bluuebunny/crossref_metadata_2025_split huggingface dataset:
ESG: Extended Similarity Group method for automated protein function prediction
Authors: Chitale Meghana , Hawkins Troy , Park Changsoon , Kihara Daisuke 
Published: August 2008

AbstractWe present here the Extended Similarity Group (ESG) method, which annotates query sequences with Gene Ontology (GO) terms by assigning probability to each annotation computed based on iterative PSI-BLAST searches. Conventionally sequence homology based function annotation methods, such as BLAST, retrieve function information from top hits with a significant score (E-values). In contrast, the PFP method, which we have presented previously, goes one step ahead in utilizing a PSI-BLAST result by considering very weak hits even an E-value of up to 100 and also by incorporating the functional association between GO terms (FAM matrix) computed using term co-occurrence frequencies in the UniProt database. PFP is very successful which is evidenced by the top rank in the function prediction category in CASP7 competition. Our new approach, ESG method, further improves the accuracy of PFP by essentially employing PFP in an iterative fashion. An advantage of ESG is that it is built in a rigorous statistical framework: Unlike PFP method that assigns a weighted score to each GO term, ESG assigns a probability based on weights computed using the E-value of each hit sequence on the path between the original query sequence and the current hit sequence.
GIMSAN: a Gibbs motif finder with significance analysis
Authors: Ng Patrick , Keich Uri 
Published: August 2008

Abstract
Summary: We present GIMSAN (GIbbsMarkov with Significance ANalysis): a novel tool for de novo motif finding. GIMSAN combines GibbsMarkov, our variant of the Gibbs Sampler, described here for the first time, with our recently introduced significance analysis.
Availability: GIMSAN is currently available as a web application and a stand-alone application on Unix and PBS (Portable Batch System) cluster through links from http://www.cs.cornell.edu/~keich.
Contact: keich@cs.cornell.edu
Motor and Somatosensory Evoked Potentials Are Well Maintained in Patients Given Dexmedetomidine during Spine Surgery
Authors: Bala Endrit , Sessler Daniel I. , Nair Dileep R. , McLain Robert , Dalton Jarrod E. , Farag Ehab 
Published: August 2008

Background
Many commonly used anesthetic agents produce a dose-dependent amplitude reduction and latency prolongation of evoked responses, which may impair diagnosis of intraoperative spinal cord injury. Dexmedetomidine is increasingly used as an adjunct for general anesthesia. Therefore, the authors tested the hypothesis that dexmedetomidine does not have a clinically important effect on somatosensory and transcranial motor evoked responses.

Methods
Thirty-seven patients were enrolled and underwent spinal surgery with instrumentation during desflurane and remifentanil anesthesia with dexmedetomidine as an anesthetic adjunct. Upper- and lower-extremity transcranial motor evoked potentials and somatosensory evoked potentials were recorded during four defined periods: baseline without dexmedetomidine; two periods with dexmedetomidine (0.3 and 0.6 ng/ml), in a randomly determined order; and a final period 1 h after drug discontinuation. The primary outcomes were amplitude and latency of P37/N20, and amplitude, area under the curve, and voltage threshold for transcranial motor evoked potential stimulation.

Results
Of the total, data from 30 patients were evaluated. Use of dexmedetomidine, as an anesthetic adjunct, did not have an effect on the latency or amplitude of sensory evoked potentials greater than was prespecified as clinically relevant, and though the authors were unable to claim equivalence on the amplitude of transcranial motor evoked responses due to variability, recordings were made throughout the study in all patients.

Conclusion
Use of dexmedetomidine as an anesthetic adjunct at target plasma concentrations up to 0.6 ng/ml does not change somatosensory or motor evoked potential responses during complex spine surgery by any clinically significant amount.
Ambulatory Continuous Posterior Lumbar Plexus Nerve Blocks after Hip Arthroplasty
Authors: Ilfeld Brian M. , Ball Scott T. , Gearen Peter F. , Le Linda T. , Mariano Edward R. , Vandenborne Krista , Duncan Pamela W. , Sessler Daniel I. , Enneking F Kayser , Shuster Jonathan J. , Theriaque Douglas W. , Meyer R Scott 
Published: August 2008

Background
The authors tested the hypotheses that after hip arthroplasty, ambulation distance is increased and the time required to reach three specific readiness-for-discharge criteria is shorter with a 4-day ambulatory continuous lumbar plexus block (cLPB) than with an overnight cLPB.

