bluuebunny/crossref_metadata_2025_split huggingface dataset:
PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome
Authors: Shen J. , Wong G. L.‐H. , Chan H. L.‐Y. , Chan H.‐Y. , Yeung D. K.‐W. , Chan R. S.‐M. , Chim A. M.‐L. , Chan A. W.‐H. , Choi P. C.‐L. , Woo J. , Chu W. C.‐W. , Wong V. W.‐S. 
Published: January 2014

SummaryBackgroundThe rs738409 GG variant in patatin‐like phospholipase 3 (PNPLA3) is associated with non‐alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern.AimTo examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD.MethodsLiver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire.ResultsThe prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern.ConclusionsThe G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.
Absolute beat‐to‐beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia‐induced ventricular fibrillation
Authors: Sarusi Annamária , Rárosi Ferenc , Szűcs Mónika , Csík Norbert , Farkas Attila S , Papp Julius Gy , Varró András , Forster Tamás , Curtis Michael J , Farkas András 
Published: January 2014

Background and PurposePredicting lethal arrhythmia liability from beat‐to‐beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia‐free ECGs for this. Recently, it was shown that drug‐induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia‐induced ventricular fibrillation (VF).Experimental ApproachLangendorff‐perfused rat hearts were subjected to regional ischaemia for 15 min. Absolute BVI parameters were derived from ECG intervals measured in 40 consecutive ventricular complexes (irrespective of rhythm) immediately preceding VF onset and compared with time‐matched values in hearts not expressing VF.Key ResultsIncreased frequency of non‐sinus beats and ‘R on T’ arrhythmic beats, shortened mean RR and electrical diastolic intervals, and increased BVI of cycle length and repolarization predicted VF occurrence. Absolute BVI parameters that quantify variability of repolarization (e.g. ‘short‐term variability’ of QT interval) had the best predictive power with high sensitivity and specificity. In contrast, VF was not predicted by any BVI parameter derived from the last arrhythmia‐free interlude before VF.Conclusions and ImplicationsThe novel absolute BVI parameters that predicted TdP in rabbit also predict ischaemia‐induced VF in rat, indicating a diagnostic and mechanistic congruence. Repolarization inhomogeneity represents a pivotal biomarker of ischaemia‐induced VF. The newly validated biomarkers could serve as surrogates for VF in pre‐clinical drug investigations.
Assessing the Distribution and Protection Status of two Types of Cool Environment to Facilitate Their Conservation under Climate Change
Authors: GOLLAN JOHN R. , RAMP DANIEL , ASHCROFT MICHAEL B. 
Published: January 2014

AbstractStrategies to mitigate climate change can protect different types of cool environments. Two are receiving much attention: protection of ephemeral refuges (i.e., places with low maximum temperatures) and of stable refugia (i.e., places that are cool, have a stable environment, and are isolated). Problematically, they are often treated as equivalents. Careful delineation of their qualities is needed to prevent misdirected conservation initiatives; yet, no one has determined whether protecting one protects the other. We mapped both types of cool environments across a large (∼3.4M ha) mixed‐use landscape with a geographic information system and conducted a patch analysis to compare their spatial distributions; examine relations between land use and their size and shape; and assess their current protection status. With a modest, but arbitrary, threshold for demarcating both types of cool environments (i.e., values below the 0.025 quantile) there were 146,523 ha of ephemeral refuge (62,208 ha) and stable refugia (62,319 ha). Ephemeral refuges were generally aggregated at high elevation, and more refuge area occurred in protected areas (55,184 ha) than in unprotected areas (7,024 ha). In contrast, stable refugia were scattered across the landscape, and more stable‐refugium area occurred on unprotected (40,135 ha) than on protected land (22,184 ha). Although sensitivity analysis showed that varying the thresholds that define cool environments affected outcomes, it also exposed the challenge of choosing a threshold for strategies to address climate change; there is no single value that is appropriate for all of biodiversity. The degree of overlap between ephemeral refuges and stable refugia revealed that targeting only the former for protection on currently unprotected land would capture ∼17% of stable refugia. Targeting only stable refugia would capture ∼54% of ephemeral refuges. Thus, targeting one type of cool environment did not fully protect the other.Evaluación de la Distribución y Estado de Protección de Dos Tipos de Ambientes Fríos para Facilitar su Conservación bajo el Cambio Climático
Assessment of Association between Common Variants at 17q12 and Prostate Cancer Risk—Evidence from Serbian Population and Meta‐Analysis
Authors: Nikolić Zorana Z. , Branković Ana S. , Savić‐Pavićević Dušanka L.J. , Preković Stefan M. , Vukotić Vinka D. , Cerović Snežana J. , Filipović Nataša N. , Tomović Saša M. , Romac Stanka P. , Brajušković Goran N. 
Published: January 2014

