bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Ability of Tree‐Based Methods and Logistic Regression for the Detection of SNP‐SNP Interaction
Authors: García‐Magariños M. , López‐de‐Ullibarri I. , Cao R. , Salas A. 
Published: March 2009

SummaryMost common human diseases are likely to have complex etiologies. Methods of analysis that allow for the phenomenon of epistasis are of growing interest in the genetic dissection of complex diseases. By allowing for epistatic interactions between potential disease loci, we may succeed in identifying genetic variants that might otherwise have remained undetected. Here we aimed to analyze the ability of logistic regression (LR) and two tree‐based supervised learning methods, classification and regression trees (CART) and random forest (RF), to detect epistasis. Multifactor‐dimensionality reduction (MDR) was also used for comparison. Our approach involves first the simulation of datasets of autosomal biallelic unphased and unlinked single nucleotide polymorphisms (SNPs), each containing a two‐loci interaction (causal SNPs) and 98 ‘noise’ SNPs. We modelled interactions under different scenarios of sample size, missing data, minor allele frequencies (MAF) and several penetrance models: three involving both (indistinguishable) marginal effects and interaction, and two simulating pure interaction effects. In total, we have simulated 99 different scenarios. Although CART, RF, and LR yield similar results in terms of detection of true association, CART and RF perform better than LR with respect to classification error. MAF, penetrance model, and sample size are greater determining factors than percentage of missing data in the ability of the different techniques to detect true association. In pure interaction models, only RF detects association. In conclusion, tree‐based methods and LR are important statistical tools for the detection of unknown interactions among true risk‐associated SNPs with marginal effects and in the presence of a significant number of noise SNPs. In pure interaction models, RF performs reasonably well in the presence of large sample sizes and low percentages of missing data. However, when the study design is suboptimal (unfavourable to detect interaction in terms of e.g. sample size and MAF) there is a high chance of detecting false, spurious associations.
Effects of a communication course for clinicians on parents’ perception of care – a randomized controlled trial
Authors: Ammentorp Jette , Sabroe Svend , Kofoed Poul‐Erik , Mainz Jan 
Published: March 2009

Introduction:  In paediatric care, it is a great challenge to make sure that all parties feel involved and heard, they all have had the opportunity to take part in the decisions and all the participants experienced that their expectations to the consultation are fulfilled. Previous research in communication skills training has primarily focused on the behavioural changes of clinicians, and only few studies have investigated the effect from the perspective of the user.Method:  A randomized controlled trial including medical doctors and nurses from paediatric outpatients’ clinics was carried out. The intervention group completed a 5‐day communication course, whereas the control group had no intervention. The intervention was evaluated using questionnaires measuring parents’ perception of the communication and their satisfaction. The questionnaires were filled out by parents to children consulting a clinician in the outpatient’s clinic.Results:  Before the intervention, 75% (314/419) answered the questionnaire and 65% (271/419) were included in the precourse analysis. After the intervention, 68% (946/1395) answered the questionnaire and 55% (764/1395) were included in the postcourse analysis. There were no significant differences between the satisfaction of parents visiting clinicians from the intervention group and those visiting clinicians from the control group; however, the proportion of parents who had a positive perception of the communication was up to 9.8% higher in the intervention group compared with the control group. For example: ‘the clinician told my child what he/she could do in order to feel better’.Discussion:  Although no statistically significant differences were found, the study indicates that parents who had visited a clinician from the intervention group have experienced the communication as more positive.
Using connectivity metrics in conservation planning – when does habitat quality matter?
Authors: Visconti Piero , Elkin Ché 
Published: March 2009

