bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and Design of the Cardiac Magnetic Resonance Imaging Substudy of the ONTARGET Trial Programme
Authors: Anderson C 
Published: February 2013

Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve cardiovascular disease outcomes in high-risk patients, but evidence for the cardioprotective effects of angiotensin II receptor blockers (ARBs) is less extensive. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the parallel Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) - which together form The ONTARGET Trial Programme – are long-term, large-scale, double-blind, multinational outcome studies with the primary objectives of determining if the combination of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg is more effective than ramipril 10 mg alone, and if telmisartan is at least as effective as ramipril (in the case of ONTARGET), and if telmisartan is superior to placebo (in the case of TRANSCEND), in providing cardiovascular protection for high-risk patients. A pre-defined substudy is being conducted within The ONTARGET Trial Programme to compare the effects of these agents, alone and in combination, on cardiac structure and function. The substudy overcomes criticisms of many previous studies, which have been performed in small numbers of patients using suboptimal methodology, by evaluating changes in left ventricular structure and function using sophisticated technology provided by magnetic resonance imaging (MRI). Some 300 randomized patients within ONTARGET, recruited from selected centres in Australia, Canada, Germany, Hong Kong, New Zealand and Thailand, will have MRI undertaken at baseline and at 2-year follow-up. As this method of assessing left ventricular dysfunction is somewhat time-consuming, expensive and complex, and in the light of current interest in the role of B-type natriuretic peptide (BNP) as a simple, inexpensive diagnostic and prognostic tool, the substudy will also examine whether changes in BNP during follow-up correlated with changes in left ventricular dysfunction.
Cryoablation Combined with Molecular Target Therapy Improves the Curative Effect in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Gu XY , Jiang Z , Fang W 
Published: February 2013

This study investigated the curative effect of cryoablation combined with molecular target therapy for advanced non-small cell lung cancer (NSCLC). Thirty-six female patients with NSCLC and epidermal growth factor receptor gene mutations were randomly divided into two groups: 18 patients received the molecular target therapy gefitinib (group I), an epidermal growth factor receptor-tyrosine kinase inhibitor; and 18 patients were treated with cryoablation prior to the administration of gefitinib (group II). Treatment with gefitinib was continued for 6 months. Compared with group I, the rates of partial regression, stabilization of disease and progression of disease were improved in group II at the end of the 6 months of gefitinib treatment. Moreover, the 1-year survival rate in group II was significantly higher than that in group I. This suggests that cryoablation therapy combined with gefitinib could improve the effects of treatment and the prognosis of patients with advanced NSCLC.
The Expression and Clinical Significance of GTP-Binding RAS-Like 3 (ARHI) and MicroRNA 221 and 222 in Prostate Cancer
Authors: Lin D , Cui F , Bu Q , Yan C 
Published: February 2013

Globally, prostate cancer is the most common malignancy among men and there is no biomarker for defining tumour invasion and progression. Guanosine-5′-triphosphate (GTP)-binding RAS-like 3 (ARHI) is a tumour suppressor gene that has been found to be downregulated in the prostate cancer cell line PC-3. MicroRNA 221 and 222 have been shown to regulate ARHI expression negatively. This study evaluated tissue samples from patients with prostate cancer ( n = 35) that were designated as aggressive or non-aggressive according to their Gleason grade. Expression of ARHI and microRNA 221 and 222 was measured by real-time reverse transcription-polymerase chain reaction. The level of ARHI mRNA was significantly lower in aggressive compared with nonaggressive prostate cancer tissue samples. In contrast, microRNA 221 and 222 levels were significantly higher in aggressive compared with non-aggressive prostate cancer tissue samples. Whether ARHI and microRNA 221 and 222 could be considered as biomarkers for disease progression in prostate cancer requires further investigation.
Does farm environment protect against type 1 diabetes mellitus?
Authors: Heikkinen Sanna MM , Pitkäniemi Janne M , Kilpeläinen Maritta L , Koskenvuo Markku J 
Published: February 2013