AbstractThis study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy‐one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR‐RFLP) analysis. We conducted meta‐analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best‐fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05–2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50–0.87) with the best‐fitting model of inheritance being log‐additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49–0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta‐analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta‐analysis suggest the association of these SNPs with PCa risk.
Serum 25‐hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load
Authors: Atsukawa Masanori , Tsubota Akihito , Shimada Noritomo , Kondo Chisa , Itokawa Norio , Nakagawa Ai , Hashimoto Satomi , Fukuda Takeshi , Matsushita Yoko , Narahara Yoshiyuki , Iwakiri Katsuhiko , Nakatsuka Katsuhisa , Kawamoto Chiaki , Sakamoto Choitsu 
Published: January 2014

AimMuch is unknown about the effect of 25‐hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus‐related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25‐hydroxyvitamin D3, that contribute to a sustained virological response (SVR) in patients with cirrhosis.MethodsWe analyzed whether 25‐hydroxyvitamin D3 contributes to the response to PEG IFN/RBV therapy among 134 cirrhotic patients.ResultsSVR was achieved in 43 patients. The median 25‐hydroxyvitamin D3 level was 20 ng/mL. Univariate analysis showed that the following factors contributed to SVR: low‐density lipoprotein cholesterol, albumin, 25‐hydroxyvitamin D3, core a.a.70 (a.a.70) substitutions, the number of mutations at the interferon sensitivity‐determining region and IL28B genotype. Multivariate analysis identified IL28B genotype and 25‐hydroxyvitamin D3 as independent factors contributing to SVR. Subsequently, SVR rate was examined by using 25‐hydroxyvitamin D3 and other important factors. The SVR rate was 51.8% in patients with core a.a.70 wild and ≥15 ng/mL of 25‐hydroxyvitamin D3, whereas the SVR rate was 7.1% in patients with core a.a.70 wild and <15 ng/mL of 25‐hydroxyvitamin D3. The SVR rate was 56.9% in patients with IL28B major genotype and ≥15 ng/mL of 25‐hydroxyvitamin D3. Surprisingly, the SVR rate was 0% in patients with IL28B minor genotype and <15 ng/mL of 25‐hydroxyvitamin D3.ConclusionIL28B genotype and 25‐hydroxyvitamin D3 were identified as independent factors contributing to SVR. Stratified analyses according to core a.a.70 substitution and IL28B genotype suggested that 25‐hydroxyvitamin D3 influences the outcome of PEG IFN/RBV therapy for cirrhosis.
Living and dying in a multi‐predator landscape of fear: roe deer are squeezed by contrasting pattern of predation risk imposed by lynx and humans
Authors: Lone Karen , Loe Leif Egil , Gobakken Terje , Linnell John D. C. , Odden John , Remmen Jørgen , Mysterud Atle 
Published: January 2014

The theory of predation risk effects predicts behavioral responses in prey when risk of predation is not homogenous in space and time. Prey species are often faced with a tradeoff between food and safety in situations where food availability and predation risk peak in the same habitat type. Determining the optimal strategy becomes more complex if predators with different hunting mode create contrasting landscapes of risk, but this has rarely been documented in vertebrates. Roe deer in southeastern Norway face predation risk from lynx, as well as hunting by humans. These two predators differ greatly in their hunting methods. The predation risk from lynx, an efficient stalk‐and‐ambush predator is expected to be higher in areas with dense understory vegetation, while predation risk from human hunters is expected to be higher where visual sight lines are longer. Based on field observations and airborne LiDAR data from 71 lynx predation sites, 53 human hunting sites, 132 locations from 15 GPS‐marked roe deer, and 36 roe deer pellet locations from a regional survey, we investigated how predation risk was related to terrain attributes and vegetation classes/structure. As predicted, we found that increasing cover resulted in a contrasting lower predation risk from humans and higher predation risk from lynx. Greater terrain ruggedness increased the predation risk from both predators. Hence, multiple predators may create areas of contrasting risk as well as double risk in the same landscape. Our study highlights the complexity of predator–prey relationship in a multiple predator setting.SynthesisIn this study of risk effects in a multi‐predator context, LiDAR data were used to quantify cover in the habitat and relate it to vulnerability to predation in a boreal forest. We found that lynx and human hunters superimpose generally contrasting landscapes of fear on a common prey species, but also identified double‐risk zones. Since the benefit of anti‐predator responses depends on the combined risk from all predators, it is necessary to consider complete predator assemblages to understand the potential for and occurrence of risk effects across study systems.
Inflammatory cytokines promote growth of intestinal smooth muscle cells by induced expression of PDGF‐Rβ
Authors: Nair Dileep G. , Miller Kurtis G. , Lourenssen Sandra R. , Blennerhassett Michael G. 
Published: January 2014

