bluuebunny/crossref_metadata_2025 huggingface dataset:
Sandwich‐Structured Graphene–Nickel Silicate–Nickel Ternary Composites as Superior Anode Materials for Lithium‐Ion Batteries
Authors: Jin Renxi , Yang Yang , Li Yunfeng , Liu Xianchun , Xing Yan , Song Shuyan , Shi Zhan
Published: May 2015

We report the synthesis of sandwich‐structured graphene–nickel silicate–Ni ternary composites by using the solvothermal method followed by a simple in situ reduction procedure. The composites show an interesting structure with graphene sandwiched between two layers of well‐dispersed Ni nanoparticles (NPs) anchored on ultrathin nickel silicate nanosheets. These ternary composites exhibit enhanced performance as anode materials owing to the synergistic effect between the graphene matrix and electrochemically inert Ni nanoparticles, an effect that holds promise for the design and fabrication of other advanced electrode materials.
Speciation Control During Suzuki–Miyaura Cross‐Coupling of Haloaryl and Haloalkenyl MIDA Boronic Esters
Authors: Fyfe James W. B. , Valverde Elena , Seath Ciaran P. , Kennedy Alan R. , Redmond Joanna M. , Anderson Niall A. , Watson Allan J. B.
Published: May 2015

Boronic acid solution speciation can be controlled during the Suzuki–Miyaura cross‐coupling of haloaryl N‐methyliminodiacetic acid (MIDA) boronic esters to enable the formal homologation of boronic acid derivatives. The reaction is contingent upon control of the basic biphase and is thermodynamically driven: temperature control provides highly chemoselective access to either BMIDA adducts at room temperature or boronic acid pinacol ester (BPin) products at elevated temperature. Control experiments and solubility analyses have provided some insight into the mechanistic operation of the formal homologation process.
Synthesis and Confinement of Carbon Dots in Lysozyme Single Crystals Produces Ordered Hybrid Materials with Tuneable Luminescence
Authors: England Matt W. , Patil Avinash J. , Mann Stephen
Published: May 2015

The synthesis and confinement of graphitic nanoparticles (carbon dots) in the nanoscale solvent channels of cross‐linked lysozyme single crystals is used to prepare novel biohybrid luminescent materials. Co‐sequestration of acridine orange within the biohybrid crystals from acidic or neutral solutions yields FRET‐mediated phosphors emitting white or green light, respectively. The results offer a route to new types of tuneable multicolour luminescent materials based on microcrystalline host–guest energy‐transfer systems.
Drug Metabolism by Cytochrome P450 Enzymes: What Distinguishes the Pathways Leading to Substrate Hydroxylation Over Desaturation?
Authors: Ji Li , Faponle Abayomi S. , Quesne Matthew G. , Sainna Mala A. , Zhang Jing , Franke Alicja , Kumar Devesh , van Eldik Rudi , Liu Weiping , de Visser Sam P.
Published: May 2015

Invited for the cover of this issue are the groups of Sam P. de Visser at the University of Manchester and Weiping Liu from Zhejiang University and colleagues. The cover shows the competitive routes that can be taken to convert drug and other xenobiotic molecules in the body, and most importantly in the liver. Read the full text of the article at 10.1002/chem.201500329.
Brugada Syndrome, Exercise, and Exercise Testing
Authors: Masrur Shihab , Memon Sarfaraz , Thompson Paul D.
Published: May 2015

There are few data on the risk of exercise and the role of exercise stress testing in Brugada syndrome. We sought to address this deficiency using a systematic literature review. We identified 98 English‐language articles possibly addressing exercise in Brugada syndrome by searching PubMed and Google Scholar from January 1990 through November 2013 using the keywords “Brugada syndrome,” “exercise,” “exercise testing,” and “syncope” alone and in combinations. Abstracts were reviewed, and those articles pertaining to Brugada syndrome and exercise were reviewed in full. We identified 18 articles reporting on Brugada syndrome and exercise. This pool included 2 large studies of 93 and 50 Brugada subjects undergoing exercise testing, plus 16 case reports. There were no reports of exercise‐related sudden death, but there were 4 cases of syncope after exercise. We identified 166 Brugada patients who underwent exercise testing. During exercise testing, there were 2 reports of ventricular tachycardia and 1 report of multiple ventricular extrasystoles. ST‐segment elevation increased (ST augmentation) during the early recovery phase of exercise in 57% of patients. Exercise unmasked a Brugada electrocardiographic pattern in 5 patients. Exercise is associated with syncope and ST augmentation after exercise and may be helpful in unmasking Brugada syndrome. There are insufficient data on the risks of exercise in Brugada syndrome to make recommendations for exercise, but the observations that exercise can worsen the ST abnormalities in Brugada and produce ventricular arrhythmias suggest that patients with Brugada syndrome should be restricted from vigorous exercise.
The role of Epstein‐Barr virus–encoded microRNA BART7 status of resection margins in the prediction of local recurrence after salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma
Authors: Chan Jimmy Yu Wai , Wong Stanley Thian Sze , Wei William Ignace
Published: May 2015

BACKGROUND

Local recurrence is the major cause of treatment failure in patients who undergo surgical salvage of recurrent nasopharyngeal carcinoma (NPC) after radiotherapy. The authors investigated the role of Epstein‐Barr virus (EBV)‐encoded Bam HI‐A rightward transcript 7 microRNA (BART7) status in resection margins in the identification of a subgroup of patients who may benefit from adjuvant reradiation after surgery.