Methods
A cLPB consisting of 0.2% ropivacaine was provided from surgery until the following morning. Patients were then randomly assigned either to continue ropivacaine or to be switched to normal saline. Primary endpoints included (1) time to attain three discharge criteria (adequate analgesia, independence from intravenous analgesics, and ambulation > or = 30 m) and (2) ambulatory distance in 6 min the afternoon after surgery. Patients were discharged with their cLPB and a portable infusion pump, and catheters were removed on the fourth postoperative day.

Results
Patients given 4 days of perineural ropivacaine (n = 24) attained all three discharge criteria in a median (25th-75th percentiles) of 29 (24-45) h, compared with 51 (42-73) h for those of the control group (n = 23; estimated ratio = 0.62; 95% confidence interval, 0.45-0.92; P = 0.011). Patients assigned to receive ropivacaine ambulated a median of 34 (9-55) m the afternoon after surgery, compared with 20 (6-46) m for those receiving normal saline (estimated ratio = 1.3; 95% confidence interval, 0.6-3.0; P = 0.42). Three falls occurred in subjects receiving ropivacaine (13%), versus none in subjects receiving normal saline.

Conclusions
Compared with an overnight cLPB, a 4-day ambulatory cLPB decreases the time to reach three predefined discharge criteria by an estimated 38% after hip arthroplasty. However, the extended infusion did not increase ambulation distance to a statistically significant degree.
Direct Assessments of the Antioxidant Effects of Propofol Medium Chain Triglyceride/Long Chain Triglyceride on the Brain of Stroke-prone Spontaneously Hypertensive Rats Using Electron Spin Resonance Spectroscopy
Authors: Kobayashi Kyo , Yoshino Fumihiko , Takahashi Shun-Suke , Todoki Kazuo , Maehata Yojiro , Komatsu Tomoko , Yoshida Kazu-Ichi , Lee Masaichi-Chang-Il 
Published: August 2008

Background
Antioxidant anesthetics such as propofol (2,6-diisopropylphenol) directly inhibit lipid peroxidation via the generation of reactive oxygen species. Currently, there are no other studies regarding the direct effects of propofol medium chain triglyceride/long chain triglyceride (MCT/LCT) on reactive oxygen species generation or in experimental models of reactive oxygen species-induced oxidative stress in the brain.

Methods
The authors investigated the effects of propofol MCT/LCT on reactive oxygen species (hydroxyl radical or superoxide) by electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. The effects of propofol MCT/LCT on oxidative stress in the brain of Wistar-Kyoto rats or stroke-prone spontaneously hypertensive rats were investigated by using an in vivo L-band electron spin resonance system to monitor the decay rate of 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl as a nitroxyl spin probe.

Results
These studies provided direct evidence that propofol MCT/LCT inhibited hydroxyl radical generation, but not superoxide generation. Regarding the hydroxyl radical from the Fenton system, it is likely to be due to the scavenging effects of vehicle. Anesthesia with propofol MCT/LCT reduced the degree of the high oxidative stress in the brain of stroke-prone spontaneously hypertensive rats.

Conclusion
The current data show that propofol, mixed with clinical reagents (propofol MCT/LCT), resulted in the down-regulation of high oxidative stress due to scavenging hydroxyl radical, as demonstrated by in vitro or in vivo electron spin resonance analysis. These results led to reduced levels of hydroxyl radical, formed by brain injury such as stroke, and may therefore provide advantages for neuroprotection during anesthesia for craniotomy, e.g., in cases of brain disease.
Using Permutation Entropy to Measure the Electroencephalographic Effects of Sevoflurane
Authors: Li Xiaoli , Cui Suyuan , Voss Logan J. 
Published: August 2008

Background
Approximate entropy (AE) has been proposed as a measure of anesthetic drug effect in electroencephalographic data. Recently, a new method called permutation entropy (PE) based on symbolic dynamics was also proposed to measure the complexity in an electroencephalographic series. In this study, the AE and PE were applied to electroencephalographic recordings for revealing the effect of sevoflurane on brain activity. The dose-response relation of PE during sevoflurane anesthesia was compared with that of AE.

Methods
Nineteen patients' electroencephalographic data were collected during the induction of general anesthesia with sevoflurane. PE and AE were applied to the electroencephalographic recordings, and the performance of both measures was assessed by pharmacokinetic-pharmacodynamic modeling and prediction probability. To ensure an accurate complexity measure of electroencephalographic recordings, a wavelet-based preprocessor was built in advance.

Results
Both PE and AE could distinguish between the awake and anesthetized states and were highly correlated to each other (r = 0.8, P = 0.004). The pharmacokinetic-pharmacodynamic model adequately described the dose-response relation between PE and AE and sevoflurane effect site concentration. The coefficient R between PE and effect site concentration was 0.89 +/- 0.07 for all patients, compared with 0.60 +/- 0.14 for AE. Prediction probabilities of 0.86 +/- 0.04 and 0.79 +/- 0.09 for PE and AE showed that PE has a stronger ability to differentiate between the awake and anesthetic states.

