bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features
Authors: Scott Adam C , Bilesky Jennifer , Lamanna Arvin , Cullen Louise , FT Brown Anthony , Denaro Charles , Parsonage William 
Published: April 2014

AbstractObjectiveNational guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated.MethodsA retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule‐out acute coronary syndrome. Chart review was completed on patients with positive stress tests.ResultsThe 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty‐seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non‐invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients).ConclusionsRoutine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome.
IL10 low‐frequency variants in Behçet's disease patients
Authors: Matos Mafalda , Xavier Joana M. , Abrantes Patrícia , Sousa Inês , Rei Nádia , Davatchi Fereydoun , Shahram Farhad , Jesus Gorete , Barcelos Filipe , Vedes Joana , Salgado Manuel , Abdollahi Bahar Sadeghi , Nadji Abdolhadi , Moraes‐Fontes Maria Francisca , Shafiee Niloofar Mojarad , Ghaderibarmi Fahmida , Vaz Patto José , Crespo Jorge , Oliveira Sofia A. 
Published: April 2014

AbstractAimTo explain the missing heritability after the genome‐wide association studies era, sequencing studies allow the identification of low‐frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low‐frequency IL10 variants in BD susceptibility.MethodsTo identify IL10 low‐frequency variants, a discovery group of 50 Portuguese BD patients were Sanger‐sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD‐ and/or Portuguese‐specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian).ResultsRare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non‐coding variants in five heterozygous cases. ss836185595, located in the IL10 3′ untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset.ConclusionThis study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non‐coding variants and statistical tests which incorporate these predictions.
Selecting food web models using normalized maximum likelihood
Authors: Staniczenko Phillip P. A. , Smith Matthew J. , Allesina Stefano 
Published: April 2014

SummaryEcological models link theory and data. They distil processes into a mathematical form that explains the salient features of observed data. Food webs describe the pattern of interactions between species in an ecosystem, and many models have been proposed to explain their structure. When selecting the most appropriate model for data, it is important to penalize against overly complicated models.Here, we introduce to ecology the use of normalized maximum likelihood (NML) for model selection and demonstrate its application to models for food web structure. Unlike AIC, which penalizes models using the number of parameters, NML normalizes the likelihood of data given a model by the sum of likelihoods for all possible food webs with the same number of species. NML favours models that fit observed data well and all other data sets poorly, in contrast with overly flexible models that fit many (unobserved) data sets by the same amount and thus provide little information on the system under investigation. As such, NML represents a natural measure for comparing very different models and enables ecologists to determine not only whether a particular model is superior to others, but also whether, objectively, the model is a poor description of data.We used NML to compare models from four popular model families (cascade, niche, modular and group) and found that the best models performed much better than random graphs incorporating no ecological principles. However, models specified by empirical characteristics such as species body mass, taxonomic classification or habitat were frequently far‐from‐optimal and, in some cases, performed worse than random graphs. This suggests that ecological interactions cannot be explained by a single species trait or coarse‐grained environmental factor. The ranking of empirically determined models using NML was generally consistent with model selection according to AIC, BIC and Bayes factors. We also show how NML can improve the development of new model families by measuring the effectiveness of incremental changes to existing families or combining families.NML offers ecologists a rigorous and elegant framework for revealing the defining features of data through the systematic formulation, testing and modification of models.
Functional and phylogenetic similarity among communities
Authors: Pavoine Sandrine , Ricotta Carlo 
Published: April 2014

Summary

Ecological studies often rely on coefficients of intercommunity (dis)similarity to decipher effects of ecological, evolutionary and human‐driven mechanisms on the composition of communities. Yet, two main criticisms have been levelled at (dis)similarity coefficients. First, few developments include information on species' abundances, and either phylogeny or functional traits. Secondly, some (dis)similarity coefficients fail to always provide maximum dissimilarity between two completely distinct communities, that is, communities without common species and with zero similarities among their species.

Here, we introduce a new family of similarity coefficients responding to these criticisms. Within this family, we concentrate on four coefficients and compare them to Rao's dissimilarity on macroinvertebrate communities, and simulated data.

Our new coefficients correctly treat maximally dissimilar communities: similarities are always zero between two completely distinct communities. The originality of these new coefficients is even more profound as the existence of maximally dissimilar communities was not a requirement for the new coefficients to behave differently than Rao's dissimilarity coefficient.

