bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene name ambiguity of eukaryotic nomenclatures
Authors: Chen Lifeng , Liu Hongfang , Friedman Carol 
Published: August 2004

AbstractMotivation: With more and more scientific literature published online, the effective management and reuse of this knowledge has become problematic. Natural language processing (NLP) may be a potential solution by extracting, structuring and organizing biomedical information in online literature in a timely manner. One essential task is to recognize and identify genomic entities in text. ‘Recognition’ can be accomplished using pattern matching and machine learning. But for ‘identification’ these techniques are not adequate. In order to identify genomic entities, NLP needs a comprehensive resource that specifies and classifies genomic entities as they occur in text and that associates them with normalized terms and also unique identifiers so that the extracted entities are well defined. Online organism databases are an excellent resource to create such a lexical resource. However, gene name ambiguity is a serious problem because it affects the appropriate identification of gene entities. In this paper, we explore the extent of the problem and suggest ways to address it.Results: We obtained gene information from 21 organisms and quantified naming ambiguities within species, across species, with English words and with medical terms. When the case (of letters) was retained, official symbols displayed negligible intra-species ambiguity (0.02%) and modest ambiguities with general English words (0.57%) and medical terms (1.01%). In contrast, the across-species ambiguity was high (14.20%). The inclusion of gene synonyms increased intra-species ambiguity substantially and full names contributed greatly to gene-medical-term ambiguity. A comprehensive lexical resource that covers gene information for the 21 organisms was then created and used to identify gene names by using a straightforward string matching program to process 45 000 abstracts associated with the mouse model organism while ignoring case and gene names that were also English words. We found that 85.1% of correctly retrieved mouse genes were ambiguous with other gene names. When gene names that were also English words were included, 233% additional ‘gene’ instances were retrieved, most of which were false positives. We also found that authors prefer to use synonyms (74.7%) to official symbols (17.7%) or full names (7.6%) in their publications.Contact: lifeng.chen@dbmi.columbia.edu
Filtering of Ineffective siRNAs and Improved siRNA Design Tool
Authors: Yiu S. M. , Wong Prudence W. H. , Lam T.W. , Mui Y.C. , Kung H. F. , Lin Marie , Cheung Y. T. 
Published: August 2004

Abstract
Motivation: Short interfering RNAs (siRNAs) can be used to suppress gene expression and possess many potential applications in therapy, but how to design an effective siRNA is still not clear. Based on the MPI (Max-Planck-Institute) basic principles, a number of siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. In view of this, we initiate the study of filtering ineffective siRNAs.
Results: The contribution of this paper is 2-fold. First, we propose a fair scheme to compare existing design tools based on real data in the literature. Second, we attempt to improve the MPI principles and existing tools by an algorithm that can filter ineffective siRNAs. The algorithm is based on some new observations on the secondary structure, which we have verified by AI techniques (decision trees and support vector machines). We have tested our algorithm together with the MPI principles and the existing tools. The results show that our filtering algorithm is effective.
Availability: The siRNA design software tool can be found in the website http://www.cs.hku.hk/~sirna/
Contact: smyiu@cs.hku.hk
Missing value estimation for DNA microarray gene expression data: local least squares imputation
Authors: Kim Hyunsoo , Golub Gene H. , Park Haesun 
Published: August 2004

Abstract
Motivation: Gene expression data often contain missing expression values. Effective missing value estimation methods are needed since many algorithms for gene expression data analysis require a complete matrix of gene array values. In this paper, imputation methods based on the least squares formulation are proposed to estimate missing values in the gene expression data, which exploit local similarity structures in the data as well as least squares optimization process.
Results: The proposed local least squares imputation method (LLSimpute) represents a target gene that has missing values as a linear combination of similar genes. The similar genes are chosen by k-nearest neighbors or k coherent genes that have large absolute values of Pearson correlation coefficients. Non-parametric missing values estimation method of LLSimpute are designed by introducing an automatic k-value estimator. In our experiments, the proposed LLSimpute method shows competitive results when compared with other imputation methods for missing value estimation on various datasets and percentages of missing values in the data.
Availability: The software is available at http://www.cs.umn.edu/~hskim/tools.html
Contact: hpark@cs.umn.edu
Preoperative Pregnancy Testing in Ambulatory Surgery
Authors: Manley Steven , de Kelaita Grace , Joseph Ninos J. , Salem M. Ramez , Heyman Harold J. 
Published: August 2004

Background
The incidence of unrecognized early pregnancy and its influence on the surgical and anesthetic course in patients presenting for elective ambulatory surgery have not been previously determined. The current study was designed to determine the incidence of unrecognized pregnancy in women presenting for ambulatory surgery. In addition, it examined how discovery of the pregnancy altered the anesthetic or surgical course.