METHODS

One hundred two consecutive patients who had histologically clear resection margins after undergoing nasopharyngectomy for recurrent NPC were studied. The status of EBV microRNA BART7 in resection margins was investigated and correlated with the pattern of subsequent disease recurrence.

RESULTS

After a median follow‐up of 64 months, 20 patients (19.6%) developed local recurrence after surgery despite histologically uninvolved margins. The risk of local recurrence in patients with histologically close (<5 mm) and clear (≥5 mm) margins was 31.6% and 12.5%, respectively. In patients with clear histologic margins, those with margins that were positive for EBV microRNA BART7 has a significantly higher chance of developing local tumor recurrence (P = .016) than those with negative molecular margins. The difference was not significant when the histologic clearance at the resection margins was <5 mm.

CONCLUSIONS

Tissue EBV microRNA BART7 is useful for identifying a subgroup of patients with histologically clear margins who are at increased risk of subsequent local tumor recurrence. Postoperative adjuvant treatment is warranted for these patients. Cancer 2015;121:2358–2366. © 2015 American Cancer Society.
Heterojunction Solar Cells Based on Silicon and Composite Films of Graphene Oxide and Carbon Nanotubes
Authors: Yu LePing , Tune Daniel , Shearer Cameron , Shapter Joseph
Published: May 2015

Graphene oxide (GO) sheets have been used as the surfactant to disperse single‐walled carbon nanotubes (CNT) in water to prepare GO/CNT electrodes that are applied to silicon to form a heterojunction that can be used in solar cells. GO/CNT films with different ratios of the two components and with various thicknesses have been used as semitransparent electrodes, and the influence of both factors on the performance of the solar cell has been studied. The degradation rate of the GO/CNT‐silicon devices under ambient conditions has also been explored. The influence of the film thickness on the device performance is related to the interplay of two competing factors, namely, sheet resistance and transmittance. CNTs help to improve the conductivity of the GO/CNT film, and GO is able to protect the silicon from oxidation in the atmosphere.
Antimetastatic Effects of Gambogic Acid are Mediated via the Actin Cytoskeleton and NF‐κB Pathways in SK‐HEP1 Cells
Authors: Park Min‐Seok , Kim Nan‐Hee , Kang Chang‐Won , Oh Chul‐Woong , Kim Gun‐Do
Published: May 2015

Preclinical Research

Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with a high metastatic potential. The prevention of HCC metastasis is a critical target for effective therapies in HCC. Gambogic acid (GA), a natural compound obtained from Garcinia hanburyi has reported anticancer activity in cell lines. However, the antimetastatic mechanisms of GA are unclear, particularly with respect to HCC. In this study, the influence of GA on migration and invasion of SK‐HEP1 cells was evaluated. At concentrations above 0.6 μM, GA reduced cell proliferation in SK‐HEP1 cells without affecting proliferation of noncancerous HEK‐293 cells. GA also suppressed migration and invasion of SK‐HEP1 cells. GA downregulated the expression of the integrin β1/rho family GTPase signaling pathway, suppressed the actin rearrangement related to cell cytoskeleton and migration and decreased matrix metalloproteinases MMP‐2, MMP‐9, and NF‐κB expression involved in cancer invasion. These results suggest that GA may be a potential lead in developing an antimetastatic therapeutic for the treatment of HCC. © 2015 Wiley Periodicals, Inc. Drug Dev Res 73 : 132–142, 2015. © 2015 Wiley Periodicals, Inc.
In Vivo Wound‐Healing Effects of Novel Benzalkonium Chloride‐Loaded Hydrocolloid Wound Dressing
Authors: Jin Sung Giu , Yousaf Abid Mehmood , Jang Sun Woo , Son Mi‐Won , Kim Kyung Soo , Kim Dong‐Wuk , Li Dong Xun , Kim Jong Oh , Yong Chul Soon , Choi Han‐Gon
Published: May 2015

Preclinical Research

The purpose of this study was to evaluate the wound‐healing effects of a novel benzalkonium chloride (BC)‐loaded hydrocolloid wound dressing (HCD). A BC‐loaded HCD was prepared with various constituents using a hot melting method, and its mechanical properties and antimicrobial activities were assessed. The in vivo wound healings of the BC‐loaded HCD in various would models were evaluated in rats compared with a commercial wound dressing, Duoderm™. This BC‐loaded HCD gave better skin adhesion, swelling, mechanical strength, and flexibility compared with the commercial wound dressing. It showed excellent antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In addition, as compared with the commercial wound dressing, it showed more improved wound healings and tissue restoration effect on the excision, infection, and abrasion wounds in rats. Thus, this novel BC‐loaded HCD would be an excellent alternative to the commercial wound dressing for treatment of various wounds. Drug Dev Res 73 : 157–165, 2015. © 2015 Wiley Periodicals, Inc.
Healthcare costs and resource utilization of patients with binge‐eating disorder and eating disorder not otherwise specified in the Department of Veterans Affairs
Authors: Bellows Brandon K. , DuVall Scott L. , Kamauu Aaron W.C. , Supina Dylan , Babcock Thomas , LaFleur Joanne
Published: May 2015

Objective

The objective of this study was to compare the one‐year healthcare costs and utilization of patients with binge‐eating disorder (BED) to patients with eating disorder not otherwise specified without BED (EDNOS‐only) and to matched patients without an eating disorder (NED).