Aims/Hypothesis: Hygiene hypothesis has been shown valid in respect of allergies and asthma but has not been, however, sufficiently studied in relation to type 1 diabetes mellitus. This study investigates the effect of childhood farm environment on the prevalence of type 1 diabetes mellitus in Finnish children and young adults. Methods: Data come from a questionnaire study carried out in 2007 (N = 5805). Prevalence of type 1 diabetes mellitus was analysed according to the type of the rural exposure below the age of 18 years. Associations were estimated and tested using Bayesian methods. Results: Consistent suggestive evidence of the inverse association of childhood’s farm environment with the occurrence of type 1 diabetes mellitus was shown, even though conclusive results were not reached. Conclusion/Interpretation: Exposure to a broad variety of non-pathogenic environmental microorganisms during childhood might have a protective effect on type 1 diabetes mellitus. Results clearly suggest that further research is well grounded with larger samples.
Comparison of transhepatic and extrahepatic routes for EUS‐guided rendezvous procedure for distal CBD obstruction
Authors: Dhir Vinay , Bhandari Suryaprakash , Bapat Mukta , Joshi Nitin , Vivekanandarajah Suhirdan , Maydeo Amit 
Published: February 2013

BackgroundEUS‐guided rendezvous procedure (EUS‐RV) can be done by the transhepatic (TH) or the extrahepatic (EH) route. There is no data on the preferred access route when both routes are available.Study aimTo compare the success, complications, and duration of hospitalization for patients undergoing EUS‐RV by the TH or the EH route.Patients and methodsPatients with distal common bile duct (CBD) obstruction, who failed selective cannulation, underwent EUS‐RV by the TH route through the stomach or the EH route through the duodenum.ResultsA total of 35 patients were analysed (17 TH, 18 EH). The mean procedure time was significantly longer for the TH group (34.4 vs. 25.7 min; p  = 0.0004). There was no difference in the technical success (94.1 vs. 100%). However, the TH group had a higher incidence of post‐procedure pain (44.1 vs. 5.5%; p  = 0.017), bile leak (11.7 vs. 0; p  = 0.228), and air under diaphragm (11.7 vs. 0; p  = 0.228). All bile leaks were small and managed conservatively. Duration of hospitalization was significantly higher for the TH group (2.52 vs. 0.17 days; p  = 0.015).ConclusionsEUS‐RV has similar success rate by the TH or the EH route. However, the TH route has higher post‐procedure pain, longer procedure time, and longer duration of hospitalization. The EH route should be preferred for EUS‐RV in patients with distal CBD obstruction when both access routes are technically feasible.
Characteristics and Follow-up of Newly Managed HIV-Infected Patients in the National Referral Center in Ouagadougou, Burkina Faso
Authors: Tiéno Hervé , Guira Oumar , Sagna Yempabou , Diendéré Eric Arnaud , Diallo Ismael , Bognounou Réné , Zoungrana Lassane , Zida Seidou , Nikiéma Péré , Drabo Youssouf Joseph 
Published: February 2013

Background: In sub-Saharan countries, HIV testing and treatment facilities are available, especially at subsidized rates for the past few years. Methods: A prospective and descriptive review was conducted at Yalgado Ouédraogo Teaching Hospital Internal Medicine department in Ouagadougou, using personal case report forms, between June 2009 and August 2010 in all newly diagnosed adults with positive HIV antibody. Results: The study participants consisted of 191 patients at a median age of 37 years (range, 18-65 years) and sex ratio (men/women): 0.66. In all, 110 (57.6%) patients were symptomatic. Fourteen patients were lost to follow-up. Of the 177 patients, 144 had CD4 count <350 cells/mm3 and all have been treated. At the ninth month, weight gain and immune restoration were significant ( P < .01); only 79 of the 144 patients had viral load measurement, and 76 of the 79 were undetectable. Mortality rate of treated patients was 6.25%. Conclusion: Laboratory tests and highly active antiretroviral therapy make the management of patients easier, but a majority of them still presented late and were still lost to follow-up. Nevertheless, we have excellent treatment success.
CD4 Counts in Laboratory Monitoring of HIV Disease—Experience from Western India
Authors: Ingole Nayana , Nataraj Gita , Mehta Preeti , Paranjpe Supriya , Sarkate Purva 
Published: February 2013

