bluuebunny/crossref_metadata_2025 huggingface dataset:
The interfascicular trigeminal nucleus: A precerebellar nucleus in the mouse defined by retrograde neuronal tracing and genetic fate mapping
Authors: Fu Yuhong , Tvrdik Petr , Makki Nadja , Machold Robert , Paxinos George , Watson Charles
Published: July 2012

We have found a previously unreported precerebellar nucleus located among the emerging fibers of the motor root of the trigeminal nerve in the mouse, which we have called the interfascicular trigeminal nucleus (IF5). This nucleus had previously been named the tensor tympani part of the motor trigeminal nucleus (5TT) in rodent brain atlases, because it was thought to be a subset of small motor neurons of the motor trigeminal nucleus innervating the tensor tympani muscle. However, following injection of retrograde tracer in the cerebellum, the labeled neurons in IF5 were found to be choline acetyltransferase (ChAT) negative, indicating that they are not motor neurons. The cells of IF5 are strongly labeled in mice from Wnt1Cre and Atoh1 CreER lineage fate mapping, in common with the major precerebellar nuclei that arise from the rhombic lip and that issue mossy fibers. Analysis of sections from mouse Hoxa3, Hoxb1, and Egr2 Cre labeled lineages shows that the neurons of IF5 arise from rhombomeres caudal to rhombomere 4, most likely from rhombomeres 6–8. We conclude that IF5 is a significant precerebellar nucleus in the mouse that shares developmental gene expression characteristics with mossy fiber precerebellar nuclei that arise from the caudal rhombic lip. J. Comp. Neurol. 521:697–708, 2013. © 2012 Wiley Periodicals, Inc.
Setting tolerances on color and texture for automotive coatings
Authors: Kirchner, E. J. J. , Ravi J.
Published: July 2012

In the automotive industry, color quality control is increasingly done by reflection measurements. We discuss how color tolerances are set in specifications to suppliers of add‐on parts and to paint suppliers. We mention several factors that often lead to unrealistically tight settings, and therefore to incorrect rejections and unnecessary high productions costs. We show that this is likely to occur when the dEab color difference equation is used, or when a strict criterion separating pass from fail is used instead of specifying a “grey area” where instrumental monitoring needs to be followed by visual assessments. Unrealistically, tight tolerances also result from halving tolerances in the supply‐customer chain in an attempt to compensate color variations due to uncontrolled application conditions. Tolerances should be widened further when a gap separates an add‐on part from the car body, making visual discrimination of color differences less critical. Other common situations where tolerances should be widened are the presence of visual texture in effect coatings, the lightness of metallic coatings becoming very high (L*> 100) and measurement geometries close to the gloss angle. Finally, we address the issue that instrumental color tolerances should not be tighter than what is allowed by instrumental reproducibility, repeatability, and inter‐instrument agreement. Accounting for these factors, we provide a set of reasonable values for tolerances on color and on visual texture parameters, based on our own practical experience. But realistic tolerance values depend very much on actual conditions, and should be agreed in tripartite discussions among automotive industry, suppliers of add‐on parts, and paint supplier. © 2012 Wiley Periodicals, Inc. Col Res Appl, 39, 88–98, 2014
Solvent‐Free Palladium‐Catalyzed Direct Arylation of Heteroaromatics with Aryl Bromides
Authors: Bensaid Souhila , Doucet Henri
Published: July 2012

Solvent is one of the major sources of waste in the course of catalyzed direct arylations. Some palladium‐catalyzed direct arylations of heteroaromatics can be advantageously performed without any solvent. In the presence of palladium catalysts (1 mol %) and potassium acetate as the base, the direct 5‐arylation of some thiazoles, thiophenes, furans, or pyrroles with aryl bromides as coupling partners proceeds highly regioselectively and in moderate to high yields. However, the use of these solvent‐free conditions is limited to electron‐deficient aryl bromides.
Canid hybridization: contemporary evolution in human‐modified landscapes
Authors: Stronen Astrid V. , Tessier Nathalie , Jolicoeur Hélène , Paquet Paul C. , Hénault Michel , Villemure Mario , Patterson Brent R. , Sallows Tim , Goulet Gloria , Lapointe François‐Joseph
Published: July 2012

Contemporary evolution through human‐induced hybridization occurs throughout the taxonomic range. Formerly allopatric species appear especially susceptible to hybridization. Consequently, hybridization is expected to be more common in regions with recent sympatry owing to human activity than in areas of historical range overlap. Coyotes (Canis latrans) and gray wolves (C. lupus) are historically sympatric in western North America. Following European settlement gray wolf range contracted, whereas coyote range expanded to include eastern North America. Furthermore, wolves with New World (NW) mitochondrialDNA(mtDNA) haplotypes now extend from Manitoba to Québec in Canada and hybridize with gray wolves and coyotes. Using mtDNAand 12 microsatellite markers, we evaluated levels of wolf‐coyote hybridization in regions where coyotes were present (the Canadian Prairies,n = 109 samples) and absent historically (Québec,n = 154). Wolves withNWmtDNAextended from central Saskatchewan (51°N, 69°W) to northeastern Québec (54°N, 108°W). On the Prairies, 6.3% of coyotes and 9.2% of wolves had genetic profiles suggesting wolf‐coyote hybridization. In contrast, 12.6% of coyotes and 37.4% of wolves in Québec had profiles indicating hybrid origin. Wolves withNWand Old World (C. lupus) mtDNAappear to form integrated populations in both regions. Our results suggest that hybridization is more frequent in historically allopatric populations. Range shifts, now expected across taxa following climate change and other human influence on the environment, might therefore promote contemporary evolution by hybridization.
SPANphos Ligands in Palladium‐Catalyzed Asymmetric Fluorination
Authors: Jacquet Olivier , Clément Nicolas D. , Blanco Carolina , Belmonte Marta Martinez , Benet‐Buchholz Jordi , van Leeuwen Piet W. N. M.
Published: July 2012