AbstractThickening of the inflamed intestinal wall involves growth of smooth muscle cells (SMC), which contributes to stricture formation. Earlier, the growth factor platelet‐derived growth factor (PDGF)‐BB was identified as a key mitogen for SMC from the rat colon (CSMC), and CSMC growth in colitis was associated with both appearance of its receptor, PDGF‐Rβ and modulation of phenotype. Here, we examined the role of inflammatory cytokines in inducing and modulating the growth response to PDGF‐BB. CSMC were enzymatically isolated from Sprague–Dawley rats, and the effect of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, transforming growth factor (TGF), IL‐17A and IL‐2 on CSMC growth and responsiveness to PDGF‐BB were assessed using proliferation assays, PCR and western blotting. Conditioned medium (CM) was obtained at 48 hrs of trinitrobenzene sulphonic acid‐induced colitis. Neither CM alone nor cytokines caused proliferation of early‐passage CSMC. However, CM from inflamed, but not control colon significantly promoted the effect of PDGF‐BB. IL‐1β, TNF‐α and IL‐17A, but not other cytokines, increased the effect of PDGF‐BB because of up‐regulation of mRNA and protein for PDGF‐Rβ without change in receptor phosphorylation. PDGF‐BB was identified in adult rat serum (RS) and RS‐induced CSMC proliferation was inhibited by imatinib, suggesting that blood‐derived PDGF‐BB is a local mitogen in vivo. In freshly isolated CSMC, CM from the inflamed colon as well as IL‐1β and TNF‐α induced the early expression of PDGF‐Rβ, while imatinib blocked subsequent RS‐induced cell proliferation. Thus, pro‐inflammatory cytokines both initiate and maintain a growth response in CSMC via PDGF‐Rβ and serum‐derived PDGF‐BB, and control of PDGF‐Rβ expression may be beneficial in chronic intestinal inflammation.
The Self‐Efficacy Scale for Preschool Teachers Regarding Asthma Care: Instrument Development and Validation
Authors: Gau Bih‐Shya , Hung Chao‐Chia 
Published: January 2014

ABSTRACTBACKGROUNDThe purpose of this study was to develop and test the psychometric properties of a questionnaire that assesses preschool teachers' self‐efficacy in providing asthma care.METHODSA total of 407 teachers from 54 preschools in Taiwan participated in the study by completing the asthma management self‐efficacy scale. We assessed validity of the scale through expert opinion, exploratory factor analysis, and confirmatory factor analysis. The reliability of the scale was assessed using Cronbach's alpha.RESULTSA 10‐items questionnaire was developed to assess self‐efficacy concerning asthma treatment. On the basis of explorative factor analysis, 2 major factors emerged from the 10 self‐efficacy items that together explained 61.68% of the total variance in teachers' self‐efficacy with regard to asthma care. We named these factors “prevention of an asthma episode” and “the treatment of an asthma exacerbation.” Confirmatory factor analysis revealed that the 2‐factor model provided the best goodness‐of‐fit.CONCLUSIONSThis scale could provide health professionals with useful information concerning preschool teachers' self‐efficacy with respect to the management of asthma in the preschool setting.
A phytochemical comparison of saw palmetto products using gas chromatography and 1H nuclear magnetic resonance spectroscopy metabolomic profiling
Authors: Booker Anthony , Suter Andy , Krnjic Ana , Strassel Brigitte , Zloh Mire , Said Mazlina , Heinrich Michael 
Published: January 2014

Abstract

Objectives
Preparations containing saw palmetto berries are used in the treatment of benign prostatic hyperplasia (BPH). There are many products on the market, and relatively little is known about their chemical variability and specifically the composition and quality of different saw palmetto products notwithstanding that in 2000, an international consultation paper from the major urological associations from the five continents on treatments for BPH demanded further research on this topic. Here, we compare two analytical approaches and characterise 57 different saw palmetto products.