Our new family of similarity coefficients relies on the abundances or occurrences of species within communities and on phylogenetic, taxonomic or functional similarities among species. We demonstrate that this new family embeds many of the recent developments in both functional and phylogenetic diversity. It provides a unique framework for comparing traditional compositional turnover with functional or phylogenetic similarities among communities.
Are mitochondrial lineages, mitochondrial lysis and respiration rate associated with phosphine susceptibility in the maize weevil Sitophilus zeamais?
Authors: Corrêa A.S. , Tomé H.V.V. , Braga L.S. , Martins G.F. , de Oliveira L.O. , Guedes R.N.C. 
Published: April 2014

AbstractPhosphine is the most widely used fumigant with ever‐growing problems of phosphine resistance among insect pests of stored products. One such insect is the maize weevil Sitophilus zeamais, a key pest of stored cereals. Despite its importance as a fumigant, the mechanisms of phosphine toxicity and resistance remain unclear, although the mitochondrion is broadly recognised as its site of action. Here we explored the phosphine susceptibility of maize weevil populations and its association with insect respiration rate, and we tested the association of phosphine susceptibility with the mitochondrial lineages from the field populations studied. We also assessed the action of phosphine in the degradation of mitochondria from muscle cells. Survival under phosphine treatment varied among weevil populations and was negatively correlated with the respiration rate and body mass of the insect. Phosphine produced little lysis of mitochondria and the more phosphine‐resistant population exhibited a slightly higher mitochondria fluorescence intensity under confocal imaging. Therefore, reduced respiration rate is correlated with reduced phosphine activity, but its association with high mitochondria fluorescence intensity in muscle cells seems marginal. There was no association between mitochondrial lineages and phosphine susceptibility, which evolved independently, and the mitochondrial gene fragments of cytochrome oxidase I and II were not useful molecular markers of phosphine susceptibility.
Allopurinol for mania: a randomized trial of allopurinol versus placebo as add‐on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder
Authors: Weiser Mark , Burshtein Shimon , Gershon Ari A , Marian Gabriela , Vlad Nicolae , Grecu Iosif G , Tocari Elena , Tiugan Alexandru , Hotineanu Mihail , Davis John M 
Published: April 2014

ObjectiveAn emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists; there is a well‐characterized interaction between adenosine and dopamine receptors in the ventral striatum, and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. Allopurinol increases adenosine levels in the brain, and hence is hypothesized to reduce the symptoms of mania. Two randomized, placebo‐controlled trials administering add‐on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale (YMRS) scores for drug compared to placebo, while a more recent, relatively small, add‐on study showed negative results. Based on these data, our objective was to examine the efficacy of allopurinol as add‐on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder.MethodsWe performed a large, well‐powered, multicenter, six‐week, randomized, placebo‐controlled trial of allopurinol added to mood stabilizers and/or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode.ResultsBoth groups showed improvement on the YMRS (effect size of 1.5 for placebo and 1.6 for allopurinol), with no difference observed between groups on YMRS scores (t = 0.28, p = 0.78). There was no difference in the proportion of patients who responded to treatment (defined as showing at least 50% improvement in YMRS score) between the two groups (p = 0.92), or in dropout rates (p = 0.84).LimitationsNone of our patients received lithium. However, the side effects of lithium and its narrow therapeutic index made the use of lithium less common and, therefore, our study results reflect common current clinical practice. In the present study, we used a variety of antipsychotic and/or mood stabilizing treatments, to which we added allopurinol; one might hypothesize that add‐on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers.ConclusionsThe findings of this large, well‐powered study do not support add‐on allopurinol as a treatment for acute mania. This study did not test the efficacy of allopurinol as monotherapy.
Methyl salicylate lactoside inhibits inflammatory response of fibroblast‐like synoviocytes and joint destruction in collagen‐induced arthritis in mice
Authors: Xin Wenyu , Huang Chao , Zhang Xue , Xin Sheng , Zhou Yiming , Ma Xiaowei , Zhang Dan , Li Yongjie , Zhou Sibai , Zhang Dongming , Zhang Tiantai , Du Guanhua 
Published: April 2014