Methods
In a prospective study over a 1-yr period, all women of childbearing potential (defined as menstruating women without prior hysterectomy or tubal ligation) were preoperatively evaluated and tested for urine or serum human chorionic gonadotropin, to determine unrecognized pregnancy. If a pregnancy was detected, the disposition of the surgical procedure and the effect on the surgical and anesthetic management was recorded.

Results
Of 2,056 women of childbearing potential presenting for ambulatory surgery, testing revealed 7 previously unrecognized pregnancies, an incidence of 0.3%. Included among these patients were two patients scheduled to undergo fertility procedures. On learning the test result and even before being advised of available options, all patients elected to cancel or postpone the surgical procedure.

Conclusions
The incidence of previously unrecognized pregnancy in menstruating women presenting for ambulatory, nonobstetric surgery was 0.3%. The knowledge of a positive test resulted in cancellation or postponement of the operative procedure. Patient desire for cancellation was the main determining factor in each case.
Prolonged Alleviation of Tactile Allodynia by Intravenous Lidocaine in Neuropathic Rats
Authors: Chaplan Sandra R. , Bach Flemming W. , Shafer Steven L. , Yaksh Tony L. 
Published: August 2004

Background
Lidocaine may be useful in the treatment of neuropathic pain states. The authors hypothesized that lidocaine would reduce tactile allodynia observed in a rat nerve injury model. In an effort to determine the site of drug action, effects after intravenous, intrathecal, and regional administration were compared.

Methods
Rats underwent ligation of the left fifth and sixth lumbar spinal nerves. The 50% thresholds (g) for left hind paw withdrawal of awake rats to von Frey hairs were documented before, during, and after intravenous administration of lidocaine at programmed/documented pseudo-steady-state plasma concentrations, and correlated with measured plasma concentrations. Responses to lidocaine application intrathecally and regionally to the injured nerves were also recorded.

Results
In rats with tactile allodynia, intravenous lidocaine yielded 66 +/- 11% of the maximal possible effect on thresholds (100% = normal threshold), versus -1.3 +/- 2.7% for saline infusion. Twenty-one days after lidocaine infusion, 30-40% of the maximal possible effect persisted. Threshold increases depended on plasma concentration, rather than quantity of drug administered: rats receiving 15 mg/kg with higher plasma concentrations (1.2 +/- 0.1 micrograms/ml) showed significant allodynia suppression throughout 7 days of follow-up, whereas rats receiving 15 mg/kg at a slower rate with lower plasma concentrations (0.6 +/- 0.1 microgram/ml) did not. The EC50 for acute allodynia suppression was 0.75 microgram/ml. No such allodynia suppression was seen after intrathecal or regional administration of lidocaine despite transient neural blockade.

Conclusions
Intravenous, but not intrathecal or regionally applied, lidocaine produces dose-dependent suppression of allodynia associated with nerve injury. The effects far outlast plasma concentrations of lidocaine. The mechanism of these prolonged effects is unknown.
α2-Adrenergic Receptors in Human Dorsal Root Ganglia
Authors: Ongjoco Rita R. S. , Richardson Charlene D. , Rudner Xiaowen L. , Stafford-Smith Mark , Schwinn Debra A. 
Published: August 2004

Background
Nonselective alpha2-adrenergic receptor (alpha2AR) agonists (e.g., clonidine) mediate antinociception in part through alpha2ARs in spinal cord dorsal horn; however, use of these agents for analgesia in humans is limited by unwanted sedation and hypotension. The authors previously demonstrated alpha2a approximately alpha2b > > > alpha2c mRNA in human spinal cord dorsal horn cell bodies. However, because 20% of dorsal horn alpha2ARs derive from cell bodies that reside in the associated dorsal root ganglion (DRG), it is important to evaluate alpha2AR expression in this tissue as well. Therefore, the authors evaluated the hypothesis that alpha2b mRNA, alpha2c mRNA, or both are present in human DRG.

Methods
Molecular approaches were used to determine alpha2AR expression in 28 human DRGs because of low overall receptor mRNA expression and small sample size. After creation of synthetic competitor cDNA and establishment of amplification conditions with parallel efficiencies, competitive reverse transcription polymerase chain reaction was performed using RNA isolated from human DRG.