The synthesis of new enantiopure wide‐bite‐angle diphosphanes is described as well as their use in the palladium‐catalyzed asymmetric fluorination of α‐cyanoacetates. Enantiomeric excesses up to 93 % were obtained when Pd(OAc)2‐SPANphos was used as catalyst for the fluorination of ethyl 2‐cyano‐2‐phenylacetate with N‐fluorobenzenesulfonimide (NFSI).
Selective Detection of Nerve Agent Simulants by Using Triarylmethanol‐Based Chromogenic Chemodosimeters
Authors: Costero Ana M. , Parra Margarita , Gil Salvador , Gotor Raúl , Martínez‐Mañez Ramón , Sancenón Félix , Royo Santiago
Published: July 2012

A family of triarylcarbinols 1–11 has been synthesised, and the chromogenic behaviour of the members in the presence of nerve‐agent simulants diethylcyanophosphonate (DCNP) and diisopropylfluorophosphate (DFP) in acetonitrile and in buffered mixed water/acetonitrile solutions has been investigated. Hydrophobic polyethylene oxide films of these compounds have been prepared. Some of these triarylcarbinols act as OFF/ON chemodosimeters for the nerve agent simulants. The sensing mechanism includes phosphorylation of the hydroxyl group in the triarylcarbinol derivatives, followed by a dephosphatation reaction induced by the electron‐donor groups present in the structure. The existence of additional tert‐butyldimethylsilyl ether groups in compounds 2 and 3 permits these reagents to act as double probes by allowing selective signalling of DFP. The reactivity between 1 and 4–6 with DFP and DCNP in acetonitrile or water/acetonitrile solutions under pseudo first‐order kinetic conditions was studied to determine rate constants (k) and the half‐life times (t1/2) for the corresponding reactions. Films containing compound 2 were used to detect simulants both in solution and in the vapour phase. Finally, a logic device was designed that incorporated compounds 2, 14, and 15 that allowed detection of DFP (a Sarin and Soman simulant) and DCNP (a Tabun simulant), even in the presence of possible interferents such as acids.
The Δ2,2′‐Bi(2H‐1,4‐benzothiazine) Structural Motif of Red Hair Pigments Revisited: Photochromism and Acidichromism in a Unique Four‐State System
Authors: Leone Loredana , Crescenzi Orlando , Napolitano Alessandra , Barone Vincenzo , d'Ischia Marco
Published: July 2012

Complete spectral and computational characterization of Δ2,2′‐bi(2H‐1,4‐benzothiazine) (BBTZ) demonstrated that the structures of the stable yellow form and the photogenerated red form were assigned incorrectly and should be revised to the cis (Z) and trans (E) isomers, respectively. A blue elusive dication generated upon further protonation of the violet cationic form was also identified by UV spectroscopy and DFT calculations. On the basis of these data, BBTZ can be appreciated as a robust four‐state system for various applications.
Effects of griseofulvin on in vitro porcine oocyte maturation and embryo development
Authors: Miao Yi‐Liang , Zhang Xia , Zhao Jian‐Guo , Spate Lee , Zhao Ming‐Tao , Murphy Clifton N. , Prather Randall S. , Sun Qing‐Yuan , Schatten Heide
Published: July 2012

Griseofulvin is an orally administered antifungal drug that affects microtubule formation in vitro and interferes with microtubule dynamics in vivo as clearly shown for mitotic cells in several cell systems. This article reports the effects of griseofulvin on in vitro maturation of porcine oocytes and subsequent effects on embryo development. Our results revealed a concentration‐dependent effect on meiotic spindles with 20–40 μM griseofulvin affecting oocyte maturation, and 40 μM affecting fertilization and embryo development. These concentrations of griseofulvin did not affect mitochondrial and cortical granule distribution that also depend on microtubule and cytoskeletal functions during oocyte maturation. Specific effects on the meiotic spindle included spindle disorganization and aberrant chromosome separation displayed as prominent chromosome clusters in oocytes treated with 40 μM griseofulvin. These results strongly suggested that griseofulvin affected porcine oocyte in vitro maturation and following embryo development by disturbing microtubule dynamics. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
Thermal stabilities and flame retardancies of phloroglucinol‐based organo phosphates when applied to polycarbonate
Authors: Vothi Hai , Halm Soekmin , Nguyen Congtranh , Bae Imhyuck , Kim Jinhwan
Published: July 2012

