bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Race and Racism in Nursing: Insights from Aboriginal Nurses
Authors: Vukic Adele , Jesty Charlotte , Mathews Sr. Veronica , Etowa Josephine
Published: June 2012

Purpose. Indigenous Peoples are underrepresented in the health professions. This paper examines indigenous identity and the quality and nature of nursing work-life. The knowledge generated should enhance strategies to increase representation of indigenous peoples in nursing to reduce health inequities. Design. Community-based participatory research employing Grounded Theory as the method was the design for this study. Theoretical sampling and constant comparison guided the data collection and analysis, and a number of validation strategies including member checks were employed to ensure rigor of the research process. Sample. Twenty-two Aboriginal nurses in Atlantic Canada. Findings. Six major themes emerged from the study: Cultural Context of Work-life, Becoming a Nurse, Navigating Nursing, Race Racism and Nursing, Socio-Political Context of Aboriginal Nursing, and Way Forward. Race and racism in nursing and related subthemes are the focus of this paper. Implications. The experiences of Aboriginal nurses as described in this paper illuminate the need to understand the interplay of race and racism in the health care system. Our paper concludes with Aboriginal nurses’ suggestions for systemic change at various levels.
Effect of Variation Aluminum Oxide Concentration on the Modified Novolac Stalk Composite
Authors: El-Meligy Magda G. , Nagieb Zenat A. , Isis K. B.
Published: June 2012

Strength properties and water repellency of cotton stalk fibers esterified with propionic anhydride that are used as reinforcing of novolac resin were greatly improved than untreated. Adding aluminum oxide to the prepared composite improved bending strength and enhanced water repellant. The alternating current conductivity and dielectric constant were greatly enhanced at different frequencies by adding aluminum oxide. The more percent of aluminum oxide, the more value of alternating current conductivity and lower value of dielectric constant were obtained at different frequencies. Infrared and X-ray diffraction as well as scanning electron microscope were studied.
Factors Contributing to Job Engagement in Ugandan Nurses and Midwives
Authors: Bakibinga Pauline , Forbech Vinje Hege , Mittelmark Maurice
Published: June 2012

Despite the difficult working conditions many nurses in Sub-Saharan Africa experience resulting in their migration or leaving the profession, there are nurses who thrive and stay engaged. Understanding what factors play a role in enhancing nurses' job engagement might help health care and training institutions develop interventions to enable nurses learn methods to help retain their job engagement. Research in Norway has produced a theory about how job engagement can be protected, called the Self-tuning Model of Self-Care, which was used to explore the phenomenon of job engagement in Ugandan nurses. In-depth interviews were conducted in 2010, with a purposive sample of 15 nurses and midwives. Qualitative content analysis of the data was conducted. Findings from Uganda show that the Self-Tuning Model can be used both as a framework for analysis and as a model of how nurses can promote their experience of job engagement. Nurses should be encouraged to practice habitual introspection and reflection about the satisfactions they derive from work, to enable them retain a high level of job engagement despite the adversities of nursing practice.
Synergistic Effect between Maternal Infection and Adolescent Cannabinoid Exposure on Serotonin 5HT1A Receptor Binding in the Hippocampus: Testing the “Two Hit” Hypothesis for the Development of Schizophrenia
Authors: Dalton Victoria S. , Verdurand Mathieu , Walker Adam , Hodgson Deborah M. , Zavitsanou Katerina
Published: June 2012

Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5HT1A receptor binding (5HT1AR) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14 days starting on postnatal day (PND) 35. Hippocampal and cortical 5HT1AR binding was quantified autoradiographically using [3H]8-OH-DPAT, in late adolescent (PND 55), young adult (PND 65) and adult (PND 90) rats. Descendants of poly I:C treated rats showed significant increases of 15–18% in 5HT1AR in the hippocampus (CA1) compared to controls at all developmental ages. Offspring of poly I:C treated rats exposed to HU210 during adolescence exhibited even greater elevations in 5HT1AR (with increases of 44, 29, and 39% at PNDs 55, 65, and 90). No effect of HU210 alone was observed. Our results suggest a synergistic effect of prenatal infection and adolescent cannabinoid exposure on the integrity of the serotoninergic system in the hippocampus that may provide the neurochemical substrate for abnormal hippocampal-related functions relevant to schizophrenia.
The Separation Power of Nanotubes in Membranes: A Review
Authors: Van der Bruggen Bart
Published: June 2012

Research on mixed matrix membranes in which nanoparticles are used to enhance the membrane's performance in terms of flux, separation, and fouling resistance has boomed in the last years. This review probes on the specific features and benefits of one specific type of nanoparticles with a well-defined cylindrical structure, known as nanotubes. Nanotube structures for potential use in membranes are reviewed. These comprise mainly single-wall carbon nanotubes (SWCNTs) and multiwall carbon nanotubes (MWCNTs), but also other structures and materials, which are less studied for membrane applications, can be used. Important issues related to polymer-nanotube interactions such as dispersion and alignment are outlined, and a categorization is made of the resultant membranes. Applications are reviewed in four different areas, that is, gas separation, water filtration, drug delivery, and fuel cells.
Interpretation of Falling-Head Tests in Presence of Random Measurement Error
Authors: Chiasson Paul
Published: June 2012

