bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole
Authors: Gerber Bernhard , Guggenberger Roman , Fasler David , Nair Gayathri , Manz Markus G. , Stussi Georg , Schanz Urs 
Published: August 2012

AbstractWe here investigate the occurrence of fluoride intake-associated alterations in patients with hematologic disease on triazol antifungal medication. Clinical, laboratory, and radiology data of overall 43 patients with hematologic malignancies taking voriconazole (n = 20), posaconazole (n = 8), and itraconazole (n = 4), and a hematologic patient control group (n = 11) are described. Bone pain and radiologic evidence of periostitis were exclusively observed in patients receiving long-term voriconazole. Cessation of treatment led to clinical improvement in all cases. In line with clinical evidence, fluoride serum concentration was elevated in patients receiving voriconazole (median, 156.5 μg/L; interquartile range, 96.8 μg/L; normal < 30 μg/L) but not in the other treatment groups (P < .001 for all comparisons vs voriconazole). We conclude that serum fluoride levels were elevated on average 5-fold above normal levels in hematologic patients receiving voriconazole. Clinically relevant skeletal disease was associated with renal insufficiency and above 10-fold elevated fluoride levels, and was reversible on termination of voriconazole treatment.
Cell-type specificity of ChIP-predicted transcription factor binding sites
Authors: Håndstad Tony , Rye Morten , Močnik Rok , Drabløs Finn , Sætrom Pål 
Published: August 2012

Abstract

Background
Context-dependent transcription factor (TF) binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding?

Results
We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity.

Conclusions
Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.
High throughput sequencing reveals novel and abiotic stress-regulated microRNAs in the inflorescences of rice
Authors: Barrera-Figueroa Blanca E , Gao Lei , Wu Zhigang , Zhou Xuefeng , Zhu Jianhua , Jin Hailing , Liu Renyi , Zhu Jian-Kang 
Published: August 2012

Abstract

Background
MicroRNAs (miRNAs) are small RNA molecules that play important regulatory roles in plant development and stress responses. Identification of stress-regulated miRNAs is crucial for understanding how plants respond to environmental stimuli. Abiotic stresses are one of the major factors that limit crop growth and yield. Whereas abiotic stress-regulated miRNAs have been identified in vegetative tissues in several plants, they are not well studied in reproductive tissues such as inflorescences.

Results
We used Illumina deep sequencing technology to sequence four small RNA libraries that were constructed from the inflorescences of rice plants that were grown under control condition and drought, cold, or salt stress. We identified 227 miRNAs that belong to 127 families, including 70 miRNAs that are not present in the miRBase. We validated 62 miRNAs (including 10 novel miRNAs) using published small RNA expression data in DCL1, DCL3, and RDR2 RNAi lines and confirmed 210 targets from 86 miRNAs using published degradome data. By comparing the expression levels of miRNAs, we identified 18, 15, and 10 miRNAs that were regulated by drought, cold and salt stress conditions, respectively. In addition, we identified 80 candidate miRNAs that originated from transposable elements or repeats, especially miniature inverted-repeat elements (MITEs).

Conclusion
We discovered novel miRNAs and stress-regulated miRNAs that may play critical roles in stress response in rice inflorescences. Transposable elements or repeats, especially MITEs, are rich sources for miRNA origination.
Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data
Authors: Strutton David R , Farkouh Raymond A , Rubin Jaime L , McGarry Lisa J , Loiacono Paul M , Klugman Keith P , Pelton Steven I , Gilmore Kristen E , Weinstein Milton C 
Published: August 2012

Abstract

Background
Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%.

Methods
This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant.

Results
Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program.

Conclusions
Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort.
Detection of P. aeruginosa harboring bla
CTX-M-2, bla
GES-1 and bla
GES-5,
bla
IMP-1 and bla
SPM-1causing infections in Brazilian tertiary-care hospital
Authors: Polotto Milena , Casella Tiago , de Lucca Oliveira Maria Gabriela , Rúbio Fernando G , Nogueira Mauricio L , de Almeida Margarete TG , Nogueira Mara CL 
Published: August 2012

Abstract

Background
Nosocomial infections caused by Pseudomonas aeruginosa presenting resistance to beta-lactam drugs are one of the most challenging targets for antimicrobial therapy, leading to substantial increase in mortality rates in hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms of resistance, such as production of metallo-beta-lactamase (MBLs) and extended-spectrum beta-lactamases (ESBLs) have the highest clinical impact. Hence, this study was designed to investigate the presence of genes codifying for MBLs and ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed teaching tertiary care hospital.