Methods

A natural language processing (NLP) algorithm identified adults with BED from clinical notes in the Department of Veterans Affairs (VA) electronic health record database from 2000 to 2011. Patients with EDNOS‐only were identified using ICD‐9 code (307.50) and those with NLP‐identified BED were excluded. First diagnosis date defined the index date for both groups. Patients with NED were randomly matched 4:1, as available, to patients with BED on age, sex, BMI, depression diagnosis, and index month. Patients with cost data (2005–2011) were included. Total healthcare, inpatient, outpatient, and pharmacy costs were examined. Generalized linear models were used to compare total one‐year healthcare costs while adjusting for baseline patient characteristics.

Results

There were 257 BED, 743 EDNOS‐only, and 823 matched NED patients identified. The mean (SD) total unadjusted one‐year costs, in 2011 US dollars, were $33,716 ($38,928) for BED, $37,052 ($40,719) for EDNOS‐only, and $19,548 ($35,780) for NED patients. When adjusting for patient characteristics, BED patients had one‐year total healthcare costs $5,589 higher than EDNOS‐only (p = 0.06) and $18,152 higher than matched NED patients (p < 0.001).

Discussion

This study is the first to use NLP to identify BED patients and quantify their healthcare costs and utilization. Patients with BED had similar one‐year total healthcare costs to EDNOS‐only patients, but significantly higher costs than patients with NED. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:1082–1091).
Recipient expression of ligands for donor inhibitory KIRs enhances NK‐cell function to control leukemic relapse after haploidentical transplantation
Authors: Zhao Xiang‐Yu , Chang Ying‐Jun , Zhao Xiao‐Su , Xu Lan‐Ping , Zhang Xiao‐Hui , Liu Kai‐Yan , Li Dan , Huang Xiao‐Jun
Published: May 2015

Natural killer (NK) cells that express self‐HLA‐specific receptors (where HLA is human leukocyte antigen) are “licensed” and more readily activated than unlicensed cells; therefore, NK‐cell licensing could influence the antileukemia effects of NK cells following haploidentical stem cell transplantation (haplo‐SCT). In this study, we compared the functionality of reconstituting NK cells, based on CD107α expression and interferon‐γsecretion, in a cohort of 29 patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte antigens for donor inhibitory killer cell immunoglobulin‐like receptors (KIRs) following T‐cell‐replete haplo‐SCT. We also addressed whether recipient expression of class I ligands for donor inhibitory KIRs could predict relapse occurrence in another cohort of 188 patients. A longitudinal analysis indicated that patients presenting class I for all donor inhibitory KIRs showed more capable functional NK effector cells when tested against class I negative K562 cells and primary leukemic cells within 3 months of transplantation. The lowest 7‐year relapse incidence was observed when donor KIRs were ligated by recipient class I (n = 60) compared with donor–host partnerships where donor KIR+ cells were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This study suggests that haplo‐SCT recipients presenting class I for donor inhibitory KIRs promote NK‐cell licensing, leading to decreased relapse rates.
Diversity‐Oriented Synthesis of β‐Lactams and γ‐Lactams by Post‐Ugi Nucleophilic Cyclization: Lewis Acids as Regioselective Switch
Authors: Li Zhenghua , Sharma Upendra Kumar , Liu Zhen , Sharma Nandini , Harvey Jeremy N. , Van der Eycken Erik V.
Published: May 2015

Heterocyclic fused α‐methylene β‐lactams were successfully synthesized by a post‐Ugi InIII‐catalyzed intramolecular addition reaction. Switching from InCl3 to AlCl3 led to the regioselective synthesis of α,β‐unsaturated γ‐lactams. Moreover, replacing terminal alkynes by substituted alkynes in the Ugi adducts resulted in the exclusive formation of γ‐lactams with both catalytic systems.
A One‐Pot Copper(II)‐Catalyzed Tandem Synthesis of 2‐Substituted Pyrrolo[1,2‐b]pyridazin‐4(1H)‐ones
Authors: Tan Cun , Xiang Haoyue , He Qian , Yang Chunhao
Published: May 2015

A one‐pot copper(II)‐catalyzed tandem synthesis of 2‐substituted pyrrolo[1,2‐b]pyridazin‐4(1H)‐ones from N‐aminopyrroles was developed. This tandem reaction involves a Conrad–Limpach‐type reaction, including the thermal condensation of N‐aminopyrroles with the carbonyl group of β‐oxo esters followed by the cyclization of Schiff base intermediates. Compared to the traditional Conrad–Limpach quinoline synthesis, we herein successfully applied copper(II) as a catalyst in this transformation to furnish 2‐substituted pyrrolo[1,2‐b]pyridazin‐4(1H)‐ones for the first time. Most of the substrates bearing electron‐donating (EDG) and electron‐withdrawing (EWG) groups worked well with this procedure. The corresponding products could be converted directly into diverse pyrrolo[1,2‐b]pyridazine for drug discovery and materials science.
A Coupled Reservoir/Wellbore Model to Simulate the Steam Injection Performance of Horizontal Wells
Authors: Li Mingzhong , Chen Huijuan , Zhang Yanyu , Li Weiwei , Wang Yiping , Yu Meng
Published: May 2015

