bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imputation reliability on DNA biallelic markers for drug metabolism studies
Authors: Mijatovic Vladan , Iacobucci Ilaria , Sazzini Marco , Xumerle Luciano , Mori Antonio , Pignatti Pier Franco , Martinelli Giovanni , Malerba Giovanni 
Published: September 2012

Abstract

Background
Imputation is a statistical process used to predict genotypes of loci not directly assayed in a sample of individuals. Our goal is to measure the performance of imputation in predicting the genotype of the best known gene polymorphisms involved in drug metabolism using a common SNP array genotyping platform generally exploited in genome wide association studies.

Methods
Thirty-nine (39) individuals were genotyped with both Affymetrix Genome Wide Human SNP 6.0 (AFFY) and Affymetrix DMET Plus (DMET) platforms. AFFY and DMET contain nearly 900000 and 1931 markers respectively. We used a 1000 Genomes Pilot + HapMap 3 reference panel. Imputation was performed using the computer program Impute, version 2. SNPs contained in DMET, but not imputed, were analysed studying markers around their chromosome regions. The efficacy of the imputation was measured evaluating the number of successfully imputed SNPs (SSNPs).

Results
The imputation predicted the genotypes of 654 SNPs not present in the AFFY array, but contained in the DMET array. Approximately 1000 SNPs were not annotated in the reference panel and therefore they could not be directly imputed. After testing three different imputed genotype calling threshold (IGCT), we observed that imputation performs at its best for IGCT value equal to 50%, with rate of SSNPs (MAF > 0.05) equal to 85%.

Conclusions
Most of the genes involved in drug metabolism can be imputed with high efficacy using standard genome-wide genotyping platforms and imputing procedures.
Genome-wide gene expression profiling of introgressed indica rice alleles associated with seedling cold tolerance improvement in a japonica rice background
Authors: Zhang Fan , Huang Liyu , Wang Wensheng , Zhao Xiuqin , Zhu Linghua , Fu Binying , Li Zhikang 
Published: September 2012

Abstract

Background
Rice in tropical and sub-tropical areas is often subjected to cold stress at the seedling stage, resulting in poor growth and yield loss. Although japonica rice is generally more cold tolerant (CT) than indica rice, there are several favorable alleles for CT exist in indica that can be used to enhance CT in rice with a japonica background. Genome-wide gene expression profiling is an efficient way to decipher the molecular genetic mechanisms of CT enhancement and to provide valuable information for CT improvement in rice molecular breeding. In this study, the transcriptome of the CT introgression line (IL) K354 and its recurrent parent C418 under cold stress were comparatively analyzed to explore the possible CT enhancement mechanisms of K354.

Results
A total of 3184 differentially expressed genes (DEGs), including 195 transcription factors, were identified in both lines under cold stress. About half of these DEGs were commonly regulated and involved in major cold responsive pathways associated with OsDREB1 and OsMyb4 regulons. K354-specific cold-induced genes were functionally related to stimulus response, cellular cell wall organization, and microtubule-based movement processes that may contribute to increase CT. A set of genes encoding membrane fluidity and defensive proteins were highly enriched only in K354, suggesting that they contribute to the inherent CT of K354. Candidate gene prediction based on introgressed regions in K354 revealed genotype-dependent CT enhancement mechanisms, associated with Sir2, OsFAD7, OsWAK112d, and programmed cell death (PCD) related genes, present in CT IL K354 but absent in its recurrent parent C418. In K354, a number of DEGs were co-localized onto introgressed segments associated with CT QTLs, providing a basis for gene cloning and elucidation of molecular mechanisms responsible for CT in rice.

Conclusions
Genome-wide gene expression analysis revealed that genotype-specific cold induced genes and genes with higher basal expression in the CT genotype contribute jointly to CT improvement. The molecular genetic pathways of cold stress tolerance uncovered in this study, as well as the DEGs co-localized with CT-related QTLs, will serve as useful resources for further functional dissection of the molecular mechanisms of cold stress response in rice.
Clock-controlled mir-142-3p can target its activator, Bmal1
Authors: Tan Xiaochao , Zhang Peng , Zhou Lan , Yin Bin , Pan Hui , Peng Xiaozhong 
Published: September 2012

Abstract

Background
microRNAs (miRNAs) are shown to be involved in the regulation of circadian clock. However, it remains largely unknown whether miRNAs can regulate the core clock genes (Clock and Bmal1).

