bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area
Authors: Krabbe Sabine , Duda Johanna , Schiemann Julia , Poetschke Christina , Schneider Gaby , Kandel Eric R. , Liss Birgit , Roeper Jochen , Simpson Eleanor H. 
Published: February 2015

Significance
Patients with schizophrenia suffer from cognitive and negative deficits that are largely resistant to current therapeutic strategies. Here, using a genetic mouse model that displays phenotypes similar to these cognitive and negative symptoms, we found that increased postsynaptic D2 receptor (D2R) activity in the striatum leads to changes in the firing pattern of presynaptic dopamine (DA) neurons of the midbrain. These alterations occur in the ventral tegmental area (VTA) of the midbrain, but not in the substantia nigra, suggesting that DA pathways may be differently regulated by striatal D2R hyperactivity. The changes in neuron firing patterns were accompanied by a reduction in NMDA receptor subunits selectively in dopaminergic VTA neurons, providing a potential new target for the treatment of schizophrenia symptoms.
Preliminary detection method for added rice- and sugarcane-derived brewer’s alcohol in bulk samples of sake by measurement of hydrogen, oxygen, and carbon isotopes
Authors: Hashiguchi Tomokazu , Akamatsu Fumikazu , Izu Hanae , Fujii Tsutomu 
Published: February 2015

Abstract
The δD and δ18O of sake without ethanol extraction as well as the δ13C of ethanol were determined in order to detect rice-derived brewer’s alcohol. Brewing tests demonstrated that the δD decreases upon addition of brewer’s alcohol (both rice- and sugarcane-derived), while the δ18O has little response to either, and the δ13C increases only for added sugarcane-derived alcohol.
FUN-L: gene prioritization for RNAi screens
Authors: Lees Jonathan G. , Hériché Jean-Karim , Morilla Ian , Fernández José M. , Adler Priit , Krallinger Martin , Vilo Jaak , Valencia Alfonso , Ellenberg Jan , Ranea Juan A. , Orengo Christine 
Published: February 2015

Abstract
Motivation: Most biological processes remain only partially characterized with many components still to be identified. Given that a whole genome can usually not be tested in a functional assay, identifying the genes most likely to be of interest is of critical importance to avoid wasting resources.
Results: Given a set of known functionally related genes and using a state-of-the-art approach to data integration and mining, our Functional Lists (FUN-L) method provides a ranked list of candidate genes for testing. Validation of predictions from FUN-L with independent RNAi screens confirms that FUN-L-produced lists are enriched in genes with the expected phenotypes. In this article, we describe a website front end to FUN-L.
Availability and implementation: The website is freely available to use at http://funl.org
Contact: ucbcjle@live.ucl.ac.uk
Large-scale exploration and analysis of drug combinations
Authors: Li Peng , Huang Chao , Fu Yingxue , Wang Jinan , Wu Ziyin , Ru Jinlong , Zheng Chunli , Guo Zihu , Chen Xuetong , Zhou Wei , Zhang Wenjuan , Li Yan , Chen Jianxin , Lu Aiping , Wang Yonghua 
Published: February 2015

Abstract
Motivation: Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered.
Results: We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications.
Availability and implementation: The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php.
Contact: yh_wang@nwsuaf.edu.cn
Supplementary Information: Supplementary data are available at Bioinformatics online.
Up-regulation of silent information regulator 2 (Sir2) is associated with amphotericin B resistance in clinical isolates of Leishmania donovani
Authors: Purkait Bidyut , Singh Ruby , Wasnik Kirti , Das Sushmita , Kumar Ashish , Paine Mark , Dikhit Manas , Singh Dharmendra , Sardar Abul H. , Ghosh Ayan K. , Das Pradeep 
Published: February 2015

Abstract

Objective
Silent information regulator 2 (Sir2) is involved in parasite survival and apoptosis. Here, we aimed to explore the involvement of Sir2 in amphotericin B (AmB) resistance mechanism in Leishmania donovani.

