bluuebunny/crossref_metadata_2025_split huggingface dataset:
TOWERS: T‐One with Enhanced Robustness and Speed
Authors: Eldeniz Cihat , Finsterbusch Jürgen , Lin Weili , An Hongyu 
Published: July 2015

PurposeA new T1 mapping method is proposed that is accurate, rapid, and robust to motion. Considering these features, the method is dubbed “T‐One with Enhanced Robustness and Speed (TOWERS).”MethodsTOWERS is composed of inversion recovery (IR) and saturation recovery (SR) acquisitions. In the IR acquisitions, a slice reordering scheme is used to sample all slices in an efficient manner, whereas the SR acquisitions serve as references for motion estimation. Furthermore, as opposed to the usual way of running generalized autocalibrating partially parallel acquisitions (GRAPPA) calibration only once at the beginning, GRAPPA coefficients are updated in the middle and at the end, and are later used for retrospectively correcting for motion artifacts. Finally, sub‐voxel magnetization tracking is deployed to account for motion‐induced signal evolution changes.ResultsWhole‐brain T1 mapping data with a spatial resolution of 1.56 × 1.56 × 2.00 mm can be collected within 2.5 min. TOWERS and the gold‐standard IR method agree well in phantom, while high reproducibility is achieved in vivo. High‐quality T1 maps in the presence of severe motion show the robustness of the method.ConclusionThe proposed method, TOWERS, is shown to be rapid, accurate, and robust. Multiple GRAPPA calibrations and sub‐voxel magnetization tracking make TOWERS unique. Magn Reson Med 76:118–126, 2016. © 2015 Wiley Periodicals, Inc.
Walking is a Feasible Physical Activity for People with Rheumatoid Arthritis: A Feasibility Randomized Controlled Trial
Authors: Baxter Susan V. , Hale Leigh A. , Stebbings Simon , Gray Andrew R. , Smith Catherine M. , Treharne Gareth J. 
Published: July 2015

AbstractBackgroundExercise has been recognized as important in the management of rheumatoid arthritis (RA). Walking is a low‐cost and low‐impact activity, requiring little supervision. It requires no specialist training, is suited to a variety of environments and is inherently a clinically meaningful measure of independence. The aim of the present study was to determine whether a designed walking programme for people with RA successfully facilitated regular physical activity in participants, without detriment to pain levels.MethodsThirty‐three people with RA were recruited from Dunedin Hospital rheumatology outpatient clinics and enrolled in a walking randomized controlled trial (RCT) feasibility study. Participants were randomly allocated to the walking intervention (n = 11) or control (n = 22) groups. Control participants received a nutrition education session, and the walking intervention group received instructions on a walking route with three loops, to be completed 3–4 times per week. The walking route shape was designed so that the length of the walk could be tailored by participants. Both groups were assessed at baseline and six weeks later. The primary outcome measures were feasibility, acceptability and safety. The principal secondary outcome was change in walking speed after the intervention. Additional outcome measures were a step‐up test, activity limitations (on the Health Assessment Questionnaire), global well‐being (on the European Quality of Life Questionnaire), self‐efficacy for managing arthritis symptoms, self‐efficacy for physical activity, daily pedometer readings and a daily visual analogue scale for pain.ResultsParticipants successfully completed the walk for the suggested frequency, indicating feasibility and acceptability. There were no reported adverse effects of participation and the walking intervention group did not have higher daily pain levels than the control group, indicating safety. The walking intervention group showed a pattern of improvements in self‐efficacy and global well‐being; no changes in these outcomes were noted in the control group. No outcome measure showed statistically significant between‐group differences.ConclusionsWalking appears to be a feasible, acceptable and safe intervention for people with RA. These findings inform the design and power requirements of larger trials of structured walking interventions. Copyright © 2015 John Wiley & Sons, Ltd.
Unravelling detrusor underactivity: Development of a bladder outlet resistance—Bladder contractility nomogram for adult male patients with lower urinary tract symptoms
Authors: Oelke Matthias , Rademakers Kevin L. J. , van Koeveringe Gommert A. ,   on behalf of the FORCE Research Group, Maastricht & Hannover
Published: July 2015