Methods
Fifty-six carbapenem-resistant P. aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains presenting MBL and/or ESBL genes were submitted to pulsed-field gel electrophoresis for genetic similarity evaluation.

Results
Despite the carbapenem resistance, genes for MBLs (bla
SPM-1 or bla
IMP-1) were detected in only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates. The bla
CTX-M-2 was the most prevalent ESBL gene (19.6%), followed by bla
GES-1 and bla
GES-5 detected in one isolate each. In all isolates presenting MBL phenotype by double-disc synergy test (DDST), the bla
SPM-1 or bla
IMP-1 genes were detected. In addition, bla
IMP-1 was also detected in three isolates which did not display any MBL phenotype. These isolates also presented the bla
CTX-M-2 gene. The co-existence of bla
CTX-M-2 with bla
IMP-1 is presently reported for the first time, as like as co-existence of bla
GES-1 with bla
IMP-1.

Conclusions
In this study MBLs production was not the major mechanism of resistance to carbapenems, suggesting the occurrence of multidrug efflux pumps, reduction in porin channels and production of other beta-lactamases. The detection of bla
CTX-M-2,
bla
GES-1 and bla
GES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P. aeruginosa and the extraordinary ability presented by this pathogen to acquire multiple resistance mechanisms. These findings raise the concern about the future of antimicrobial therapy and the capability of clinical laboratories to detect resistant strains, since simultaneous production of MBLs and ESBLs is known to promote further complexity in phenotypic detection. Occurrence of intra-hospital clonal dissemination enhances the necessity of better observance of infection control practices.
The risk for chronic kidney disease in patients with heart diseases: a 7-year follow-up in a cohort study in Taiwan
Authors: Liu Jiung-Hsiun , Lin Shih-Yi , Hsu Chung-Yi , Lin Hsin-Hung , Liang Chih-Chia , Sung Fung-Chang , Huang Chiu-Ching 
Published: August 2012

Abstract

Background
The worldwide increasing trend of chronic kidney disease (CKD) is of great concern and the role of heart disease deserves longitudinal studies. This study investigated the risk of developing CKD among patients with heart diseases.

Methods
From universal insurance claims data in Taiwan, we retrospectively identified a cohort of 26005 patients with newly diagnosed heart diseases and 52010 people without such disease from the 2000–2001 claims. We observed prospectively both cohorts until the end of 2007 to measure CKD incidence rates in both cohorts and hazard ratios (HR) of CKD.

Results
The incidence of CKD in the cohort with heart disease was 4.1 times greater than that in the comparison cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37 (95% confidence interval (CI) = 2.05 – 2.74) in the multivariate Cox proportional hazard model after controlling for sociodemographic characteristics and comorbidity. Compared with individuals aged < 40 years, the HRs for CKD ranged from 2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD observed in our patients were also independently associated with hypertension (HR = 2.26, 95% CI = 1.94 - 2.63) and diabetes mellitus (HR = 2.44, 95% CI = 2.13 - 2.80), but not with hyperlipidemia (HR =1.13, 95% CI = 0.99-1.30).

Conclusions
This population study provides evidence that patients with heart disease are at an elevated risk of developing CKD. Hypertension and diabetes mellitus are also comorbidity associated with increasing the CKD risk independently.
Clinical utility of PKD2 mutation testing in a polycystic kidney disease cohort attending a specialist nephrology out-patient clinic
Authors: Robinson Caroline , Hiemstra Thomas F , Spencer Deborah , Waller Sarah , Daboo Laura , Karet Frankl Fiona E , Sandford Richard N 
Published: August 2012