Methods
The expression levels of Sir2, MDR1 and NAD+ biosynthetic pathway enzymes in AmB-resistant and -susceptible parasites were measured and total intracellular NAD+/NADH ratios were compared. Overexpression and knockout constructs of Sir2 were transfected in AmB-resistant and -susceptible parasites. Both resistant and susceptible parasites were inhibited with sirtinol for 4 h. The deacetylase activity of Sir2, the expression level of MDR1, the rate of AmB efflux, concentrations of reactive oxygen species (ROS) and levels of apoptosis were examined in WT, inhibited and transfected parasites, and the AmB susceptibility of the respective parasites was measured by determining the LD50 of AmB.

Results
Levels of mRNA, protein and NAD+-dependent deacetylase activity of Sir2 were elevated in resistant versus susceptible parasites. Inhibition and/or deletion of Sir2 allele showed a decreased mRNA level of MDR1, lower drug efflux, increased ROS concentration, apoptosis-like phenomenon and decreased LD50 of AmB in resistant parasites. In contrast, Sir2 overexpression in susceptible parasites reversed drug susceptibility producing a resistant phenotype. This was associated with increased LD50 of AmB along with increased expression levels of MDR1, drug efflux and reduced concentrations of ROS, corresponding to decreased apoptosis of resistant to WT sensitive.

Conclusions
Sir2 plays a critical role in AmB resistance by regulating MDR1, ROS concentration and apoptosis-like phenomena and may be a new resistance marker for visceral leishmaniasis.
Novel user interface design for medication reconciliation: an evaluation of Twinlist
Authors: Plaisant Catherine , Wu Johnny , Hettinger A. Zach , Powsner Seth , Shneiderman Ben 
Published: February 2015

Abstract
Objective The primary objective was to evaluate time, number of interface actions, and accuracy on medication reconciliation tasks using a novel user interface (Twinlist, which lays out the medications in five columns based on similarity and uses animation to introduce the grouping - www.cs.umd.edu/hcil/sharp/twinlist) compared to a Control interface (where medications are presented side by side in two columns). A secondary objective was to assess participant agreement with statements regarding clarity and utility and to elicit comparisons.
Material and Methods A 1 × 2 within-subjects experimental design was used with interface (Twinlist or Control) as an independent variable; time, number of clicks, scrolls, and errors were used as dependent variables. Participants were practicing medical providers with experience performing medication reconciliation but no experience with Twinlist. They reconciled two cases in each interface (in a counterbalanced order), then provided feedback on the design of the interface.
Results Twenty medical providers participated in the study for a total of 80 trials. The trials using Twinlist were statistically significantly faster (18%), with fewer clicks (40%) and scrolls (60%). Serious errors were noted 12 and 31 times in Twinlist and Control trials, respectively.
Discussion Trials using Twinlist were faster and more accurate. Subjectively, participants rated Twinlist more favorably than Control. They valued the novel layout of the drugs, but indicated that the included animation would be valuable for novices, but not necessarily for advanced users. Additional feedback from participants provides guidance for further development and clinical implementations.
Conclusions Cognitive support of medication reconciliation through interface design can significantly improve performance and safety.
Rural EMR adoption rates overtake those in urban areas
Authors: Whitacre Brian E. 
Published: February 2015

