bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probability-based pattern recognition and statistical framework for randomization: modeling tandem mass spectrum/peptide sequence false match frequencies
Authors: Feng Jian , Naiman Daniel Q. , Cooper Bret 
Published: May 2007

AbstractMotivation: In proteomics, reverse database searching is used to control the false match frequency for tandem mass spectrum/peptide sequence matches, but reversal creates sequences devoid of patterns that usually challenge database-search software.Results: We designed an unsupervised pattern recognition algorithm for detecting patterns with various lengths from large sequence datasets. The patterns found in a protein sequence database were used to create decoy databases using a Monte Carlo sampling algorithm. Searching these decoy databases led to the prediction of false positive rates for spectrum/peptide sequence matches. We show examples where this method, independent of instrumentation, database-search software and samples, provides better estimation of false positive identification rates than a prevailing reverse database searching method. The pattern detection algorithm can also be used to analyze sequences for other purposes in biology or cryptology.Availability: On request from the authors.Contact: Bret.Cooper@ars.usda.govSupplementary information: http://bioinformatics.psb.ugent.be/
The Cytochrome P450 Engineering Database: a navigation and prediction tool for the cytochrome P450 protein family
Authors: Fischer Markus , Knoll Michael , Sirim Demet , Wagner Florian , Funke Sonja , Pleiss Juergen 
Published: May 2007

AbstractSummary: The Cytochrome P450 Engineering Database (CYPED) has been designed to serve as a tool for a comprehensive and systematic comparison of protein sequences and structures within the vast and diverse family of cytochrome P450 monooxygenases (CYPs). The CYPED currently integrates sequence and structure data of 3911 and 25 proteins, respectively. Proteins are grouped into homologous families and superfamilies according to Nelson's classification. Nonclassified CYP sequences are assigned by similarity. Functionally relevant residues are annotated. The web accessible version contains multisequence alignments, phylogenetic trees and HMM profiles. The CYPED is regularly updated and supplies all data for download. Thus, it provides a valuable data source for phylogenetic analysis, investigation of sequence–function relationships and the design of CYPs with improved biochemical properties.Abbreviations: Cytochrome P450 Engineering Database, CYPED; cytochrome P450 monooxygenase, CYP; Hidden Markov Model, HMM.Availability: www.cyped.uni-stuttgart.deContact: Juergen.Pleiss@itb.uni-stuttgart.de
Abnormal Sensorimotor Integrative Function of the Larynx in Congenital Laryngomalacia: A New Theory of Etiology
Authors: Thompson Dana Mara 
Published: May 2007

AbstractObjectives/Hypothesis: Laryngomalacia is an enigmatic disease in which laryngeal tone is weak, resulting in dynamic prolapse of tissue into the larynx. Sensorimotor integrative function of the brainstem and peripheral reflexes are responsible for laryngeal tone and airway patency. The goal of this study was to elucidate the etiology of decreased laryngeal tone through evaluating the sensorimotor integrative function of the larynx. The secondary goal was to evaluate factors and medical comorbidities that contribute to the wide spectrum of symptoms and outcomes.Study Design: Prospective and retrospective collection of evaluative data on infants with congenital laryngomalacia at two tertiary care pediatric referral centers.Methods: Two hundred one infants with laryngomalacia were divided into three groups on the basis of disease severity (mild, moderate, severe). Patients were followed prospectively every 8 to 12 weeks until symptom resolution or loss to follow‐up. Sensorimotor integrative function of the larynx was evaluated in 134 infants by laryngopharyngeal sensory testing (LPST) of the laryngeal adductor reflex (LAR) by delivering a duration‐ (50 ms) and intensity‐ (2.5–10 mm Hg) controlled air pulse to the aryepiglottic fold to induce the LAR. Medical records were retrospectively reviewed for medical comorbidities.Results: The initial LPST was higher (P < .001) in infants with moderate (6.8 mm Hg) and severe disease (7.4 mm Hg) compared with those with mild disease (4.1 mm Hg). At 1, 3, and 6 months, infants with moderate and severe disease continued to have a higher LPST compared with those with mild disease. At 9 months, the LPST decreased in all subjects (3.1–3.5 mm Hg, P = .14), which also correlated with symptom resolution. Neurologic, genetic, and cardiac diseases were more common in infants with severe disease (P < .001). Gastroesophageal reflux disease (GERD) and feeding problems more common in those with moderate and severe disease (P < .001). Apgar scores were lower in those with severe disease (P < .001). Most symptoms resolved within 12 months of presentation. Those with GERD benefited from treatment. Supraglottoplasty resulted in few complications. Multiple comorbidities (>3) influenced the need for tracheotomy.Conclusions: Laryngeal tone and sensorimotor integrative function of the larynx is altered. The degree of alteration correlated with disease severity, indicating that factors that alter the peripheral and central reflexes of the LAR have a role in the etiology of signs and symptoms of laryngomalacia. GERD, neurologic disease, and low Apgar scores influenced disease severity and clinical course, explaining the spectrum of disease symptoms and outcomes. Sensorimotor integrative function improved as symptoms resolved.
Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate
Authors: Tayab Zia R. , Fardon Tom C. , Lee Daniel K. C. , Haggart Kay , McFarlane Lesley C. , Lipworth Brian J. , Hochhaus Günther 
Published: May 2007