Background: CD4 counts vary in different populations. The present study was conducted to determine CD4 counts in different World Health Organization (WHO) clinical stages in antiretroviral therapy naïve individuals and to find out optimum CD4 cutoffs. Method: Data of adult HIV seropositive patients who underwent CD4 count and total lymphocyte count (TLC) testing were included for analysis. The severity of immunosuppression was graded based on WHO criteria. To establish optimum CD4 cutoff values, receiver–operator characteristics (ROC) curves were generated. Results: Of 754 patients, 52.2% had CD4 counts <200 cells/mm3, but only 2.3% belonged to WHO stage IV. Newer CD4 cutoffs generated were 280, 120-280, <120 cells/mm3. Spearman rank correlation between CD4 counts and TLC was found to be weak ( r = .32). Conclusion: The cutoff values of CD4 counts for HIV disease may need to be revised for India. Regular CD4 count estimation is a must for monitoring disease progression in people living with HIV/AIDS.
Mi2β-mediated silencing of the fetal γ-globin gene in adult erythroid cells
Authors: Amaya Maria , Desai Megha , Gnanapragasam Merlin Nithya , Wang Shou Zhen , Zu Zhu Sheng , Williams David C. , Ginder Gordon D. 
Published: February 2013

Key PointsMi2β exerts a major part of its silencing effect on embryonic and fetal globin genes by positively regulating the BCL11A and KLF1 genes. Partial depletion of Mi2β induces increased γ-globin gene expression in primary human erythroid cells without impairing differentiation.
Expression, purification and biochemical characterization of Schizosaccharomyces pombe Mcm4, 6 and 7
Authors: Xu Meng , Chang Y Paul , Chen Xiaojiang S 
Published: February 2013

Abstract

Background
The hetero-hexamer of the eukaryotic minichromosome maintenance (MCM) proteins plays an essential role in replication of genomic DNA. The ring-shaped Mcm2-7 hexamers comprising one of each subunit show helicase activity in vitro, and form double-hexamers on DNA. The Mcm4/6/7 also forms a hexameric complex with helicase activity in vitro.

Results
We used an Escherichiai coli expression system to express various domains of Schizosaccharomyces pombe Mcm4, 6 and 7 in order to characterize their domain structure, oligomeric states, and possible inter-/intra-subunit interactions. We also successfully employed a co-expression system to express Mcm4/6/7 at the same time in Escherichiai coli, and have purified functional Mcm4/6/7 complex in a hexameric state in high yield and purity, providing a means for generating large quantity of proteins for future structural and biochemical studies.

Conclusions
Based on our results and those of others, models were proposed for the subunit arrangement and architecture of both the Mcm4/6/7 hexamer and the Mcm2-7 double-hexamer.
Identification and functional analysis of cytochrome P450 complement in Streptomyces virginiaeIBL14
Authors: Li Zhi-Zhen , Li Xiao-Fei , Yang Wei , Dong Xiang , Yu Jie , Zhu Shu-Liang , Li Man , Xie Li , Tong Wang-Yu 
Published: February 2013

Abstract

Background
As well known, both natural and synthetic steroidal compounds are powerful endocrine disrupting compounds (EDCs) which can cause reproductive toxicity and affect cellular development in mammals and thus are generally regarded as serious contributors to water pollution. Streptomyces virginiae IBL14 is an effective degradative strain for many steroidal compounds and can also catalyze the C25 hydroxylation of diosgenin, the first-ever biotransformation found on the F-ring of diosgenin.

Results
To completely elucidate the hydroxylation function of cytochrome P450 genes (CYPs) found during biotransformation of steroids by S. virginiae IBL14, the whole genome sequencing of this strain was carried out via 454 Sequencing Systems. The analytical results of BLASTP showed that the strain IBL14 contains 33 CYPs, 7 ferredoxins and 3 ferredoxin reductases in its 8.0 Mb linear chromosome. CYPs from S. virginiae IBL14 are phylogenetically closed to those of Streptomyces sp. Mg1 and Streptomyces sp. C. One new subfamily was found as per the fact that the CYP Svu001 in S. virginiae IBL14 shares 66% identity only to that (ZP_05001937, protein identifer) from Streptomyces sp. Mg1. Further analysis showed that among all of the 33 CYPs in S. virginiae IBL14, three CYPs are clustered with ferredoxins, one with ferredoxin and ferredoxin reductase and three CYPs with ATP/GTP binding proteins, four CYPs arranged with transcriptional regulatory genes and one CYP located on the upstream of an ATP-binding protein and transcriptional regulators as well as four CYPs associated with other functional genes involved in secondary metabolism and degradation.