Background and PurposeMethyl salicylate 2‐O‐β‐d‐lactoside (MSL), whose chemical structure is similar to that of salicylic acid, is a natural product derivative isolated from a traditional Chinese herb. The aim of this study was to investigate the therapeutic effect of MSL in mice with collagen‐induced arthritis (CIA) and explore its underlying mechanism.Experimental ApproachThe anti‐arthritic effects of MSL were evaluated on human rheumatoid fibroblast‐like synoviocytes (FLS) in vitro and CIA in mice in vivo by obtaining clinical scores, measuring hind paw thickness and inflammatory cytokine levels, radiographic evaluations and histopathological assessments.Key ResultsTreatment with MSL after the onset of arthritis significantly prevented the progression and development of rheumatoid arthritis (RA) in CIA mice without megascopic gastric mucosa damage. In addition, MSL inhibited the production of pro‐inflammatory mediators, the phosphorylation and translocation of NF‐κB, and cell proliferation induced by TNF‐α in FLS. MSL non‐selectively inhibited the activity of COX in vitro, but was a more potent inhibitor of COX‐2 than COX‐1. MSL also inhibited the phosphorylation of inhibitor of NF‐κB kinase, IκBα and p65, thus blocking the nuclear translocation of NF‐κB in TNF‐α‐stimulated FLS.Conclusion and ImplicationsMSL exerts therapeutic effects on CIA mice, suppressing the inflammatory response and joint destruction by non‐selectively inhibiting the activity of COX and suppressing activation of the NF‐κB signalling pathway, but without damaging the gastric mucosa. Therefore, MSL has great potential to be developed into a novel therapeutic agent for the treatment of RA.
Grass‐specific CD4+ T‐cells exhibit varying degrees of cross‐reactivity, implications for allergen‐specific immunotherapy
Authors: Archila L. D. , DeLong J. H. , Wambre E. , James E. A. , Robinson D. M. , Kwok W. W. 
Published: April 2014

SummaryBackgroundConceptually, allergic responses may involve cross‐reactivity by antibodies or T‐cells. While IgE cross‐reactivity among grass‐pollen allergens has been observed, cross‐reactivity at the allergen‐specific T‐cell level has been less documented. Identification of the patterns of cross‐reactivity may improve our understanding, allowing optimization of better immunotherapy strategies.ObjectivesWe use Phleum pratense as model for the studying of cross‐reactivity at the allergen‐specific CD4+ T cell level among DR04:01 restricted Pooideae grass‐pollen T‐cell epitopes.MethodsAfter in vitro culture of blood mono‐nucleated cells from grass‐pollen‐allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC‐labelled DR04:01/Phleum pratense tetramers and PE‐labelled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross‐reactivity among allergen‐specific DR04:01‐restricted T‐cells in six subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass‐pollen reactive T‐cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T‐cells.ResultsT‐cells with various degrees of cross‐reactive profiles could be detected. Poa p 1 97–116, Lol p 1 221–240, Lol p 5a 199–218, and Poa p 5a 199–218 were identified as minimally cross‐reactive T‐cell epitopes that do not show cross‐reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T‐cells that recognized these minimally cross‐reactive T‐cell epitopes are present in Grass‐pollen‐allergic subjects.ConclusionsOur results suggest that not all Pooideae grass epitopes with sequence homology are cross‐reactive. Non‐cross‐reactive T‐cells with comparable frequency, phenotype and functionality to Phl p‐specific T‐cells suggest that a multiple allergen system should be considered for immunotherapy instead of a mono‐allergen system.
Out‐of‐Core Construction of Sparse Voxel Octrees
Authors: Baert J. , Lagae A. , Dutré Ph. 
Published: April 2014

AbstractVoxel‐based rendering has recently received significant attention due to its potential in the context of efficiently rendering massively large and highly detailed scenes. Unfortunately, few scenes are available in the form of sparse voxel octrees. In this paper, we present an out‐of‐core algorithm for constructing a sparse voxel octree from a triangle mesh. Our algorithm allows the input triangle mesh, the output sparse voxel octree and, most importantly, the intermediate high‐resolution 3D voxel grid, to be larger than available memory. We demonstrate that our out‐of‐core algorithm can construct sparse voxel octrees from triangle meshes using only a fraction of the memory required by an in‐core algorithm in roughly the same time, and that our out‐of‐core algorithm can also handle extremely large triangle meshes.
Amelioration of Ischemic Mitochondrial Injury and Bax‐Dependent Outer Membrane Permeabilization by Mdivi‐1
Authors: Zhao Yan‐Xin , Cui Mei , Chen Shu‐Fen , Dong Qiang , Liu Xue‐Yuan 
Published: April 2014