Field data are tainted by random and several types of systematic errors. The paper presents a review of interpretation methods for falling-head tests. The statistical robustness of each method is then evaluated through the use of synthetic data tainted by random error. Six synthetic datasets are used for this evaluation. Each dataset has an average relative error for water elevationZ, respectively, of 0.04%, 0.11%, 0.22%, 0.34%, 0.45%, and 0.90% (absolute errors on elevation are, respectively, 0.10, 0.25, 0.50, 1.0, and 2.0 mm for a range of water elevation change of 150 mm during test). Each synthetic dataset is composed of 40 synthetic tests (each test consisting of 18 data couples of synthetic falling-head measurements). Results show that theZ-tmethod is the most accurate and precise, followed by the Hvorslev method when a correction is applied and the velocity method when appropriately interpreted. Advice on how to interpret falling-head tests tainted by random error concludes the study.
Formulation and In Vitro Evaluation of Ufasomes for Dermal Administration of Methotrexate
Authors: Sharma Arvind , Arora Sandeep
Published: June 2012

Dermal drug delivery system that is required to localizes methotrexate (MTX) in the synovial joint is needed to treat inflammation in rheumatoid arthritis (RA). The present investigation aims at exploring the potential of fatty acid vesicles for the topical delivery of methotrexate. Vesicles were prepared by film hydration method using oleic acid as a fatty acid principal component. Developed vesicles were characterized for size, size distribution, shape, in vitro release, pH dependent, and storage stability. Interaction between MTX and oleic acid was investigated using differential scanning calorimetry. The MTX amount permeated through rat skin was three- to fourfold higher using oleic acid compared to those from plain drug solution or carbopol gel. At the end of the skin permeation assay using ufasomes, up to 50% of the administered dose was found in the skin. These results suggest that methotrexate encapsulated in oleic acid vesicles may be of value for the topical administration of MTX in the treatment of psoriasis.
Ultra-Performance Liquid Chromatography for the Multicomponent Analysis of a Ternary Mixture Containing Thiamine, Pyridoxine, and Lidocaine in Ampules
Authors: Dinç Erdal , Baleanu Dumitru
Published: June 2012

New chemometric approaches based on the application of partial least squares (PLS) and principal component regression (PCR) algorithms with fractional wavelet transform (FWT) and continuous wavelet transform (CWT) are proposed for the spectrophotometric multicomponent determination of thiamine hydrochloride (B1), pyridoxine hydrochloride (B6), and lidocaine hydrochloride (LID) in ampules without any separation step. In this study PLS and PCR techniques were applied to the raw spectral data, FWT-coefficients, and FWT-CWT-coefficients. These calibration models were labeled as Raw-PLS and Raw-PCR, FWT-PLS and FWT-PCR, and FWT-CWT-PLS and FWT-CWT-PCR, respectively. A new ultra-performance liquid chromatographic (UPLC) method was developed for the comparison of the results obtained by applying the chemometric calibration methods. Chromatographic separation and determination of B1, B6, and LID in ampules were performed on an Acquity UPLC® BEH C18 column (50 × 2.1 mm id, 1.7 μm particle size) using gradient elution with a mobile phase consisting of methanol and 0.01 M HCl at a constant flow rate of 0.6 mL/min. These combined chemometric calibrations and UPLC were validated by analyzing various ternary mixtures, B1, B6, and LID. The proposed chemometric approaches (signal processing-multivariate calibrations) and UPLC method were applied to the quantitative multicomponent analysis of marketed ampules containing the vitamins B1 and B6 with LID.
Determination of the Isoflavone Genistein in Soybeans by High-Performance Liquid Chromatography Following Cloud Point Extraction
Authors: Mirzaei Mohammad , Naeini Atieh Karimi , Behzadi Mansoureh
Published: June 2012

A simple and sensitive method has been developed for preconcentration and determination of genistein in soybeans. This method is based on cloud point extraction (CPE) of genistein from soybeans using ethylene glycol monoalkyl ether (Genapol X-080) as a nonionic surfactant. The concentration of extracted genistein was determined by HPLC with a UV detector. Optimum experimental conditions were established. With 5% Genapol X-080 (v/v), a liquid/solid ratio of 25:1 mL/g, and ultrasonic-assisted extraction at 40°C for 45 min, the extraction percentage of genistein reached its highest value. The preconcentration factor for genistein was about 16.5. The RSD for seven replicate measurements and the LOD were ±4.45% and 15.0 ng/mL, respectively. CPE is simple, inexpensive, and suitable for extraction of genistein from soybean. It uses environmentally friendly surfactants and offers a convenient alternative to more conventional extraction systems.
SDIX RapidChek™ Listeria F.A.S.T.™ Environmental Test System for the Detection of Listeria species on Environmental Surfaces
Authors: Muldoon Mark T , Allen Anne-Christine Olsson , Gonzales Vera , Sutzko Meredith , Lindpaintner Klaus
Published: June 2012

