bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFRSF1B +676 T>G polymorphism predicts survival of non-Small cell lung cancer patients treated with chemoradiotherapy
Authors: Guan Xiaoxiang , Liao Zhongxin , Ma Hongxia , Qian Ji , Liu Zhensheng , Yuan Xianglin , Gomez Daniel , Komaki Ritsuko , Wang Li-E , Wei Qingyi 
Published: November 2011

Abstract

Background
The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in TNF-α and TNFRSF1B genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both TNF-α and TNFRSF1B and prognosis of NSCLC patients treated with chemoradiotherapy.

Methods
We genotyped five potentially functional polymorphisms of TNF-α and TNFRSF1B genes [TNF-α -308 G>A (rs1800629) and -1031 T>C (rs1799964); TNFRSF1B +676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).

Results
We found that the TNFRSF1B +676 GG genotype was associated with a significantly better OS of NSCLC (GG vs. TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG vs. GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the TNFRSF1B +676 GG was an independent prognosis predictor in this NSCLC cohort (GG vs. GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N2-3
vs. N0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T3-4
vs. T0-2: HR = 1.48, 95% CI = 1.08-2.03).

Conclusions
Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of TNFRSF1B +676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.
Comparative void-volume analysis of psychrophilic and mesophilic enzymes: Structural bioinformatics of psychrophilic enzymes reveals sources of core flexibility
Authors: Paredes Diana I , Watters Kyle , Pitman Derek J , Bystroff Christopher , Dordick Jonathan S 
Published: November 2011

Abstract

Background
Psychrophiles, cold-adapted organisms, have adapted to live at low temperatures by using a variety of mechanisms. Their enzymes are active at cold temperatures by being structurally more flexible than mesophilic enzymes. Even though, there are some indications of the possible structural mechanisms by which psychrophilic enzymes are catalytic active at cold temperatures, there is not a generalized structural property common to all psychrophilic enzymes.

Results
We examine twenty homologous enzyme pairs from psychrophiles and mesophiles to investigate flexibility as a key characteristic for cold adaptation. B-factors in protein X-ray structures are one way to measure flexibility. Comparing psychrophilic to mesophilic protein B-factors reveals that psychrophilic enzymes are more flexible in 5-turn and strand secondary structures. Enzyme cavities, identified using CASTp at various probe sizes, indicate that psychrophilic enzymes have larger average cavity sizes at probe radii of 1.4-1.5 Å, sufficient for water molecules. Furthermore, amino acid side chains lining these cavities show an increased frequency of acidic groups in psychrophilic enzymes.

Conclusions
These findings suggest that embedded water molecules may play a significant role in cavity flexibility, and therefore, overall protein flexibility. Thus, our results point to the important role enzyme flexibility plays in adaptation to cold environments.
Impact of computerized physician order entry (CPOE) system on the outcome of critically ill adult patients: a before-after study
Authors: Al-Dorzi Hasan M , Tamim Hani M , Cherfan Antoine , Hassan Mohamad A , Taher Saadi , Arabi Yaseen M 
Published: November 2011

Abstract

Background
Computerized physician order entry (CPOE) systems are recommended to improve patient safety and outcomes. However, their effectiveness has been questioned. Our objective was to evaluate the impact of CPOE implementation on the outcome of critically ill patients.

Methods
This was an observational before-after study carried out in a 21-bed medical and surgical intensive care unit (ICU) of a tertiary care center. It included all patients admitted to the ICU in the 24 months pre- and 12 months post-CPOE (Misys®) implementation. Data were extracted from a prospectively collected ICU database and included: demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, admission diagnosis and comorbid conditions. Outcomes compared in different pre- and post-CPOE periods included: ICU and hospital mortality, duration of mechanical ventilation, and ICU and hospital length of stay. These outcomes were also compared in selected high risk subgroups of patients (age 12-17 years, traumatic brain injury, admission diagnosis of sepsis and admission APACHE II > 23). Multivariate analysis was used to adjust for imbalances in baseline characteristics and selected clinically relevant variables.

