactions. In many cases, the interacting loci were known to be important for the disease, but were not individually associated in the genome-wide scan.
Availability: http://bix.ucsd.edu/projects/rapid
Contact: vbafna@cs.ucsd.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
SylArray: a web server for automated detection of miRNA effects from expression data
Authors: Bartonicek Nenad , Enright Anton J. 
Published: September 2010

Abstract
Summary: A useful step for understanding the function of microRNAs (miRNA) or siRNAs is the detection of their effects on genome-wide expression profiles. Typically, approaches look for enrichment of words in the 3′UTR sequences of the most deregulated genes. A number of tools are available for this purpose, but they require either in-depth computational knowledge, filtered 3′UTR sequences for the genome of interest, or a set of genes acquired through an arbitrary expression cutoff. To this end, we have developed SylArray; a web-based resource designed for the analysis of large-scale expression datasets. It simply requires the user to submit a sorted list of genes from an expression experiment. SylArray utilizes curated sets of 3′UTRs to attach sequences to these genes and then applies the Sylamer algorithm for detection of miRNA or siRNA signatures in those sequences. An intuitive system for visualization and interpretation of the small RNA signatures is included.
Availability: SylArray is written in Perl-CGI, Perl and Java and also uses the R statistical package. The source-code, database and web resource are freely available under GNU Public License (GPL). The web server is freely accessible at http://www.ebi.ac.uk/enright/sylarray.
Contact: aje@ebi.ac.uk
HybridNET: a tool for constructing hybridization networks
Authors: Chen Zhi-Zhong , Wang Lusheng 
Published: September 2010

Abstract
Motivations: When reticulation events occur, the evolutionary history of a set of existing species can be represented by a hybridization network instead of an evolutionary tree. When studying the evolutionary history of a set of existing species, one can obtain a phylogenetic tree of the set of species with high confidence by looking at a segment of sequences or a set of genes. When looking at another segment of sequences, a different phylogenetic tree can be obtained with high confidence too. This indicates that reticulation events may occur. Thus, we have the following problem: given two rooted phylogenetic trees on a set of species that correctly represent the tree-like evolution of different parts of their genomes, what is the hybridization network with the smallest number of reticulation events to explain the evolution of the set of species under consideration?
Results: We develop a program, named HybridNet, for constructing a hybridization network with the minimum number of reticulate vertices from two input trees. We first implement the O(3dn)-time algorithm by Whidden et al. for computing a maximum (acyclic) agreement forest. Our program can output all the maximum (acyclic) agreement forests. We then augment the program so that it can construct an optimal hybridization network for each given maximum acyclic agreement forest. To our knowledge, this is the first time that optimal hybridization networks can be rapidly constructed.
Availability: The program is available for non-commercial use, at http://www.cs.cityu.edu.hk/∼lwang/software/Hn/treeComp.html
Contact: zzchen@mail.dendai.ac.jp; lwang@cs.cityu.edu.hk
Supplementary information: Supplementary data are available at Bioinformatics online.
Mitochondrial Malate Dehydrogenase Lowers Leaf Respiration and Alters Photorespiration and Plant Growth in Arabidopsis
Authors: Tomaz Tiago , Bagard Matthieu , Pracharoenwattana Itsara , Lindén Pernilla , Lee Chun Pong , Carroll Adam J. , Ströher Elke , Smith Steven M. , Gardeström Per , Millar A. Harvey 
Published: September 2010