The SDIX RapidChekTMListeria F.A.S.T. test system was validated against the U. S. Department of Agriculture-Food Safety and Inspection Service (USDA-FSIS) cultural reference method for the detection of Listeria species on stainless steel, plastic, rubber, and painted concrete. The SDIX method uses a proprietary RapidChek Listeria enrichment media for a one-step, 24–40 h enrichment at 30°C, and detects Listeria on an immunochromatographic lateral flow device in 10 min. Different Listeria species were used to spike each of the environmental surfaces. Environmental surfaces were spiked at levels ranging from 50 to 400 CFU/surface (1 in.2 swabs for painted concrete, 4 in.2 for sponge). A total of 120 spiked samples were tested by the SDIX method at 24 and 40 h and the cultural reference method. Total confirmed positives were 49, 54, and 48 for the SDIX 24 h method, the SDIX 40 h method, and the USDA-FSIS cultural reference method, respectively. Nonspiked samples from all environmental surfaces were reported as negative for Listeria spp. by all methods. The overall Chi square was 0.017 (P = 0.104) and 0.611 (P = 0.566) after a 24 and 40 h enrichment, respectively, indicating that the test method was equivalent in performance to the reference method at both enrichment times. The SDIX method was evaluated for the detection of 50 Listeria and 35 non-Listeria bacterial strains. All 50 Listeria strains were detected by the method (100% sensitivity). Five out of 35 non-Listeria species gave light test signals when grown in nonselective broth culture and tested undiluted. However, when grown in the RapidChek Listeria F.A.S.T. proprietary media, only one bacterial strain (Staphylococcus aureus) was detected, giving a very low test signal (97% specificity). The method was shown to be robust toward several alterations in testing and storage conditions.
RAZOR® EX Anthrax Air Detection System
Authors: Spaulding Usha K , Christensen Clarissa J , Crisp Robert J , Vaughn Michael B , Trauscht Robert C , Gardner Jordan R , Thatcher Stephanie A , Clemens Kristine M , Teng David H , Bird Abigail , Ota Irene M , Hadfield Ted , Ryan Valorie , brUnelle sharon l
Published: June 2012

The RAZOR® EX Anthrax Air Detection System, developed by Idaho Technology, Inc. (ITI), is a qualitative method for the detection of Bacillus anthracis spores collected by air collection devices. This system comprises a DNA extraction kit, a freeze-dried PCR reagent pouch, and the RAZOR EX real-time PCR instrument. Each pouch contains three assays, which distinguish potentially virulent B. anthracis from avirulent B. anthracis and other Bacillus species. These assays target the pXO1 and pXO2 plasmids and chromosomal DNA. When all targets are detected, the instrument makes an “anthrax detected” call, meaning that virulence genes of the anthrax bacillus are present. This report describes results from AOAC Method Developer (MD) and Independent Laboratory Validation (ILV) studies, which include matrix, inclusivity/exclusivity, environmental interference, upper and lower LOD of DNA, robustness, product consistency and stability, and instrument variation testing. In the MD studies, the system met the acceptance criteria for sensitivity and specificity, and the performance was consistent, stable, and robust for all components of the system. For the matrix study, the acceptance criteria of 95/96 expected calls was met for three of four matrixes, clean dry filters being the exception. Ninety-four of the 96 clean dry filter samples tested gave the expected calls. The nucleic acid limit of detection was 5-fold lower than AOAC's acceptable minimum detection limit. The system demonstrated no tendency for false positives when tested with Bacillus cereus. Environmental substances did not inhibit accurate detection of B. anthracis. The ILV studies yielded similar results for the matrix and inclusivity/exclusivity studies. The ILV environmental interference study included environmental substances and environmental organisms. Subsoil at a high concentration was found to negatively interfere with the pXO1 reaction. No interference was observed from the environmental organisms. The nucleic acid LOD, however, was 10 times higher (1 pg/reaction, equivalent to about 200 spores) than that found in the MD study. These results indicate that the RAZOR System is a sensitive and specific system that accurately identifies B. anthracis in aerosol matrixes and in the presence of interfering substances, and that the method can be performed by an independent laboratory and achieve similar results.
Application of Inductively Coupled Plasma/Mass Spectrometry for the Measurement of Chromium, Selenium, and Molybdenum in Infant Formula and Adult Nutritional Products: First Action 2011.19
Authors: Pacquette Lawrence H , Szabo Andre , Thompson Joseph J , Baugh Steve
Published: June 2012