Results
There were 1638 and 898 patients admitted to the ICU in the specified pre- and post-CPOE periods, respectively (age = 52 ± 22 vs. 52 ± 21 years, p = 0.74; APACHE II = 24 ± 9 vs. 24 ± 10, p = 0.83). During these periods, there were no differences in ICU (adjusted odds ratio (aOR) 0.98, 95% confidence interval [CI] 0.7-1.3) and in hospital mortality (aOR 1.00, 95% CI 0.8-1.3). CPOE implementation was associated with similar duration of mechanical ventilation and of stay in the ICU and hospital. There was no increased mortality or stay in the high risk subgroups after CPOE implementation.

Conclusions
The implementation of CPOE in an adult medical surgical ICU resulted in no improvement in patient outcomes in the immediate phase and up to 12 months after implementation.
Primary hepatic carcinoid tumor
Authors: Gao Jinbo , Hu Zhijian , Wu Junwei , Bai Lishan , Chai Xinqun 
Published: November 2011

Abstract
Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.
FITC and Ru(phen)3
2+ co-doped silica particles as visualized ratiometric pH indicator
Authors: Xu Jianquan , Sun Lei , Li Jun , Liang Jinglun , Zhang Huimao , Yang Wensheng 
Published: November 2011

Abstract
The performance of fluorescein isothiocyanate (FITC) and tris(1, 10-phenanathroline) ruthenium ion (Ru(phen)3
2+) co-doped silica particles as pH indicator was evaluated. The emission intensity ratios of the pH sensitive dye (FITC) and the reference dye (Ru(phen)3
2+) in the particles were dependent on pH of the environment. The changes in emission intensity ratios of the two dyes under different pH could be measured under single excitation wavelength and readily visualized by naked eye under a 365-nm UV lamp. In particular, such FITC and Ru(phen)3
2+ co-doped silica particles were identified to show high sensitivity to pH around the pKa of FITC (6.4), making them be potential useful as visualized pH indicator for detection of intracellular pH micro-circumstance.
Salmonella Typhimurium-specific bacteriophage ΦSH19 and the origins of species specificity in the Vi01-like phage family
Authors: Hooton Steven PT , Timms Andrew R , Rowsell Joanna , Wilson Ray , Connerton Ian F 
Published: November 2011

Abstract

Background
Whole genome sequencing of bacteriophages suitable for biocontrol of pathogens in food products is a pre-requisite to any phage-based intervention procedure. Trials involving the biosanitization of Salmonella Typhimurium in the pig production environment identified one such candidate, ΦSH19.

Results
This phage was sequenced and analysis of its 157,785 bp circular dsDNA genome revealed a number of interesting features. ΦSH19 constitutes another member of the recently-proposed Myoviridae Vi01-like family of phages, containing S. Typhi-specific Vi01 and Shigella-specific SboM-AG3. At the nucleotide level ΦSH19 is highly similar to phage Vi01 (80-98% pairwise identity over the length of the genome), with the major differences lying in the region associated with host-range determination. Analyses of the proteins encoded within this region by ΦSH19 revealed a cluster of three putative tail spikes. Of the three tail spikes, two have protein domains associated with the pectate lyase family of proteins (Tsp2) and P22 tail spike family (Tsp3) with the prospect that these enable Salmonella O antigen degradation. Tail spike proteins of Vi01 and SboM-AG3 are predicted to contain conserved right-handed parallel β-helical structures but the internal protein domains are varied allowing different host specificities.