A series of organo phosphorus flame retardants (FRs) based on aromatic phosphate and cyclic phosphate were synthesized in an attempt to develop an efficient FR for polycarbonate. Their successful synthesis was confirmed by FT‐IR and 1 H and 31P NMR. Their thermal stability and flame retarding efficiency as a single‐component additive were investigated and compared with the commercial FR, resorcinol bis(diphenyl phosphate). The thermogravimetric analysis results revealed that the aromatic phosphate synthesized in this study, phloroglucinol diphenyl phosphate (PDP), shows a higher thermal degradation temperature and better flame retardancy even though it has a lower P content than cyclic phosphate‐based FRs. The flame retarding efficiency was evaluated by the UL‐94 test method. The V‐0 rating was achieved at a PDP loading of 2 wt% in polycarbonate in the presence of an anti‐dripping agent (1 wt%), which is better than that of resorcinol bis(diphenyl phosphate) and cyclic phosphate‐based FRs. The high thermal stability and P–OH generation tendency is responsible for the better flame‐retarding performance of PDP. The degradation path of PDP is also discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Identification of frequent BRAF copy number gain and alterations of RAF genes in chinese prostate cancer
Authors: Ren Guoping , Liu Xiaoyan , Mao Xueying , Zhang Yanling , Stankiewicz Elzbieta , Hylands Lucy , Song Rongrong , Berney Daniel M. , Clark Jeremy , Cooper Colin , Lu Yong‐Jie
Published: July 2012

We recently found that TMPRSS2:ERG fusion genes and PTEN loss, which are common in Western prostate cancers are infrequent in Chinese cases. As previous studies indicated a higher frequency of RAS and BRAF mutation rates in Eastern Asian than in Western prostate cancers and fusion genes involving the RAF family genes BRAF and RAF1 were recently identified in prostate cancer in the American population, we investigated BRAF and RAF1 alterations in Chinese prostate cancer. Using fluorescence in situ hybridization, we found that BRAF was truncated in five of 200 informative Chinese cases (2.5%) and that RAF1 was truncated in three of 204 informative cases (1.5%) and genomic rearrangements of these genes were significantly correlated with high Gleason scores (>7; P < 0.01) and have a trend to appear in high clinical stage disease. A high frequency of BRAF and RAF1 copy number gain was found (29 and 15%, respectively). BRAF copy number gain in Chinese cancers was significantly higher than in UK cases (9.2%)(P < 0.001) and correlated with a number of clinical parameters. High‐level expression of BRAF was found by immunohistochemistry in Chinese cancer samples compared with adjacent nonmalignant epithelial cells, which was correlated with high BRAF copy number. We also identified KRAS codon 12 mutations in three of 96 Chinese cases, no BRAF V600E mutations were observed. Our finding suggests that the activation of the RAS/RAF/MEK/ERK pathway may be frequent in Chinese prostate cancer, with RAF gene copy number gain potentially being the main contributor. © 2012 Wiley Periodicals, Inc.
Evaluating the predictive skill of post‐processed NCEP GFS ensemble precipitation forecasts in China's Huai river basin
Authors: Liu Y. , Duan Q. , Zhao L. , Ye A. , Tao Y. , Miao C. , Mu X. , Schaake J. C.
Published: July 2012

The National Center for Environmental Predictions (NCEP) has produced an ensemble meteorological reforecast product by using a fixed version of Global Forecast System (GFS) ensemble prediction system since 1 January 1979. The 15‐member ensemble product, with a global coverage at a 2.5° × 2.5° spatial resolution and a 14‐day lead time, has been used successfully by the River Forecast Centers of the National Weather Service (NWS) to produce basin scale precipitation and temperature ensemble forecasts in the US for several years now. This study evaluates the predictive skill of post‐processed ensemble forecasts based on GFS precipitation reforecast in China's Huai river basin. The evaluation is carried out in 15 sub‐areas of the Huai river basin and covers the 1/1/1981–31/12/2003 period. The Ensemble Pre‐Processing system version 3 (EPP3), developed at NWS, is used to develop joint probability distributions between forecasted ensemble mean precipitation and corresponding observations and to generate individual ensemble members that preserve space–time correlation of the observed precipitation data. Several statistical verification measures are used to quantify the goodness of fit between post‐processed (i.e. EPP3 processed) ensemble mean and observation and to assess the ensemble spread. Results indicate that the post‐processed forecasts have meaningful predictive skill for the first few days for ensemble daily precipitation forecasts. Predictive skill of ensemble forecasts of cumulative precipitation for lead times up to 14 days are significant. The forecast skill is highly dependent on seasonality, with relatively lower skills seen for wet summer season, when convective storm patterns dominate, as compared with other seasons. The predictive skill of the post‐processed ensemble precipitation is much better than the raw forecasts and the climatological ensemble forecasts. The results from this study suggest that the NCEP's GFS reforecasts can be a valuable resource for places other than the US. Copyright © 2012 John Wiley & Sons, Ltd.
Effect of fiber crosslinking on collagen‐fiber reinforced collagen–chondroitin‐6‐sulfate materials for regenerating load‐bearing soft tissues
Authors: Shepherd J. H. , Ghose S. , Kew S. J. , Moavenian A. , Best S. M. , Cameron R. E.
Published: July 2012

Porous collagen–glycosaminoglycan structures are bioactive and exhibit a pore architecture favorable for both cellular infiltration and attachment; however, their inferior mechanical properties limit use, particularly in load‐bearing situations. Reinforcement with collagen fibers may be a feasible route for enhancing the mechanical characteristics of these materials, providing potential for composites used for the repair and regeneration of soft tissue such as tendon, ligaments, and cartilage. Therefore, this study investigates the reinforcement of collagen–chondroitin‐6‐sulfate (C6S) porous structures with bundles of extruded, reconstituted type I collagen fibers. Fiber bundles were produced through extrusion and then, where applicable, crosslinked using a solution of 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide/N‐hydroxysuccinimide. Fibers were then submerged in the collagen–C6S matrix slurry before being lyophilized. A second 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide and N‐hydroxysuccinimide crosslinking process was then applied to the composite material before a secondary lyophilization cycle. Where bundles had been previously crosslinked, composites withstood a load of approximately 60 N before failure, the reinforcing fibers remained dense and a favorable matrix pore structure resulted, with good interaction between fiber and matrix. Fibers that had not been crosslinked before lyophilization showed significant internal porosity and a channel existed between them and the matrix. Mechanical properties were significantly reduced, but the additional porosity could prove favorable for cell migration and has potential for directing aligned tissue growth. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:176–184, 2013.
Microgrooved patterns enhanced PC12 cell growth, orientation, neurite elongation, and neuritogenesis
Authors: Su Wen‐Ta , Liao Yung‐Feng , Wu Tai‐Wei , Wang Bo‐Jeng , Shih Yu‐Yin
Published: July 2012