Conclusion
The results show that PE can estimate the sevoflurane drug effect more effectively than AE. This method could be applied to design a new electroencephalographic monitoring system to estimate sevoflurane anesthetic drug effect.
Novel Ryanodine Receptor Mutation That May Cause Malignant Hyperthermia
Authors: Kaufmann Alexius , Kraft Birgit , Michalek-Sauberer Andrea , Weigl Lukas G. 
Published: August 2008

Background
Malignant hyperthermia (MH) is a hypermetabolic condition caused by a genetic disposition leading to increased Ca release from the sarcoplasmic reticulum after exposure to triggering agents. In the authors' ongoing evaluation of patients undergoing MH testing in Austria, they detected a family with a new variant of the ryanodine receptor 1. Guidelines suggest that genetic tests are possible only for individuals from families in which the mutations are known. The aim of this study was to provide functional data that establish a potential link between this new variant and susceptibility to MH, and thus enable application in genetic tests.

Methods
Messenger RNA was isolated from skeletal muscle cells grown in culture and used for synthesis of complementary DNA, which served as a template for 23 polymerase chain reactions. The sequences of all reaction products were analyzed. Functional studies in differentiated muscle cells included the Ca releasing activity of caffeine and 4-chloro-m-cresol. The authors measured the intracellular Ca concentration and, in combined patch clamp-Ca detection experiments, the voltage dependence of the Ca release.

Results
In a single family, the authors found a transition from a highly conserved thymine to cysteine at position 11953, leading to the exchange of tryptophan to arginine at position 3985. This variant was absent in 100 MH-nonsusceptible individuals. Functionally, cells carrying this variant were more sensitive to caffeine and 4-chloro-m-cresol than wild-type cells and showed a shift in the voltage-dependent Ca release to more negative potentials.

Conclusion
These data document a role of the new W3985R variant in MH susceptibility.
Low-tidal-volume Mechanical Ventilation Induces a Toll-like Receptor 4–dependent Inflammatory Response in Healthy Mice
Authors: Vaneker Michiel , Joosten Leo A. , Heunks Leo M. A. , Snijdelaar Dirk G. , Halbertsma Feico J. , van Egmond Jan , Netea Mihai G. , van der Hoeven Johannes G. , Scheffer Gert Jan 
Published: August 2008

Background
Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung.

Methods
Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue.

Results
MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of keratinocyte-derived chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes.

Conclusions
The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.
Perineural Administration of Dexmedetomidine in Combination with Bupivacaine Enhances Sensory and Motor Blockade in Sciatic Nerve Block without Inducing Neurotoxicity in Rat
Authors: Brummett Chad M. , Norat Mary A. , Palmisano John M. , Lydic Ralph 
Published: August 2008

Background
The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.

Methods
Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage.

Results
High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control.

Conclusion
The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.
Bis(μ-biphenyl-2,2′-dicarboxylato)bis[(2,2′-bipyridine)copper(II)]
Authors: Guo Hong-Xu , Liang Min , Lin Bin , Wang Qing-Hua , Li Xi-Zhong 
Published: August 2008

The title compound, [Cu2(C14H8O4)2(C10H8N2)2], is a centrosymmetric binuclear copper(II) complex, with a Cu...Cu separation of 6.136 (16) Å. The Cu atom displays a cis-CuN2O2 square-planar geometry, although two long (> 2.43 Å) Cu...O contacts complete a distorted cis-CuN2O4 octahedron. Extensive C—H...O hydrogen bonds link the molecules into a three-dimensional network.
Different pathotypes of the sunflower downy mildew pathogen Plasmopara halstedii all contain isometric virions†
Authors: HELLER‐DOHMEN MARION , GÖPFERT JENS C. , HAMMERSCHMIDT RAY , SPRING OTMAR 
Published: August 2008