Abstract
Objective To assess rural-urban differences in electronic medical record (EMR) adoption among office-based physician practices in the United States.
Methods Survey data on over 270 000 office-based physician sites (representing over 1 280 000 physicians) in the United States from 2012 was used to assess differences in EMR adoption rates among practices in rural and urban areas. Logistic regression tests for differences in the determinants of EMR adoption by geography, and a nonlinear decomposition is used to quantify how much of the rural-urban gap is due to differences in measureable characteristics (such as type of practice or affiliation with a health system).
Results Overall EMR adoption rates were significantly higher for practices in rural areas (56%) vs those in urban areas (49%) in 2012 (P &lt; 0.001). Twenty-nine states had statistically significantly different adoption rates between rural and urban areas, with only two states demonstrating higher rates in urban areas. EMR adoption continues to be higher for primary care practices when compared to specialists (51% vs 49%, P &lt; 0.001), and state-level rural-urban differences in adoption are more pronounced for specialists. The decomposition technique finds that only 14% of the rural-urban gap can be explained by differences in measurable characteristics between practices.
Conclusions At the national level, rates of EMR adoption are higher for rural practices than for their urban counterparts, reversing earlier trends. This suggests that outreach efforts, namely the Regional Extension Centers created by the Office of the National Coordinator, have been particularly effective in increasing EMR adoption in rural areas.
The Response of Drug Expenditure to Nonlinear Contract Design: Evidence from Medicare Part D *
Authors: Einav Liran , Finkelstein Amy , Schrimpf Paul 
Published: February 2015

AbstractWe study the demand response to nonlinear price schedules using data on insurance contracts and prescription drug purchases in Medicare Part D. We exploit the kink in individuals’ budgets set created by the famous “donut hole,” where insurance becomes discontinuously much less generous on the margin, to provide descriptive evidence of the drug purchase response to a price increase. We then specify and estimate a simple dynamic model of drug use that allows us to quantify the spending response along the entire nonlinear budget set. We use the model for counterfactual analysis of the increase in spending from “filling” the donut hole, as will be required by 2020 under the Affordable Care Act. In our baseline model, which considers spending decisions within a single year, we estimate that filling the donut hole will increase annual drug spending by about $150, or about 8 percent. About one-quarter of this spending increase reflects anticipatory behavior, coming from beneficiaries whose spending prior to the policy change would leave them short of reaching the donut hole. We also present descriptive evidence of cross-year substitution of spending by individuals who reach the kink, which motivates a simple extension to our baseline model that allows—in a highly stylized way—for individuals to engage in such cross-year substitution. Our estimates from this extension suggest that a large share of the $150 drug spending increase could be attributed to cross-year substitution, and the net increase could be as little as $45 a year.
The Value of Hiring through Employee Referrals *
Authors: Burks Stephen V. , Cowgill Bo , Hoffman Mitchell , Housman Michael 
Published: February 2015

AbstractUsing personnel data from nine large firms in three industries (call centers, trucking, and high-tech), we empirically assess the benefit to firms of hiring through employee referrals. Compared to nonreferred applicants, referred applicants are more likely to be hired and more likely to accept offers, even though referrals and nonreferrals have similar skill characteristics. Referred workers tend to have similar productivity compared to nonreferred workers on most measures, but referred workers have lower accident rates in trucking and produce more patents in high-tech. Referred workers are substantially less likely to quit and earn slightly higher wages than nonreferred workers. In call centers and trucking, the two industries for which we can calculate worker-level profits, referred workers yield substantially higher profits per worker than nonreferred workers. These profit differences are driven by lower turnover and lower recruiting costs for referrals.
Safeguards to Prevent Neurologic Complications after Epidural Steroid Injections
Authors: Rathmell James P. , Benzon Honorio T. , Dreyfuss Paul , Huntoon Marc , Wallace Mark , Baker Ray , Riew K. Daniel , Rosenquist Richard W. , Aprill Charles , Rost Natalia S. , Buvanendran Asokumar , Kreiner D. Scott , Bogduk Nikolai , Fourney Daryl R. , Fraifeld Eduardo , Horn Scott , Stone Jeffrey , Vorenkamp Kevin , Lawler Gregory , Summers Jeffrey , Kloth David , O’Brien David , Tutton Sean 
Published: February 2015

AbstractAbstract
Epidural corticosteroid injections can lead to rare, catastrophic neurologic injuries. Seventeen clinical considerations aimed at improving safety were produced by stakeholder societies. Adherence to specific recommended practices should lead to a reduction in the incidence of neurologic injuries.

Background:
Epidural corticosteroid injections are a common treatment for radicular pain caused by intervertebral disc herniations, spinal stenosis, and other disorders. Although rare, catastrophic neurologic injuries, including stroke and spinal cord injury, have occurred with these injections.