Conclusions
These characteristics found in CYPs from S. virginiae IBL14 show that the EXXR motif in the K-helix is not absolutely conserved in CYP157 family and I-helix not absolutely essential for the CYP structure, too. Experimental results showed that both CYP Svh01 and CYP Svu022 are two hydroxylases, capable of bioconverting diosgenone into isonuatigenone and β-estradiol into estriol, respectively.
Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate
Authors: Kluge Michael , Hegerl Ulrich , Sander Christian , Dietzel Jens , Mergl Roland , Bitter Istvan , Demyttenaere Koen , Gusmão Ricardo , Gonzalez-Pinto Ana , Perez-Sola Victor , Vieta Eduard , Juckel Georg , Zimmermann Ulrich S , Bauer Michael , Sienaert Pascal , Quintão Sónia , Edel Marc-Andreas , Bolyos Csilla , Ayuso-Mateos Jose Luis , López-García Pilar 
Published: February 2013

Abstract

Background
Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the ‘vigilance regulation model of mania’ which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania.

Methods/design
A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression–Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-‘Vigilance Algorithm Leipzig’ (VIGALL).

Discussion
A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives.

Trial registration
ClinicalTrials.gov:NCT01541605
Influencing factors on cardiac structure and function beyond glycemic control in patients with type 2 diabetes mellitus
Authors: Ichikawa Ryoko , Daimon Masao , Miyazaki Tetsuro , Kawata Takayuki , Miyazaki Sakiko , Maruyama Masaki , Chiang Shuo-Ju , Suzuki Hiromasa , Ito Chiharu , Sato Fumihiko , Watada Hirotaka , Daida Hiroyuki 
Published: February 2013

AbstractBackgroundWe hypothesized that clinical factors other than glycemic control may influence abnormal cardiac function in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the independent factors for abnormal cardiac function among clinical factors in T2DM.MethodsWe studied 148 asymptomatic patients with T2DM without overt heart disease. Echocardiographic findings were compared between diabetic patients and 68 age-matched healthy subjects. Early (E) and late (A) diastolic mitral flow velocity and early diastolic mitral annular velocity (e’) were measured for assessing left ventricular (LV) diastolic function. We evaluated insulin resistance, non-esterified fatty acid, high-sensitive CRP, estimated glomerular filtration rate, waist/hip ratio, abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and other clinical characteristics in addition to glycemic control. VAT and SAT were quantified by computed tomography.ResultsIn T2DM, E/A and e’ were significantly lower, and E/e’, left atrial volume and LV mass were significantly greater than in control subjects. In multivariate liner regression analysis, VAT was an independent determinant of left atrial volume (β =0.203, p=0.011), E/A (β =−0.208, p=0.002), e’ (β =−0.354, p<0.001) and E/e’ (β=0.220, p=0.003). Age was also an independent determinant, whereas fasting plasma glucose and hemoglobin A1c levels were not. In addition to systolic blood pressure, waist-hip ratio (β=0.173, p=0.024) and VAT/SAT ratio (β=0.162, p=0.049) were independent determinants of LV mass.ConclusionExcessive visceral fat accompanied by adipocyte dysfunction may play a greater role than glycemic control in the development of diastolic dysfunction and LV hypertrophy in T2DM.
Optical and microstructural properties of ZnO/TiO2 nanolaminates prepared by atomic layer deposition
Authors: Gu Yu-Zhu , Lu Hong-Liang , Geng Yang , Ye Zhi-Yuan , Zhang Yuan , Sun Qing-Qing , Ding Shi-Jin , Zhang David Wei 
Published: February 2013