An inductively coupled plasma/MS method was developed for the simultaneous determination of Cr, Se, and Mo in infant formula and other nutritional products. All samples were digested using a closed vessel microwave oven system, together with Ni and Te internal standards. The practical quantitation limits for Cr, Se, and Mo were 0.4, 0.2, and 0.4 ng/mL, respectively; dilution factors were 250 for powders and 50 for liquids. The Cr, Se, and Mo concentrations in 10 nutritional products were within specification limits; within-day and day-to-day (6 independent days) precision values were <5% RSD. For two control samples, the observed precision was ≤2% RSD over 10 independent days. Cr, Se, and Mo results were within the certified limits in three National Institute of Standards and Technology standard reference materials. The average sample spike recoveries for 10 nutritional products ranged from 93 to 107%. Robustness studies showed a minimal effect from concomitant easily ionized element concentrations. However, the choice of internal standard and matrix-matching carbon content were critical to obtaining accurate Se results. All indications are that this method would be a suitable candidate as a global reference method for the determination of these trace elements in infant formula, adult nutritionals, and other nutritional products.
Feature Selection Methods in QSAR Studies
Authors: Goodarzi Mohammad , Dejaegher Bieke , Heyden Yvan Vander
Published: June 2012

A quantitative structure-activity relationship (QSAR) relates quantitative chemical structure attributes (molecular descriptors) to a biological activity. QSAR studies have now become attractive in drug discovery and development because their application can save substantial time and human resources. Several parameters are important in the prediction ability of a QSAR model. On the one hand, different statistical methods may be applied to check the linear or nonlinear behavior of a data set. On the other hand, feature selection techniques are applied to decrease the model complexity, to decrease the overfitting/overtraining risk, and to select the most important descriptors from the often more than 1000 calculated. The selected descriptors are then linked to a biological activity of the corresponding compound by means of a mathematical model. Different modeling techniques can be applied, some of which explicitly require a feature selection. A QSAR model can be useful in the design of new compounds with improved potency in the class under study. Only molecules with a predicted interesting activity will be synthesized. In the feature selection problem, a learning algorithm is faced with the problem of selecting a relevant subset of features upon which to focus attention, while ignoring the rest. Up to now, many feature selection techniques, such as genetic algorithms, forward selection, backward elimination, stepwise regression, and simulated annealing have been used extensively. Swarm intelligence optimizations, such as ant colony optimization and partial swarm optimization, which are feature selection techniques usually simulated based on animal and insect life behavior to find the shortest path between a food source and their nests, recently are also involved in QSAR studies. This review paper provides an overview of different feature selection techniques applied in QSAR modeling.
Chemometric Processing of Pharmaceutical Essential Oil Fingerprints—Comparison of GC, HPLC, TLC, IR Spectroscopy, and Differential Scanning Calorimetry
Authors: Pietraś Rafał , Skibiński Robert , Trębacz Hanna , Gumieniczek Anna
Published: June 2012

Fifteen essential oils of pharmaceutical grade were fingerprinted by five techniques: TLC, GC, HPLC, attenuated total reflectance FTIR spectroscopy, and differential scanning calorimetry (DSC). Denoising and baseline removal was found to be a crucial step for correct comparative analysis. Standardization of the signal was not necessary in the presented case; however, it should be considered and checked in each case. Due to small variance explained by first two principal components (below 50%) and outlying observations, the main analysis was performed by Euclidean dendrograms. It was found that almost all techniques besides DSC find real chemical similarities; however, DSC can be used as an additional tool. The similarities among the five techniques were also compared and discussed.
Effect of lifestyle activities on alzheimer disease biomarkers and cognition
Authors: Vemuri Prashanthi , Lesnick Timothy G. , Przybelski Scott A. , Knopman David S. , Roberts Rosebud O. , Lowe Val J. , Kantarci Kejal , Senjem Mathew L. , Gunter Jeffrey L. , Boeve Bradley F. , Petersen Ronald C. , Jack Clifford R.
Published: June 2012

Objective:

A study was undertaken to investigate the association of intellectual and physical activity with biomarkers of Alzheimer disease (AD) pathophysiology and cognition in a nondemented elderly population. The biomarkers evaluated were brain Aβ load via Pittsburgh compound B (PiB)‐positron emission tomography (PET), neuronal dysfunction via 18F‐fluorodeoxyglucose (FDG)‐PET, and neurodegeneration via structural magnetic resonance imaging (MRI).

Methods:

We studied 515 nondemented (428 cognitively normal and 87 mild cognitive impairment) participants in the population‐based Mayo Clinic Study of Aging who completed a 3T MRI, PET scans, and APOE genotype, and had lifestyle activity measures and cognition data available. The imaging measures computed were global PiB‐PET uptake, and global FDG‐PET and MRI based hippocampal volume. We consolidated activity variables into lifetime intellectual, current intellectual, and current physical activities. We used a global cognitive z score as a measure of cognition. We applied 2 independent methods—partial correlation analysis adjusted for age and gender and path analysis using structural equations—to evaluate the associations between lifestyle activities, imaging biomarkers, and global cognition.