Understanding neurite outgrowth, orientation, and migration is important for the design of biomaterials that interface with the neuronal tissue. Micropatterns can significantly influence neurite outgrowth, neurite length, orientation, extracellular matrix expression, neuron differentiation, and migrating velocity. We analyzed the neuritogenesis and neurite outgrowth of PC12 cells in three‐dimensional Si wafer with various micropatterns fabricated using photolithography and etching techniques. When nerve growth factor was added into culture medium, PC12 cells started to grow neurites. Extended neurites were significantly affected by different patterns and displayed higher growth‐associated protein‐43 expression. Cellular performance including growth rate, bipolar phenotype elongation, neurite extension, and growth‐associated protein‐43 expression of the PC12 cells with a differentiated character are higher on a grooved substrate. However, the grooved pattern can restrict the motility of PC12 cells and decrease the velocity of cellular movement. The average of the number of neurites per cell is the highest on the pillar substrate, but their neurite length is the shortest. In contrast, actin and lamimin expression, motion track, angular deviation, and movement velocity of PC12 cells are most excellent on the planar Si wafer. These findings confirmed that topographical features can cooperatively act with nerve growth factor, signaling the regulation of the formation of neurites. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:185–194, 2013.
The effects of zoledronic acid in the bone and vasculature support of hematopoietic stem cell niches
Authors: Soki Fabiana N. , Li Xin , Berry Janice , Koh Amy , Sinder Benjamin P. , Qian Xu , Kozloff Kenneth M. , Taichman Russell S. , McCauley Laurie K.
Published: July 2012

Hematopoietic stem cells (HSC) are maintained in a tightly regulated bone microenvironment constituted by a rich milieu of cells. Bone cells such as osteoblasts are associated with niche maintenance as regulators of the endosteal microenvironment. Bone remodeling also plays a role in HSC mobilization although it is poorly defined. The effects of zoledronic acid (ZA), a potent bisphosphonate that inhibits bone resorption, were investigated on bone marrow cell populations focusing on HSCs, and the endosteal and vascular niches in bone. ZA treatment significantly increased bone volume and HSCs in both young and adult mice (4 week and 4 month old, respectively). ZA increased vessel numbers with no overall change in vascular volume in bones of young and had no effect on vasculature in adult mice. Since both young and adult mice had increased HSCs and bone mass with differing vasculature responses, this suggests that ZA indirectly supports HSCs via the osteoblastic niche and not the vascular niche. Additionally, gene expression in Lin‐ cells demonstrated increased expression of self‐renewal‐related genes Bmi1 and Ink4a suggesting a role of ZA in the modulation of cell commitment and differentiation toward a long‐term self‐renewing cell. Genes that support the osteoblastic niche, BMP2 and BMP6 were also augmented in ZA treated mice. In conclusion, ZA‐induced HSC expansion occurs independent of the vascular niche via indirect modulation of the osteoblastic niche. J. Cell. Biochem. 114: 67–78, 2012. © 2012 Wiley Periodicals, Inc.
The Mycobacterium DosR regulon structure and diversity revealed by comparative genomic analysis
Authors: Chen Tian , He Liming , Deng Wanyan , Xie Jianping
Published: July 2012

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), which claims approximately two million people annually, remains a global health concern. The non‐replicating or dormancy like state of this pathogen which is impervious to anti‐tuberculosis drugs is widely recognized as the culprit for this scenario. The dormancy survival regulator (DosR) regulon, composed of 48 co‐regulated genes, is held as essential for Mtb persistence. The DosR regulon is regulated by a two‐component regulatory system consisting of two sensor kinases—DosS (Rv3132c) and DosT (Rv2027c), and a response regulator DosR (Rv3133c). The underlying regulatory mechanism of DosR regulon expression is very complex. Many factors are involved, particularly the oxygen tension. The DosR regulon enables the pathogen to persist during lengthy hypoxia. Comparative genomic analysis demonstrated that the DosR regulon is widely distributed among the mycobacterial genomes, ranging from the pathogenic strains to the environmental strains. In‐depth studies on the DosR response should provide insights into its role in TB latency in vivo and shape new measures to combat this exceeding recalcitrant pathogen. J. Cell. Biochem. 114: 1–6, 2012. © 2012 Wiley Periodicals, Inc.
Intestinal myofibroblasts produce nitric oxide in response to combinatorial cytokine stimulation
Authors: Wu Jianfeng , Chitapanarux Taned , Chen Yishi , Soon Russell K. , Yee Hal F.
Published: July 2012