AbstractAim The objective of conservation planning is often to prioritize patches based on their estimated contribution to metapopulation or metacommunity viability. The contribution that an individual patch makes will depend on its intrinsic characteristics, such as habitat quality, as well as its location relative to other patches, its connectivity. Here we systematically evaluate five patch value metrics to determine the importance of including an estimate of habitat quality into the metrics.Location We tested the metrics in landscapes designed to represent different degrees of variability in patch quality and different levels of patch aggregation.Methods In each landscape, we simulated population dynamics using a spatially explicit, continuous time metapopulation model linked to within patch logistic growth models. We tested five metrics that are used to estimate the contribution that a patch makes to metapopulation viability: two versions of the probability of connectivity index, two versions of patch centrality (a graph theory metric) and the metapopulation capacity metric.Results All metrics performed best in environments where patch quality was very variable and high quality patches were aggregated. Metrics that incorporated some measure of patch quality did better in all environments, but did particularly well in environments with high variance of patch quality and spatial aggregation of good quality patches.Main conclusions Including an estimate of patch quality significantly increased the ability of a given connectivity metric to rank correctly habitat patches according to their contribution to metapopulation viability. Incorporating patch quality is particularly important in landscapes where habitat quality is highly variable and good quality patches are spatially aggregated. However, caution should be used when applying patch metrics to homogeneous landscapes, even if good estimates of patch quality are available. Our results demonstrate that landscape structure and the degree of variability in patch quality need to be assessed prior to selecting a suitable method for estimating patch value.
The role of nitric oxide‐ and prostacyclin‐independent vasodilatation in the human cutaneous microcirculation: effect of cytochrome P450 2C9 inhibition
Authors: Lenasi Helena 
Published: March 2009

SummaryThe component of the flow‐ or agonist‐dependent vasodilatation, insensitive to inhibitors of nitric oxide (NO) synthases (NOS) or cyclooxygenases (COX), is suggested to reflect the production of an endothelium‐dependent hyperpolarizing factor (EDHF). The identity of EDHF in humans remains controversial; in coronary arterioles, it appears to be a cytochrome P450 (CYP) 2C9‐derived metabolite, whereas there are no data for human skin microcirculation. Therefore, the aim of our study was to investigate the role of the NO‐ and prostacyclin (PGI2)‐independent mechanism, particularly the potential involvement of CYP 2C9, in skin microcirculation. We measured skin blood flow on the volar aspect of the forearm in 12 healthy subjects by laser‐Doppler fluxmetry (LDF). The inhibitors of NOS, Nω‐monomethyl‐L‐arginine (L‐NMMA), and cyclooxygenase (COX), diclofenac, as well as sulfaphenazole, the specific CYP 2C9 inhibitor, and saline as control, were administered to the measurement sites by an intradermal microinjection in different combinations. Afterwards, baseline LDF was assessed and iontophoresis of acetycholine (ACh) applied. Combined NOS and COX inhibition had no effect on baseline LDF, whereas it significantly reduced the ACh‐induced increase in LDF (t‐test, P<0·05). Sulfaphenazole did not affect baseline LDF either in the control site or in the L‐NMMA‐ and diclofenac‐pretreated site. In addition, sulfaphenazole did not attenuate the ACh‐induced vasodilatation in either site. We conclude that a NO‐ and PGI2‐independent vasodilator mechanism, potentially attributable to EDHF, contributes substantialy to the ACh‐induced vasodilatation in human skin microcirculation and that it is probably not a CYP 2C9‐derived metabolite.
Correctable and non‐correctable visual impairment among young males: a 12‐year prevalence study of the Military Service in Poland
Authors: Nowak Michal S. , Gos Roman , Jurowski Piotr , Smigielski Janusz 
Published: March 2009

AbstractPurpose:  To evaluate the prevalence of correctable and non‐correctable visual impairment in a representative sample of young males commissioned for Military Service in Poland.Material and methods:  Data concerning vision status was retrospectively reviewed in 969 subjects of European Caucasian origin, most of whom live and have lived in Poland. They were selected from the original database comprising 105017 subjects examined in the period 1993–2004. Based on the age of subjects they were divided into two groups; group I aged 18–24 and group II aged 25–34 years. Visual impairment was defined as distance visual acuity of <20/40 in one or both eyes. Non‐correctable impairment was defined as that which was not eliminated by refractive correction.Results:  A total of 1938 eyes of 969 white males were examined. There was statistically significant association between rates of visual impairment and increasing age (p < 0.001). Visual impairment was found in 128 (13.2%) subjects in at least one eye. Non‐correctable visual impairment was found in 12 (1.2%) subjects. Amblyopia was the main cause, accounting for eight cases (66.67%). Correctable visual impairment was found in the remaining 116 (12.0%) patients. Among them myopia was the most common refractive error and accounted for 75.8%. Differences between age‐specific rates of refractive errors were statistically significant (p = 0.003).Conclusions:  Appropriate refractive correction improves visual acuity in most subjects presenting with visual impairment. There was a relatively low prevalence of non‐correctable visual impairment in a population of young adults in Poland, and this was mainly due to amblyopia.
Custom‐devised and generic digital enhancement of images for people with maculopathy
Authors: Leat Susan J. , Mei Ming 
Published: March 2009