A coupled reservoir/wellbore model of horizontal wells in a steam injection process is presented, which considers the three‐dimensional simultaneous flow of three phases in the reservoir and gas–liquid two‐phase flow in the wellbore. Based on the model, the steam injection performance of a horizontal well is simulated. The pressure, temperature, and steam quality distribution in the wellbore as well as the steam injection profile and reservoir temperature along the horizontal wellbore are discussed. Results show that the wellbore pressure, temperature, and steam quality decrease from the horizontal wellbore heel to the toe. The steam flux rate and reservoir temperature are higher at the wellbore heel and toe. Furthermore, the variations of the steam flux rate and reservoir temperature along the wellbore increase with sustained injections, which is a disadvantage for thermal horizontal wells. Therefore, developing techniques to guarantee a uniform flow along horizontal wellbores is crucial.
Cytochrome P450–mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken
Authors: Watanabe Kensuke P. , Kawata Minami , Ikenaka Yoshinori , Nakayama Shouta M. M. , Ishii Chihiro , Darwish Wageh Sobhi , Saengtienchai Aksorn , Mizukawa Hazuki , Ishizuka Mayumi
Published: May 2015

Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4′-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. Environ Toxicol Chem 2015;34:2328–2334. © 2015 SETAC
Identification of microRNAs specific for epithelial cell adhesion molecule–positive tumor cells in hepatocellular carcinoma
Authors: Ji Junfang , Zheng Xin , Forgues Marshonna , Yamashita Taro , Wauthier Eliane L. , Reid Lola M. , Wen Xinyu , Song Young , Wei Jun S. , Khan Javed , Thorgeirsson Snorri S. , Wang Xin Wei
Published: May 2015

Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted owing to their similarities to CSCs. It is established that epithelial cell adhesion molecule (EpCAM) is a biomarker for normal hepatic stem cells (HpSCs), and EpCAM+AFP+ hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine whether specific microRNAs (miRNAs) exist in hepatic CSCs that are not expressed in normal HpSCs. We performed a pair‐wise comparison of the miRNA transcriptome of EpCAM+ and corresponding EpCAM− cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors by small RNA deep sequencing. We found that miR‐150, miR‐155, and miR‐223 were preferentially highly expressed in EpCAM+ HCC cells, which was further validated. Their gene surrogates, identified using miRNA and messenger RNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR‐155 was highly expressed in EpCAM+ HCC cells, compared to corresponding EpCAM− HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR‐155 resulted in a decreased EpCAM+ fraction in HCC cells and reduced HCC cell colony formation, migration, and invasion in vitro. The reduced levels of identified miR‐155 targets predicted the shortened overall survival and time to recurrence of HCC patients. Conclusion: miR‐155 is highly elevated in EpCAM+ HCC cells and might serve as a molecular target to eradicate the EpCAM+ CSC population in human HCCs. (Hepatology 2015;62:829–840)
MicroRNA‐125b attenuates epithelial‐mesenchymal transitions and targets stem‐like liver cancer cells through small mothers against decapentaplegic 2 and 4
Authors: Zhou Jun‐Nian , Zeng Quan , Wang Hai‐Yang , Zhang Biao , Li Si‐Ting , Nan Xue , Cao Ning , Fu Chun‐Jiang , Yan Xin‐Long , Jia Ya‐Li , Wang Jing‐Xue , Zhao Ai‐Hua , Li Zhi‐Wei , Li Yan‐Hua , Xie Xiao‐Yan , Zhang Xiao‐Mei , Dong Yan , Xu Ying‐Chen , He Li‐Juan , Yue Wen , Pei Xue‐Tao
Published: May 2015

Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
The BH3‐only protein BID impairs the p38‐mediated stress response and promotes hepatocarcinogenesis during chronic liver injury in mice
Authors: Orlik Johanna , Schüngel Sven , Buitrago‐Molina Laura Elisa , Marhenke Silke , Geffers Robert , Endig Jessica , Lobschat Katharina , Rössler Stephanie , Goeppert Benjamin , Manns Michael P. , Gross Atan , Vogel Arndt
Published: May 2015

Apoptosis is critical for maintaining tissue homeostasis, and apoptosis evasion is considered as a hallmark of cancer. However, increasing evidence also suggests that proapoptotic molecules can contribute to the development of cancer, including liver cancer. The aim of this study was to further clarify the role of the proapoptotic B‐cell lymphoma 2 homology domain 3 (BH3)‐only protein BH3 interacting‐domain death agonist (BID) for chronic liver injury (CLI) and hepatocarcinogenesis (HCG). Loss of BID significantly delayed tumor development in two mouse models of Fah‐mediated and HBsTg‐driven HCG, suggesting a tumor‐promoting effect of BID. Liver injury as well as basal and mitogen‐stimulated hepatocyte proliferation were not modulated by BID. Moreover, there was no in vivo or in vitro evidence that BID was involved in DNA damage response in hepatocytes and hepatoma cells. Our data revealed that CLI was associated with strong activation of oxidative stress (OS) response and that BID impaired full activation of p38 after OS. Conclusion: We provide evidence that the tumor‐promoting function of BID in CLI is not related to enhanced proliferation or an impaired DNA damage response. In contrast, BID suppresses p38 activity and facilitates malignant transformation of hepatocytes. (Hepatology 2015;62:816–828)
Tree ring analysis of hydro‐climatic thresholds that trigger ice jams on the Mistassini River, Quebec
Authors: Lagadec Annie , Boucher Étienne , Germain Daniel
Published: May 2015