Inflammatory bowel disease (IBD) patients display elevated levels of intraluminal nitric oxide (NO). NO can react with other molecules to form toxic compounds, which has led to the idea that NO may be an important mediator of IBD. However, the cellular source of NO and how its production is regulated in the intestine are unclear. In this study we aimed to determine if intestinal myofibroblasts produce NO in response to the IBD‐associated cytokines IL‐1β, TNFα, and IFNγ. Intestinal myofibroblasts were isolated from mice and found to express inducible nitric oxide synthase (iNOS) mRNA, but not endothelial NOS or neuronal NOS. Individual treatment of myofibroblasts with IL‐1β, TNFα, or IFNγ had no effect on NO production, but stimulation with combinations of these cytokines synergistically increased iNOS mRNA and protein expression. Treatment with TNFα or IFNγ increased cell surface expression of IFNγRI or TNFRII, respectively, suggesting that these cytokines act in concert to prime NO production by myofibroblasts. Impairment of NF‐κB activity with a small molecule inhibitor was sufficient to prevent increased expression of IFNγRI or TNFRII, and inhibition of Akt, JAK/STAT, or NF‐κB blocked nearly all NO production induced by combinatorial cytokine treatment. These data indicate that intestinal myofibroblasts require stimulation by multiple cytokines to produce NO and that these cytokines act through a novel pathway involving reciprocal cytokine receptor regulation and signaling by Akt, JAK/STAT, and NF‐κB. J. Cell. Physiol. 228: 572–580, 2013. © 2012 Wiley Periodicals, Inc.
AKT as locus of cancer positive feedback loops and extreme robustness
Authors: Radisavljevic Ziv
Published: July 2012

A positive feedback loops induce extreme robustness in metastatic cancer, relapsed leukemia, myeloma or lymphoma. The loops are generated by the signaling interactome networks of autocrine and paracrine elements from cancer hypoxic microenvironment. The elements of the networks are signaling proteins synthesized in hypoxic microenvironment such as the vascular endothelial growth factor, HIF‐1α, hepatocyte growth factor, and molecules nitric oxide and H2O2. The signals from upstream or rebound downstream pathways are amplified by the short or wide positive feedback loops, hyperstimulating AKT‐inducing cancer extreme robustness. Targeting the phosphorylated AKT locus by an oxidant/antioxidant modulation induces collapse of positive feedback loops and establishment of negative feedback loops leading to stability of the system and disappearance of cancer extreme robustness. This is a new principle for the conversion of cancer positive loops into negative feedback loops by the locus chemotherapy. J. Cell. Physiol. 228: 522–524, 2013. © 2012 Wiley Periodicals, Inc.
5′‐ectonucleotidase mediates multiple‐drug resistance in glioblastoma multiforme cells
Authors: Quezada Claudia , Garrido Wallys , Oyarzún Carlos , Fernández Katia , Segura Rodrigo , Melo Rómulo , Casanello Paola , Sobrevia Luis , San Martín Rody
Published: July 2012

Glioblastoma multiforme (GBM) cells are characterised by their extreme chemoresistance. The activity of multiple‐drug resistance (MDR) transporters that extrude antitumor drugs from cells plays the most important role in this phenomenon. To date, the mechanism controlling the expression and activity of MDR transporters is poorly understood. Activity of the enzyme ecto‐5′‐nucleotidase (CD73) in tumor cells, which hydrolyses AMP to adenosine, has been linked to immunosuppression and prometastatic effects in breast cancer and to the proliferation of glioma cells. In this study, we identify a high expression of CD73 in surgically resected samples of human GBM. In primary cultures of GBM, inhibition of CD73 activity or knocking down its expression by siRNA reversed the MDR phenotype and cell viability was decreased up to 60% on exposure to the antitumoral drug vincristine. This GBM chemosensitization was caused by a decrease in the expression and activity of the multiple drug associated protein 1 (Mrp1), the most important transporter conferring multiple drug resistance in these cells. Using pharmacological modulators, we have recognized the adenosine A3 receptor subtype in mediation of the chemoresistant phenotype in these cells. In conclusion, we have determined that the activity of CD73 to trigger adenosine signaling sustains chemoresistant phenotype in GBM cells. J. Cell. Physiol. 228: 602–608, 2013. © 2012 Wiley Periodicals, Inc.
New Bounds on the Grundy Number of Products of Graphs
Authors: Campos Victor , Gyárfás András , Havet Frédéric , Sales Claudia Linhares , Maffray Frédéric
Published: July 2012

The Grundy number of a graph G is the largest k such that G has a greedy k‐coloring, that is, a coloring with k colors obtained by applying the greedy algorithm according to some ordering of the vertices of G. In this article, we give new bounds on the Grundy number of the product of two graphs. © 2011 Wiley Periodicals, Inc. J Graph Theory 71:78–88, 2012
Discordant antibiotic therapy and length of stay in children hospitalized for urinary tract infection
Authors: Jerardi Karen E. , Auger Katherine A. , Shah Samir S. , Hall Matthew , Hain Paul D. , Myers Angela L. , Williams Derek J. , Tieder Joel S.
Published: July 2012

BACKGROUND:

Urinary tract infections (UTIs) are a common reason for pediatric hospitalizations.

OBJECTIVE:

To determine the effect of discordant antibiotic therapy (in vitro nonsusceptibility of the uropathogen to initial antibiotic) on clinical outcomes for children hospitalized for UTI.

DESIGN/SETTING:

Multicenter retrospective cohort study in children aged 3 days to 18 years, hospitalized at 5 children's hospitals with a laboratory‐confirmed UTI. Data were obtained from medical records and the Pediatric Hospital Information System (PHIS) database.