AbstractAim:  The purpose of this study was to compare the effectivity, in terms of the potential usefulness, of digital filters based on either contrast sensitivity (CS) or supra‐threshold contrast matching (CM) in enhancing pictures images for people with maculopathy and to investigate whether generic filters (not based on an individual’s vision loss) are equally as effective. Effectivity is measured by changes in perceived visibility.Methods:  Thirty‐five subjects with maculopathy, aged 20–92 years, took part [13 atrophic age‐related macular degeneration (ARMD), 14 exudative ARMD, and 8 juvenile macular dystrophy (JMD)]. CS and supra‐threshold CM were measured. A range of CS filters (1 or 2‐octave wide band‐pass filter using a Gabor or polynomial envelope) with different strengths were developed based on the ratio of the individual’s contrast threshold and that of a normal age‐related group. Similarly filters were developed based on CM at 3.6% and 27.9% contrast. The following generic filters were also applied with different ‘strengths’: edge enhancement; sharpening; contrast enhancement; Peli’s adaptive enhancement; difference of Gaussian; and an equi‐emphasis band‐pass filter. The filters were applied to images of faces and general scenes. Subjects were asked to rank the perceived visibility of images (to obtain the best version of each filter) and then to rate the perceived visibility of each image filtered with a particular filter.Results:  In general, subjects with atrophic ARMD and JMD preferred the weaker versions of most of the filters, while those with exudative ARMD did not show such a clear preference. Generally, images of faces were preferred with less enhancement than scenes. The filters based on CM were rated as giving significant improvement, while those based on CS and peak emphasis were not preferred. Of the generic filters, the Peli adaptive enhancement filter was most frequently rated as giving a significant improvement (p < 0.05) followed by the contrast enhancement filter. They gave the same perceived enhancement as the custom‐devised filters.Conclusions:  Generic filters, which are easier to apply than the custom‐devised filters, are appropriate for rehabilitation purposes.
Inhibition of inducible NO synthase, cyclooxygenase‐2 and interleukin‐1β by torilin is mediated by mitogen‐activated protein kinases in microglial BV2 cells
Authors: Choi Y , Lee MK , Lim SY , Sung SH , Kim YC 
Published: March 2009

Background and purpose:  Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) have been known to be anti‐inflammatory in Korea. Anti‐inflammatory effects of torilin, isolated from this plant and the underlying mechanisms were examined by using lipopolysaccharide (LPS)‐stimulated microglial BV2 cells.Experimental approach:  The cells were treated with torilin prior to LPS exposure and the effects on pro‐inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2), and a pro‐inflammatory cytokine, interleukin‐1β (IL‐1β) were analysed by RT‐PCR, Western blot or elisa. To reveal the mechanism of action of torilin we investigated the involvement of mitogen‐activated protein kinase (MAPK) cascades and their downstream transcription factors, nuclear factor‐κB (NF‐κB) and cyclic AMP‐responsive element (CRE)‐binding protein (CREB).Key results:  Torilin significantly reduced the LPS‐induced expression of iNOS, COX‐2 and IL‐1β, and the subsequent release of NO, prostaglandin E2 and IL‐1β into culture medium. LPS stimulation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38 MAPK was inhibited by torilin. In addition, the inhibitory effect of torilin on NF‐κB and CREB was shown by torilin‐mediated recovery of LPS‐induced degradation of inhibitor κB‐α and suppression of LPS‐induced phosphorylation of CREB respectively.Conclusion and implications:  This study indicates that torilin inhibited LPS‐induced iNOS, COX‐2 and IL‐1β via down‐regulation of ERK1/2, p38 MAPK, NF‐κB and CREB and suggests that torilin has a potential as an anti‐inflammatory drug candidate.
Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium‐dependent activation of HIF‐1α and P‐glycoprotein overexpression
Authors: Riganti C , Doublier S , Viarisio D , Miraglia E , Pescarmona G , Ghigo D , Bosia A 
Published: March 2009