What is already known about this subject • Mometasone furoate (MF) is a new inhaled glucocorticoid for which the first reports suggested a low degree of systemic side‐effects and low systemic availability.• Recent studies of Fardon and colleagues have shown that MF's cortisol suppression is similar to that of fluticasone.• Pharmacokinetic/dynamic evaluations of MF's systemic side‐effects, probing whether systemic side‐effects can be explained by systemic availability, plasma protein binding and receptor binding affinity, are lacking in the literature. What this study adds • This study shows that the systemic availability of MF and fluticasone propionate (FP) are similar and that systemic availability is directly related to the dose.• It also shows that the metabolites of MF are present only in very low concentrations at most, contrary to results in rats.• The observed cortisol suppression of FP and MF is related to the trough plasma concentrations and seems to be in agreement with its observed systemic availability, plasma protein binding and receptor binding affinity.AimFluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%. We hypothesize that FP and MF have comparable systemic availabilities that can explain their potential to cause systemic effects.MethodsSteady‐state FP and MF trough plasma samples were determined from a clinical study by Fardon et al. in patients with persistent asthma (forced expiratory volume in 1 s = 91%). The percent plasma protein binding of FP and MF was measured using ultracentrifugation. Free FP plasma concentrations were normalized for their differences in receptor binding affinity compared with MF and linked to overnight urinary cortisol/creatinine with an inhibitory Emax.ResultsA plot of steady‐state FP and MF total trough plasma concentrations vs. dose showed that both drugs exhibit dose linearity. MF has comparable bioavailability to FP based on the steady‐state concentrations observed for the different doses. The free plasma concentration producing 50% of urinary cortisol suppression (IC50) for MF was not statistically different from the free, normalized IC50 for FP.ConclusionFP and MF have similar pulmonary deposition and the same potential to cause systemic side‐effects due to their similar IC50 values. The observed urinary cortisol suppression of FP and MF is in agreement with their systemic availability, their differences in plasma protein binding and receptor binding affinity.
Anti‐factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old
Authors: Berges A. , Laporte S. , Epinat M. , Zufferey P. , Alamartine E. , Tranchand B. , Decousus H. , Mismetti P. ,   for the PROPHRE.75 study group
Published: May 2007