PARTICIPANTS:

Patients with laboratory‐confirmed UTI.

MAIN EXPOSURE:

Discordant antibiotic therapy.

MEASUREMENTS:

Length of stay and fever duration. Covariates included age, sex, insurance, race, vesicoureteral reflux, antibiotic prophylaxis, genitourinary abnormality, and chronic care conditions.

RESULTS:

The median age of the 216 patients was 2.46 years (interquartile range [IQR]: 0.27, 8.89) and 25% were male. The most common causative organisms were E. coli and Klebsiella species. Discordant therapy occurred in 10% of cases and most commonly in cultures positive for Klebsiella species, Enterobacter species, and mixed organisms. In adjusted analyses, discordant therapy was associated with a 1.8 day (95% confidence interval [CI]: 1.5, 2.1) longer length of stay [LOS], but not with fever duration.

CONCLUSIONS:

Discordant antibiotic therapy for UTI is common and associated with longer hospitalizations. Further research is needed to understand the clinical factors contributing to the increased LOS and to inform decisions for empiric antibiotic selection in children with UTIs. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine
There's a fever in healthcare called physician acquisition
Authors: Dennis Johnnye L.
Published: July 2012

Some of you may remember the Donna Reed television show from the early 1960s. Donna played wife (and sometimes nurse) to her TV husband, Dr. Alex Stone. He was a pediatrician whose office was nearby, enabling Dr. Stone to come home for lunch. For those of you too young to know or remember this television program, Dr. Stone's practice of medicine was seemingly uncomplicated, and discussion at the dinner table was never centered on concerns of the practice. It is highly unlikely the same can be said for today's practicing physicians.
Ontogeny and homology of the skeletal elements that form the sucking disc of remoras (Teleostei, Echeneoidei, Echeneidae)
Authors: Britz Ralf , Johnson G. David
Published: July 2012

The sucking disc of the sharksuckers of the family Echeneidae is one of the most remarkable and most highly modified skeletal structures among vertebrates. We studied the development of the sucking disc based on a series of larval, juvenile, and adult echeneids ranging from 9.3 mm to 175 mm standard length. We revisited the question of the homology of the different skeletal parts that form the disc using an ontogenetic approach. We compared the initial stages of development of the disc with early developmental stages of the spinous dorsal fin in a representative of the morphologically basal percomorph Morone. We demonstrate that the “interneural rays” of echeneids are homologous with the proximal‐middle radials of Morone and other teleosts and that the “intercalary bones” of sharksuckers are homologous with the distal radials of Morone and other teleosts. The “intercalary bones” or distal radials develop a pair of large wing‐like lateral extensions in echeneids, not present in this form in any other teleost. Finally the “pectinated lamellae” are homologous with the fin spines of Morone and other acanthomorphs. The main part of each pectinated lamella is formed by bilateral extensions of the base of the fin spine just above its proximal tip, each of which develops a row of spinous projections, or spinules, along its posterior margin. The number of rows and the number of spinules increase with size, and they become autogenous from the body of the lamellae. We also provide a historical review of previous studies on the homology of the echeneid sucking disc and demonstrate that the most recent hypotheses, published in 2002, 2005 and 2006, are erroneous. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.
Treatment‐related morbidity and toxicity of CRS and oxaliplatin‐based HIPEC compared to a mitomycin and doxorubicin‐based HIPEC protocol in patients with peritoneal carcinomatosis: A matched‐pair analysis
Authors: Glockzin Gabriel , von Breitenbuch Philipp , Schlitt Hans J. , Piso Pompiliu
Published: July 2012

Introduction

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising therapeutic option for selected patients with peritoneal carcinomatosis. The use of intraperitoneal oxaliplatin seems to further improve the efficacy of the combined treatment concept. Nevertheless, additional toxicity might be expected.

Patients and Methods

Between 03/2004 and 08/2010 307 patients underwent CRS and HIPEC at the University Medical Center Regensburg. Forty of these patients received oxaliplatin‐based HIPEC. A matched‐pair analysis was performed to compare IP oxaliplatin to our former standard HIPEC protocol with mitomycin C (MMC) and doxorubicin.

Results

The mean operating time in the OX and the MMC group was 315 and 313 min, respectively. Median hospital stay was 15.5 days in the OX group and 17 days in the MMC group. The grade 3/4 morbidity rate according to CTCAEv3.0 was 42.5% versus 37.5% (P = 0.648). Perioperative mortality was 2.5% versus 0%.

Conclusion

Our data suggest that the use of IP oxaliplatin in the context of CRS and HIPEC does not significantly increase perioperative morbidity and/or mortality rates. Nevertheless, randomized controlled trials are required to determine the optimal intraperitoneal chemotherapeutic regimen regarding toxicity, postoperative complications, and oncological outcome. J. Surg. Oncol. 2013;107:574–578. © 2012 Wiley Periodicals, Inc.
Prospective testing of mucoepidermoid carcinoma for the MAML2 translocation: Clinical Implications
Authors: Chiosea Simion I. , Dacic Sanja , Nikiforova Marina N. , Seethala Raja R.
Published: July 2012

Objectives/Hypothesis:

Mucoepidermoid carcinoma (MEC) with MAML2 translocation is believed to be associated with lower clinical stage, lower histologic grade, and better outcome. We summarized our prospective experience testing MEC for the MAML2 translocation.

Study Design:

Prospective cohort study.