SUMMARYEight pathotypes of Plasmopara halstedii were screened to investigate the occurrence of virions and the potential viral influence on the pathogenicity of the sunflower downy mildew pathogen. In 23 of 26 P. halstedii isolates derived from eight countries in Europe, North America and South America, virions were detected by transmission electron microscopy. By contrast, there were no ultrastructural indications of virus‐like particles in eight other related Oomycetes. The virions of representative P. halstedii isolates were morphologically and biochemically characterized and compared among each other. Regardless of their host's pathotypes, the geographical origin of the isolate and the sensitivity towards the fungicide metalaxyl, the viral characters obtained were uniform. The virions were isometric and measured approximately 37 nm in diameter. One polypeptide of c. 36 kDa and two segments of single‐stranded RNA (3.0 and 1.6 kb) were detected. Both viral RNA segments were detected by capillary electrophoresis in the three remaining P. halstedii isolates where virions were undetectable by transmission electron microscopy. Virus‐specific primers for the 1.6 kb‐segment were synthesized and used to determine and compare a partial sequence of the viral coat protein among virions of different P. halstedii pathotypes. In all tested isolates, fragments of 0.7 kb were amplified which were directly sequenced. Sequence variation was insignificant. As both less aggressive and more aggressive P. halstedii isolates contained virions, the presence or absence of virions could not explain the diverse aggressiveness of the downy mildew pathogen towards sunflower. Moreover, the results indicated that pathogenicity of P. halstedii was not related to variation in morphological or biochemical characters of the virions.
Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib
Authors: Schwartz Jules I. , Agrawal Nancy G. B. , Wehling Martin , Musser Bret J. , Gumbs Carol P. , Michiels Nicole , De Smet Marina , Wagner John A. 
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Digoxin is a well‐recognized inotropic agent with a narrow therapeutic index.• Nonsteroidal anti‐inflammatory drugs, including the selective cyclooxygenase‐2 inhibitor etoricoxib, are very likely to be used in patients receiving digoxin due to the similar populations requiring the drugs.• Digoxin drug interactions should be assessed and described to clinicians when new drugs become available. WHAT THIS STUDY ADDS • This study is the first to provide the practitioner with a detailed description of the influence of etoricoxib on the pharmacokinetics of digoxin.• Due to the methods used, it shows that etoricoxib does not interfere with P‐glycoprotein in the kidney, a method of digoxin disposition.• In addition, this paper provides confidence to the practitioner that there will be no clinically important reason to avoid the combination of the two drugs.AIMSDigoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. The aim was to investigate whether the cyclooxygenase‐2 selective nonsteroidal anti‐inflammatory drug etoricoxib affects the steady‐state pharmacokinetics of digoxin.METHODSThis was a double‐blind, randomized, placebo‐controlled, two‐period cross‐over study. In each period, 14 healthy volunteers ranging in age from 21 to 35 years received oral digoxin 0.25 mg daily and were randomized to either etoricoxib 120 mg or matching placebo tablets once daily for 10 days. Trough digoxin plasma concentrations were analysed by linear regression to examine digoxin accumulation over time.RESULTSThe geometric mean ratios (etoricoxib/placebo) for AUC0–24h, Cmax and urinary excretion were 1.06 (90% confidence interval 0.97, 1.17), 1.33 (1.21, 1.46) and 1.10 (1.00, 1.20), respectively. The median (range) for digoxin Tmax (h) values with etoricoxib and placebo were 0.5 (0.5, 1.5) and 1.0 (0.5, 1.5), respectively. Steady‐state digoxin plasma concentrations were achieved by day 7 in each treatment period. No serious adverse experiences were reported.CONCLUSIONSAlthough etoricoxib 120 mg did produce an approximately 33% increase in digoxin Cmax, this increase does not appear to be clinically meaningful, as cardiotoxicity with digoxin has been associated with elevations in steady‐state rather than peak concentrations. From these results, it appears that etoricoxib does not cause any changes in digoxin steady‐state pharmacokinetics that would necessitate a dose adjustment.
The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range
Authors: Kalliokoski Annikka , Neuvonen Mikko , Neuvonen Pertti J. , Niemi Mikko 
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Organic anion transporting polypeptide 1B1 is an influx transporter expressed on the basolateral membrane of hepatocytes.• A common single nucleotide polymorphism, c.521T→C (p.Val174Ala), of the SLCO1B1 gene has been associated with increased plasma repaglinide concentrations in healthy volunteers.• Previous studies at low repaglinide doses have suggested that the effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide could be dose‐dependent. WHAT THIS STUDY ADDS • Repaglinide peak plasma concentration and area under the plasma concentration–time curve increased linearly along with repaglinide dose ranging from 0.25 to 2 mg in both the predominant c.521TT and rare c.521CC genotype group.• The effect of SLCO1B1 c.521T→C polymorphism on repaglinide pharmacokinetics persists over a wide dose range.AIMSTo establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose‐dependent.METHODSTwelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25‐, 0.5‐, 1‐ or 2‐mg dose of repaglinide in a dose‐escalation study with a wash‐out period of ≥1 week.RESULTSThe mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype.CONCLUSIONSThe effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range.