Abstract
Malate dehydrogenase (MDH) catalyzes a reversible NAD+-dependent-dehydrogenase reaction involved in central metabolism and redox homeostasis between organelle compartments. To explore the role of mitochondrial MDH (mMDH) in Arabidopsis (Arabidopsis thaliana), knockout single and double mutants for the highly expressed mMDH1 and lower expressed mMDH2 isoforms were constructed and analyzed. A mmdh1mmdh2 mutant has no detectable mMDH activity but is viable, albeit small and slow growing. Quantitative proteome analysis of mitochondria shows changes in other mitochondrial NAD-linked dehydrogenases, indicating a reorganization of such enzymes in the mitochondrial matrix. The slow-growing mmdh1mmdh2 mutant has elevated leaf respiration rate in the dark and light, without loss of photosynthetic capacity, suggesting that mMDH normally uses NADH to reduce oxaloacetate to malate, which is then exported to the cytosol, rather than to drive mitochondrial respiration. Increased respiratory rate in leaves can account in part for the low net CO2 assimilation and slow growth rate of mmdh1mmdh2. Loss of mMDH also affects photorespiration, as evidenced by a lower postillumination burst, alterations in CO2 assimilation/intercellular CO2 curves at low CO2, and the light-dependent elevated concentration of photorespiratory metabolites. Complementation of mmdh1mmdh2 with an mMDH cDNA recovered mMDH activity, suppressed respiratory rate, ameliorated changes to photorespiration, and increased plant growth. A previously established inverse correlation between mMDH and ascorbate content in tomato (Solanum lycopersicum) has been consolidated in Arabidopsis and may potentially be linked to decreased galactonolactone dehydrogenase content in mitochondria in the mutant. Overall, a central yet complex role for mMDH emerges in the partitioning of carbon and energy in leaves, providing new directions for bioengineering of plant growth rate and a new insight into the molecular mechanisms linking respiration and photosynthesis in plants.
Nontransgenic Genome Modification in Plant Cells
Authors: Marton Ira , Zuker Amir , Shklarman Elena , Zeevi Vardit , Tovkach Andrey , Roffe Suzy , Ovadis Marianna , Tzfira Tzvi , Vainstein Alexander 
Published: September 2010

Abstract
Zinc finger nucleases (ZFNs) are a powerful tool for genome editing in eukaryotic cells. ZFNs have been used for targeted mutagenesis in model and crop species. In animal and human cells, transient ZFN expression is often achieved by direct gene transfer into the target cells. Stable transformation, however, is the preferred method for gene expression in plant species, and ZFN-expressing transgenic plants have been used for recovery of mutants that are likely to be classified as transgenic due to the use of direct gene-transfer methods into the target cells. Here we present an alternative, nontransgenic approach for ZFN delivery and production of mutant plants using a novel Tobacco rattle virus (TRV)-based expression system for indirect transient delivery of ZFNs into a variety of tissues and cells of intact plants. TRV systemically infected its hosts and virus ZFN-mediated targeted mutagenesis could be clearly observed in newly developed infected tissues as measured by activation of a mutated reporter transgene in tobacco (Nicotiana tabacum) and petunia (Petunia hybrida) plants. The ability of TRV to move to developing buds and regenerating tissues enabled recovery of mutated tobacco and petunia plants. Sequence analysis and transmission of the mutations to the next generation confirmed the stability of the ZFN-induced genetic changes. Because TRV is an RNA virus that can infect a wide range of plant species, it provides a viable alternative to the production of ZFN-mediated mutants while avoiding the use of direct plant-transformation methods.
Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in collagen disease patient
Authors: NOMURA Masayo , MAEDA Manabu , SEISHIMA Mariko 
Published: September 2010