Methods:

One hundred eighteen head and neck tumors (55 MECs and 63 mimics) were prospectively tested for MAML2 translocation by fluorescence in situ hybridization as part of clinical care during a 36‐month period.

Results:

MAML2 translocation was identified in 41 of 55 (75%) cases diagnosed as MEC. Translocation status did not correlate significantly with histologic grade, age, gender, tumor site, or T stage.

Conclusions:

Routine testing for MAML2 translocation by fluorescence in situ hybridization is feasible and useful in confirming the diagnosis of MEC. The lack of significant correlation with histologic grade or pathologic stage implies that the previously reported prognostic value of the MAML2 translocation may be an artifact of misclassification of MEC as other tumors.
Toxicity, quality of life, and functional outcomes of 176 hypopharyngeal cancer patients treated by (Chemo)radiation: The impact of treatment modality and radiation technique
Authors: Al‐Mamgani Abrahim , Mehilal Robert , van Rooij Peter H. , Tans Lisa , Sewnaik Aniel , Levendag Peter C.
Published: July 2012

Objectives/Hypothesis:

The main goal of the current study was to comprehensively address the impact of chemoradiation and radiation techniques on toxicity, quality of life (QoL), and functional outcome.

Study Design:

Retrospective analysis of toxicity and functional outcome and prospective QoL assessment.

Methods:

From 1996 to 2010, 176 consecutive patients with hypopharyngeal cancer (HPC) were treated with (chemo)radiotherapy. End points were acute and late toxicity, QoL assessment, and functional outcome using laryngoesophageal dysfunction‐free survival (LED‐FS) defined by the Laryngeal Preservation Consensus Panel.

Results:

Chemoradiation significantly increased grade 3 acute toxicity compared to radiotherapy alone (71% vs. 55%, P = .02). The 3‐year grade ≥2 late toxicity was 32%. Intensity‐modulated radiotherapy (IMRT) significantly reduced late toxicity compared to three‐dimensional conformal radiotherapy (3DCRT) (24% vs. 44%, P = .007). Slight deterioration in QoL scores was observed on almost all scales, and was more pronounced in patients treated with chemoradiation, albeit not statistically significant except for xerostomia. Chemoradiation, compared to radiotherapy alone, improved LED‐FS at 3 years (51% vs. 24% for the entire group and 83% vs. 63% for the 78 living patients at last follow‐up, respectively [P = .05]).

Conclusions:

Compared to radiotherapy alone, chemoradiation significantly improved functional outcome, increased acute toxicity, but without significant increase in late radiation‐induced side effects. Statistically significant deterioration in QoL scores was reported only for xerostomia. IMRT, compared to 3DCRT, reduced the incidence and severity of acute and late toxicity, thereby broadening the therapeutic window, and may allow dose escalation for further improvement of outcomes of laryngeal preservation protocols.
Readability assessment of internet‐based patient education materials related to facial fractures
Authors: Sanghvi Saurin , Cherla Deepa V. , Shukla Pratik A. , Eloy Jean Anderson
Published: July 2012

Objective/Hypothesis:

Various professional societies, clinical practices, hospitals, and health care‐related Web sites provide Internet‐based patient education material (IPEMs) to the general public. However, this information may be written above the 6th‐grade reading level recommended by the US Department of Health and Human Services. The purpose of this study is to assess the readability of facial fracture (FF)‐related IPEMs and compare readability levels of IPEMs provided by four sources: professional societies, clinical practices, hospitals, and miscellaneous sources.

Study Design:

Analysis of IPEMs on FFs available on Google.com.

Methods:

The readability of 41 FF‐related IPEMs was assessed with four readability indices: Flesch‐Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG), and Gunning Frequency of Gobbledygook (Gunning FOG). Averages were evaluated against national recommendations and between each source using analysis of variance and t tests.

Results:

Only 4.9% of IPEMs were written at or below the 6th‐grade reading level, based on FKGL. The mean readability scores were: FRES 54.10, FKGL 9.89, SMOG 12.73, and Gunning FOG 12.98, translating into FF‐related IPEMs being written at a “difficult” writing level, which is above the level of reading understanding of the average American adult.

Conclusions:

IPEMs related to FFs are written above the recommended 6th‐grade reading level. Consequently, this information would be difficult to understand by the average US patient.
Expression pattern of IQGAP1 in sinonasal inverted papillomas and squamous cell carcinomas
Authors: Jin Jun , Lee Jin Woo , Rha Ki‐Sang , Kim Dong Woon , Kim Yong Min
Published: July 2012

Objectives/Hypothesis:

The scaffold protein IQGAP1 is a ubiquitously expressed 190 kDa protein that participates in protein‐protein interactions, integrating diverse signaling pathways. In this study, we examined the expression of IQGAP1 in sinonasal inverted papillomas (IP) and sinonasal squamous cell carcinomas (SCC), which include IP with SCC (IPcSCC) and SCC alone. We also tried to elucidate whether the amount of IQGAP1 expression is related with any clinicopathologic features of sinonasal SCCs.

Study Design:

This was a retrospective study.

Methods:

The expression of IQGAP1 was analyzed by means of immunohistochemistry. The degrees of IQGAP1 expression and subcellular localization (rim formation) were analyzed with respect to the following clinicopathologic variables: age, gender, T stage, histologic differentiation, local recurrence, and distant metastasis.