Methods
An established method – gas chromatography – was used for the quantification of nine fatty acids, while a novel approach of metabolomic profiling using 1H nuclear magnetic resonance (NMR) spectroscopy was used as a fingerprinting tool to assess the overall composition of the extracts.

Key findings
The phytochemical analysis determining the fatty acids showed a high level of heterogeneity of the different products in the total amount and of nine single fatty acids. A robust and reproducible 1H NMR spectroscopy method was established, and the results showed that it was possible to statistically differentiate between saw palmetto products that had been extracted under different conditions but not between products that used a similar extraction method. Principal component analysis was able to determine those products that had significantly different metabolites.

Conclusions
The metabolomic approach developed offers novel opportunities for quality control along the value chain of saw palmetto and needs to be followed further, as with this method, the complexity of a herbal extract can be better assessed than with the analysis of a single group of constituents.
Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the β′ subunit of RNA polymerase
Authors: Song Taeksun , Park Yumi , Shamputa Isdore Chola , Seo Sunghwa , Lee Sun Young , Jeon Han‐Seung , Choi Hongjo , Lee Myungsun , Glynne Richard J. , Barnes S. Whitney , Walker John R. , Batalov Serge , Yusim Karina , Feng Shihai , Tung Chang‐Shung , Theiler James , Via Laura E. , Boshoff Helena I. M. , Murakami Katsuhiko S. , Korber Bette , Barry Clifton E. , Cho Sang‐Nae 
Published: January 2014

SummaryRifampicin resistance, a defining attribute of multidrug‐resistant tuberculosis, is conferred by mutations in the β subunit of RNA polymerase. Sequencing of rifampicin‐resistant (RIF‐R) clinical isolates of Mycobacterium tuberculosis revealed, in addition to RIF‐R mutations, enrichment of potential compensatory mutations around the double‐psi β‐barrel domain of the β′ subunit comprising the catalytic site and the exit tunnel for newly synthesized RNA. Sequential introduction of the resistance allele followed by the compensatory allele in isogenic Mycobacterium smegmatis showed that these mutations respectively caused and compensated a starvation enhanced growth defect by altering RNA polymerase activity. While specific combinations of resistance and compensatory alleles converged in divergent lineages, other combinations recurred among related isolates suggesting transmission of compensated RIF‐R strains. These findings suggest nutrient poor growth conditions impose larger selective pressure on RIF‐R organisms that results in the selection of compensatory mutations in a domain involved in catalysis and starvation control of RNA polymerase transcription.
Biological and clinical significance of the intratumour heterogeneity of PTEN protein expression and the corresponding molecular abnormalities of the PTEN gene in glioblastomas
Authors: Idoate Miguel A. , Echeveste Jose , Diez‐Valle Ricardo , Lozano Maria Dolores , Aristu José 
Published: January 2014

AimsGlioblastomas display marked phenotypic and molecular heterogeneity. The expression of the PTEN protein in glioblastomas also shows great intratumour heterogeneity, but the significance of this heterogeneity has so far received little attention.MethodsWe conducted a comparative study on paraffin and frozen samples from 60 glioblastomas. Based on PTEN immunostaining, paraffin glioblastomas were divided into positive (homogeneous staining) and both positive and negative (heterogeneous staining) tumours. DNA was extracted from manually microdissected samples from representative areas, and from frozen samples taken randomly from the same tumours. Loss of heterozygosity (LOH) of 10q23 and hypermethylation status of the PTEN promoter were studied, and the molecular findings were correlated with overall survival.ResultsPTEN protein was present heterogeneously in 42 cases and homogeneously in 18 cases. In homogeneous glioblastomas, no correlation was found between PTEN protein expression and the LOH of the gene. Surprisingly, in the heterogeneous glioblastomas, LOH was found significantly more frequently (P < 0.001) in PTEN‐positive areas (81%) than in PTEN‐negative ones (35.7%). In general, molecular results of frozen tissue were representative of the tumour. Only two cases of methylation of the PTEN promoter were identified. A significant difference was found for overall survival for LOH10q23 status (P = 0.005) and for homogeneous vs. heterogeneous tumours (P = 0.014).ConclusionThe expression of PTEN protein does not correlate with the abnormalities of the LOH of the gene. Interestingly, patients with glioblastomas presenting either LOH of 10q23 or heterogeneous PTEN expression have a poorer prognosis.