What is already known about this subject • Major bleeds with low‐molecular‐weight heparin have been reported at curative and prophylactic dosages.• Enoxaparin clearance depends on body weight, and therefore weight‐adjusted dosing is recommended to minimize interindividual variability in drug exposure and the risk of haemorrhage in patients treated at curative doses.• Monitoring of this treatment is recommended in curative indications in patients at risk.• The need for monitoring of patients at risk receiving prophylactic doses of enoxaparin, in this case the elderly, remains unclear. What this study adds • Clearance of enoxaparin at prophylactic doses is predictably related to body weight and creatinine clearance in the elderly.• The simplified Modification of Diet in Renal Disease formula seems to be most discriminating and powerful in detecting any influence of glomerular filtration rate in the elderly.• The influence of these covariates does not seem to be sufficiently clinically relevant to support routine assessment in the elderly.AimsMajor bleeding complications with low‐molecular‐weight heparin (LMWH) treatment have been reported both in clinical studies and during postmarketing surveillance. Monitoring of antifactor Xa (anti‐Xa) activities is therefore recommended in special populations often predisposed to renal impairment. The PROPHRE.75 study was conducted to estimate the distribution parameters of anti‐Xa activity in the elderly.MethodsPROPHRE.75 was a prospective study of a cohort of consecutive patients aged >75 years and treated with 4000 IU of enoxaparin once daily for venous thromboembolism prophylaxis. Dosing history and measurements of anti‐Xa activity in sparse samples were recorded throughout treatment. The covariates included weight, gender, age, renal function, medical history and concomitant medication. Population parameters and interindividual variability were estimated using NONMEM® V software.ResultsAnti‐Xa activity was studied in 189 patients (mean age 82 ± 5 years, 22% weighing <50 kg, 50% presenting renal impairment according to the Cockcroft and Gault formula). A first‐order input two‐compartment model best fitted the data. Clearance was significantly related to body weight and creatinine clearance based on the simplified Modification of Diet in Renal Disease formula, central volume being related to body weight. According to individual Bayesian estimations, 4% of patients presented with a peak anti‐Xa activity >1.0 IU ml−1, but this group did not include the sole patient experiencing a major bleed (0.53%).ConclusionsSystematic monitoring of anti‐Xa activity in elderly patients treated with enoxaparin at prophylactic doses does not seem to be necessary to prevent the occurrence of major bleeding.
When a placebo is not a ‘placebo’: a placebo effect on postprandial glycaemia
Authors: Sievenpiper John L. , Ezatagha Adish , Dascalu Anamaria , Vuksan Vladimir 
Published: May 2007

What is already known about this subject • Although placebo effects have been shown on subjective continuous variables such as pain, placebo effects on objective continuous variables remain uncertain.• The present, pilot, follow‐up investigation represents the first to assess a placebo effect on the objective continuous measurement of acute postprandial plasma glucose. What this study adds • Placebo effects may be operating on postprandial plasma glucose outcomes.• Cornstarch sources of placebo may decrease the plasma glucose response to a 75‐g oral glucose tolerance test, rendering them as positive controls when assessing postprandial outcomes.• Other carbohydrate sources used as placebos in research may show similar effects.AimsPlacebo effects in clinical trials remain uncertain. To investigate a placebo effect on acute postprandial plasma glucose, we conducted a follow‐up investigation on a previous study.MethodsThe effect of placebo (9 g encapsulated cornstarch +500 ml water, taken at −40 min) on the plasma glucose response to a 75‐g oral glucose tolerance test (OGTT) was assessed in a previous study in 12 healthy subjects (gender, five male, seven female; age 27 ± 6 years; body mass index 24 ± 3.4 kg m−2). This was compared with the effect of a water control (500 ml water taken alone at −40 min) on the same outcome in the same subjects in a follow‐up study.ResultsCornstarch placebo decreased plasma glucose area under the curve during the 75‐g OGTT by 28% [Δ (95% confidence interval) −63.3 min mmol−1 l−1 (−218.33, 91.66), P < 0.02] compared with the water control (P < 0.05).ConclusionsPostprandial plasma glucose outcomes may be vulnerable to placebo effects.
Diclofenac and acute myocardial infarction in patients with no major risk factors
Authors: Jick Susan S. , Kaye James A. , Jick Hershel 
Published: May 2007

