bluuebunny/crossref_metadata_2025_split huggingface dataset:
A2B adenosine receptor activation switches differentiation of bone marrow cells to a CD11c+Gr‐1+ dendritic cell subset that promotes the Th17 response
Authors: Liang Dongchun , Zuo Aijun , Shao Hui , Chen Mingjiazi , Kaplan Henry J. , Sun Deming 
Published: July 2015

AbstractAdenosine is one of the major molecules associated with inflammation. We have previously reported that an adenosine receptor (AR) agonist has an enhancing effect on Th17 autoimmune responses, even though it suppressed Th1 responses. To determine the mechanism involved, we have examined the effect of AR agonists on mouse bone marrow dendritic cell (BMDC) differentiation and function. We show that mouse bone marrow cells (BMCs) differentiated into CD11c+Gr‐1+ dentritic cells (DCs) when cultured in granulocyte macrophage colony‐stimulating factor (GM‐CSF)‐containing medium containing an AR agonist. The non‐selective AR agonist NECA and an A2BR‐specific agonist had a similar effect, and the effect of NECA could be blocked by an A2BR‐specific antagonist. Unlike CD11c+Gr‐1− BMDCs, which have a greater stimulatory effect on Th1 T cells than Th17 cells, CD11c+Gr‐1+ BMDCs had a greater stimulatory effect on Th17 autoreactive T cells than on Th1 autoreactive T cells and this effect depended on γδ T cell activation.
Two Rare Mutations in theCOL1A2Gene Associate With Low Bone Mineral Density and Fractures in Iceland
Authors: Styrkarsdottir Unnur , Thorleifsson Gudmar , Eiriksdottir Berglind , Gudjonsson Sigurjon A , Ingvarsson Thorvaldur , Center Jacqueline R , Nguyen Tuan V , Eisman John A , Christiansen Claus , Thorsteinsdottir Unnur , Sigurdsson Gunnar , Stefansson Kari 
Published: August 2015

ABSTRACT We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures of osteoporosis in Icelanders. Mutations in COL1A2 are known to cause the autosomal dominant disorder osteogenesis imperfecta. Both variants associate with low BMD and with osteoporotic fractures. p.Gly496Ala (frequency of 0.105%) shows the strongest association with low BMD at the spine (p = 1.8 × 10−7, odds ratio [OR] = 4.61 [95% confidence interval (CI) 2.59, 8.18]), whereas p.Gly703Ser (frequency of 0.050%) is most strongly associated with low BMD at the hip (p = 1.9 × 10−8, OR = 9.34 [95% CI 4.28, 20.3]). Association with fractures was p = 2.2 × 10−5, OR = 3.75 (95% CI 2.03, 6.93) and p = 0.0023, OR = 4.32 (95% CI 1.69, 11.1), respectively. The carriers of these variants do not have signs of osteogenesis imperfecta other than low BMD, demonstrating that similar mutations in COL1A2 can affect skeletal phenotypes in more than one way. © 2015 American Society for Bone and Mineral Research.
The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Is Poorly Associated With Vertebral Strength
Authors: Maquer Ghislain , Lu Yongtao , Dall'Ara Enrico , Chevalier Yan , Krause Matthias , Yang Lang , Eastell Richard , Lippuner Kurt , Zysset Philippe K 
Published: August 2015

ABSTRACT

Trabecular bone score (TBS) rests on the textural analysis of dual-energy X-ray absorptiometry (DXA) to reflect the decay in trabecular structure characterizing osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible because prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly owing to an unrealistic setup and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings were used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation (“full vertebra”); 2) via the classical endplate embedding (“vertebral body”); or 3) via a ball joint to induce anterior wedge failure (“vertebral section”). High-resolution peripheral quantitative computed tomography (HR-pQCT) scans acquired from prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (Fexp) and apparent failure stress (σexp) was assessed, and their relative contribution to a multilinear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with Fexp and σexp, except for the “vertebral body” case (r2 = 0.396, p = 0.028). Aside from the “vertebra section” setup where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing setup, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk. © 2015 American Society for Bone and Mineral Research.
A preoperative metabolic marker of parkinsonian apathy following subthalamic nucleus stimulation
Authors: Gesquière‐Dando Aude , Guedj Eric , Loundou Anderson , Carron Romain , Witjas Tatiana , Fluchère Frédérique , Delfini Marie , Mundler Laura , Regis Jean , Azulay Jean‐Philippe , Eusebio Alexandre 
Published: July 2015

AbstractBackgroundSubthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) has been associated with the development of postoperative apathy. Debate on the causes of postoperative apathy continues, and the dominant hypothesis is that stimulation or dopaminergic drug reductions are causal in its development. We hypothesized that a preoperative predisposition to apathy also could exist. To this end, we sought to identify a preoperative metabolic pattern using [18]Fluorodeoxyglucose Positron Emission Tomography (PET), which could be associated with the occurrence of postoperative apathy after STN‐DBS for PD.MethodsThirty‐four patients with PD, not clinically apathetic, underwent an [18]Fluorodeoxyglucose‐PET scan before surgery of STN‐DBS, and were tested for the occurrence of apathy 1 y after surgery. Whole‐brain voxel‐based PET intergroup comparison (P < 0.005; corrected for the cluster) was evaluated between patients who developed apathy at 1 y and those who did not.ResultsEight patients (23.5%) became apathetic after surgery. Motor improvement and decrease in dopaminergic treatment were similar in both postoperative apathy and non‐apathy groups. We found a cluster of significantly greater metabolism in the postoperative apathy group within the cerebellum, brainstem (in particular ventral tegmental area), temporal lobe, insula, amygdala, lentiform nucleus, subgenual anterior cingulate, and inferior frontal gyrus. A metabolic value above 68 could discriminate patients who would develop postoperative apathy with 100% sensitivity and 88.5% specificity.ConclusionsWe describe a preoperative metabolic pattern associated with the development of apathy after STN‐DBS in PD. This suggests the existence of a predisposition to apathy, which may further be triggered by perioperative drug modifications. © 2015 International Parkinson and Movement Disorder Society
Repair of complex vesicovaginal fistulas by combining a rotational bladder flap and full thick vascular peritoneal interposition
Authors: Chen Yuke , Yu Wei , Yang Yang , Jin Jie , Wu Shiliang , Xiao Yunxiang 
Published: July 2015

PurposeTo present the experience of repairing iatrogenic vesicovaginal fistulas (VVFs) using a rotational bladder flap and peritoneal interposition technique.MethodsBetween January 2009 and June 2014, a total of 18 patients (mean age, 44.0 years; age range, 29–51 years) with VVFs were treated using a transperitoneal approach. All VVFs were complications of gynecologic procedures. Twelve patients experienced recurrent VVFs and one patient had a concomitant rectovaginal fistula after radiotherapy. The fistula was approached transabdominally. The peritoneum covering the bladder was isolated to expose the bladder and prepare for the interposition. The bladder was opened along the sagittal plane to the fistula and a bladder flap was rotated downward to fill the fistula defect. The vaginal defect was closed, then a flap using the isolated peritoneum was interposed and fixed between the vagina and bladder. A ureteral re‐implantation was performed in one patient. All VVF procedures were performed by one urologist (SW). Repair of the rectovaginal fistula was performed by a general surgeon at the same time.ResultsSeventeen patients (success rate = 94% [100% for primary cases and 92% for recurrent cases]) had no evidence of recurrent VVF at a mean follow‐up of 20 months (range, 6–36 months). The only patient who had previously undergone a repair procedure failed.ConclusionsA transperitoneal approach with the use of a rotational bladder flap and peritoneal interposition might be a feasible and reliable procedure for surgical management of iatrogenic VVFs, especially in complicated cases. Neurourol. Urodynam. 35:934–938, 2016. © 2015 Wiley Periodicals, Inc.
Carboplatin Rechallenge After Hypersensitivity Reactions in Pediatric Patients With Low‐Grade Glioma
Authors: Shah Amish C. , Minturn Jane E. , Li Yimei , Belasco Jean B. , Phillips Peter C. , Kang Tammy I. , Cole Kristina A. , Waanders Angela J. , Pollack Rosanna , Didomenico Concetta , Wildes Cynthia , Fisher Michael J. 
Published: July 2015