AbstractBackgroundADPKD affects approximately 1:1000 of the worldwide population. It is caused by mutations in two genes,PKD1andPKD2. Although allelic variation has some influence on disease severity, genic effects are strong, withPKD2mutations predicting later onset of ESRF by up to 20 years. We therefore screened a cohort of ADPKD patients attending a nephrology out-patient clinic forPKD2mutations, to identify factors that can be used to offer targeted gene testing and to provide patients with improved prognostic information.Methods142 consecutive individuals presenting to a hospital nephrology out-patient service with a diagnosis of ADPKD and CKD stage 4 or less were screened for mutations inPKD2, following clinical evaluation and provision of a detailed family history (FH).ResultsPKD2mutations were identified in one fifth of cases. 12% of non-PKD2patients progressed to ESRF during this study whilst none with aPKD2mutation did (median 38.5 months of follow-up, range 16–88 months,p < 0.03). A significant difference was found in age at ESRF of affected family members (non-PKD2vs.PKD2, 54 yrs vs. 65 yrs;p < 0.0001). NoPKD2mutations were identified in patients with a FH of ESRF occurring before age 50 yrs, whereas aPKD2mutation was predicted by a positive FH without ESRF.ConclusionsPKD2testing has a clinically significant detection rate in the pre-ESRF population. It did not accurately distinguish those individuals with milder renal disease defined by stage of CKD but did identify a group less likely to progress to ESRF. When used with detailed FH, it offers useful prognostic information for individuals and their families. It can therefore be offered to all but those whose relatives have developed ESRF before age 50.
Intraocular pressure vs intracranial pressure in disease conditions: A prospective cohort study (Beijing iCOP study)
Authors: Li Zhen , Yang Yingxin , Lu Yan , Liu Dachuan , Xu Erhe , Jia Jianping , Yang Diya , Zhang Xiaojun , Yang Huiqing , Ma Daqing , Wang Ningli 
Published: August 2012

Abstract

Background
The correlation between intracranial pressure (ICP) and intraocular pressure (IOP) is still controversial in literature and hence whether IOP can be used as a non-invasive surrogate of ICP remains unknown. The aim of the current study was to further clarify the potential correlation between ICP and IOP.

Methods
The IOP measured with Goldmann applanation tonometer was carried out on 130 patients whose ICP was determined via lumber puncture. The Pearson correlation coefficient between ICP and IOP was calculated, the fisher line discriminated analysis to evaluate the effectivity of using IOP to predict the ICP level.

Results
A significant correlation between ICP and IOP was found. ICP was correlated significantly with IOP of the right eyes (p < 0.001) and IOP of the left eyes (p = 0.001) and mean IOP of both eyes (p < 0.001), respectively. However, using IOP as a measurement to predict ICP, the accuracy rate was found to be 65.4%.

Conclusion
Our data suggested that although a significant correlation exists between ICP and IOP, caution needs to be taken when using IOP readings by Goldmann applanation tonometer as a surrogate for direct cerebrospinal fluid pressure measurement of ICP.
The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma
Authors: Qu Xu-Dong , Chen Cheng-Shi , Wang Jian-Hua , Yan Zhi-ping , Chen Jie-min , Gong Gao-quan , Liu Qin-xin , Luo Jian-jun , Liu Lin-xiao , Liu Rong , Qian Sheng 
Published: August 2012

Abstract

Background
The long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC.

Methods
Between June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded.

Results
The median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed.

Conclusion
TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.
Characterization of purified and Xerogel immobilized Novel Lignin Peroxidase produced from Trametes versicolor IBL-04 using solid state medium of Corncobs
Authors: Asgher Muhammad , Iqbal Hafiz Muhammad Nasir , Irshad Muhammad 
Published: August 2012