AimsVoiding dysfunction in adult men may be caused by bladder outlet obstruction (BOO) and/or detrusor underactivity (DU). Until now, it is only possible to classify BOO and DU by pressure‐flow analysis. Low values of the maximum Watts factor (Wmax) indicate DU but thresholds for the diagnosis have not been established. Purpose of this study was to construct a nomogram using bladder outlet resistance and detrusor contractility in order to classify BOO and DU simultaneously.MethodsTreatment naïve men aged ≥40 years with uncomplicated lower urinary tract symptoms (LUTS) were prospectively evaluated. Patients were assessed with IPSS, prostate volume, uroflowmetry, post‐void residual, and pressure‐flow measurement. The bladder outlet obstruction index (BOOI) was used to determine BOO‐grade and Wmax to calculate detrusor contractility. Individual BOOI‐Wmax values were plotted in a graph. Linear interpolation was applied to determine the 10th, 25th, 50th, 75th, and 90th percentiles.ResultsRetrospective analysis of 822 male patients with means of 64 years, IPSS 16, and prostate volume of 40 cc. Patient and clinical parameters of the <25th percentile groups were significantly different compared to the 25th–50th percentiles: age (66 vs. 63 years, P = 0.006), bladder capacity (503 vs. 442 ml, P = 0.009), post‐void residual urine (167 vs. 116 ml, P = 0.001), and voiding efficiency (67% vs. 73%, P = 0.015).ConclusionsThe nomogram quantifies the relationship between detrusor contractility and BOO in men with LUTS. A measurement value <25th percentile correlates with clinical indicators of DU and is proposed as a cut‐off value for DU‐diagnosis. Higher age, bladder capacity, and PVR as well as lower voiding efficiency indicate DU. Neurourol. Urodynam. 35:980–986, 2016. © 2015 Wiley Periodicals, Inc.
Hunting attacks in the dark: clustering and correlation analysis for unsupervised anomaly detection
Authors: Mazel Johan , Casas Pedro , Fontugne Romain , Fukuda Kensuke , Owezarski Philippe 
Published: July 2015

SummaryNetwork anomalies and attacks represent a serious challenge to ISPs, who need to cope with an increasing number of unknown events that put their networks' integrity at risk. Most of the network anomaly detection systems proposed so far employ a supervised strategy to accomplish their task, using either signature‐based detection methods or supervised‐learning techniques. The former fails to detect unknown anomalies, exposing the network to severe consequences; the latter requires labeled traffic, which is difficult and expensive to produce. In this paper, we introduce a powerful unsupervised approach to detect and characterize network anomalies in the dark, that is, without relying on signatures or labeled traffic. Unsupervised detection is accomplished by means of robust clustering techniques, combining subspace clustering with correlation analysis to blindly identify anomalies. To alleviate network operator's post‐processing tasks and to speed up the deployment of effective countermeasures, anomaly ranking and characterization are automatically performed on the detected events. The system is extensively tested with real traffic from the Widely Integrated Distributed Environment backbone network, spanning 6years of flows captured from a trans‐Pacific link between Japan and the USA, using the MAWILab framework for ground‐truth generation. We additionally evaluate the proposed approach with synthetic data, consisting of traffic from an operational network with synthetic attacks. Finally, we compare the performance of the unsupervised detection against different previously used unsupervised detection techniques, as well as against multiple anomaly detectors used in MAWILab. Copyright © 2015 John Wiley & Sons, Ltd.
A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma
Authors: Mitchell Deanna , Bergendahl Genevieve , Ferguson William , Roberts William , Higgins Timothy , Ashikaga Takamaru , DeSarno Mike , Kaplan Joel , Kraveka Jacqueline , Eslin Don , Werff Alyssa Vander , Hanna Gina K. , Sholler Giselle L. Saulnier 
Published: July 2015