Conclusions
The addition or exchange of tail spike protein modules is a major contributor to host range determination in the Vi01-like phage family.
Pretreatment of microcrystalline cellulose in organic electrolyte solutions for enzymatic hydrolysis
Authors: Tian Xiao-fei , Fang Zhen , Jiang Dan , Sun Xi-yan 
Published: November 2011

Abstract

Background
Previous studies have shown that the crystalline structure of cellulose is negatively correlated with enzymatic digestibility, therefore, pretreatment is required to break down the highly ordered crystalline structure in cellulose, and to increase the porosity of its surface. In the present study, an organic electrolyte solution (OES) composed of an ionic liquid (1-allyl-3-methylimidazolium chloride ([AMIM]Cl)) and an organic solvent (dimethyl sulfoxide; DMSO) was prepared, and used to pretreat microcrystalline cellulose for subsequent enzymatic hydrolysis; to our knowledge, this is the first time that this method has been used.

Results
Microcrystalline cellulose (5 wt%) rapidly dispersed and then completely dissolved in an OES with a molar fraction of [AMIM]Cl per OES (χ [AMIM]Cl) of greater than or equal to 0.2 at 110°C within 10 minutes. The cellulose was regenerated from the OES by precipitation with hot water, and enzymatically hydrolyzed. As the χ [AMIM]Cl of the OES increased from 0.1 to 0.9, both the hydrolysis yield and initial hydrolysis rate of the regenerated cellulose also increased gradually. After treatment using OES with χ [AMIM]Cl of 0.7, the glucose yield (54.1%) was 7.2 times that of untreated cellulose. This promotion of hydrolysis yield was mainly due to the decrease in the degree of crystallinity (that is, the crystallinity index of cellulose I).

Conclusions
An OES of [AMIM]Cl and DMSO with χ [AMIM]Cl of 0.7 was chosen for cellulose pretreatment because it dissolved cellulose rapidly to achieve a high glucose yield (54.1%), which was only slightly lower than the value (59.6%) obtained using pure [AMIM]Cl. OES pretreatment is a cost-effective and environmentally friendly technique for hydrolysis, because it 1) uses the less expensive OES instead of pure ionic liquids, 2) shortens dissolution time, 3) requires lower energy for stirring and transporting, and 4) is recyclable.
Stem cells for cardiac regeneration and possible roles of the transforming growth factor-β superfamily
Authors: Kawaguchi Nanako 
Published: November 2011

AbstractHeart failure is a leading cause of death worldwide. Studies of stem cell biology are essential for developing efficient treatments. Recently, we established and characterized c-kit-positive cardiac stem cells from the adult rat heart. Using a MethoCult culture system with a methyl-cellulose-based medium, stem-like left-atrium-derived pluripotent cells could be regulated to differentiate into skeletal/cardiac myocytes or adipocytes with almost 100% purity. Microarray and pathway analyses of these cells showed that transforming growth factor-β1 (TGF-β1) and noggin were significantly involved in the differentiation switch. Furthermore, TGF-β1 may act as a regulator for this switch because it simultaneously inhibits adipogenesis and activates myogenesis in a dose-dependent manner. However, the effect of TGF-β varies with developmental stage, dosage, and timing of treatment. In the present review, the findings of recent studies, in particular the use of c-kit-positive cardiac stem cells, are discussed. The effects of the TGF-β superfamily on differentiation, especially on adipogenesis and/or myogenesis, have important implications for future regenerative medicine.
Implementation of standardization in clinical practice: not always an easy task
Authors: Panteghini Mauro 
Published: November 2011