BackgroundThe high prevalence of carboplatin hypersensitivity reactions (HSR) significantly affects the treatment of pediatric patients with low‐grade glioma (LGG). Rechallenging patients is an option that must balance the risks of repeat allergic reaction to the benefits of retaining an effective anti‐tumor regimen.ProcedureWe performed a retrospective review of children with LGG treated with carboplatin and vincristine between October 2000 and April 2013, who had a documented HSR to carboplatin. Patients were re‐exposed to carboplatin using either precautionary measures (prolonged infusion time and premedication with H1 antagonists, H2 antagonists, and corticosteroids), a desensitization protocol, or both.ResultsWe report the results of our institutional experience of carboplatin re‐exposure using both premedication with a prolonged infusion time and a desensitization protocol. Overall, 40 of 55 (73%) patients were successfully rechallenged with carboplatin, including 19 of 25 (76%) patients who underwent desensitization.ConclusionOur results demonstrate re‐exposure to be a safe alternative to abandoning carboplatin for patients with a hypersensitivity reaction. We propose a clinical algorithm for treatment. Pediatr Blood Cancer 2015; 9999:1–6 © 2015 Wiley Periodicals, Inc.
Inhibition of hERG potassium channel by the antiarrhythmic agent mexiletine and its metabolite m‐hydroxymexiletine
Authors: Gualdani Roberta , Tadini‐Buoninsegni Francesco , Roselli Mariagrazia , Defrenza Ivana , Contino Marialessandra , Colabufo Nicola Antonio , Lentini Giovanni 
Published: August 2015

AbstractMexiletine is a sodium channel blocker, primarily used in the treatment of ventricular arrhythmias. Moreover, recent studies have demonstrated its therapeutic value to treat myotonic syndromes and to relieve neuropathic pain. The present study aims at investigating the direct blockade of hERG potassium channel by mexiletine and its metabolite m‐hydroxymexiletine (MHM). Our data show that mexiletine inhibits hERG in a time‐ and voltage‐dependent manner, with an IC50 of 3.7 ± 0.7 μmol/L. Analysis of the initial onset of current inhibition during a depolarizing test pulse indicates mexiletine binds preferentially to the open state of the hERG channel. Looking for a possible mexiletine alternative, we show that m‐hydroxymexiletine (MHM), a minor mexiletine metabolite recently reported to be as active as the parent compound in an arrhythmia animal model, is a weaker hERG channel blocker, compared to mexiletine (IC50 = 22.4 ± 1.2 μmol/L). The hERG aromatic residues located in the S6 helix (Tyr652 and Phe656) are crucial in the binding of mexiletine and the different affinities of mexiletine and MHM with hERG channel are interpreted by modeling their corresponding binding interactions through ab initio calculations. The simulations demonstrate that the introduction of a hydroxyl group on the meta‐position of the aromatic portion of mexiletine weakens the interaction of the drug xylyloxy moiety with Tyr652. These results provide further insights into the molecular basis of drug/hERG interactions and, in agreement with previously reported results on clofilium and ibutilide analogs, support the possibility of reducing hERG potency and related toxicity by modifying the aromatic pattern of substitution of clinically relevant compounds.
Fano‐like resonance and scattering in dielectric(core)–metal(shell) composites embedded in active host matrices
Authors: Jule Leta , Mal'nev Vadim , Mesfin Belayneh , Senbeta Teshome , Dejene Francis , Rorro Kittesa 
Published: July 2015

AbstractWe investigate light scattering by core–shell consisting of metal/dielectric composites considering spherical and cylindrical nanoinclusions, within the framework of the conventional Rayleigh approximation. By writing the electric potential distribution of the dielectric core, metal shell and host matrices in the core–shell composites, we have derived an analytical expression for the polarization of individual metal cover spherical and cylindrical inclusions, under long wave approximation. Moreover, we demonstrated that modeling the dielectric function of the dispersive core for both frequency dependent (the scattering cross‐section) and frequency independent dielectric function of the core, one can tune Fano regions in the core–shell composites. We find that Fano‐like resonances can occur at the same input volume fraction of the metal coated provided the dielectric function of active host medium () has negative values. Such Fano‐like resonance are induced by interaction between dipolar modes of the inner core, and multipolar plasmon modes of the coated shell. These findings provide a new and promising direction which are highly desirable in ultra thin films, for designing selective solar cell absorber, sensing, lasing, nonlinear switching which have high contrast and low threshold.
A high‐resolution accurate mass (HR/AM) approach to identification, profiling and characterization of in vitro nefazodone metabolites using a hybrid quadrupole Orbitrap (Q‐Exactive)
Authors: Perry Simon J. , Nász Szilárd , Saeed Mansoor 
Published: July 2015