This study documents the spatiotemporal variations in the frequency and magnitude of ice jams in the Mistassini River and applies that information to the identification of the hydro‐climatic threshold conditions associated with major events. Ice jams cause severe upheavals in water flow, which result in flooding upstream of the ice jam front, and therefore represent a significant geohazard to riparian populations. To analyze the spatiotemporal variations in the magnitude–frequency of ice jams, the Mistassini River was first divided into six different sites representing different geomorphological contexts. A 50‐year ice jam chronology was constructed from 85 damaged trees from all of the study sites. This chronology was then coupled with hydro‐climatic variables to construct classification trees, which helped identify the conditions and hydro‐climatic thresholds favourable to the triggering of ice jams in a predictive model. The results indicate complex interactions between the characteristics of flow, ice cover and river morphology that affect the frequency and magnitude of ice jam events on the Mistassini River. These factors affect the frequency and magnitude of ice jam events. The triggering of extreme events seems particularly influenced by exceptional ice conditions and sites with high sinuosity and islands. Copyright © 2015 John Wiley & Sons, Ltd.
In vivobiological response to highly cross‐linked and vitamin e‐doped polyethylene—a particle‐Induced osteolysis animal study
Authors: Huang Chang‐Hung , Lu Yung‐Chang , Chang Ting‐Kuo , Hsiao I‐Lin , Su Yi‐Ching , Yeh Shu‐Ting , Fang Hsu‐Wei , Huang Chun‐Hsiung
Published: May 2015

Polyethylene particle‐induced osteolysis is the primary limitation in the long‐term success of total joint replacement with conventional ultra high molecular weight polyethylene (UHMWPE). Highly cross‐linked polyethylene (HXLPE) and vitamin E‐doped cross‐linked polyethylene (VE‐HXLPE) have been developed to increase the wear resistance of joint surfaces. However, very few studies have reported on the incidence of particle‐induced osteolysis for these novel materials. The aim of this study was to use a particle‐induced osteolysis animal model to compare thein vivobiological response to different polymer particles. Three commercially available polymers (UHMWPE, HXLPE, and VE‐HXLPE) were compared. Osseous properties including the bone volume relative to the tissue volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD) were examined using micro computed tomography. Histological analysis was used to observe tissue inflammation in each group. This study demonstrated that the osseous properties and noticeable inflammatory reactions were obviously decreased in the HXLPE group. When compared with the sham group, a decrease of 12.7% was found in BV/TV, 9.6% in BMD and 8.3% in Tb.Th for the HXLPE group. The heightened inflammatory response in the HXLPE group could be due to its smaller size and greater amount of implanted particles. Vitamin E diffusedin vivomay not affect the inflammatory and osteolytic responses in this model. The morphological size and total cumulative amount of implanted particles could be critical factors in determining the biological response. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 561–567, 2016.
Dimensionally stable and bioactive membrane for guided bone regeneration: An in vitro study
Authors: Rowe Matthew J. , Kamocki Krzysztof , Pankajakshan Divya , Li Ding , Bruzzaniti Angela , Thomas Vinoy , Blanchard Steve B. , Bottino Marco C.
Published: May 2015

Composite fibrous electrospun membranes based on poly(dl‐lactide) (PLA) and poly(ε‐caprolactone) (PCL) were engineered to include borate bioactive glass (BBG) for the potential purposes of guided bone regeneration (GBR). The fibers were characterized using scanning and transmission electron microscopies, which respectively confirmed the submicron fibrous arrangement of the membranes and the successful incorporation of BBG particles. Selected mechanical properties of the membranes were evaluated using the suture pullout test. The addition of BBG at 10 wt % led to similar stiffness, but more importantly, it led to a significantly stronger (2.37 ± 0.51 N mm) membrane when compared with the commercially available Epiguide® (1.06 ± 0.24 N mm) under hydrated conditions. Stability (shrinkage) was determined after incubation in a phosphate buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL‐based membranes with or without BBG incorporation (10.07–16.08%) was similar to that of Epiguide (14.28%). Cell proliferation assays demonstrated a higher rate of preosteoblasts proliferation on BBG‐containing membranes (6.4‐fold) over BBG‐free membranes (4‐ to 5.8‐fold) and EpiGuide (4.5‐fold), following 7 days of in vitro culture. Collectively, our results demonstrated the ability to synthesize, via electrospinning, stable, polymer‐based submicron fibrous BBG‐containing membranes capable of sustaining osteoblastic attachment and proliferation—a promising attribute in GBR. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 594–605, 2016.
The influence of poly(ethylene glycol) ether tetrasuccinimidyl glutarate on the structural, physical, and biological properties of collagen fibers
Authors: Sanami Mohammad , Sweeney India , Shtein Zvi , Meirovich Sigal , Sorushanova Anna , Mullen Anne Maria , Miraftab Mohsen , Shoseyov Oded , O'Dowd Colm , Pandit Abhay , Zeugolis Dimitrios I.
Published: May 2015