Methods:
A collaboration was undertaken between the U.S. Food and Drug Administration Safe Use Initiative, an expert multidisciplinary working group, and 13 specialty stakeholder societies. The goal of this collaboration was to review the existing evidence regarding neurologic complications associated with epidural corticosteroid injections and produce consensus procedural clinical considerations aimed at enhancing the safety of these injections. U.S. Food and Drug Administration Safe Use Initiative representatives helped convene and facilitate meetings without actively participating in the deliberations or decision-making process.

Results:
Seventeen clinical considerations aimed at improving safety were produced by the stakeholder societies. Specific clinical considerations for performing transforaminal and interlaminar injections, including the use of nonparticulate steroid, anatomic considerations, and use of radiographic guidance are given along with the existing scientific evidence for each clinical consideration.

Conclusion:
Adherence to specific recommended practices when performing epidural corticosteroid injections should lead to a reduction in the incidence of neurologic injuries.
Can rodents conceive hyperbolic spaces?
Authors: Urdapilleta Eugenio , Troiani Francesca , Stella Federico , Treves Alessandro 
Published: February 2015

SummaryThe grid cells discovered in the rodent medial entorhinal cortex have been proposed to provide a metric for Euclidean space, possibly even hardwired in the embryo. Yet one class of models describing the formation of grid unit selectivity is entirely based on developmental self-organization, and as such it predicts that the metric it expresses should reflect the environment to which the animal has adapted. We show that, according to self-organizing models, if raised in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids. For a given range of grid spacing relative to the radius of negative curvature of the hyperbolic surface, such grids are predicted to appear as multi-peaked firing maps, in which each peak has seven neighbours instead of the Euclidean six, a prediction that can be tested in experiments. We thus demonstrate that a useful universal neuronal metric, in the sense of a multi-scale ruler and compass that remain unaltered when changing environments, can be extended to other than the standard Euclidean plane.AbbreviationmECmedial entorhinal cortexPSpseudosphere
TheGreening after Extended Darkness1Is an N-End Rule Pathway Mutant with High Tolerance to Submergence and Starvation
Authors: Riber Willi , Müller Jana T. , Visser Eric J.W. , Sasidharan Rashmi , Voesenek Laurentius A.C.J. , Mustroph Angelika 
Published: February 2015

AbstractPlants respond to reductions in internal oxygen concentrations with adaptive mechanisms (for example, modifications of metabolism to cope with reduced supply of ATP). These responses are, at the transcriptional level, mediated by the group VII Ethylene Response Factor transcription factors, which have stability that is regulated by the N-end rule pathway of protein degradation. N-end rule pathway mutants are characterized by a constitutive expression of hypoxia response genes and abscisic acid hypersensitivity. Here, we identify a novel proteolysis6 (prt6) mutant allele, named greening after extended darkness1 (ged1), which was previously discovered in a screen for genomes uncoupled-like mutants and shows the ability to withstand long periods of darkness at the seedling stage. Interestingly, this ethyl methanesulfonate-derived mutant shows unusual chromosomal rearrangement instead of a point mutation. Furthermore, the sensitivity of N-end rule pathway mutants ged1 and prt6-1 to submergence was studied in more detail to understand previously contradicting experiments on this topic. Finally, it was shown that mutants for the N-end rule pathway are generally more tolerant to starvation conditions, such as prolonged darkness or submergence, which was partially associated with carbohydrate conservation.
S-Nitrosylation Positively Regulates Ascorbate Peroxidase Activity during Plant Stress Responses
Authors: Yang Huanjie , Mu Jinye , Chen Lichao , Feng Jian , Hu Jiliang , Li Lei , Zhou Jian-Min , Zuo Jianru 
Published: February 2015