Results:

None of the lifestyle variables were correlated with the biomarkers, and the path associations between lifestyle variables and biomarkers were not significant (p > 0.05). Conversely, all the biomarkers were correlated with global cognitive z score (p < 0.05), and the path associations between (lifetime and current) intellectual activities and global z score were significant (p < 0.01).

Interpretation:

Intellectual and physical activity lifestyle factors were not associated with AD biomarkers, but intellectual lifestyle factors explained variability in the cognitive performance in this nondemented population. This study provides evidence that lifestyle activities may delay the onset of dementia but do not significantly influence the expression of AD pathophysiology. ANN NEUROL 2012;72:730–738
Power and Sample Size Calculations for SNP Association Studies With Censored Time‐to‐Event Outcomes
Authors: Owzar Kouros , Li Zhiguo , Cox Nancy , Jung Sin-Ho
Published: June 2012

For many clinical studies in cancer, germline DNA is prospectively collected for the purpose of discovering or validating single‐nucleotide polymorphisms (SNPs) associated with clinical outcomes. The primary clinical endpoint for many of these studies are time‐to‐event outcomes such as time of death or disease progression which are subject to censoring mechanisms. The Cox score test can be readily employed to test the association between a SNP and the outcome of interest. In addition to the effect and sample size, and censoring distribution, the power of the test will depend on the underlying genetic risk model and the distribution of the risk allele. We propose a rigorous account for power and sample size calculations under a variety of genetic risk models without resorting to the commonly used contiguous alternative assumption. Practical advice along with an open‐source software package to design SNP association studies with survival outcomes are provided.
Background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma
Authors: Cai Xiong , Zhai Jian , Kaplan David E. , Zhang Yijun , Zhou Lining , Chen Xutao , Qian Guangyang , Zhao Qiudong , Li Yonghai , Gao Lu , Cong Wenming , Zhu Minghua , Yan Zhenlin , Shi Lehua , Wu Dong , Wei Lixin , Shen Feng , Wu Mengchao
Published: June 2012

Hepatic progenitor cells (HPC) play important roles in both liver regeneration and carcinogenesis. Combined hepatocellular-cholangiocarcinoma (CHC), a malignant primary liver tumor with poor prognosis, is thought to be of HPC origin. However, the prognostic significance of this etiology is not well defined. Therefore, we retrospectively investigated the relationship of HPC-related pathological features and long-term outcome in patients with CHC in our department. In a cohort of 80 patients identified between 1997 and 2003, including 70 patients who underwent resection with curative intent, overall survival (OS) and disease-free survival (DFS) were correlated with the proliferative activity of nontumor ductular reaction (DR) and the expression levels of HPC and biliary markers including α-fetoprotein (AFP), keratin 7 (K7), keratin 19 (K19), oval cell (OV)-6, epithelial cell adhesion molecule (EpCAM), and c-Kit in both tumor and nontumor liver. We found that nontumor ductular reactions (DRs), specifically the proliferating cell nuclear antigen (PCNA) labeling index of the ductular reaction (PI-DR), a surrogate for transit-amplifying compartments, was an independent prognostic factor for both OS and DFS. By contrast, intratumoral expression of only one marker, absence of AFP, was associated with OS. PI-DR was also independently associated with synchronous “multicentric occurrence” in hepatocellular carcinoma components, a feature of CHC that may predispose to metachronous multifocal tumorigenesis.

Conclusion:

Proliferative ductular reaction related to HPC activation is associated with recurrence of CHC. Background HPC activation is strongly associated with multifocal occurrence and related tumor recurrence, highlighting the critical role of background liver disease, a “field effect,” in the recurrence of CHC.
Assessment of environmental flow requirements
Authors: Jain Sharad K.
Published: June 2012

Flow is considered to be the master variable for a river because the fluvial processes and health of its ecosystem critically depend upon flow. Increasing water withdrawals from many rivers of the world are leading to severe degradation in river ecosystems. Water is allocated for environmental needs so that a river can perform its natural functions. This article discusses the concept of environmental flow, methods to assess it, and issues in implementation. Copyright © 2012 John Wiley & Sons, Ltd.
Germline variants of base excision repair genes and breast cancer: A polymorphism in DNA polymerase gamma modifies gene expression and breast cancer risk
Authors: Popanda Odilia , Seibold Petra , Nikolov Ivaylo , Oakes Christopher C. , Burwinkel Barbara , Hausmann Sebastian , Flesch‐Janys Dieter , Plass Christoph , Chang‐Claude Jenny , Schmezer Peter
Published: June 2012