RationaleThis paper describes a strategy for the profiling and identification of metabolites based on chemical group classification using high‐resolution accurate mass (HR/AM) full scan mass spectrometry (MS) and All‐Ion fragmentation (AIF) MS2 data.MethodsThe proposed strategy uses a hybrid quadrupole Orbitrap (Q‐Exactive) employing stepped normalised collision energy (NCE) at 35% and 80% to produce key chemically diagnostic product ions from full coverage of the product ion spectrum. This approach allows filtering of high‐resolution AIF MS2 data in order to identify parent‐related compounds produced following incubation in rat liver microsomes (RLMs).ResultsAn antidepressant drug, nefazodone (NEF), was selected as the model test compound to demonstrate the proposed workflow for metabolite profiling. This resulted in the identification of three indicative chemical groups within NEF: triazolone, phenoxy and chlorophenylpiperazine. High‐resolution mass spectrometry provides increased specificity to distinguish between two characteristic product ion masses m/z 154.0975 (C7H12N3O) and 154.0419 (C8H9NCl), which are not fully resolved by spectrometers operating at nominal mass resolution, indicative of compounds containing the triazolone and chlorophenylpiperazine moieties, respectively.ConclusionsThis post‐acquisition processing strategy provides comprehensive detection and identification of high‐ and low‐level metabolites from an 'all‐in‐one' analysis. This enables functional groups to be systematically traced across a wide range of metabolites, leading to the successful identification of 28 in vitro NEF‐related metabolites. In our hands this approach has been applied to agrochemical environmental fate and dietary metabolism studies, as well as metabolomics and biomarker analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Use of flower‐like gold nanoparticles in time‐of‐flight mass spectrometry
Authors: Kolářová Lenka , Kučera Lukáš , Vaňhara Petr , Hampl Aleš , Havel Josef 
Published: July 2015

RationaleMany kinds of nanoparticles (NPs) have been used for mass spectrometry (MS) so far. Here we report the first use of flower‐like gold nanoparticles (AuNPs) as a mediator to enhance ionization in MS of peptides and proteins.MethodsFlower‐like AuNPs were characterized using transmission and scanning electron microscopy, UV‐VIS spectrophotometry, and laser desorption/ionization (LDI)‐MS and compared with polyhedral AuNPs. Mass spectra were obtained in positive ion mode using a time‐of‐flight (TOF) analyzer coupled with either matrix‐assisted laser desorption/ionization (MALDI) or surface‐assisted laser desorption/ionization (SALDI) methods.ResultsThe intensities of peptide peaks (m/z 500–3500) were up to 7.5× and up to 7× higher using flower‐like AuNPs and flower‐like AuNPs‐enriched α‐cyano‐4‐hydroxycinnamic acid (CHCA) matrix respectively, than the classical CHCA matrix. The signals of higher mass peptide/protein peaks (m/z 3600–17000) were up to 2× higher with using flower‐like AuNPs‐enriched CHCA matrix than conventional CHCA matrix. The signal of profile peaks generated by intact cell MALDI‐TOFMS of fibroblast suspension (m/z 4000–20000) was 2× higher with using flower‐like AuNPs combined with sinapinic acid (SA) compared to SA matrix alone. The use of flower‐like AuNPs as internal calibration standard for the calibration of MS spectra of peptides was performed.ConclusionsFlower‐like AuNPs and flower‐like AuNPs combined with CHCA or SA as combined matrices for MS measurement of peptides and proteins were used. Comparison of the conventional MALDI method and our method with flower‐like AuNPs was carried out. In addition, gold clusters generated from flower‐like AuNPs by SALDI provide a suitable internal calibration standard for MS analysis of peptides. Copyright © 2015 John Wiley & Sons, Ltd.
Microwave Energy Increases Fatty Acid Methyl Ester Yield in Human Whole Blood Due to Increased Sphingomyelin Transesterification
Authors: Metherel Adam H. , Aristizabal Henao Juan J. , Ciobanu Flaviu , Taha Ameer Y. , Stark Ken D. 
Published: August 2015