AbstractNitric oxide (NO) and reactive oxygen species (ROS) are two classes of key signaling molecules involved in various developmental processes and stress responses in plants. The burst of NO and ROS triggered by various stimuli activates downstream signaling pathways to cope with abiotic and biotic stresses. Emerging evidence suggests that the interplay of NO and ROS plays a critical role in regulating stress responses. However, the underpinning molecular mechanism remains poorly understood. Here, we show that NO positively regulates the activity of the Arabidopsis (Arabidopsis thaliana) cytosolic ascorbate peroxidase1 (APX1). We found that S-nitrosylation of APX1 at cysteine (Cys)-32 enhances its enzymatic activity of scavenging hydrogen peroxide, leading to the increased resistance to oxidative stress, whereas a substitution mutation at Cys-32 causes the reduction of ascorbate peroxidase activity and abolishes its responsiveness to the NO-enhanced enzymatic activity. Moreover, S-nitrosylation of APX1 at Cys-32 also plays an important role in regulating immune responses. These findings illustrate a unique mechanism by which NO regulates hydrogen peroxide homeostasis in plants, thereby establishing a molecular link between NO and ROS signaling pathways.
Thin part identification for CAD model classification
Authors: Pernot Jean-Philippe , Giannini Franca , Petton Cédric 
Published: February 2015

Purpose
– The purpose of this paper is to focus on the characterization and classification of parts with respect to the meshing issue, and notably the meshing of thin parts difficulty handled automatically and which often requires adaptation steps. The objective is to distinguish the so-called thin parts and parts with thin features from the other parts.

Design/methodology/approach
– The concepts of thin part and part with thin features are introduced together with the mechanisms and criteria used for their identification in a CAD models database. The criteria are built on top of a set of shape descriptors and notably the distance distribution which is used to characterize the thickness of the object. To speed up the identification process, shape descriptors are computed from tessellated parts.

Findings
– A complete modular approach has been designed. It computes shape descriptors over parts stored in a directory and it uses criteria to distinguish three categories: thin parts, parts with thin features and other parts. Being the three categories identified, the user can spend more time on the parts that are considered as more difficulty meshable.

Research limitations/implications
– The approach is limited to the three above mentioned categories. However, it has been designed so that the values corresponding to the shape descriptors and associated meshing qualities can easily be inserted within a machining learning tool later on.

Practical implications
– The use of the developed tool can be seen as a pre-processing step during the preparation of finite element (FE) simulation models. It is automatic and can be run in batch and in parallel.

Originality/value
– The approach is modular, it is simple and easy to implement. Categories are built on top of several shape descriptors and not on a unique signature. It is independent of the CAD modeler. This approach is integrated within a FE simulation model preparation framework and help engineers anticipating difficulties when meshing CAD models.
Generalized periodic surface model and its application in designing fibrous porous media
Authors: Huang Wei , Didari Sima , Wang Yan , Harris Tequila A.L. 
Published: February 2015

Purpose
– Fibrous porous media have a wide variety of applications in insulation, filtration, acoustics, sensing, and actuation. To design such materials, computational modeling methods are needed to engineer the properties systematically. There is a lack of efficient approaches to build and modify those complex structures in computers. The paper aims to discuss these issues.

Design/methodology/approach
– In this paper, the authors generalize a previously developed periodic surface (PS) model so that the detailed shapes of fibers in porous media can be modeled. Because of its periodic and implicit nature, the generalized PS model is able to efficiently construct the three-dimensional representative volume element (RVE) of randomly distributed fibers. A physics-based empirical force field method is also developed to model the fiber bending and deformation.

Findings
– Integrated with computational fluid dynamics (CFD) analysis tools, the proposed approach enables simulation-based design of fibrous porous media.

Research limitations/implications
– In the future, the authors will investigate robust approaches to export meshes of PS models directly to CFD simulation tools and develop geometric modeling methods for composite materials that include both fibers and resin.

Originality/value
– The proposed geometric modeling method with implicit surfaces to represent fibers is unique in its capability of modeling bent and deformed fibers in a RVE and supporting design parameter-based modification for global configuration change for the purpose of macroscopic transport property analysis.