Results
In this study, we found that mir-142-3p directly targeted the 3’UTR of human BMAL1 and mouse Bmal1. The over-expression (in 293ET and NIH3T3 cells) and knockdown (in U87MG cells) of mir-142-3p reduced and up-regulated the Bmal1/BMAL1 mRNA and protein levels, respectively. Moreover, the expression level of mir-142-3p oscillated in serum-shocked NIH3T3 cells and the results of ChIP and luciferase reporter assays suggested that the expression of mir-142-3p was directly controlled by CLOCK/BMAL1 heterodimers in NIH3T3 cells.

Conclusions
Our study demonstrates that mir-142-3p can directly target the 3’UTR of Bmal1. In addition, the expression of mir-142-3p is controlled by CLOCK/BMAL1 heterodimers, suggesting a potential negative feedback loop consisting of the miRNAs and the core clock genes. These findings open new perspective for studying the molecular mechanism of circadian clock.
Effect of vitamin-D analogue on albuminuria in patients with non-dialysed chronic kidney disease stage 4–5: a retrospective single center study
Authors: Jørgensen Hanne Skou , Winther Simon , Povlsen Johan Vestergaard , Ivarsen Per 
Published: September 2012

Abstract

Background
The vitamin D receptor activator paricalcitol has been shown to reduce albuminuria. Whether this is a unique property of paricalcitol, or common to all vitamin D analogues, is unknown. The primary aim of this study was to evaluate the effect of alfacalcidol on proteinuria, measured as 24 hour (24 h) albuminuria, in patients with chronic kidney disease (CKD) stage 4–5 being treated for secondary hyperparathyroidism (sHPT).

Methods
A retrospective single-center study including adult patients with CKD 4–5, undergoing treatment for sHPT with alfacalcidol, with macroalbuminuria in minimum one 24 h urine collection. Patients were identified in a prospectively collected database of all patients with S-creatinine > 300 μM or creatinine clearance < 30 ml/min. The observation period was from 1st of January 2005 to 31st of December 2009. Phosphate binders and alfacalcidol were provided to patients free of charge.

Results
A total of 146 macroalbuminuric patients were identified, and of these, 59 started alfacalcidol treatment during the observation period. A 12% reduction in 24 h albuminuria was seen after starting treatment. In 19 patients with no change in renin-angiotensin-aldosteron-system (RAAS) inhibition, the reduction in albuminuria was 16%. The reduction remained stable over time (9%) in a subgroup of patients (n = 20) with several urine collections before and after the start of alfacalcidol-treatment.

Conclusion
The present study supports experimental and clinical data on antiproteinuric actions of activated vitamin D analogues, and suggests that this may be a class-effect.
Content validity and test-retest reliability of patient perception of intensity of urgency scale (PPIUS) for overactive bladder
Authors: Notte Sherilyn M , Marshall Thomas S , Lee Misun , Hakimi Zalmai , Odeyemi Isaac , Chen Wen-Hung , Revicki Dennis A 
Published: September 2012

Abstract

Background
The Patient Perception of Intensity of Urgency Scale (PPIUS) is a patient-reported outcome instrument intended to measure the intensity of urgency associated with each urinary or incontinence episode. The objectives of this study were to assess the content validity, test-retest reliability, and acclimation effect of the PPIUS in overactive bladder (OAB) patients.

Methods
Patients undergoing treatment for OAB were recruited to participate in a non-interventional study by completing a three-day micturition diary including the PPIUS for three consecutive weeks. Following completion of the three-week study, participants from two select sites also completed a cognitive interview to assess their comprehension of the PPIUS.

Results
Thirty-nine participants successfully completed the three-week test-retest study; twelve of these participants completed the cognitive interview. Test-retest reliability was high based on intra-class correlation coefficient of 0.95. Among stable patients, the difference between the mean ratings of any two weeks was non-significant. Among the twelve interview participants, nine found it simple to choose a PPIUS rating for each of their micturition episodes and most found the urgency rating definitions consistent with their urgency experiences.

Conclusions
The results demonstrated content validity based on qualitative interviews, and excellent test-retest reliability among stable patients. In addition, no acclimation effect was observed among stable patients. These findings support the use of the PPIUS as a reliable measure of urgency in both clinical trial and real life settings. The validity of PPIUS could be further established with future studies investigating the relationship between discretely graded urgency and incontinence continuum.
Red wine and component flavonoids inhibit UGT2B17 in vitro
Authors: Jenkinson Carl , Petroczi Andrea , Naughton Declan P 
Published: September 2012

AbstractBackgroundThe metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17.MethodsTestosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analyzed using HPLC; and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17.ResultsOver the concentration range of 2 to 8%, the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HPLC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 μM despite a ten-fold excess of testosterone.ConclusionThis study reports that in anin vitrosupersome-based assay, the key steroid-metabolizing enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidationin vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the health implications.
Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in stage III non-small cell lung cancer patients
Authors: Govaert Stephanie LA , Troost Esther GC , Schuurbiers Olga CJ , de Geus-Oei Lioe-Fee , Termeer Ariën , Span Paul N , Bussink Johan 
Published: September 2012

Abstract

Purpose
The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III non-small cell lung cancer (NSCLC).