Various chemical, natural, or synthetic in origin, crosslinking methods have been proposed over the years to stabilise collagen fibers. However, an optimal method has yet to be identified. Herein, we ventured to assess the potential of 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate, as opposed to glutaraldehyde (GTA), genipin and carbodiimide, on the structural, physical and biological properties of collagen fibers. The 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate induced an intermedium surface smoothness, denaturation temperature and swelling. The 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers had significantly higher stress at break values than the carbodiimide fibers, but significantly lower than the GTA and genipin fibers. With respect to strain at break, no significant difference was observed among the crosslinking treatments. The 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate fibers exhibited significantly higher cell metabolic activity and DNA concentration that all other crosslinking treatments, promoted consistently cellular elongation along the longitudinal fiber axis and by day 7 they were completely covered by cells. Collectively, this work clearly demonstrates the potential of 4‐star poly(ethylene glycol) ether tetrasuccinimidyl glutarate as collagen crosslinker. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 914–922, 2016.
Serum 25-Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of a Desirable Range
Authors: El-Hajj Fuleihan Ghada , Bouillon Roger , Clarke Bart , Chakhtoura Marlene , Cooper Cyrus , McClung Michael , Singh Ravinder J
Published: May 2015

Hypovitaminosis D is prevalent worldwide but proportions vary widely between regions, depending on genetic and lifestyle factors, the threshold to define deficiency, and accuracy of 25-hydroxyvitamin D (25OHD) assays used. Latitude, pollution, concealing clothing, sun exposure, gender, dietary habits, and lack of government regulation account for up to 50% in variations in serum 25OHD levels, whereas genetic polymorphisms in the vitamin D pathway account for less than 5%. Organizations/societies have developed guidelines for recommended desirable 25OHD levels and vitamin D doses to reach them, but their applicability across age groups and populations are still debated. This article and the accompanying online Supporting Information highlight sources of variations in circulating 25OHD levels, uncertainties and knowledge gaps, and analytical problems facing 25OHD assays, while keeping efficacy and safety data as the dominant factors when defining a desirable range for 25OHD levels. We propose a desirable range of 20 to 40 ng/mL (50 to 100 nmol/L), provided precise and accurate assays are used. Although slightly lower levels, 15 to 20 ng/mL, may be sufficient for some infants and adults, higher levels, 40 to 60 ng/mL, may still be safe. This desirable range allows physicians to tailor treatment while taking season, lifestyle, vitamin D intake, and other sources of variation into account. We reserve 25OHD measurements for at-risk patients, defined by disease or lifestyle, and the use of 25OHD assays calibrated against the recommended international standards. Most target groups reach desirable target levels by a daily intake of 400 to 600 IU for children and 800 IU for adults. A total daily allowance of vitamin D of up to 1000 IU in the pediatric age groups, and up to 2000 IU in adults, tailored to an individual patient risk profile, is probably safe over long durations. Additional data are needed to validate the proposed range and vitamin D doses, especially in children, pregnant women, and non-white populations. © 2015 American Society for Bone and Mineral Research.
Global Gene Deregulations in FASN Silenced Retinoblastoma Cancer Cells: Molecular and Clinico‐Pathological Correlations
Authors: Sangeetha Manoharan , Deepa Perinkulam Ravi , Rishi Pukhraj , Khetan Vikas , Krishnakumar Subramanian
Published: May 2015

Activation of fatty acid synthase (FASN) enzyme in the de novo lipogenic pathway has been reported in various cancers including retinoblastoma (RB), a pediatric ocular cancer. The present study investigates lipogenesis‐dependent survival of RB cancer cells and the associated molecular pathways in FASN silenced RB cells. The siRNA‐mediated FASN gene knockdown in RB cancer cells (Y79, WERI RB1) repressed FASN mRNA and protein expressions, and decreased cancer cell viability. Global gene expression microarray analysis was performed in optimized FASN siRNA transfected and untransfected RB cells. Deregulation of various downstream cell signaling pathways such as EGFR (n = 55 genes), TGF‐beta (n = 45 genes), cell cycle (n = 41 genes), MAPK (n = 39 genes), lipid metabolism (n = 23 genes), apoptosis (n = 21 genes), GPCR signaling (n = 21 genes), and oxidative phosporylation (n = 18 genes) were observed. The qRT‐PCR validation in FASN knockdown RB cells revealed up‐regulation of ANXA1, DAPK2, and down‐regulation of SKP2, SREBP1c, RXRA, ACACB, FASN, HMGCR, USP2a genes that favored the anti‐cancer effect of lipogenic inhibition in RB. The expression of these genes in primary RB tumor tissues were correlated with FASN expression, based on their clinico‐pathological features. The differential phosphorylation status of the various PI3K/AKT pathway proteins (by western analysis) indicated that the FASN gene silencing indeed mediated apoptosis in RB cells through the PI3K/AKT pathway. Scratch assay clearly revealed that FASN silencing reduced the invading property of RB cancer cells. Dependence of RB cancer cells on lipid metabolism for survival and progression is implicated. Thus targeting FASN is a promising strategy in RB therapy. J. Cell. Biochem. 116: 2676–2694, 2015. © 2015 Wiley Periodicals, Inc.
C/EBPβ Mediates TNF‐α‐Induced Cancer Cell Migration by Inducing MMP Expression Dependent on p38 MAPK
Authors: Xia Peiyi , Zhang Rui , Ge Gaoxiang
Published: May 2015

