bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probe measurements of electron-energy distributions in plasmas: what can we measure and how can we achieve reliable results?
Authors: Godyak V A , Demidov V I 
Published: June 2011

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Template-free detection of macromolecular complexes in cryo electron tomograms
Authors: Xu Min , Beck Martin , Alber Frank 
Published: June 2011

Abstract
Motivation: Cryo electron tomography (CryoET) produces 3D density maps of biological specimen in its near native states. Applied to small cells, cryoET produces 3D snapshots of the cellular distributions of large complexes. However, retrieving this information is non-trivial due to the low resolution and low signal-to-noise ratio in tomograms. Current pattern recognition methods identify complexes by matching known structures to the cryo electron tomogram. However, so far only a small fraction of all protein complexes have been structurally resolved. It is, therefore, of great importance to develop template-free methods for the discovery of previously unknown protein complexes in cryo electron tomograms.
Results: Here, we have developed an inference method for the template-free discovery of frequently occurring protein complexes in cryo electron tomograms. We provide a first proof-of-principle of the approach and assess its applicability using realistically simulated tomograms, allowing for the inclusion of noise and distortions due to missing wedge and electron optical factors. Our method is a step toward the template-free discovery of the shapes, abundance and spatial distributions of previously unknown macromolecular complexes in whole cell tomograms.
Contact: alber@usc.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Uncover disease genes by maximizing information flow in the phenome–interactome network
Authors: Chen Yong , Jiang Tao , Jiang Rui 
Published: June 2011

Abstract
Motivation: Pinpointing genes that underlie human inherited diseases among candidate genes in susceptibility genetic regions is the primary step towards the understanding of pathogenesis of diseases. Although several probabilistic models have been proposed to prioritize candidate genes using phenotype similarities and protein–protein interactions, no combinatorial approaches have been proposed in the literature.
Results: We propose the first combinatorial approach for prioritizing candidate genes. We first construct a phenome–interactome network by integrating the given phenotype similarity profile, protein–protein interaction network and associations between diseases and genes. Then, we introduce a computational method called MAXIF to maximize the information flow in this network for uncovering genes that underlie diseases. We demonstrate the effectiveness of this method in prioritizing candidate genes through a series of cross-validation experiments, and we show the possibility of using this method to identify diseases with which a query gene may be associated. We demonstrate the competitive performance of our method through a comparison with two existing state-of-the-art methods, and we analyze the robustness of our method with respect to the parameters involved. As an example application, we apply our method to predict driver genes in 50 copy number aberration regions of melanoma. Our method is not only able to identify several driver genes that have been reported in the literature, it also shed some new biological insights on the understanding of the modular property and transcriptional regulation scheme of these driver genes.
Contact: ruijiang@tsinghua.edu.cn
MeSH: a window into full text for document summarization
Authors: Bhattacharya Sanmitra , Ha−Thuc Viet , Srinivasan Padmini 
Published: June 2011

Abstract
Motivation: Previous research in the biomedical text-mining domain has historically been limited to titles, abstracts and metadata available in MEDLINE records. Recent research initiatives such as TREC Genomics and BioCreAtIvE strongly point to the merits of moving beyond abstracts and into the realm of full texts. Full texts are, however, more expensive to process not only in terms of resources needed but also in terms of accuracy. Since full texts contain embellishments that elaborate, contextualize, contrast, supplement, etc., there is greater risk for false positives. Motivated by this, we explore an approach that offers a compromise between the extremes of abstracts and full texts. Specifically, we create reduced versions of full text documents that contain only important portions. In the long-term, our goal is to explore the use of such summaries for functions such as document retrieval and information extraction. Here, we focus on designing summarization strategies. In particular, we explore the use of MeSH terms, manually assigned to documents by trained annotators, as clues to select important text segments from the full text documents.
Results: Our experiments confirm the ability of our approach to pick the important text portions. Using the ROUGE measures for evaluation, we were able to achieve maximum ROUGE-1, ROUGE-2 and ROUGE-SU4 F-scores of 0.4150, 0.1435 and 0.1782, respectively, for our MeSH term-based method versus the maximum baseline scores of 0.3815, 0.1353 and 0.1428, respectively. Using a MeSH profile-based strategy, we were able to achieve maximum ROUGE F-scores of 0.4320, 0.1497 and 0.1887, respectively. Human evaluation of the baselines and our proposed strategies further corroborates the ability of our method to select important sentences from the full texts.
Contact: sanmitra-bhattacharya@uiowa.edu; padmini-srinivasan@uiowa.edu
A conditional random fields method for RNA sequence–structure relationship modeling and conformation sampling
Authors: Wang Zhiyong , Xu Jinbo 
Published: June 2011