Results
Overall expression of alpha2AR mRNA in DRG is low but reproducible at all spinal levels. alpha2b and alpha2cAR subtype mRNAs predominate (alpha2b approximately alpha2c), accounting for more than 95% of the total alpha2AR mRNA in DRG at all human spinal nerve root levels.

Conclusions
Predominance of alpha2b and alpha2cAR mRNA in human DRG is distinct from alpha2AR mRNA expression in cell bodies originating in human spinal cord dorsal horn, where alpha2a and alpha2b predominate with little or absent alpha2c expression. These findings also highlight species heterogeneity in alpha2AR expression in DRG. If confirmed at a protein level, these findings provide an additional step in unraveling mechanisms involved in complex neural pathways such as those for pain.
Reliability of Pharmacodynamic Analysis by Logistic Regression
Authors: Lu Wei , Bailey James M. 
Published: August 2004

Background
Many pharmacologic studies record data as binary yes-or-no variables, and analysis is performed using logistic regression. This study investigates the accuracy of estimation of the drug concentration associated with a 50% probability of drug effect (C50) and the term describing the steepness of the concentration-effect relation (gamma).

Methods
The authors developed a technique for simulating pharmacodynamic studies with binary yes-or-no responses. Simulations were conducted assuming either that each data point was derived from the same patient or that data were pooled from multiple patients in a population with log-normal distributions of C50 and gamma. Coefficients of variation were calculated. The authors also determined the percentage of simulations in which the 95% confidence intervals contained the true parameter value.

Results
The coefficient of variation of parameter estimates decreased with increasing n and gamma. The 95% confidence intervals for C50 estimation contained the true parameter value in more than 90% of the simulations. However, the 95% confidence intervals of gamma did not contain the true value in a substantial number of simulations of data from multiple patients.

Conclusion
The coefficient of variation of parameter estimates may be as large as 40-50% for small studies (n < or = 20). The 95% confidence intervals of C50 almost always contain the true value, underscoring the need for always reporting confidence intervals. However, when data from multiple patients is naively pooled, the estimates of gamma may be biased, and the 95% confidence intervals may not contain the true value.
A Dose-ranging Study of Rapacuronium in Pediatric Patients
Authors: Meakin George H. , Meretoja Olli A. , Motsch Johann , Taivainen Tomi , Wirtavuori Kari , Schönstedt Rüdiger , Perkins Russell , McCluskey Anthony 
Published: August 2004

Background
The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children.

Methods
Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph.

Results
Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious.

Conclusions
Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.
Mechanisms of Ventricular Arrhythmias Induced by Myocardial Contusion
Authors: Robert Emmanuelle , de La Coussaye Jean E. , Aya Antoine G. M. , Bertinchant Jean-Pierre , Polge Anne , Fabbro-Pèray Pascale , Pignodel Christine , Eledjam Jean-Jacques 
Published: August 2004

Background
The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia.

Methods
Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed.

Results
The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block.

Conclusions
Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle.
Airway Management during Spaceflight
Authors: Keller Christian , Brimacombe Joseph , Giampalmo Marzia , Kleinsasser Axel , Loeckinger Alex , Giampalmo Giuseppe , Pühringer Fritz 
Published: August 2004

Background
The authors compared airway management in normogravity and simulated microgravity with and without restraints for laryngoscope-guided tracheal intubation, the cuffed oropharyngeal airway, the standard laryngeal mask airway, and the intubating laryngeal mask airway.

Methods
Four trained anesthesiologist-divers participated in the study. Simulated microgravity during spaceflight was obtained using a submerged, full-scale model of the International Space Station Life Support Module and neutrally buoyant equipment and personnel. Customized, full-torso manikins were used for performing airway management. Each anesthesiologist-diver attempted airway management on 10 occasions with each device in three experimental conditions: (1) with the manikin at the poolside (poolside); (2) with the submerged manikin floating free (free-floating); and (3) with the submerged manikin fixed to the floor using a restraint (restrained). Airway management failure was defined as failed insertion after three attempts or inadequate device placement after insertion.

Results
For the laryngoscope-guided tracheal intubation, airway management failure occurred more frequently in the free-floating (85%) condition than the restrained (8%) and poolside (0%) conditions (both, P < 0.001). Airway management failure was similar among conditions for the cuffed oropharyngeal airway (poolside, 10%; free-floating, 15%; restrained, 15%), laryngeal mask airway (poolside, 0%; free-floating, 3%; restrained, 0%), and intubating laryngeal mask airway (poolside, 5%; free-floating, 5%; restrained, 10%). Airway management failure for the laryngoscope-guided tracheal intubation was usually caused by failed insertion (> 90%), and for the cuffed oropharyngeal airway, laryngeal mask airway, and intubating laryngeal mask airway, it was always a result of inadequate placement.