Methods and materials
Eighty-six patients with advanced stage NSCLC, treated with either IMRT only (66 Gy) or combined with (sequential or concurrent) chemotherapy were retrospectively included in this study. Overall survival and metastasis-free survival were assessed as well as acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity Scoring Criteria.

Results
Irrespective of the treatment modality, the overall survival rate for patients receiving 66 Gy was 71% (±11%; 95% CI) after one year and 56% (±14%) after two years resulting in a median overall survival of 29.7 months. Metastasis-free survival was 73% (±11%) after both one and two years. There were no statistically significant differences between the treatment groups. Treatment related esophageal toxicity was significantly more pronounced in the concurrent chemoradiotherapy group (p = 0.013) with no differences in pulmonary toxicity.

Conclusions
This retrospective cohort study in advanced non-small cell lung cancer patients shows that IMRT is an effective technique with acceptable acute toxicity, also when (sequentially or concomitantly) combined with chemotherapy.
Elucidation of the effect of ionic liquid pretreatment on rice husk via structural analyses
Authors: Ang Teck Nam , Ngoh Gek Cheng , Chua Adeline Seak May , Lee Min Gyu 
Published: September 2012

AbstractBackgroundIn the present study, three ionic liquids, namely 1-butyl-3-methylimidazolium chloride ([BMIM]Cl), 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc), and 1-ethyl-3-methylimidazolium diethyl phosphate ([EMIM]DEP), were used to partially dissolve rice husk, after which the cellulose were regenerated by the addition of water. The aim of the investigation is to examine the implications of the ionic liquid pretreatments on rice husk composition and structure.ResultsFrom the attenuated total reflectance Fourier transform-infrared (ATR FT-IR) spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM) results, the regenerated cellulose were more amorphous, less crystalline, and possessed higher structural disruption compared with untreated rice husk. The major component of regenerated cellulose from [BMIM]Cl and [EMIM]DEP pretreatments was cellulose-rich material, while cellulose regenerated from [EMIM]OAc was a matrix of cellulose and lignin. Cellulose regenerated from ionic pretreatments could be saccharified via enzymatic hydrolysis, and resulted in relatively high reducing sugars yields, whereas enzymatic hydrolysis of untreated rice husk did not yield reducing sugars. Rice husk residues generated from the ionic liquid pretreatments had similar chemical composition and amorphousity to that of untreated rice husk, but with varying extent of surface disruption and swelling.ConclusionsThe structural architecture of the regenerated cellulose and rice husk residues showed that they could be used for subsequent fermentation or derivation of cellulosic compounds. Therefore, ionic liquid pretreatment is an alternative in the pretreatment of lignocellulosic biomass in addition to the conventional chemical pretreatments.
Absence of dry season Plasmodium parasitaemia, but high rates of reported acute respiratory infection and diarrhoea in preschool-aged children in Kaédi, southern Mauritania
Authors: Touray Sunkaru , Bâ Hampâté , Bâ Ousmane , Koïta Mohamedou , Salem Cheikh B Ould Ahmed , Keïta Moussa , Traoré Doulo , Sy Ibrahima , Winkler Mirko S , Utzinger Jürg , Cissé Guéladio 
Published: September 2012

Abstract

Background
The epidemiology of malaria in the Senegal River Gorgol valley, southern Mauritania, requires particular attention in the face of ongoing and predicted environmental and climate changes. While “malaria cases” are reported in health facilities throughout the year, past and current climatic and ecological conditions do not favour transmission in the dry season (lack of rainfall and very high temperatures). Moreover, entomological investigations in neighbouring regions point to an absence of malaria transmission in mosquito vectors in the dry season. Because the clinical signs of malaria are non-specific and overlap with those of other diseases (e.g. acute respiratory infections and diarrhoea), new research is needed to better understand malaria transmission patterns in this region to improve adaptive, preventive and curative measures.