Abstract
Accurate tertiary structures are very important for the functional study of non-coding RNA molecules. However, predicting RNA tertiary structures is extremely challenging, because of a large conformation space to be explored and lack of an accurate scoring function differentiating the native structure from decoys. The fragment-based conformation sampling method (e.g. FARNA) bears shortcomings that the limited size of a fragment library makes it infeasible to represent all possible conformations well. A recent dynamic Bayesian network method, BARNACLE, overcomes the issue of fragment assembly. In addition, neither of these methods makes use of sequence information in sampling conformations. Here, we present a new probabilistic graphical model, conditional random fields (CRFs), to model RNA sequence–structure relationship, which enables us to accurately estimate the probability of an RNA conformation from sequence. Coupled with a novel tree-guided sampling scheme, our CRF model is then applied to RNA conformation sampling. Experimental results show that our CRF method can model RNA sequence–structure relationship well and sequence information is important for conformation sampling. Our method, named as TreeFolder, generates a much higher percentage of native-like decoys than FARNA and BARNACLE, although we use the same simple energy function as BARNACLE.
Contact: zywang@ttic.edu; j3xu@ttic.edu
Supplementary Information: Supplementary data are available at Bioinformatics online.
Predicting site-specific human selective pressure using evolutionary signatures
Authors: Sadri Javad , Diallo Abdoulaye Banire , Blanchette Mathieu 
Published: June 2011

Abstract
Motivation: The identification of non-coding functional regions of the human genome remains one of the main challenges of genomics. By observing how a given region evolved over time, one can detect signs of negative or positive selection hinting that the region may be functional. With the quickly increasing number of vertebrate genomes to compare with our own, this type of approach is set to become extremely powerful, provided the right analytical tools are available.
Results: A large number of approaches have been proposed to measure signs of past selective pressure, usually in the form of reduced mutation rate. Here, we propose a radically different approach to the detection of non-coding functional region: instead of measuring past evolutionary rates, we build a machine learning classifier to predict current substitution rates in human based on the inferred evolutionary events that affected the region during vertebrate evolution. We show that different types of evolutionary events, occurring along different branches of the phylogenetic tree, bring very different amounts of information. We propose a number of simple machine learning classifiers and show that a Support-Vector Machine (SVM) predictor clearly outperforms existing tools at predicting human non-coding functional sites. Comparison to external evidences of selection and regulatory function confirms that these SVM predictions are more accurate than those of other approaches.
Availability: The predictor and predictions made are available at http://www.mcb.mcgill.ca/~blanchem/sadri.
Contact: blanchem@mcb.mcgill.ca
Multi-view methods for protein structure comparison using latent dirichlet allocation
Authors: Shivashankar S. , Srivathsan S. , Ravindran B. , Tendulkar Ashish V. 
Published: June 2011