What is already known about this subject • We recently published the results of a study on the risk of acute myocardial infarction (AMI) in users of five nonsteroidal anti‐inflammatory drugs during the years 2001 to 2005.• The results demonstrated, as has been reported in randomized trials, that rofecoxib and celecoxib increase the risk of AMI when taken for at least 10 months.• As expected, ibuprofen and naproxen did not materially increase the risk.• However, long‐term users of diclofenac were at an increased risk of AMI similar to that of users of rofecoxib and celecoxib. What this study adds • Extensive use of diclofenac, similarly to rofecoxib and celecoxib, substantially increases the risk of AMI.• There is little suggestion of such an effect in users of ibuprofen and naproxen.AimsTo explore further a recent finding that long‐term users of diclofenac are at increased risk of acute myocardial infarction (AMI) similar to users of rofecoxib and celecoxib.MethodsUsing the General Practice Research Database, we conducted three separate nested case–control studies of three nonsteroidal anti‐inflammatory drugs (NSAIDs) where use started after 1 January 1993 — diclofenac, ibuprofen and naproxen. Cases of AMI were identified between 1 January 1993 and 31 December 2000. Relative risk (RR) estimates for AMI in patients with no major clinical risk factors were determined for each NSAID according to number of prescriptions received compared with one prescription. Results were adjusted for variables possibly related to risk of AMI.ResultsThere was no material elevation of AMI risk according to the number of prescriptions for ibuprofen [RRs and 95% confidence intervals (CIs) 1.0 (0.6, 1.6) and 1.7 (0.9, 3.1) for use of 10–19 and 20+ prescriptions, respectively, compared with one prescription] or naproxen [RRs 1.0 (0.5, 2.2) and 2.0 (0.9, 4.5) for use of 10–19 and 20+ prescriptions, respectively]. However, a substantial increased risk similar to that obtained in our prior study was found in patients who received ≥10 prescriptions for diclofenac [RRs 1.9 (1.3, 2.7) and 2.0 (1.3, 3.0) for use of 10–19 and 20+ prescriptions, respectively].ConclusionsExtensive use of diclofenac substantially increases the risk of AMI. There is little suggestion of such an effect in users of ibuprofen and naproxen.
The effect of ABCG2 V12M, Q141K and Q126X, known functional variantsin vitro, on the disposition of lamivudine
Authors: Kim Ho‐Sook , Sunwoo Yu Eun , Ryu Ji Young , Kang Ho‐Jin , Jung Hye‐Eun , Song Im‐Sook , Kim Eun‐Young , Shim Joo‐Cheol , Shon Ji‐Hong , Shin Jae‐Gook 
Published: May 2007

AimsTo evaluate the effects of three ABCG2 variants (Q141K, V12M and Q126X), which are known to have altered transport propertiesin vitro, on the disposition of lamivudine in healthy subjects.MethodsTo evaluate whether lamivudine is a substrate of ABCG2, intracellular accumulation and vectorial transport of3H‐lamivudine were determined in MDCK‐ABCG2 cells. The pharmacokinetic parameters of lamivudine were compared among subjects with four different ABCG2 genotypes, including wild type (seven subjects), K141/K141 (six subjects), Q126/Stop126 (four subjects) and M12/M12 (five subjects) after a single oral dose of 100 mg lamivudine.ResultsThe intracellular accumulation of lamivudine in MDCK‐ABCG2 cells was significantly lower than that in MDCK‐mock cells, but fumitremorgin C reversed the intracellular lamivudine concentration to that of MDCK‐mock cells. The ABCG2‐mediated transport of lamivudine was saturable and the values ofKmandVmaxwere 216.5 ± 58 µmand 20.42 ± 2.9 nmol h−1per 106cells, respectively. After lamivudine administration to healthy subjects, the AUC of lamivudine showed no difference among subjects with different ABCG2 genotypes; 2480 ± 502, 2207 ± 1019, 2422 ± 239, 2552 ± 698 ng h−1 ml−1for wild type, K141/K141, Q126/Stop126 and M12/M12 genotype, respectively (P = 0.85). The estimated 95% confidence intervals for the mean difference between K141/K141, Q126/Stop126, M12/M12 and wild as reference were (−1053, 507), (−555, 439) and (−552, 696), respectively. No other pharmacokinetic parameters were estimated to be significantly different among four different ABCG2 genotypes tested.ConclusionsLamivudine appeared to be a substrate of ABCG2in vitro, but the disposition of lamivudine was not significantly influenced by knownin vitrofunctional variants of ABCG2, Q141K, V12M and Q126X in healthy subjects.
Effects of rain forest logging on species richness and assemblage composition of small mammals in Southeast Asia
Authors: Wells Konstans , Kalko Elisabeth K. V. , Lakim Maklarin B. , Pfeiffer Martin 
Published: May 2007