Conclusion
The emphasis placed on the use of restraints for conventional tracheal intubation in microgravity is appropriate. Extratracheal airway devices may be useful when restraints cannot be applied or intubation is difficult.
Succinylcholine Metabolite Succinic Acid Alters Steady State Activation in Muscle Sodium Channels
Authors: Haeseler Gertrud , Petzold Jacqueline , Hecker Hartmut , Würz Axel , Dengler Reinhard , Piepenbrock Siegfried , D M. , Leuwer Martin 
Published: August 2004

Background
Animal experiments revealed that succinylcholine produced masseter muscle rigidity and activated myotonic discharges despite neuromuscular blockade with a nondepolarizing blocker. These results suggest that either succinylcholine or its metabolites might interfere directly with voltage-operated ion channels of the sarcolemma. The aim of this study was to examine effects of one product of succinylcholine hydrolysis, succinic acid, on voltage-gated muscle sodium (Na+) channels.

Methods
Alpha subunits of human muscle sodium channels were heterologously expressed in HEK293 cells. Activation of Na+ currents was examined applying standard whole-cell voltage-clamp protocols in the absence (control and washout) and presence of succinic acid in different concentrations (0.05-10 mm).

Results
Succinic acid shifted the midpoints of steady state activation plots in the direction of more negative test potentials, indicating that channels open during smaller depolarizations in the presence of the drug. The maximum amount of the negative shift in 10 mm succinic acid was -6.3 +/- 1.7 mV; the EC50 for this effect was 0.39 mm. In addition, succinic acid (10 mm) significantly enhanced maximum currents after depolarizations with respect to a series of control experiments.

Conclusion
Succinic acid facilitates voltage-dependent activation in muscle sodium channels in vitro. This might lead to muscle hyperexcitability in vivo.
Intravenous Anesthetics Differentially Modulate Ligand-gated Ion Channels
Authors: Flood Pamela , Krasowski Matthew D. 
Published: August 2004

Background
Heteromeric neuronal nicotinic acetylcholine receptors (nAChRs) are potently inhibited by volatile anesthetics, but it is not known whether they are affected by intravenous anesthetics. Ketamine potentiates gamma-aminobutyric acid type A (GABAA) receptors at high concentrations, but it is unknown whether there is potentiation at clinically relevant concentrations. Information about the effects of intravenous anesthetics with different behavioral profiles on specific ligand-gated ion channels may lead to hypotheses as to which ion channel effect produces a specific anesthetic behavior.

Methods
A heteromeric nAChR composed of alpha4 and beta4 subunits was expressed heterologously in Xenopus laevis oocytes. Using the two-electrode voltage clamp technique, peak ACh-gated current was measured before and during application of ketamine, etomidate, or thiopental. The response to GABA of alpha1beta2gamma2s GABAA receptors expressed in human embryonic kidney cells and Xenopus oocytes was compared with and without coapplication of ketamine from 1 microm to 10 mm.

Results
Ketamine caused potent, concentration-dependent inhibition of the alpha4beta4 nAChR current with an IC50 of 0.24 microm. The inhibition by ketamine was use-dependent; the antagonist was more effective when the channel had been opened by agonist. Ketamine did not modulate the alpha1beta2gamma2s GABAA receptor response in the clinically relevant concentration range. Thiopental caused 27% inhibition of ACh response at its clinical EC50. Etomidate did not modulate the alpha4beta4 nAChR response in the clinically relevant concentration range, although there was inhibition at very high concentrations.

Conclusions
The alpha4beta4 nAChR, which is predominantly found in the central nervous system (CNS), is differentially affected by clinically relevant concentrations of intravenous anesthetics. Ketamine, commonly known to be an inhibitor at the N-methyl-D-aspartate receptor, is also a potent inhibitor at a central nAChR. It has little effect on a common CNS GABAA receptor in a clinically relevant concentration range. Interaction between ketamine and specific subtypes of nAChRs in the CNS may result in anesthetic behaviors such as inattention to surgical stimulus and in analgesia. Thiopental causes minor inhibition at the alpha4beta4 nAChR. Modulation of the alpha4beta4 nAChR by etomidate is unlikely to be important in anesthesia practice based on the insensitivity of this receptor to clinically used concentrations.