Abstract
Motivation: With rapidly expanding protein structure databases, efficiently retrieving structures similar to a given protein is an important problem. It involves two major issues: (i) effective protein structure representation that captures inherent relationship between fragments and facilitates efficient comparison between the structures and (ii) effective framework to address different retrieval requirements. Recently, researchers proposed vector space model of proteins using bag of fragments representation (FragBag), which corresponds to the basic information retrieval model.
Results: In this article, we propose an improved representation of protein structures using latent dirichlet allocation topic model. Another important requirement is to retrieve proteins, whether they are either close or remote homologs. In order to meet diverse objectives, we propose multi-viewpoint based framework that combines multiple representations and retrieval techniques. We compare the proposed representation and retrieval framework on the benchmark dataset developed by Kolodny and co-workers. The results indicate that the proposed techniques outperform state-of-the-art methods.
Availability: http://www.cse.iitm.ac.in/~ashishvt/research/protein-lda/.
Contact: ashishvt@cse.iitm.ac.in
Airway dysfunction in nasal polyposis: a spectrum of asthmatic disease?
Authors: Williamson P. A. , Vaidyanathan S. , Clearie K. , Barnes M. , Lipworth B. J. 
Published: June 2011

Summary
Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non‐allergic unified airway. The factors associated with airway dysfunction in CRSwNP are not fully understood.
Objective To assess the impact of nasal disease on lower airway dysfunction in CRSwNP.
Methods Fifty‐seven patients with CRSwNP underwent spirometry, nasal endoscopy, exhaled nitric oxide, methacholine bronchial challenge, blood sampling for total IgE, eosinophil count and radioallergosorbent testing (NCT00788749). Three phenotypic groups were identified: ‘asthma group’ (asthma diagnosis); ‘inflammatory group’ [no asthma diagnosis, but elevated fractionated exhaled nitric oxide (FENO) and/or bronchial‐hyperreactivity (BHR)]; and ‘non‐inflammatory group’ (no asthma diagnosis, no BHR and normal FENO). Group comparisons, univariate and multivariate analyses were performed to examine associations with airway dysfunction.
Results FEV1 and FEF25−75% were reduced in asthma, but there was no difference between the non‐asthmatic groups. Total IgE and eosinophils were elevated in asthma vs. the non‐inflammatory group, but there was no difference for asthma vs. inflammatory groups. BHR was the only significant predictor of FEV1 (P<0.001). For FEF25−75, BHR and eosinophil count were independent predictors (P<0.001 and P=0.04). Nasal outcomes were not predictors of spirometry.
Conclusion and Clinical Relevance In CRSwNP there is asymptomatic airway dysfunction suggestive of an asthmatic phenotype. Impairment of lung function is significantly associated with BHR and eosinophilia but not parameters of nasal disease suggesting that severity of airway dysfunction relates to the spectrum of asthma rather than rhinosinusitis. Lower airway dysfunction is common in CRSwNP but does not correlate to the severity of nasal disease. Signs and symptoms of asthma should be sought and treated in CRSwNP.
Cite this as: P. A. Williamson, S. Vaidyanathan, K. Clearie, M. Barnes and B. J. Lipworth, Clinical & Experimental Allergy, 2011 (41) 1379–1385.
Survey on physicians' knowledge and attitudes towards clinical practice guidelines at the Mexican Institute of Social Security
Authors: Constantino‐Casas Patricia , Medécigo‐Micete Consuelo , Millán‐Gámez Yuribia K. , Torres‐Arreola Laura d. P. , Valenzuela‐Flores Adriana A. , Viniegra‐Osorio Arturo , Echevarría‐Zuno Santiago , Sandoval‐Castellanos Fernando J. 
Published: June 2011

AbstractObjective  A survey was organized to determine the general level of knowledge and attitudes of medical personnel towards clinical practice guidelines (CPG).Methods  A questionnaire modified from two validated instruments was used. Multi‐stratified sampling was applied, and 1782 questionnaires were completed.Results  A total of 80.4% of physicians had regular employment contract, 8.6% managerial post and 9.3% temporary work contract. Average age and working time were 43.7 and 15 years respectively; 64.3% were male. It was reported that 47.9% participated in academic activities, 70.8% belonged to a medical association, 40.3% identified CPG as steps towards arriving at a diagnosis and/or treatment and 14.9% thought that CPG were norms. A total of 10.7% of the physicians believed that guidelines are based on scientific evidence, 10% perceived them as supporting tools, 10.8% had no knowledge of them, 65% said that they used them, 76.7% thought that personal experience was as important as CPG recommendations and 57.4% thought that CPG were necessary for good medical practice. Physicians preferred that CPG be produced by personnel from outside the Mexican Institute of Social Security, or who had followed validity criteria.Conclusions  The majority of physicians considered CPG to be useful tools. It was evident that few knew where to acquire CPG, and this would lead to their limited use. Findings from this study enabled procuring a broader idea of the level of knowledge and attitudes of Mexican Institute of Social Security physicians towards CPG. This information is relevant when planning strategies for the purpose of sharing and implementing CPG.
Toltrazuril sulfone sodium salt: synthesis, analytical detection, and pharmacokinetics in the Horse
Authors: DIRIKOLU L. , KARPIESIUK W. , LEHNER A. F. , TOBIN T. 
Published: June 2011