Methods
We conducted a multipurpose cross-sectional survey in the city of Kaédi in April 2011 (dry season), assessing three major disease patterns, including malaria. Plasmodium spp. parasite rates were tested among children aged 6–59 months who were recruited from a random selection of households using a rapid diagnostic test and microscopic examination of Giemsa-stained thick and thin blood films. Acute respiratory infection and diarrhoea were the two other diseases investigated, administering a parental questionnaire to determine the reported prevalence among participating children.

Findings
No Plasmodium infection was found in any of the 371 surveyed preschool-aged children using two different diagnostic methods. Acute respiratory infections and diarrhoea were reported in 43.4% and 35.0% of the participants, respectively. About two thirds of the children with acute respiratory infections and diarrhoea required medical follow-up by a health worker.

Conclusions
Malaria was absent in the present dry season survey in the capital of the Gorgol valley of Mauritania, while acute respiratory infections and diarrhea were highly prevalent. Surveys should be repeated towards the end of rainy season, which will enhance our understanding of the potential changes in malaria transmission in a region known as ‘hot spot’ of predicted climate change.
Proinflammatory effects of malondialdehyde in lymphocytes
Authors: Raghavan Somasundaram , Subramaniyam Ganesan , Shanmugam Narkunaraja 
Published: September 2012

Abstract
MDA changed cytokine/chemokines mRNA profiles in lymphocytes; increased cytokines expression is via oxidative stress, p38MAPK, and PKC pathways.
Diabetes is an inflammatory disease promoted by alterations in immune cell function. Animal study indicates that T cells are important mediators of inflammation in diabetes. Lipid peroxidation by reactive oxygen species leads to the formation of highly reactive malondialdehyde (MDA), and extensive MDA is found in diabetes. However, the biological functions of MDA have not been studied yet. We hypothesized that increased MDA, as in diabetes, can regulate inflammatory cytokines via specific signaling pathways. This could then result in increased lymphocyte activation and skewing a particular inflammatory subset thereby exacerbates diabetes complications. Commercial cytokine antibody and RT2-PCR array profiling were performed with Jurkat T cells grown with or without MDA. Ingenuity pathways analysis (IPA) and pharmacological inhibitors were used for networks and signaling pathway identification, respectively. For validation, real-time PCR, RT-PCR, and Western blots were performed. MDA induced significant increases in 47 key proinflammatory molecules such as IL-25, IL-6, IL-8, ICAM-1, and light mRNA in Jurkat T cells and primary peripheral blood lymphocytes (PBLCs). A significant 2-fold increase in serum MDA also correlated the increased IL-25 and IL-8 mRNA in PBLCs of diabetic patients. Pharmacological inhibitor studies showed that MDA induced its effect via p38MAPK and protein kinase C pathways. Furthermore, IPA uncovered 5 groups of inflammatory networks and placed our candidate genes in canonical IL-6 and NF-κB signaling pathways and also suggested 5 toxic lists and 3 major toxic functions, namely cardiotoxicity, hepatotoxicity, and nephrotoxicity. These new results suggest that MDA can promote lymphocyte activation via induction of inflammatory pathways and networks.
An interpretation of surface and borehole seismic surveys for mine planning at the Millennium uranium deposit, northern Saskatchewan, Canada
Authors: Wood Garnet , O’Dowd Clare , Cosma Calin , Enescu Nicoleta 
Published: September 2012

The Millennium uranium deposit is located within the Athabasca Basin, in northern Saskatchewan, Canada. The deposit is hosted within moderately dipping Paleoproterozoic gneisses that are unconformably overlain by more than 500 m of flat lying, porous Paleoproterozoic to late Mesoproterozoic Athabasca Group sandstones. The deposit is associated with the sandstone-basement unconformity, post-Athabasca structure, and hydrothermal alteration. These features combine to create a complex 3D hydrogeologic setting that presents challenges with respect to mine development, production, and safety. In 2007, as part of a prefeasibility study for potential mine development, a seismic program consisting of a 3D surface survey, vertical seismic profiling, moving source profiling, and side-scan surveys was undertaken to map the complex geology. The geometry and resolution of these different seismic surveys allowed for direct imaging of the geologic targets of interest, regardless of orientation and size. After integration with drill-defined geology, the program successfully imaged the location and character of the unconformity, the post-Athabasca structural setting at camp and deposit scales, and the alteration around the deposit. This information increased the understanding of geotechnical aspects of the geology hosting the deposit, and is currently being used to help minimize risk and costs associated with mine development. Seismic surveys are now viewed as an integral part of risk reduction associated with mining in the Athabasca Basin.