Abstract
As soon as a new reference measurement system is adopted, clinical validation of correctly calibrated commercial methods should take place. Tracing back the calibration of routine assays to a reference system can actually modify the relation of analyte results to existing reference intervals and decision limits and this may invalidate some of the clinical decision-making criteria currently used. To maintain the accumulated clinical experience, the quantitative relationship to the previous calibration system should be established and, if necessary, the clinical decision-making criteria should be adjusted accordingly. The implementation of standardization should take place in a concerted action of laboratorians, manufacturers, external quality assessment scheme organizers and clinicians. Dedicated meetings with manufacturers should be organized to discuss the process of assay recalibration and studies should be performed to obtain convincing evidence that the standardization works, improving result comparability. Another important issue relates to the surveillance of the performance of standardized assays through the organization of appropriate analytical internal and external quality controls. Last but not least, uncertainty of measurement that fits for this purpose must be defined across the entire traceability chain, starting with the available reference materials, extending through the manufacturers and their processes for assignment of calibrator values and ultimately to the final result reported to clinicians by laboratories.
Pharmacokinetic interaction of intramammary ceftriaxone and oral polyherbal drug (Fibrosin®) in goats
Authors: Sar Tapas Kumar , Patra Pabitra Hriday , Dash Jeevan Ranjan , Mandal Tapan Kumar 
Published: November 2011

Abstract

Background: The aim of the present study was to determine pharmacokinetic interaction of ceftriaxone and polyherbal drug (Fibrosin®) in lactating goats following single dose intramammary administration of ceftriaxone with 1 h pre-single dose oral administration of Fibrosin®.

Methods: Pharmacokinetic interaction of ceftriaxone and Fibrosin® was evaluated in lactating goats following single dose intramammary administration of ceftriaxone at 50 mg/kg with 1 h pre-single dose oral administration of Fibrosin® (1.9 g). Estimation of ceftriaxone and its metabolite, ceftizoxime, was determined by high performance liquid chromatography.

Results: Fibrosin® treated goats showed a typical absorption-reabsorption phase of ceftriaxone in plasma following intramammary administration. Neither ceftriaxone nor ceftizoxime was detected in the plasma and urine of goats without Fibrosin® treatment, however, ceftriaxone persisted for 36 h and ceftizoxime was present from 48 h to 72 h in the plasma of Fibrosin® treated goats. Ceftizoxime was also available from 72 h to 360 h post-dosing in milk in the presence of Fibrosin® following intramammary administration of ceftriaxone suggesting the polyherbal drug played a major role in the penetration of ceftriaxone from milk to systemic circulation. Furthermore, the polyherbal drug increased the bioavailability of ceftizoxime in milk following the metabolism of ceftriaxone.

Conclusions: Polyherbal drug (Fibrosin®) plays a major role in the penetration of ceftriaxone from milk to systemic circulation and may be responsible for increased bioavailability of its metabolite in the mammary gland resulting in higher concentration and longer persistence of the drug in milk.
Variation and evolution of the ABC transporter genes ABCB1, ABCC1, ABCG2, ABCG5 and ABCG8: implication for pharmacogenetics and disease
Authors: Silverton Latoya , Dean Michael , Moitra Karobi 
Published: November 2011

Abstract
The ATP-binding cassette (ABC) transporter genes are ubiquitous in the genomes of all vertebrates. Some of these transporters play a key role in xenobiotic defense and are endowed with the capacity to efflux harmful toxic substances. A major role in the evolution of the vertebrate ABC genes is played by gene duplication. Multiple gene duplication and deletion events have been identified in ABC genes, resulting in either gene birth or gene death indicating that the process of gene evolution is still ongoing in this group of transporters. Additionally, polymorphisms in these genes are linked to variations in expression, function, drug disposition and drug response. Single nucleotide polymorphisms in the ABC genes may be considered as markers of individual risk for adverse drug reactions or susceptibility to complex diseases as they can uniquely influence the quality and quantity of gene product. As the ABC genes continue to evolve, globalization will yield additional migration and racial admixtures that will have far reaching implications for the pharmacogenetics of this unique family of transporters in the context of human health.
Huntingtin Aggregation Kinetics and Their Pathological Role in aDrosophilaHuntington’s Disease Model
Authors: Weiss Kurt R , Kimura Yoko , Lee Wyan-Ching Mimi , Littleton J Troy 
Published: November 2011