Tumor necrosis factor (TNF)‐α is a pleiotropic cytokine that triggers cell proliferation, cell death, or inflammation. Besides its cytotoxic effect on cancer cells, TNF‐α exerts tumor promoting activity. Aberrant TNF‐α signaling promotes cancer cell motility, invasiveness, and enhances cancer metastasis. Exaggerated tumor cell migration, invasion, and metastasis by TNF‐α has been attributed to the activation of NF‐κB signaling. It is yet to be elucidated if other signaling pathways and effector molecules are involved in TNF‐α‐induced cancer cell migration and metastasis. Expression of C/EBPβ, a transcription factor involved in metabolism, inflammation, and cancer, is increased upon TNF‐α treatment. TNF‐α induces C/EBPβ expression by enhancing its transcription and protein stability. Activation of p38 MAPK, but not NF‐κB or JNK, is responsible for TNF‐α‐induced stabilization of C/EBPβ protein. C/EBPβ is involved in TNF‐α‐induced cancer cell migration. Knockdown of C/EBPβ inhibits TNF‐α‐induced cell migration, while overexpression of C/EBPβ increases migration of cancer cells. C/EBPβ is translated into transcriptional activator LAP1 and LAP2 and transcriptional repressor LIP utilizing alternative in‐frame translation start sites. Despite TNF‐α induces expression of all three isoforms, LAP1/2, but not LIP, promote cancer cell migration. TNF‐α induced MMP1/3 expression, which was abrogated by C/EBPβ knockdown or p38 MAPK inhibition. MMP inhibitor or knockdown of MMP1/3 diminished TNF‐α‐ and C/EBPβ‐induced cell migration. Thus, C/EBPβ mediates TNF‐α‐induced cancer cell migration by inducing MMP1/3 expression, and may participate in the regulation of inflammation‐associated cancer metastasis. J. Cell. Biochem. 116: 2766–2777, 2015. © 2015 Wiley Periodicals, Inc.
Long term persistence of NS5A inhibitor‐resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy
Authors: Yoshimi Satoshi , Imamura Michio , Murakami Eisuke , Hiraga Nobuhiko , Tsuge Masataka , Kawakami Yoshiiku , Aikata Hiroshi , Abe Hiromi , Hayes C. Nelson , Sasaki Tamito , Ochi Hidenori , Chayama Kazuaki
Published: May 2015

Although interferon‐free antiviral treatment is expected to improve treatment of hepatitis C, it is unclear to what extent pre‐existing drug‐resistant amino acid substitutions influence response to therapy. The impact of pre‐existing drug‐resistant substitutions on virological response to daclatasvir and asunaprevir combination therapy was studied in genotype 1b hepatitis C virus (HCV)‐infected patients. Thirty‐one patients were treated with daclatasvir and asunaprevir for 24 weeks. Twenty‐six patients achieved sustained virological response (SVR), three patients experienced viral breakthrough, and two patients relapsed. Direct sequencing analysis of HCV showed the existence of daclatasvir‐resistant NS5A‐L31M or ‐Y93H/F variants in nine out of 30 patients (30%) prior to treatment, while asunaprevir‐resistant NS3‐D168 mutations were not detected in any patient. All 21 patients with wild‐type NS5A‐L31 and ‐Y93 achieved SVR, whereas only four out of nine patients (44%) with L31M or Y93F/H substitutions achieved SVR (P = 0.001). Ultra‐deep sequencing analysis showed that treatment failure was associated with the emergence of both NS5A‐L31/Y93 and NS3‐D168 variants. NS5A‐L31/Y93 variants remained at high frequency through post‐treatment weeks 103 through 170, while NS3‐D168 variants were replaced by wild‐type in all patients. In conclusion, pre‐existence of NS5A inhibitor‐resistant substitutions compromised the response to daclatasvir and asunaprevir combination therapy, and treatment failure was associated with the emergence of both NS5A‐L31/Y93 and NS3‐D168 variants. While asunaprevir‐resistant variants that emerged during therapy returned to wild‐type, daclatasvir‐resistant variants tended to persist in the absence of the drug. J. Med. Virol. 87:1913–1920, 2015. © 2015 Wiley Periodicals, Inc.
Sites of disruption within E1 and E2 genes of HPV16 and association with cervical dysplasia
Authors: Tsakogiannis D. , Gortsilas P. , Kyriakopoulou Z. , Ruether I.G.A. , Dimitriou T.G. , Orfanoudakis G. , Markoulatos P.
Published: May 2015

Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or E2 genes. The present study investigated the disruption of E1, E2 genes in a total of eighty four HPV16‐positive precancerous and cervical cancer specimens derived from Greek women (seventeen paraffin‐embedded cervical biopsies and sixty seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and nine overlapping primer sets respectively, in order to define the sites of disruption. Extensive mapping analysis revealed that disruption/deletion events within E2 gene occurred in high grade and cervical cancer samples (x2 test, P < 0.01), while no evidence of E2 gene disruption was documented among low grade cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene occur both in high and low grade cervical intraepithelial neoplasia. This leads to the assumption that in low grade cervical intraepithelial neoplasias only E1 gene disruption was involved (Fisher's exact test, P < 0.05), while in high grade malignancies and cervical cancer cases deletions in both E1 and E2 genes occurred. Furthermore, the most prevalent site of disruption of E1 gene was located between nucleotides 1059 and 1323, while the most prevalent deleted region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge region). Therefore, it is proposed that each population has its own profile of frequencies and sites of disruptions and extensive mapping analysis of E1 and E2 genes is mandatory in order to determine suitable markers for HPV16 DNA integration analysis in distinct populations. J. Med. Virol. 87:1973–1980, 2015. © 2015 Wiley Periodicals, Inc.
Evaluation of a PCR/ESI‐MS platform to identify respiratory viruses from nasopharyngeal aspirates
Authors: Lin Yong , Fu Yongfeng , Xu Menghua , Su Liyun , Cao Lingfeng , Xu Jin , Cheng Xunjia
Published: May 2015