Results:

The expression of IQGAP1 was significantly higher in patients with IPcSCC (3.62 ± 0.14), and SCC (2.93 ± 0.34) compared with IP (1.43 ± 0.26). The rim formation scale was significantly higher in IPcSCC (2.39 ± 0.24) compared with IP (1.68 ± 0.15). Distant metastasis in patients with SCC significantly correlated with an increased IQGAP1 rim formation (p = 0.011). Histologic differentiation was also significantly correlated with a positive staining scale for IQGAP1 in IPcSCCs (p = 0.038).

Conclusion:

These results indicated that IQGAP1 expression is associated with both the histologic differentiation of IPcSCCs and is present in SCC cases where distant metastasis has occurred.
The use of the h‐index in academic otolaryngology
Authors: Svider Peter F. , Choudhry Zaid A. , Choudhry Osamah J. , Baredes Soly , Liu James K. , Eloy Jean Anderson
Published: July 2012

Objective/Hypothesis:

The h‐index is an objective and easily calculable measure that can be used to evaluate both the relevance and amount of scientific contributions of an individual author. Our objective was to examine how the h‐index of academic otolaryngologists relates with academic rank.

Study Design:

A descriptive and correlational design was used for analysis of academic otolaryngologists' h‐indices using the Scopus database.

Methods:

H‐indices of faculty members from 50 otolaryngology residency programs were calculated using the Scopus database, and data was organized by academic rank. Additionally, an analysis of the h‐indices of departmental chairpersons among different specialties was performed.

Results:

H‐index values of academic otolaryngologists were higher with increased academic rank among the levels of assistant professor, associate professor, and professor. There was no significant difference between the h‐indices of professors and department chairpersons within otolaryngology. H‐indices of chairpersons in different academic specialties were compared and were significantly different, suggesting that the use of this metric may not be appropriate for comparing different fields.

Conclusions:

The h‐index is a reliable tool for quantifying academic productivity within otolaryngology. This measure is easily calculable and may be useful when evaluating decisions regarding advancement within academic otolaryngology departments. Comparison of this metric among faculty members from different fields, however, may not be reliable. Laryngoscope, 2013
Protection against oxidative DNA damage and stress in human prostate by glutathione S‐transferase P1
Authors: Kanwal Rajnee , Pandey Mitali , Bhaskaran Natarajan , MacLennan Gregory T. , Fu Pingfu , Ponsky Lee E. , Gupta Sanjay
Published: July 2012

The pi‐class glutathione S‐transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (ROS) and DNA damage in cells. In this study we investigated whether loss of GSTP1 contributes to increased DNA damage that may predispose men to a higher risk of prostate cancer. We found significantly elevated (103%; P < 0.0001) levels of 8‐oxo‐2′‐deoxogunosine (8‐OHdG), an oxidative DNA damage marker, in adenocarcinomas, compared to benign counterparts, which positively correlated (r = 0.2) with loss of GSTP1 activity (34%; P < 0.0001). Silencing of GSTP1 using siRNA approach in normal human prostate epithelial RWPE1 cells caused increased intracellular production of ROS and higher susceptibility of cells to H2O2‐mediated oxidative stress. Additionally, human prostate carcinoma LNCaP cells, which contain a silenced GSTP1 gene, were genetically modified to constitutively express high levels of GSTP1. Induction of GSTP1 activity lowered endogenous ROS levels in LNCaP‐pLPCX‐GSTP1 cells, and when exposed to H2O2, these cells exhibited significantly reduced production of ROS and 8‐OHdG levels, compared to vector control LNCaP‐pLPCX cells. Furthermore, exposure of LNCaP cells to green tea polyphenols caused reexpression of GSTP1, which protected the cells from H2O2‐mediated DNA damage through decreased ROS production compared to nonexposed cells. These results suggest that loss of GSTP1 expression in human prostate cells, a process that increases their susceptibility to oxidative stress‐induced DNA damage, may be an important target for primary prevention of prostate cancer. © 2013 Wiley Periodicals, Inc.
Parkinson's disease and other neurodegenerative disorders among welders: A Danish cohort study
Authors: Kenborg Line , Funch Lassen Christina , Hansen Johnni , Olsen Jørgen H.
Published: July 2012

It has been hypothesized that welders are at increased risk for neurological disorders, including Parkinson's disease, but few well‐designed cohort studies have been conducted. The risk for Parkinson's disease and other neurodegenerative disorders was examined in an updated follow‐up study based on a previous cohort of 5867 Danish welders and 1735 nonwelding metal workers exposed to welding fume. Occupational history and information on smoking were obtained from questionnaires, supplemented by information from the compulsory Danish Supplementary Pension Fund. Hospital contacts, including outpatient data from 1994, for Parkinson's disease and other neurological disorders were ascertained from the Danish National Hospital Register. Based on first‐time hospital contacts, standardized hospitalization ratios (SHRs) were calculated for the entire cohort and for welders, metal workers, and nonresponders separately and for the general Danish population in 1987–2008. In an internal analysis of welders, Cox proportional hazard models were used to estimate hospitalization rate ratios (HRRs) for Parkinson's disease associated with lifelong exposure to welding. Overall, 45 cohort members had a hospital contact for Parkinson's disease (SHR, 1.12; 95% confidence interval [CI], 0.82–1.50), of whom 25 were welders (standardized incidence rate ratio, 1.05; 95% CI, 0.68–1.55). When duration of welding was compared among 5736 welders, the HRR was 0.83 (95% CI, 0.59–1.16) per 10 years' welding, after adjustment for smoking. The results of this study do not support the hypothesis that welders are at increased risk for Parkinson's disease; these findings are consistent with those of our previously published analysis. © 2012MovementDisorder Society