Base excision repair (BER) removes DNA damage induced by endogenous reactive oxygen species or ionizing radiation, important breast cancer risk factors. Genetic variation associated with impaired BER might thus increase breast cancer risk. Therefore, we assessed risk associations of 123 common single nucleotide polymorphisms (SNPs) in 19 BER genes in 1,639 postmenopausal breast cancer cases and 1,967 controls from the German population‐based case‐control study MARIE. SNPs were tagging SNPs representing genetic variation across the gene together with potentially functional SNPs. Risk associations were assessed using conditional logistic regression, adjusted for potential breast cancer risk factors. Significant associations between polymorphisms and breast cancer risk were found for one SNP in PARP2 and three SNPs in the mitochondrial DNA polymerase gamma, POLG. A SNP in the promoter region of POLG (rs2856268, A>G) showed a protective effect for homozygous GG carriers (odds ratio 0.81, 95% confidence intervals 0.65–1.00). Joint analysis of an enlarged sample set and haplotype analysis supported the results for POLG. Quantification of POLG mRNA expression in lymphocytes of 148 breast cancer patients revealed higher mRNA levels for rs2856268 GG carriers (p value = 0.038). A luciferase promoter assay showed significant differences between constructs harboring the respective alleles. Taken together, our results suggest that genetic variation in the POLG promoter region affects DNA polymerase gamma levels in mitochondria. This could contribute to the reported increase in mitochondrial mutation frequency resulting in dysfunction and altered breast cancer risk. Risk effects and the functional impact of the POLG promoter variant require further confirmation.
Overcoming evasive resistance from vascular endothelial growth factor a inhibition in sarcomas by genetic or pharmacologic targeting of hypoxia‐inducible factor 1α
Authors: Kim Yeo‐Jung , Lee Hae‐June , Kim Tae‐Min , Eisinger‐Mathason T.S. Karin , Zhang Alexia Y. , Schmidt Benjamin , Karl Daniel L. , Nakazawa Michael S. , Park Peter J. , Simon M. Celeste , Yoon Sam S.
Published: June 2012

Increased levels of hypoxia and hypoxia‐inducible factor 1α (HIF‐1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged antiangiogenic therapy of tumors not only delays tumor growth but may also increase hypoxia and HIF‐1α activity. In our recent clinical trial, treatment with the vascular endothelial growth factor A (VEGF‐A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene Set Enrichment Analysis of microarrays from pretreatment biopsies found that the Gene Ontology category “Response to hypoxia” was upregulated in poor responders and that the hierarchical clustering based on 140 hypoxia‐responsive genes reliably separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF‐1α binding to DNA at low metronomic doses. In four sarcoma cell lines, HIF‐1α shRNA or Dox at low concentrations blocked HIF‐1α induction of VEGF‐A by 84–97% and carbonic anhydrase 9 by 83–93%. HT1080 sarcoma xenografts had increased hypoxia and/or HIF‐1α activity with increasing tumor size and with anti‐VEGF receptor antibody (DC101) treatment. Combining DC101 with HIF‐1α shRNA or metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, at least in part via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF‐1α target genes that may promote resistance to antiangiogenic and other therapies. HIF‐1α inhibition blocks this evasive resistance and augments destruction of the tumor vasculature.
Tumor‐associated autoantibody signature for the early detection of gastric cancer
Authors: Zayakin Pawel , Ancāns Guntis , Siliņa Karīna , Meistere Irēna , Kalniņa Zane , Andrejeva Diāna , Endzeliņš Edgars , Ivanova Lāsma , Pismennaja Angelina , Ruskule Agnese , Doniņa Simona , Wex Thomas , Malfertheiner Peter , Leja Mārcis , Linē Aija
Published: June 2012

Autoantibodies against tumor‐associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display‐based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage–antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero‐positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150‐feature microarray was tested with sera from 100 patients with GC and 100 cancer‐free controls, and then the top‐ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45‐autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.
Ikaros is a critical target during simultaneous exposure to X‐rays and N‐ethyl‐N‐nitrosourea in mouse T‐cell lymphomagenesis
Authors: Hirano Shinobu , Kakinuma Shizuko , Amasaki Yoshiko , Nishimura Mayumi , Imaoka Tatsuhiko , Fujimoto Shinji , Hino Okio , Shimada Yoshiya
Published: June 2012