AbstractHuntington’s disease is a neurodegenerative disorder resulting from expansion of a polyglutamine tract in the Huntingtin protein. Mutant Huntingtin forms intracellular aggregates within neurons, although it is unclear whether aggregates or more soluble forms of the protein represent the pathogenic species. To examine the link between aggregation and neurodegeneration, we generated Drosophila melanogaster transgenic strains expressing fluorescently tagged human huntingtin encoding pathogenic (Q138) or nonpathogenic (Q15) proteins, allowing in vivo imaging of Huntingtin expression and aggregation in live animals. Neuronal expression of pathogenic Huntingtin leads to pharate adult lethality, accompanied by formation of large aggregates within the cytoplasm of neuronal cell bodies and neurites. Live imaging and Fluorescence Recovery After Photobleaching (FRAP) analysis of pathogenic Huntingtin demonstrated that new aggregates can form in neurons within 12 hr, while preexisting aggregates rapidly accumulate new Huntingtin protein within minutes. To examine the role of aggregates in pathology, we conducted haplo-insufficiency suppressor screens for Huntingtin-Q138 aggregation or Huntingtin-Q138–induced lethality, using deficiencies covering ∼80% of the Drosophila genome. We identified two classes of interacting suppressors in our screen: those that rescue viability while decreasing Huntingtin expression and aggregation and those that rescue viability without disrupting Huntingtin aggregation. The most robust suppressors reduced both soluble and aggregated Huntingtin levels, suggesting toxicity is likely to be associated with both forms of the mutant protein in Huntington’s disease.
A Conserved Transcriptional Regulator Governs Fungal Morphology in Widely Diverged Species
Authors: Cain Christopher W , Lohse Matthew B , Homann Oliver R , Sil Anita , Johnson Alexander D 
Published: November 2011

Abstract
Fungi exhibit a large variety of morphological forms. Here, we examine the functions of a deeply conserved regulator of morphology in three fungal species: Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae are transcriptional regulators that recognize the same DNA sequence. Previous work established that Wor1 regulates white–opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae is also a master regulator of a morphological transition, in this case pseudohyphal growth. Full-genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of the previously known regulators of pseudohyphal growth as well as those of many additional genes. Through a comparison of binding sites for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that the genes controlled by the orthologous regulators overlap only slightly between these two species despite the fact that the DNA binding specificity of the regulators has remained largely unchanged. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species.
Fine-Scale Estimation of Location of Birth from Genome-Wide Single-Nucleotide Polymorphism Data
Authors: Hoggart Clive J , O’Reilly Paul F , Kaakinen Marika , Zhang Weihua , Chambers John C , Kooner Jaspal S , Coin Lachlan J M , Jarvelin Marjo-Riitta 
Published: November 2011

AbstractSystematic nonrandom mating in populations results in genetic stratification and is predominantly caused by geographic separation, providing the opportunity to infer individuals’ birthplace from genetic data. Such inference has been demonstrated for individuals’ country of birth, but here we use data from the Northern Finland Birth Cohort 1966 (NFBC1966) to investigate the characteristics of genetic structure within a population and subsequently develop a method for inferring location to a finer scale. Principal component analysis (PCA) shows that while the first PCs are particularly informative for location, there is also location information in the higher-order PCs, but it cannot be captured by a linear model. We introduce a new method, pcLOCATE, which is able to exploit this information to improve the accuracy of location inference. pcLOCATE uses individuals’ PC values to estimate the probability of birth in each town and then averages over all towns to give an estimated longitude and latitude of birth using a fully Bayesian model. We apply pcLOCATE to the NFBC1966 data to estimate parental birthplace, testing with successively more PCs and finding the model with the top 23 PCs most accurate, with a median distance of 23 km between the estimated and the true location. pcLOCATE predicts the most recent residence of NFBC1966 individuals to a median distance of 47 km. We also apply pcLOCATE to Indian individuals from the London Life Sciences Prospective Population Study (LOLIPOP) data, and find that birthplace is predicated to a median distance of 54 km from the true location. A method with such accuracy is potentially valuable in population genetics and forensics.