Acute respiratory tract infection is a major cause of morbidity and mortality worldwide, particularly in infants and young children. High‐throughput, accurate, broad‐range tools for etiologic diagnosis are critical for effective epidemic control. In this study, the diagnostic capacities of an Ibis platform based on the PCR/ESI‐MS assay were evaluated using clinical samples. Nasopharyngeal aspirates (NPAs) were collected from 120 children (<5 years old) who were hospitalized with lower respiratory tract infections between November 2010 and October 2011. The respiratory virus detection assay was performed using the PCR/ESI‐MS assay and the DFA. The discordant PCR/ESI‐MS and DFA results were resolved with RT‐PCR plus sequencing. The overall agreement for PCR/ESI‐MS and DFA was 98.3% (118/120). Compared with the results from DFA, the sensitivity and specificity of the PCR/ESI‐MS assay were 100% and 97.5%, respectively. The PCR/ESI‐MS assay also detected more multiple virus infections and revealed more detailed subtype information than DFA. Among the 12 original specimens with discordant results between PCR/ESI‐MS and DFA, 11 had confirmed PCR/ESI‐MS results. Thus, the PCR/ESI‐MS assay is a high‐throughput, sensitive, specific and promising method to detect and subtype conventional viruses in respiratory tract infections and allows rapid identification of mixed pathogens. J. Med. Virol. 87:1867–1871, 2015. © 2015 Wiley Periodicals, Inc.
Rapid multicomponent relaxometry in steady state with correction of magnetization transfer effects
Authors: Liu Fang , Block Walter F. , Kijowski Richard , Samsonov Alexey
Published: May 2015

Purpose

To study the effects of magnetization transfer (MT) on multicomponent T2 parameters obtained using mcDESPOT in macromolecule‐rich tissues and to propose a new method called mcRISE to correct MT‐induced biases.

Methods

The two‐pool mcDESPOT model was modified by the addition of an exchanging macromolecule proton pool to model the MT effect in cartilage. The mcRISE acquisition scheme was developed to provide sensitivity to all pools. An incremental fitting was applied to estimate MT and relaxometry parameters with minimized coupling. The interaction between MT and relaxometry parameters, efficacy of MT correction, and feasibility of mcRISE in vivo were investigated in simulations and in healthy volunteers.

Results

The MT effect caused significant errors in multicomponent T1/T2 values and in fast‐relaxing water fraction fF, which is consistent with previous experimental observations. fF increased significantly with macromolecule content if MT was ignored. mcRISE resulted in a multifold reduction of MT biases and yielded decoupled multicomponent T1/T2 relaxometry and quantitative MT parameters.

Conclusion

mcRISE is an efficient approach for correcting MT biases in multicomponent relaxometry based on steady state sequences. Improved specificity of mcRISE may help to elucidate the sources of the previously described high sensitivity of noncorrected mcDESPOT parameters to disease‐related changes in cartilage and the brain. Magn Reson Med 75:1423–1433, 2016. © 2015 Wiley Periodicals, Inc.
Nanoprobes for enhanced electrochemical DNA sensors
Authors: Zaffino Rosa Letizia , Galan Teresa , Pardo Wilmer Alfonso , Mir Mònica , Samitier Josep
Published: May 2015

Biosensors, small devices enabling selective bioanalysis because of properly assembled biological recognition molecules, represent the fortuitous results of years of interdisciplinary and complementary investigations in different fields of science. The ultimate role of a biosensor is to provide coupling between the recognition element and the analyte of interest, bringing a quantitative value of its concentrations into a complex sample matrix. They offer many advantages. Among them, portability, low cost with fast response times, and the possibility to operate in situ without the need for sample preparation are certainly the most important. Among biosensors, a large space is occupied by DNA biosensors. Screening genomic DNA is of fundamental importance for the development of new tools available to physicians during the clinical process. Sequencing of individual human genomes, accomplished principally by microarrays with optical detection, is complex and expensive for current clinical protocols. Efforts in research are focused on simplifying and reducing the cost of DNA biosensors. For this purpose, other transduction techniques are under study to make more portable and affordable DNA biosensors. Compared with traditional optical detection tools, electrochemical methods allow the same sensitivity and specificity but are less expensive and less labor intensive. Scalability of electrochemical devices makes it possible to use the advantages introduced by nanosized components. The involvement of nanomaterials and nanostructures with custom‐tailored shapes and properties is expected to rapidly boost the field of electrochemical DNA biosensors and, in general, that of next‐generation sequencing technologies. WIREs Nanomed Nanobiotechnol 2015, 7:817–827. doi: 10.1002/wnan.1344

This article is categorized under:

Diagnostic Tools > Biosensing

Diagnostic Tools > Diagnostic Nanodevices

Diagnostic Tools > In Vitro Nanoparticle-Based Sensing