Background and purpose:  Artemisinin is an antimalarial drug exerting pleiotropic effects, such as the inhibition of the transcription factor nuclear factor‐kappa B and of the sarcoplasmic/endoplasmic reticulum Ca++‐ATPase (SERCA) of P. falciparum. As the sesquiterpene lactone thapsigargin, a known inhibitor of mammalian SERCA, enhances the expression of P‐glycoprotein (Pgp) by increasing the intracellular Ca++ ([Ca++]i) level, we investigated whether artemisinin and its structural homologue parthenolide could inhibit SERCA in human colon carcinoma HT29 cells and induce a resistance to doxorubicin.Experimental approach:  HT29 cells were incubated with artemisinin or parthenolide and assessed for SERCA activity, [Ca++]i levels, Pgp expression, doxorubicin accumulation and toxicity, and translocation of the hypoxia‐inducible factor, HIF‐1α.Key results:  Artemisinin and parthenolide, like the specific SERCA inhibitors thapsigargin and cyclopiazonic acid, reduced the activity of SERCA. They also increased intracellular calcium concentration ([Ca++]i) and Pgp expression and decreased doxorubicin accumulation and cytotoxicity. The intracellular Ca++ chelator, 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid, and the inhibitor of calmodulin‐dependent kinase II (CaMKII) KN93 prevented these effects. CaMKII is known to promote the phosphorylation and the activation of HIF‐1α, which may induce Pgp. In HT29 cells, artemisinin and parthenolide induced the phosphorylation of HIF‐1α, which was inhibited by KN93.Conclusions and implications:  Our results suggest that artemisinin and parthenolide may act as SERCA inhibitors and, like other SERCA inhibitors, induce resistance to doxorubicin in human colon cancer cells, via the CaMKII‐dependent activation of HIF‐1α and the induction of Pgp.
Mitogen‐activated protein kinase (MAPK) pathway mediates the oestrogen‐like activities of ginsenoside Rg1 in human breast cancer (MCF‐7) cells
Authors: Lau Wai‐Sum , Chen Wen‐Fang , Chan Robbie Yat‐Kan , Guo De‐An , Wong Man‐Sau 
Published: March 2009

Background and purpose:  The present study was designed to determine how ginsenoside Rg1, an active ingredient in ginseng root, exerts its oestrogenic effects. We hypothesize that Rg1 may exert oestrogen‐like actions in MCF‐7 cells by activating the mitogen‐activated protein kinase (MAPK) pathway in a ligand‐independent manner.Experimental approach:  MCF‐7 cells were co‐incubated with the MAPK inhibitor PD98059 to determine whether the stimulant effects of Rg1 on cell proliferation, the induction of IGF‐IR and pS2, the functional transactivation of oestrogen receptor‐α (ERα), as well as ERα phosphorylation are dependent on MAPK. The time‐dependent responses of mitogen‐activated protein kinase kinase (MEK) and extracellular signal‐regulated protein kinase (ERK) to Rg1 in MCF‐7 cells were studied. The responses of MEK phosphorylation to Rg1 in oestrogen receptor (ER)‐negative HEK293 cells were also determined. The effects of Rg1 on cell proliferation and IGF‐IR protein expression were studied in the presence of tyrosine kinase inhibitor genistein to elucidate the involvement of tyrosine kinase in mediating these effects.Key results:  The oestrogenic effects of Rg1 in MCF‐7 cells were abolished in the presence of PD98059. Rg1 could induce MEK protein expression and the phosphorylation level of MEK and ERK significantly in a time‐ and dose‐dependent manner. Rg1 activated MEK phosphorylation in ER‐negative HEK293 cells in a time‐ and dose‐dependent manner. Rg1 induction of cell proliferation and IGF‐IR protein expression was abolished by co‐treatment with genistein.Conclusions and implications:  Taken together, these results show that the MAPK pathway is involved in mediating the oestrogen‐like actions of Rg1 in MCF‐7 cells and suggest that Rg1 may activate ERα via MEK/ERK in a ligand‐independent manner.
Party Competition and the Resilience of Corporatism
Authors: Anthonsen Mette , Lindvall Johannes 
Published: March 2009