Cancer risk associated with radiation exposure is considered the result of concurrent exposure to other natural and manmade carcinogens. Available data on the molecular characteristics of cancer after simultaneous exposure to radiation and chemicals are insufficient. In our study, we used a mouse thymic lymphoma (TL) model that was synergistically induced by simultaneous exposure to X‐rays and N‐ethyl‐N‐nitrosourea (ENU) at subcarcinogenic doses and analyzed the mutation frequency and spectrum of the TL‐associated genes Ikaros, Notch1, p53 and Kras. We found that the point mutation frequency in Ikaros was significantly increased to 47% for simultaneous exposure compared to 13 and 0% for X‐ray and ENU exposure alone, respectively. These mutations were mostly G:C > A:T at non‐CpG sites and T:A > C:G, both of which are characteristic of ENU mutagenesis. About half of the point mutations were accompanied by loss of heterozygosity (LOH), typical of X‐irradiation. The remaining half did not include LOH, which suggests that they were dominant‐negative mutations. In Notch1, the frequency of abnormalities was high (>58%) regardless of the treatment, suggesting that Notch1 aberration may be important for T‐cell lymphomagenesis. The p53 and Kras mutation frequencies were low for all treatments (<23%). Importantly, the frequency of TLs containing mutations in multiple genes, especially both Ikaros and Notch1, increased after simultaneous exposure. Thus, after simultaneous exposure, Ikaros is a critical target and is inactivated by ENU‐induced point mutations and/or X‐ray‐induced LOH in T‐cell lymphomagenesis. Furthermore, concomitant alterations of multiple tumor‐associated genes may contribute to enhanced lymphomagenesis after simultaneous exposure.
Mini-incision right hepatic lobectomy with or without laparoscopic assistance for living donor hepatectomy
Authors: Nagai Shunji , Brown Lloyd , Yoshida Atsushi , Kim Dean , Kazimi Marwan , Abouljoud Marwan S.
Published: June 2012

Minimally invasive procedures are considered to be safe and effective approaches to the management of surgical liver disease. However, this indication remains controversial for living donor hepatectomy. Between 2000 and 2011, living donor right hepatectomy (LDRH) was performed 58 times. Standard right hepatectomy was performed in 30 patients via a subcostal incision with a midline extension. Minimally invasive procedures began to be used for LDRH in 2008. A hybrid technique (hand-assisted laparoscopic liver mobilization and minilaparotomy for parenchymal dissection) was developed and used in 19 patients. In 2010, an upper midline incision (10 cm) without laparoscopic assistance for LDRH was innovated, and this technique was used in 9 patients. The perioperative factors were compared, and the indications for minimally invasive LDRH were investigated. The operative blood loss was significantly less for the patients undergoing a minimally invasive procedure versus the patients undergoing the standard procedure (212 versus 316 mL, P = 0.001), and the operative times were comparable. The length of the hospital stay was significantly shorter for the minimally invasive technique group (5.9 versus 7.8 days, P < 0.001). The complication rates were 23% and 25% for the standard technique and minimally invasive technique groups, respectively (P = 0.88). Patients undergoing minilaparotomy LDRH had a body mass index (24.0 kg/m2) similar to that of the hybrid technique patients (25.8 kg/m2, P = 0.36), but the graft size was smaller (780 versus 948 mL, P = 0.22). In conclusion, minimally invasive LDRH can be performed without safety being impaired. LDRH with a 10-cm upper midline incision and without laparoscopic assistance may be appropriate for donors with a smaller body mass. Laparoscopic assistance can be added as needed for larger donors. This type of LDRH with a 10-cm incision is innovative and is recommended for experienced centers. Liver Transpl 18:1188–1197, 2012. © 2012 AASLD.
Retinol binding protein 4 and retinol in steatotic and nonsteatotic rat livers in the setting of partial hepatectomy under ischemia/reperfusion
Authors: Elias-Miró Maria , Massip-Salcedo Marta , Raila Jens , Schweigert Florian , Mendes-Braz Mariana , Ramalho Fernando , Jiménez-Castro Mónica B. , Casillas-Ramírez Araní , Bermudo Raquel , Rimola Antoni , Rodes Juan , Peralta Carmen
Published: June 2012

Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver. Liver Transpl 18:1198–1208, 2012. © 2012 AASLD.
Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: A meta-analysis
Authors: Liang Wenhua , Wu Linwei , Ling Xiaoting , Schroder Paul M. , Ju Weiqiang , Wang Dongping , Shang Yushu , Kong Yuan , Guo Zhiyong , He Xiaoshun
Published: June 2012

Because of the severe organ shortage, living donor liver transplantation (LDLT) offers a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatocellular carcinoma (HCC). However, the higher recurrence rate of HCC after LDLT and the indication criteria remain controversial. By conducting a quantitative meta-analysis, we sought to compare the survival outcomes and recurrence rates with LDLT and DDLT for patients with HCC. Comparative studies of LDLT and DDLT for HCC, which were identified by a comprehensive literature search, were included in this study. The evaluated outcomes included patient survival, recurrence-free survival (RFS), and recurrence rates at defined time points. Seven studies with a total of 1310 participants were included in this study. For LDLT and DDLT recipients, we found comparable patient survival rates [1 year, odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.62-1.73; 3 years, OR = 1.07, 95% CI = 0.77-1.48; and 5 years, OR = 0.64, 95% CI = 0.33-1.24] and RFS rates (1 year, OR = 0.86, 95% CI = 0.54-1.38; 3 years, OR = 1.04, 95% CI = 0.69-1.58; and 5 years, OR = 1.11, 95% CI = 0.70-1.77). Moreover, we found no significant differences in the 1-, 3-, or 5-year recurrence rates between LDLT and DDLT recipients (1 year, OR = 1.55, 95% CI = 0.36-6.58; 3 years, OR = 2.57, 95% CI = 0.53-12.41; and 5 years, OR = 1.21, 95% CI = 0.44-3.32). A subgroup analysis revealed similar outcomes for patients with HCC meeting the Milan criteria. These findings demonstrate that for HCC patients (especially those within the Milan criteria), LDLT represents an acceptable option that does not compromise patient survival or increase HCC recurrence in comparison with DDLT. Liver Transpl 18:1226–1236, 2012. © 2012 AASLD.
Three‐dimensional finite elements with embedded strong discontinuities to model material failure in the infinitesimal range
Authors: Armero F. , Kim J.
Published: June 2012