Dirikolu, L., Karpiesiuk, W., Lehner, A. F., Tobin, T. Toltrazuril sulfone sodium salt: synthesis, analytical detection, and pharmacokinetics in the Horse.J. vet. Pharmacol. Therap. 35, 265–274.Toltrazuril sulfone (ponazuril) is a triazine‐based antiprotozoal agent with clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, we synthesized and determined the bioavailability of a sodium salt formulation of toltrazuril sulfone that can be used for the treatment and prophylaxis of EPM in horses. Toltrazuril sulfone sodium salt was rapidly absorbed, with a mean peak plasma concentration of 2400 ± 169 (SEM) ng/mL occurring at 8 h after oral‐mucosal dosing and was about 56% bioavailable compared with the i.v. administration of toltrazuril sulfone in dimethylsulfoxide (DMSO). The relative bioavailability of toltrazuril sulfone suspended in water compared with toltrazuril sulfone sodium salt was 46%, indicating approximately 54% less oral bioavailability of this compound suspended in water. In this study, we also investigated whether this salt formulation of toltrazuril sulfone can be used as a feed additive formulation without significant reduction in oral bioavailability. Our results indicated that toltrazuril sulfone sodium salt is relatively well absorbed when administered with feed with a mean oral bioavailability of 52%. Based on these data, repeated oral administration of toltrazuril sulfone sodium salt with or without feed will yield effective plasma and cerebrospinal fluid (CSF) concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM and other protozoal diseases of horses and other species. As such, toltrazuril sulfone sodium salt has the potential to be used as feed additive formulations for both the treatment and prophylaxis of EPM and various other apicomplexan diseases.
Met or matched expectations: what accounts for a successful back pain consultation in primary care?
Authors: Georgy Ehab E. , Carr Eloise C.J. , Breen Alan C. 
Published: June 2011

AbstractBackground  Patients’ as well as doctors’ expectations might be key elements for improving the quality of health care; however, previous conceptual and theoretical frameworks related to expectations often overlook such complex and complementary relationship between patients’ and doctors’ expectations. The concept of ‘matched patient–doctor expectations’ is not properly investigated, and there is lack of literature exploring such aspect of the consultation.Aim  The paper presents a preliminary conceptual model for the relationship between patients’ and doctors’ expectations with specific reference to back pain management in primary care.Methods  The methods employed in this study are integrative literature review, examination of previous theoretical frameworks, identification of conceptual issues in existing literature, and synthesis and development of a preliminary pragmatic conceptual framework.Outcome  A simple preliminary model explaining the formation of expectations in relation to specific antecedents and consequences was developed; the model incorporates several stages and filters (influencing factors, underlying reactions, judgement, formed reactions, outcome and significance) to explain the development and anticipated influence of expectations on the consultation outcome.Conclusion  The newly developed model takes into account several important dynamics that might be key elements for more successful back pain consultation in primary care, mainly the importance of matching patients’ and doctors’ expectations as well as the importance of addressing unmet expectations.
Sliding baselines and shuffling species: implications of climate change for marine conservation
Authors: Hobday Alistair J. 
Published: June 2011