AbstractBackgroundCost-effective production of industrially important enzymes is a key for their successful exploitation on industrial scale. Keeping in view the extensive industrial applications of lignin peroxidase (LiP), this study was performed to purify and characterize the LiP from an indigenous strain ofTrametes versicolorIBL-04. Xerogel matrix enzyme immobilization technique was applied to improve the kinetic and thermo-stability characteristics of LiP to fulfil the requirements of the modern enzyme consumer sector of biotechnology.ResultsA novel LiP was isolated from an indigenousT. versicolorIBL-04 strain.T. versicolorIBL-04 was cultured in solid state fermentation (SSF) medium of corn cobs and maximum LiP activity of 592 ± 6 U/mL was recorded after five days of incubation under optimum culture conditions. The crude LiP was 3.3-fold purified with specific activity of 553 U/mg after passing through the DEAE-cellulose and Sephadex-G-100 chromatography columns. The purified LiP exhibited a relatively low molecular weight (30 kDa) homogenous single band on native and SDS-PAGE. The LiP was immobilized by entrapping in xerogel matrix of trimethoxysilane (TMOS) and proplytetramethoxysilane (PTMS) and maximum immobilization efficiency of 88.6% was achieved. The free and immobilized LiPs were characterized and the results showed that the free and immobilized LiPs had optimum pH 6 and 5 while optimum temperatures were 60°C and 80°C, respectively. Immobilization was found to enhance the activity and thermo-stability potential of LiP significantly and immobilized LiP remained stable over broad pH and temperature range as compare to free enzyme. Kinetic constantsKmandVmaxwere 70 and 56 μM and 588 and 417 U/mg for the free and immobilized LiPs, respectively. Activity of this novel extra thermo-stable LiP was stimulated to variable extents by Cu2+, Mn2+and Fe2+whereas, Cystein, EDTA and Ag+showed inhibitory effects.ConclusionsThe indigenously isolated white rot fungal strainT. versicolorIBL-04 showed tremendous potential for LiP synthesis in SSF of corncobs in high titters (592 U/mL) than other reportedTrametes(Coriolus,Polyporus) species. The results obtained after dual phase characterization suggested xerogel matrix entrapment a promising tool for enzyme immobilization, hyper-activation and stabilization against high temperature and inactivating agents. The pH and temperature optima, extra thermo-stability features and kinetic characteristics of this novel LiP ofT. versicolorIBL-04 make it a versatile enzyme for various industrial and biotechnological applications.
Rational improvement of the engineered isobutanol-producing Bacillus subtilis by elementary mode analysis
Authors: Li Shanshan , Huang Di , Li Yong , Wen Jianping , Jia Xiaoqiang 
Published: August 2012

Abstract

Background
Isobutanol is considered as a leading candidate for the replacement of current fossil fuels, and expected to be produced biotechnologically. Owing to the valuable features, Bacillus subtilis has been engineered as an isobutanol producer, whereas it needs to be further optimized for more efficient production. Since elementary mode analysis (EMA) is a powerful tool for systematical analysis of metabolic network structures and cell metabolism, it might be of great importance in the rational strain improvement.

Results
Metabolic network of the isobutanol-producing B. subtilis BSUL03 was first constructed for EMA. Considering the actual cellular physiological state, 239 elementary modes (EMs) were screened from total 11,342 EMs for potential target prediction. On this basis, lactate dehydrogenase (LDH) and pyruvate dehydrogenase complex (PDHC) were predicted as the most promising inactivation candidates according to flux flexibility analysis and intracellular flux distribution simulation. Then, the in silico designed mutants were experimentally constructed. The maximal isobutanol yield of the LDH- and PDHC-deficient strain BSUL05 reached 61% of the theoretical value to 0.36 ± 0.02 C-mol isobutanol/C-mol glucose, which was 2.3-fold of BSUL03. Moreover, this mutant produced approximately 70 % more isobutanol to the maximal titer of 5.5 ± 0.3 g/L in fed-batch fermentations.

Conclusions
EMA was employed as a guiding tool to direct rational improvement of the engineered isobutanol-producing B. subtilis. The consistency between model prediction and experimental results demonstrates the rationality and accuracy of this EMA-based approach for target identification. This network-based rational strain improvement strategy could serve as a promising concept to engineer efficient B. subtilis hosts for isobutanol, as well as other valuable products.
Inaccurate identification of rotavirus genotype G9 as genotype G3 strains due to primer mismatch
Authors: Mitui Marcelo Takahiro , Chandrasena TGA Nilmini , Chan Paul KS , Rajindrajith Shaman , Nelson E Anthony S , Leung Ting Fan , Nishizono Akira , Ahmed Kamruddin 
Published: August 2012

Abstract
Reverse transcription (RT)-PCR is now the standard method for typing group A rotaviruses (RVA) to monitor the circulating genotypes in a population. Selection of primers that can accurately type the circulating genotypes is crucial in the context of vaccine introduction and correctly interpreting the impact of vaccination on strain distribution. To our knowledge this study is the first report from Asia of misidentification of genotype G9 as G3 due to a primer-template mismatch. We tested two published G-genotype specific primers sets, designed by Gouvea and colleagues (Set A) and Iturriza‐Gomara and colleagues (Set B) on RVA from Hong Kong and Sri Lanka. Among 52 rotaviruses typed as G3 by set A primers, 36 (69.2%) were identified as G9 by nucleotide sequencing and set B primers. Moreover, of 300 rotaviruses tested, 28.3% were untypable by set A primers whereas only 12.3% were untypable by set B primers. Our findings reinforce the need to periodically monitor the primers used for RVA genotyping.