SummaryAimsDisturbance of the balance between mitochondrial fission and fusion has been implicated in cerebral ischemia and several neurodegenerative diseases, whereas the underlying mechanisms remain poorly understood. In the present study, we attempted to investigate the role of dynamin‐related protein 1 (Drp1), a key mitochondrial fission protein, in the pathogenesis of cerebral ischemia.MethodsUsing Drp1 siRNA or Mdivi‐1, a small molecule inhibitor of Drp1, we examined the effect of Drp1 knockdown or inhibition on oxygen‐glucose deprivation (OGD)‐induced mitochondrial dysfunction and death of SH‐SY‐5Y cells. Cell death and viability were evaluated with LDH and MTT assays, respectively, and mitochondrial morphology, mitochondrial membrane potential (Δψm), and ATP production were assessed using epifluorescence microscopy, flow cytometry, and HPLC, respectively. Moreover, to examine the effect of Drp1 inhibition on ischemic brain injury, middle cerebral artery occlusion (MCAO) mice were injected (i.p.) with Mdivi1, and blood–brain barrier permeability, brain water content, and cell apoptosis were assessed.ResultsKnockdown or inhibition of Drp1 by Mdivi‐1 significantly attenuated OGD‐induced cell death in SH‐SY‐5Y cells, associated with reduced morphological change of mitochondria and attenuated Bax insertion,oligomerization. Moreover, treatment of the MCAO mice with Mdivi‐1 remarkably reduced the infarct volume and neurological deficits in a dose‐dependent manner, associated with marked reduction of mitochondrial fragmentation and BAX expression.ConclusionsDown‐regulation or inhibition of Drp1 may reduce cerebral ischemic damage through maintaining normal mitochondrial morphology and function, and decreasing Bax insertion and oligomerization in mitochondria.
Obese sedentary patients with dyspnoea on exertion who are at low risk for coronary artery disease by clinical criteria have a very low prevalence of coronary artery disease
Authors: Bruckel J. T. , Larsen G. , Benson M. R. 
Published: April 2014

SummaryDyspnoea, a much less specific symptom of ischaemia than chest discomfort, is common among obese patients. Patients with dyspnoea often undergo stress testing as part of their evaluation. We sought to examine the yield of stress testing in non‐elderly, obese, sedentary patients with dyspnoea on exertion (DOE) as a chief complaint.We reviewed stress echocardiograms carried out on 203 patients in a stress testing laboratory at a major tertiary care centre. Of these, 81 (40%) fell into a group that was at low risk for coronary artery disease (CAD) by clinical criteria. Ischaemia was detected in two patients in the low‐risk group (2.5%), and these results were likely false positives. In the higher risk group, 9.0% of functional tests showed ischaemia; after further testing, 2.5% of the higher risk patients were found to have obstructive coronary lesions. Clinical follow‐up was performed for a mean of 815 days. New obstructive coronary disease was detected in 1.6% of all patients, and these patients were from the higher risk group. In obese sedentary patients with DOE but otherwise at low risk of coronary disease stress testing is of very low yield. DOE is generally not an anginal equivalent in this patient population.
High intra‐individual variability of cyclosporine pharmacokinetics in lung transplant recipients without cystic fibrosis
Authors: Méndez Alejandra , Monforte Víctor , Berastegui Cristina , López‐Meseguer Manuel , Bravo Carlos , Pou Leonor , Roman Antonio 
Published: April 2014

AbstractBackgroundThere has been little study on the variability of CsA pharmacokinetics in stable lung transplant (LT) recipients without cystic fibrosis. This study was conducted to determine the prevalence of high intra‐individual variability of CsA in LT recipients and its implications in CsA monitoring.MethodsTwenty‐nine pharmacokinetic curves were performed in 10 consecutive stable patients from a single center. The intra‐individual coefficient of variation (CV) of the AUC0–12 h was calculated in each case. Patients were grouped according to whether their CV was high (≥20%) or low (<20%). Correlations between cyclosporine CsA concentration at each time point, AUC0–4 h, and AUC0–12 h were also calculated.ResultsSix (60%) patients presented low CVs and four (40%) high CVs. In patients with low CVs, the best correlation of AUC0–12 h was with CsA concentration at two h post‐dose (C2) (r = 0.674, p = 0.002), whereas in those with high CV, the best correlation was with C5 (r = 0.800, p = 0.003). In the latter group, the correlation with C2 was low (r = 0.327, p = 0.32), whereas the correlation with C0 was high (r = 0.709, p < 0.05).ConclusionsIntra‐individual variability of CsA pharmacokinetics may be high in many LT recipients. In patients with high CV, the use of C0 levels may be more appropriate for CsA monitoring than C2 levels.