This paper presents new three‐dimensional finite elements with embedded strong discontinuities in the small strain infinitesimal range. The goal is to model localized surfaces of failure in solids, such as cracks at fracture, through enhancements of the finite elements that capture the propagating discontinuities of the displacement field in the element interiors. In this way, such surfaces of discontinuity can be sharply resolved in general meshes not necessarily related to the detailed geometry of the surface, unknown a priori. An important issue is also the consideration of general finite element formulations in the developments (e.g., basic displacement‐based, mixed or enhanced assumed strain finite element formulations), as needed to optimally resolve the continuum problem in the bulk. The actual modeling of the discontinuity effects, including the incorporation of the cohesive law defining the discontinuity constitutive response, is carried out at the element level with the proper enhancement of the discrete strain field of the element. The added elemental degrees of freedom approximate the displacement jumps associated with the discontinuity and are defined independently from element to element, thus allowing their static condensation at the element level without affecting the global mechanical problem in terms of the number and topology of the global degrees of freedom. In fact, this global‐local structure of the finite element methods developed in this work arises naturally from a multi‐scale characterization of these localized solutions, with the discontinuities understood to appear in the small scales, thus leading directly to these computationally efficient numerical methods for their numerical resolution, easily incorporated to an existing finite element code. The focus in this paper is on the development of finite elements incorporating a linear interpolation of the displacement jumps in the general three‐dimensional setting. These interpolations are shown to be necessary for hexahedral elements to avoid the so‐called stress locking that occurs with simpler constant approximations of the jumps (namely, a spurious transfer of stresses across the discontinuity not allowing its full release and, hence, resulting in an overstiff or locked numerical solution). The design of the new finite elements is accomplished in this work by a direct identification of the separation modes to be incorporated in the discrete strain field of the element, rather than from an assumed discontinuous interpolation of the displacements, assuring with this approach their locking‐free response by design. An additional issue addressed in the paper is the geometric characterization and propagation of the discontinuity surfaces in the general three‐dimensional setting of interest here. The paper includes a series of numerical simulations illustrating and evaluating the properties of the new finite elements. Copyright © 2012 John Wiley & Sons, Ltd.
An XFEM‐based numerical strategy to model mechanical interactions between biological cells and a deformable substrate
Authors: Farsad Mehdi , Vernerey Franck J.
Published: June 2012

Contractile cells are known to constantly probe and respond to their mechanical environment through mechanosensing. Although the very mechanisms responsible for this behavior are still obscure, it is now clear that cells make full use of cross‐talks between mechanics, chemistry, and transport to organize their structure and generate forces. To investigate these processes, it is important to derive mathematical and numerical models that can accurately capture the interactions between cells and an underlying deformable substrate. The present paper therefore introduces a computational framework, based on the extended FEM (XFEM) and the level set method, to model the evolution of two‐dimensional (plane stress) cells lying on an elastic substrate whose properties can be varied. Cells are modeled with a continuum mixture approach previously developed by the authors to describe key phenomena of cell sensing, such as stress fiber formation, mechanosensitive contraction, and molecular transport whereas cell–substrate adhesion is formulated with a linear elastic cohesive model. From a numerical viewpoint, cell and substrate are discretized on a single, regular finite element mesh, whereas the potentially complex cell geometry is defined in terms of a level set function that is independent of discretization. Field discontinuities across the cell membrane are then naturally enforced using enriched shape functions traditionally used in the XFEM formulation. The resulting method provides a flexible platform that can handle complex cell geometries, can avoid expensive meshing techniques, and can potentially be extended to study cell growth and migration on an elastic substrate. In addition, the XFEM formalism facilitates the consideration of the cell's cortical elasticity, a feature that is known to be important during cell deformation. The proposed method is illustrated with a few biologically relevant examples of cell–substrate interactions. Generally, the method is able to capture some key phenomena observed in biological systems and displays numerical versatility and accuracy at a moderate computational cost.Copyright © 2012 John Wiley & Sons, Ltd.