AbstractThis article argues that after the Golden Age of capitalism, corporatist methods of policy-making have come to depend on specific modes of party competition. In contrast to previous studies of corporatism, which have argued that corporatism depends on strong social democratic parties, this article suggests that the competition between well-defined left-wing and right-wing ‘blocs’ has become detrimental to corporatism. In countries with mixed governments or traditions of power-sharing, on the other hand, corporatism thrives. These conclusions are based on a comparison of four traditionally corporatist countries – Denmark, the Netherlands, Sweden and Switzerland – from the early 1970s to the late 1990s.
Party-System Reform in Democracy's Grey Zone: A Response to Moraski
Authors: Wilson Kenneth 
Published: March 2009

AbstractThis article analyses the party-system reforms introduced in Russia during Vladimir Putin's presidency. It contests Byron Moraski's interpretation, published in an earlier edition of this journal, which claims that the reforms introduced in Putin's second term were a response to the 2003 Duma election and were intended to preserve the unity and discipline of United Russia, the regime's ‘party of power’. This article argues that Moraski's explanation of the second-term reforms is flawed and contends that the first- and second-term reforms were part of a wider reform programme designed to centralize Russia's political system, consolidate its party system and contribute to the construction of a façade democracy. The article also challenges Moraski's argument that these reforms, while introduced to advance the regime's interests, could further democratization in the longer term by adding the crucial caveat that stronger opposition parties that could act as a democratizing influence will only emerge if practices of electoral manipulation lessen or fail.
Automated normalized FLAIR imaging in MRI‐negative patients with refractory focal epilepsy
Authors: Focke Niels K. , Bonelli Silvia B. , Yogarajah Mahinda , Scott Catherine , Symms Mark R. , Duncan John S. 
Published: March 2009

SummaryBackground:  Patients with focal epilepsy that is refractory to medical treatment are often considered candidates for resective surgery. Magnetic resonance imaging (MRI) has a very important role in the presurgical work‐up of these patients, but is unremarkable in about one‐third of cases. These patients are often deferred from surgery or have a less positive outcome if surgery is eventually undertaken. The aim of this study was to evaluate our recently described voxel‐based technique using routine T2‐FLAIR (fluid‐attenuated inversion‐recovery) scans in MRI‐negative patients and to compare the results with video‐EEG (electroencephalography) telemetry (VT) findings.Methods:  We identified 70 epilepsy patients with refractory focal seizures who underwent VT and had a normal routine MRI. T2‐FLAIR scans were bias‐corrected, and intensity and spatially normalized (nFSI) using Statistical Parametric Mapping 5 (SPM5) as previously described. Individual scans were then compared against a set of 25 normal controls using a voxel‐based method.Results:  SPM5 identified 10 patients with suprathreshold clusters (14.3%). In 50% of these there was concordance between the lobe of the most significant cluster and the presumed lobe of seizure onset, as defined by VT. All cases were concordant with respect to lateralization of the putative focus.Conclusion:  Using nFSI we identified focal structural cerebral abnormalities in 11.4% of patients with refractory focal seizures, and normal conventional MRI, that were fully or partially concordant with scalp VT. This voxel‐based analysis of FLAIR scans, which are widely available, could provide a useful tool in the presurgical evaluation of epilepsy patients. Ongoing work is to compare these imaging findings with the results of intracranial EEG and histology of surgical resections.
Does a SCN1A gene mutation confer earlier age of onset of febrile seizures in GEFS+?
Authors: Sijben Angelique E. J. , Sithinamsuwan Pasiri , Radhakrishnan Ashalata , Badawy Radwa A. B. , Dibbens Leanne , Mazarib Aziz , Lev Dorit , Lerman‐Sagie Tally , Straussberg Rachel , Berkovic Samuel F. , Scheffer Ingrid E. 
Published: March 2009

Summary SCN1A is the most clinically relevant epilepsy gene and is associated with generalized epilepsy and febrile seizure plus (GEFS+) and Dravet syndrome. We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation. This was because of the age‐related onset of Dravet syndrome, which typically begins in the first year of life. We found that patients with FS and FS+ with SCN1A mutations had earlier median onset of febrile seizures compared to the population median. Patients with GABRG2 mutations had a similar early onset in contrast to patients with SCN1B mutations where onset was later. This study is the first to demonstrate that a specific genetic abnormality directly influences the FS and FS+ phenotype in terms of age of onset.