AbstractAim  The effects of logging and habitat degradation on the richness and abundance of small mammals in Asian rain forests are largely unknown. This work compares the species richness, dominance and evenness of small non‐volant mammals between logged and unlogged forests, and assesses whether assemblage variability (β‐diversity) is similar between forest types.Location  Southeast Asia, northern Borneo (Sabah, Malaysia), Sunda‐shelf.Methods  We surveyed species‐rich assemblages of small non‐volant mammals in three unlogged and three logged forests for 2 years. At each forest site, we sampled a permanently marked transect and two additional sites in three trapping sessions. All analyses were performed at both levels to include the effects of local abundances and point estimates, separately from the relative abundances of species on a more regional scale.Results  We trapped a total of 1218 individuals of 28 species. Eleven common species accounted for 95% of all captures. Species richness and diversity were significantly higher in unlogged forest (27 species) than in logged forest (17 species). This was mainly attributable to the smaller number of rarely recorded species in logged forest (five compared with 16 in unlogged forest, with a total of fewer than 10 captures). However, all common species were present in both logged and unlogged forests, and our analyses revealed similar patterns of dominance, evenness and fluctuations in abundance. Hence overall assemblage composition in multivariate space did not differ greatly between forest types. Assemblages of Muridae and Tupaiidae showed similar population fluctuations in space and time, indicating that the ecology of these taxa may be partially driven by the same environmental factors.Main conclusions  Although species were distributed patchily within sites, analyses at local and regional scales revealed similar patterns in diversity and assemblage variability, suggesting that effects of forest modification did not differ extensively locally and regionally, but had a profound effect on rare species. Our results emphasize the importance and conservation value of logged forest stands that are able to hold a large proportion of the small mammals also found in unlogged forests. Rare and more specialized species are more vulnerable to forest degradation than commonly caught species, resulting in the complete loss, or a decrease in numbers, of certain groups, such as arboreal small mammals and Viverridae.
Levels of endemism are not necessarily biased by the co‐presence of species with different range sizes: a case study of Vilenkin and Chikatunov's models
Authors: Fattorini Simone 
Published: May 2007

AbstractAim To illustrate problems in the methods proposed by B. Vilenkin and V. Chikatunov to study levels of endemism and species–area relationships.Location The study used data on the distribution of tenebrionid beetles (Coleoptera, Tenebrionidae) on the Aegean Islands (Greece).Methods A total of 32 islands and 170 taxa (species and subspecies) were included in this study. Levels of endemism were evaluated both as the proportion of endemic taxa, and according to the methods proposed by Vilenkin and Chikatunov, which are based on the number of non‐endemic taxa and various relationships with area. A model of the species–area relationship proposed by these authors was also analysed.Results The number of endemic taxa was positively correlated with the number of taxa with different distribution types, but this positive correlation did not influence the estimation of the level of endemism. In fact, the commonly used estimate of endemicity as a percentage was strongly correlated with the endemism values calculated according to the method of Vilenkin and Chikatunov. The usual power function fitted the species–area relationship as well as the most complicated method of Vilenkin and Chikatunov.Main conclusions As hypothesized by Vilenkin and Chikatunov, the number of endemic taxa was influenced both by the number of taxa of other biogeographical ranks, and by an island's area. However, explanations for the positive relationship between the number of endemic taxa and taxa of different biogeographical ranks are equivocal. Importantly, this relationship did not necessarily influence the level of endemism, which could be expressed adequately by percentages. The method proposed by Vilenkin and Chikatunov to estimate the species–area relationship cannot be clearly justified on theoretical grounds and is of questionable practical utility.