AbstractPhaeohyphomycosis is a rare fungal infection that is more commonly associated with compromised patients. We present herein an 81‐year‐old man with collagen disease and chronic interstitial pneumonia who developed subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei. The main pathogen of phaeohyphomycosis had been considered to be E. jeanselmei complex. This has recently been divided into several species by using a molecular technique. The main pathogen of phaeohyphomycosis is Exophiala xenobiotica, and E. jeanselmei is rather a rare pathogen of this disease. Although p.o. itraconazole and terbinafine administration was not effective for this patient, these antifungal agents were used for preventing systemic dissemination in this immunocompromised host.
Impact of a focussed teaching programme on practical prescribing skills among final year medical students
Authors: Sandilands Euan A. , Reid Karen , Shaw Laura , Bateman D. Nicholas , Webb David J. , Dhaun Neeraj , Kluth David C. 
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Medication errors, and particularly prescribing errors, are common in UK hospitals.• Junior doctors make the majority of prescribing errors.• Deficiencies in prescribing education and training have been closely linked to the high frequency of medication errors. WHAT THIS STUDY ADDS • Focussed prescribing teaching can lead to an improvement in prescribing ability.• Prescribing confidence can be significantly improved through education.• Education is insufficient alone in eradicating prescribing errors.AIM To assess the impact of prescribing teaching on final year medical students.METHODS Students randomly allocated to two hospitals completed a prescribing assessment. Prescribing teaching was delivered to the intervention group while no additional teaching was provided for the control group. All students then completed a second prescribing assessment.RESULTS Teaching improved the assessment score: mean assessment 2 vs. 1, 70% vs. 62%, P= 0.007; allergy documentation: 98% vs. 74%, P= 0.0001; and confidence. However, 30% of prescriptions continued to include prescribing errors.CONCLUSION Medical students make significant errors in prescribing. Teaching improves ability and confidence but is insufficient alone in eradicating errors.
Effects of imatinib mesylate on the pharmacokinetics of paracetamol (acetaminophen) in Korean patients with chronic myelogenous leukaemia
Authors: Kim Dong‐Wook , Tan Eugene Y. , Jin Yu , Park Sahee , Hayes Michael , Demirhan Eren , Schran Horst , Wang Yanfeng 
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Imatinib mesylate, a tyrosine kinase inhibitor, exhibits a weak competitive inhibition on paracetamol (acetaminophen) O‐glucuronidation with an inhibition constant (Ki) value of 59 µm. However, the clinical significance of the inhibition has not been evaluated. The pharmacokinetics of imatinib have been studied in white patients with chronic myelogenous leukaemia (CML), but not in Korean patients with CML. WHAT THIS STUDY ADDS • Imatinib (400 mg once daily) had no clinically relevant effect on the plasma exposure and the pharmacokinetics of paracetamol (1000 mg once daily) in patients with CML.• The pharmacokinetic profile of imatinib in Korean patients with CML was similar to that in whites.AIMS The major objective of the present study was to investigate the effect of imatinib on the pharmacokinetics of paracetamol in patients with chronic myelogenous leukaemia (CML).METHODS Patients (n= 12) received a single oral dose of acetaminophen 1000 mg on day 1 (control). On days 2–8, imatinib 400 mg was administered daily. On day 8 (treatment), another 1000 mg dose of paracetamol was administered 1 h after the morning dose of imatinib 400 mg. Blood and urine samples were collected for bioanalytical analyses.RESULTS The area under the plasma concentration–time curve (AUC) for paracetamol, paracetamol glucuronide and paracetamol sulphate under control conditions was similar to that after treatment with imatinib; the 90% confidence interval of the log AUC ratio was within 0.8 to 1.25. Urinary excretion of paracetamol, paracetamol glucuronide and paracetamol sulphate was also unaffected by imatinib. The pharmacokinetics of paracetamol and imatinib in Korean patients with CML were similar to previous pharmacokinetic results in white patients with CML. Co‐administration of a single dose of paracetamol and multiple doses of imatinib was well tolerated and safety profiles were similar to those of either drug alone.CONCLUSIONS The pharmacokinetics of paracetamol and its major metabolites in the presence of imatinib were similar to those of the control conditions and the combination was well tolerated. These findings suggest that imatinib can be safely administered with paracetamol without dose adjustment of either drug.
Gender differences in the association of C‐reactive protein with coronary artery calcium in Type‐2 diabetes
Authors: Qasim Atif N. , Budharaju Venkata , Mehta Nehal N. , St Clair Caitlin , Farouk Samira , Braunstein Seth , Schutta Mark , Iqbal Nayyar , Rader Daniel J. , Reilly Muredach P. 
Published: September 2010