AbstractThe concept of shifting or sliding baselines refers to the way that significant changes to an ecological system are mistakenly measured against a previous baseline, which may be significantly different from the original state of the system. The concept assumes an ‘original state’ exists and that a return to that state might be possible, if it could be determined and there was sufficient control of human interference. The concept has been important in both marine conservation planning and fisheries management. However, long periods of exploitation, observed and projected climate change, and the disappearance of some environments, suggest that a return to an original state is unlikely to be achievable in many systems. In addition, protection based on static marine protected areas is unlikely to meet common conservation objectives, as species and habitats are moving and species assemblages shuffling with the changing climate. An alternative to modeling single species distribution changes is to examine change in environmental proxies, such as sea surface temperature (SST). Here, projected changes in SST for the period 2063–2065 from a downscaled ocean model are used to illustrate the similarity to, and movements of, present pelagic environments within conservation planning areas off Eastern Australia. The future environment of small planning areas differs from their present environment and static protected areas might not protect range‐changing species. Climate‐aware conservation planning should consider the use of mobile protected areas to afford protection to species’ changing their distribution, and develop conservation objectives that are not underpinned by a return to historical baselines.
High species density patterns in macrofaunal invertebrate communities in the marine benthos
Authors: Oliver John , Hammerstrom Kamille , McPhee‐Shaw Erika , Slattery Peter , Oakden James , Kim Stacy , Hartwell S. Ian 
Published: June 2011

AbstractSpecies density of macrofaunal invertebrates living in marine soft sediments was highest at the shelf‐slope break (100–150 m) in Monterey Bay (449 m−2). There were 337 species m−2 in the mid‐shelf mud zone (80 m). There were fewer species along the slope: 205 m−2 from the lower slope (950‐2000 m) and 335 m−2 on the upper slope (250‐750 m). Species density was highest inside the bay (328‐446 m−2) compared to outside (336‐339 m−2), when examining samples at selected water depths (60‐1000 m). There was little difference in local species density from 1 km of shoreline compared to regional species density along 1000 km of shoreline at both shelf and slope depths. The highest species densities worldwide in the literature are recorded along the Carolina slope in the Atlantic Ocean, where peak species density (436/0.81 m2) at 800 m and values at the largest sample areas are similar to those on the Monterey Bay shelf. We speculate that the highest species densities occur where ocean water exchanges energy with shoaling topography at the continental margin, bringing more food to the benthos ‐‐ areas such as the very productive waters in the upwelling system of Monterey Bay.
Radiofrequency ablation versus surgical resection as primary treatment of hepatocellular carcinoma meeting the Milan criteria: A systematic review
Authors: Cho Yun Ku , Rhim Hyunchul , Noh SangIk 
Published: June 2011

AbstractBackground and Aim:  Surgery is the standard treatment option for hepatocellular carcinoma (HCC) meeting the Milan criteria, defined as single HCC ≤ 5 cm in maximum diameter or up to three nodules ≤ 3 cm. However, favorable survival outcomes have also been reported for these HCCs following radiofrequency ablation (RFA).Methods:  We performed a systematic review to compare the results of hepatic resection and percutaneous RFA as a primary treatment option of HCC meeting the Milan criteria. Studies were identified by searching MEDLINE on PubMed, the Cochrane Library database and CANCERLIT using appropriate key words.Results:  In all six identified observational studies, there were no statistically significant differences in overall survival rates between the two treatment modalities. The results of two randomized trials are controversial, while the power of these randomized trials is too limited to reach a reliable conclusion. In practice, the choice of treatment between surgery and RFA largely depends on the relationship between the local recurrence and perioperative mortality rates of HCC patients. Following RFA, local recurrence rates are low when a minimal safety margin ≥ 4–5 mm is achieved. A previous simulation study of overall survival for very early stage HCC, defined as an asymptomatic solitary small HCC ≤ 2 cm, showed that primary RFA with a 9% local recurrence rate is comparable to surgical resection with a 3% operative mortality rate.Conclusion:  Acquisition of a sufficient safety margin seems to be a critical factor before recommending wider application of RFA as primary treatment for HCCs that meet the Milan criteria.