AbstractDried blood spots (DBS) by fingertip prick collection for fatty acid profiling are becoming increasingly popular due to ease of collection, minimal invasiveness and its amenability to high‐throughput analyses. Herein, we assess a microwave‐assisted direct transesterification method for the production of fatty acid methyl esters (FAME) from DBS. Technical replicates of human whole blood were collected and 25‐μL aliquots were applied to chromatography strips prior to analysis by a standard 3‐h transesterification method or microwave‐assisted direct transesterification method under various power (variable vs constant), time (1–5 min) and reagent (1–10 % H2SO4 in methanol) conditions. In addition, a standard method was compared to a 5‐min, 30‐W power microwave in 1 % H2SO4 method for FAME yield from whole blood sphingomyelin, and sphingomyelin standards alone and spiked in whole blood. Microwave‐assisted direct transesterification yielded no significant differences in both quantitative (nmol/100 µL) and qualitative (mol%) fatty acid assessments after as little as 1.5‐ and 1‐min reaction times, respectively, using the variable power method and 5 % H2SO4 in methanol. However, 30‐W power for 5 min increased total FAME yield of the technical replicates by 14 %. This increase appears largely due to higher sphingomyelin‐derived FAME yield of up to 109 and 399 % compared to the standard method when determined from whole blood or pure standards, respectively. In conclusion, microwave‐assisted direct transesterification of DBS achieved in as little as 1‐min, and 5‐min reaction times increase total fatty acids primarily by significantly improving sphingomyelin‐derived fatty acid yield.
Smart tourism: foundations and developments
Authors: Gretzel Ulrike , Sigala Marianna , Xiang Zheng , Koo Chulmo 
Published: July 2015

AbstractSmart tourism is a new buzzword applied to describe the increasing reliance of tourism destinations, their industries and their tourists on emerging forms of ICT that allow for massive amounts of data to be transformed into value propositions. However, it remains ill-defined as a concept, which hinders its theoretical development. The paper defines smart tourism, sheds light on current smart tourism trends, and then lays out its technological and business foundations. This is followed by a brief discussion on the prospects and drawbacks of smart tourism. The paper further draws attention to the great need for research to inform smart tourism development and management.
Helminth Parasites of the Wild Rabbit Oryctolagus cuniculus (L.) in North East England
Authors: Boag B. 
Published: July 2015

During the spring, summer and autumn of 1967, 1968 and 1969, 109 rabbits were collected from two localities in Northumberland. Post mortem worm counts indicated that six species of helminths were present, Trichostrongylus retortaeformis, Passalurus ambiguus, Strongyloides papillosus, Nematodirus battus, N. filicollis and Cittotaenia denticulata.T. retortaeformis was recovered from both localities, an overall infection rate of 88% being recorded.P. ambiguus and C. denticulata were found at only one of the localities which would indicate that these species have a locally discontinuous distribution and an explanation for this has been discussed.Both Nematodirus battus and N. filicollis which are normally sheep parasites were recorded for the first time from wild rabbits. The numbers of rabbits infected and size of infection were small and in consequence the rabbit can not be considered an important reservoir for these species.
Internal structure of Cambrian Conodonts
Authors: Müller K. J. , Hinz-Schallreuter I. 
Published: July 2015

Based on material of the Upper Cambrian of Sweden the internal structure of proto-, para- and euconodonts has been investigated. The protoconodontidsGapparodusandGumellashow some special development of the median unit of the skeletal tissue. InGapparodus, long, parallel-running lamellae suggest a continuous growth, even of previously secreted lamellae, until their eventual outcropping. InGumellathe fibrous median layer decreases considerably during growth until its complete reduction, which coincides with the disappearance of the posterior wall. Paraconodonts also produced several specialities in their mode of growth. Elements with lateral processes such asProacodusandSerratocambriadeveloped by allometric growth. The lamellae are much more widely spaced in the process than in the main cusp to attain the required length of the former. InSerratocambriaadditional lamellae are inserted in the process. Thin sections of tricuspidate westergaardodinids reveal paraconodontid growth with lamellar remains in the tip of the median denticle, which are isolated from the growth lines in the lateral denticles. Based on this observation a hypothetical growth model explains the lamellar development as a result of stress and strain. The Ordovician euconodontidChosonodinaclearly shows white matter and is thus unrelated, but homeomorphic toWestergaardodina. Cambropustulafrom the lower Upper Cambrian is the oldest euconodont yet but it lacks white matter. The latter was an evolutionary novelty, which progressively developed in the euconodont line.The systematic position of conodonts is briefly discussed; the studied material cannot contribute to the hypothesis of neural crest derived skeletal tissue.