SummaryObjectives  Plasma C‐reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type‐2 diabetes (T2DM) is unclear. We examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD.Methods  We performed cross‐sectional analyses of gender influence on CRP association with CAC in the Penn Diabetes Heart Study (N = 1299 with T2DM), the Study of Inherited Risk of Coronary Atherosclerosis (N = 860 nondiabetic subjects) and a combined sample.Results  Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. There was a strong interaction by gender in the association of CRP with CAC (interaction P < 0·001). In diabetic women, CRP was associated with higher CAC even after further adjustment for age, race, medications, metabolic syndrome, Framingham risk score and body mass index [Tobit ratio 1·60, 95% CI (1·03–2·47)]. Although this relationship was attenuated in nondiabetic women, the combined sample maintained this association in fully adjusted models [1·44, 95% CI (1·13–1·83)]. There was no association of CRP with CAC in either diabetic or nondiabetic men.Conclusions  CRP may be a useful marker of cardiovascular risk in women, particularly in diabetic women who otherwise have no known CVD. Prospective studies are needed to better assess the gender differences in CRP utility and the use of CRP in T2DM.
Immunohistochemical classification of ductular reactions in human liver
Authors: Turányi Eszter , Dezsö Katalin , Csomor Judit , Schaff Zsuzsa , Paku Sándor , Nagy Péter 
Published: September 2010

Turányi E, Dezsö K, Csomor J, Schaff Z, Paku S & Nagy P (2010) Histopathology 57, 607–614 Immunohistochemical classification of ductular reactions in human liverAims:  Ductular reactions occur in a wide variety of liver diseases. Their origin and function is still debated. Our understanding of these histological reactions is impaired by their great diversity; therefore rational classification should precede further detailed analysis. The aim was to achieve a reproducible classification of hepatic ductular reactions based on their immunophenotype.Methods and results:  Sixty‐nine liver specimens with ductular reactions were analysed by immunohistochemistry. The majority of the samples could be classified into three categories based on their immunophenotype. Type P(rimitive) reaction is characterized by CD56 immunoreactivity. Most primary biliary cirrhosis and focal nodular hyperplasia samples fall into this group; these ductules do not show any sign of differentiation. Type D(ifferentiating) ductules are positive for CD56, epithelial membrane antigen (EMA) and CD10. Cirrhotic samples and regenerating livers following fulminant hepatic failure contain such ductular reactions; this immunophenotype indicates hepatocytic differentiation. Biliary obstruction results in EMA‐positive type O(bstructive) reactions; these ductules are similar to the normal interlobular bile ducts.Conclusion:  Ductular reactions can be classified based on their immunophenotype. Our results may initiate further, similar, studies resulting in a generally accepted rational classification. We believe that such categorization is necessary for elucidating their biological and clinical significance.
Family doctors and psychologists working together: doctors' and patients' perspectives
Authors: Chomienne Marie‐Hélène , Grenier Jean , Gaboury Isabelle , Hogg William , Ritchie Pierre , Farmanova‐Haynes Elina 
Published: September 2010

AbstractBackground  Strategies to improve primary care in the Canadian Primary Care Reform include integrating different professionals to the medical team.Objective  This demonstration project explores the perceived impact on doctors and patients, of having family doctors and psychologists work together.Setting  Two family practices of Eastern Ontario, CanadaMethods  Two board certified psychologists (one per practice) were integrated in the practices for 12 months. Psychologists conducted assessments, consultations and short‐term treatments, as well as knowledge‐transfer sessions for doctors. Outcome measures included referral patterns, patient outcomes, patient and provider satisfaction as well as doctors' billing.Results  Three hundred and seventy‐six participants received psychological care; most were women (68%) and between the ages of 25–64 (67%). Anxiety and depression were the most prevalent diagnoses. Reasons for referral included: psychological treatment (70%); emotional support and counselling (35%); clarification of diagnosis and case conceptualization (25%). Referrals could be for more than one reason. After intervention, 60% of patients had improvement on the outcome questionnaire‐45 (OQ‐45). Quality of life as measured by the EuroQol‐5D also improved (P < 0.001). Over 77% of patients reported increased confidence in handling their problems after treatment. Compared with their family doctor, patients felt the psychologist had more time and was better trained (75%) Doctors felt mental health problems were diagnosed more rapidly, patient care improved as well as their own knowledge of psychological management and treatment. Doctors felt it freed up their time and improved working conditions. Audit of the doctors' billing showed reduction in doctors' mental health billing.Conclusions  Having an on‐site psychologist was highly satisfactory for patients and providers, resulting in improved patient care and outcomes.