Abstract
ZnO/TiO2 nanolaminates were grown on Si (100) and quartz substrates by atomic layer deposition at 200°C using diethylzinc, titanium isopropoxide, and deionized water as precursors. All prepared multilayers are nominally 50 nm thick with a varying number of alternating TiO2 and ZnO layers. Sample thickness and ellipsometric spectra were measured using a spectroscopic ellipsometer, and the parameters determined by computer simulation matched with the experimental results well. The effect of nanolaminate structure on the optical transmittance is investigated using an ultraviolet–visible-near-infrared spectrometer. The data from X-ray diffraction spectra suggest that layer growth appears to be substrate sensitive and film thickness also has an influence on the crystallization of films. High-resolution transmission electron microscopy images show clear lattice spacing of ZnO in nanolaminates, indicating that ZnO layers are polycrystalline with preferred (002) orientation while TiO2 layers are amorphous.
Thymine/adenine diblock-oligonucleotide monolayers and hybrid brushes on gold: a spectroscopic study
Authors: Howell Caitlin , Hamoudi Hicham , Zharnikov Michael 
Published: February 2013

Background
The establishment of spectroscopic analysis techniques for complex, surface-bound biological systems is an important step toward the further application of these powerful experimental tools to new questions in biology and medicine.

Methods
We use a combination of the complementary spectroscopic techniques of X-ray photoelectron spectroscopy, Infrared reflection-absorption spectroscopy, and near-edge x-ray absorption fine structure spectroscopy to monitor the composition and molecular orientation in adenine/thymine diblock oligonucleotide films and their hybridized brushes on gold.

Results
We demonstrate that the surface-bound probe molecules, consisting of a binding adenine block, d(A), and a sensing thymine block, d(T), deviate from the ideal L-shape model due to the internal intra- and intermolecular hybridization. This effect becomes more pronounced with increasing length of the d(A) block. Nevertheless, these films were found to hybridize well with the complementary target d(A) strands, especially if they were treated in advance to reduce internal interaction between the molecules. In spite of the structural complexity of these films, the hybridization efficiency correlated well with the potential accessibility of the sensing d(T) blocks, defined by their lateral spacing.

Conclusions
These findings are a good demonstration of the strength of multi-technique spectroscopic analysis when applied to assemblies of biological molecules intrinsically prone to complex interactions.
CoRSeqV3-C: a novel HIV-1 subtype C specific V3 sequence based coreceptor usage prediction algorithm
Authors: Cashin Kieran , Gray Lachlan R , Jakobsen Martin R , Sterjovski Jasminka , Churchill Melissa J , Gorry Paul R 
Published: February 2013

Abstract

Background
The majority of HIV-1 subjects worldwide are infected with HIV-1 subtype C (C-HIV). Although C-HIV predominates in developing regions of the world such as Southern Africa and Central Asia, C-HIV is also spreading rapidly in countries with more developed economies and health care systems, whose populations are more likely to have access to wider treatment options, including the CCR5 antagonist maraviroc (MVC). The ability to reliably determine C-HIV coreceptor usage is therefore becoming increasingly more important. In silico V3 sequence based coreceptor usage prediction algorithms are a relatively rapid and cost effective method for determining HIV-1 coreceptor specificity. In this study, we elucidated the V3 sequence determinants of C-HIV coreceptor usage, and used this knowledge to develop and validate a novel, user friendly, and highly sensitive C-HIV specific coreceptor usage prediction algorithm.

Results
We characterized every phenotypically-verified C-HIV gp120 V3 sequence available in the Los Alamos HIV Database. Sequence analyses revealed that compared to R5 C-HIV V3 sequences, CXCR4-using C-HIV V3 sequences have significantly greater amino acid variability, increased net charge, increased amino acid length, increased frequency of insertions and substitutions within the GPGQ crown motif, and reduced frequency of glycosylation sites. Based on these findings, we developed a novel C-HIV specific coreceptor usage prediction algorithm (CoRSeqV3-C), which we show has superior sensitivity for determining CXCR4 usage by C-HIV strains compared to all other available algorithms and prediction rules, including Geno2pheno[coreceptor] and WebPSSMSINSI-C, which has been designed specifically for C-HIV.

Conclusions
CoRSeqV3-C is now openly available for public use at http://www.burnet.edu.au/coreceptor. Our results show that CoRSeqV3-C is the most sensitive V3 sequence based algorithm presently available for predicting CXCR4 usage of C-HIV strains, without compromising specificity. CoRSeqV3-C may be potentially useful for assisting clinicians to decide the best treatment options for patients with C-HIV infection, and will be helpful for basic studies of C-HIV pathogenesis.