BackgroundThe primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses.ProcedureEighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28‐day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters Cmax, AUC0‐24, t1/2, CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma.ResultsWe determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m2. The non‐dose‐limiting toxicities at this dose were mainly anorexia and pain. The dose‐limiting toxicities (DLTs) of two patients at 135 mg/m2 were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy.ConclusionsOverall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m2 IV on days 1, 8, and 15 of a 28 day cycle. Pediatr Blood Cancer 2015; 9999:1–8 © 2015 Wiley Periodicals, Inc.
Frequency of Paroxysmal Nocturnal Hemoglobinuria Clones by Multiparametric Flow Cytometry in Pediatric Aplastic Anemia Patients of Indian Ethnic Origin
Authors: Sreedharanunni Sreejesh , Sachdeva Man Updesh Singh , Bose Parveen , Varma Neelam , Bansal Deepak , Trehan Amita 
Published: July 2015

BackgroundThe literature on paroxysmal nocturnal hemoglobinuria (PNH) in aplastic anemia (AA) is largely focused on adults with few studies in children. Moreover, large studies are conspicuously absent from developing countries. Knowledge of the prevalence and utility of their detection is required before widespread use of PNH screening in pediatric AA in resource‐limited settings.MethodsWe performed a retrospective audit over a period of 9 years to study the prevalence of PNH clones by flow cytometry (FCM) in children ≤12 years of age presenting with AA, and analyzed their response to immunosuppressant therapy.ResultsNine (12.9%) out of 70 patients had PNH clones comprising >1% of the target cell population, including five patients (7.14%) with PNH clone size >10%. The clone size in monocytes ranged from 3.7% to 95.2% (median 21.1%) and in neutrophils from 1.6% to 87.6% (median 19.5%). Fluorescent aerolysin (FLAER)‐based FCM screening significantly improved the detection of PNH clones compared to non‐FLAER based screening techniques (18.4% vs. 6.25%). One child showed chronic intravascular hemolysis and another developed arterial stroke during the course of illness. None of our PNH‐positive AA patients tested for chromosome breakage studies (n = 8) showed increased clastrogen‐induced breakage.ConclusionsA lower frequency but moderate/large‐sized PNH clones were seen in our pediatric AA population, compared to western data. FLAER‐based FCM screening significantly improved the detection of PNH clones. We recommend routine FLAER‐based screening of PNH in pediatric AA patients. Pediatr Blood Cancer 2015; 9999:XX–XX © 2015 Wiley Periodicals, Inc.
Power of positive thinking in quantitative proteomics
Authors: Armengaud Jean 
Published: July 2015

Derivatization of proteins with specific isotope reagents has been widely explored for quantitative proteomics where the relative abundances of proteins present in different complex samples are compared by MS. This represents an interesting arena for innovation, where protein chemistry and MS are associated for the best of both worlds. Among the numerous reagents developed, those that introduce a permanent positive charge, such as (N‐succinimidyloxycarbonylmethyl)‐tris(2,4,6‐trimethoxyphenyl)phosphonium bromide (TMPP), increase the ionizability of their targets and thus improve the sensitivity of the approach. TMPP labeling also modifies the hydrophobicity and changes the peptide fragmentation pattern. Because TMPP reacts preferably with the N‐termini of proteins and peptides, its use has been explored for proteogenomics and de novo protein sequencing. In this issue of Proteomics, Shen et al. (Proteomics 2015, 15, 2903–2909) show that accurate quantitation of proteins can be obtained with light/heavy TMPP‐labeling of peptides, which can be easily prepared and desalted in a homemade C8‐SCX‐C8 stagetip, and then monitored by nano‐LC‐MS/MS analysis. Their results demonstrate enhanced sequence coverage compared with other approaches. Combined with an efficient enrichment procedure, the higher sensitivity of this “positive attitude” reagent may facilitate much deeper investigations into the quantitative proteomics of complex samples.
A facile synthesis of catechol‐functionalized poly(ethylene oxide) block and random copolymers
Authors: Mattson Kaila M. , Latimer Allegra A. , McGrath Alaina J. , Lynd Nathaniel A. , Lundberg Pontus , Hudson Zachary M. , Hawker Craig J. 
Published: July 2015

ABSTRACTHerein we develop a facile synthetic strategy for the functionalization of well‐defined polyether copolymers with control over the number and location of catechol groups. Previously, the functionalization of polyethylene oxide (PEO)‐based polymers with catechols has been limited to functionalization of the chain ends only, hampering the synthesis of adhesive and antifouling materials based on this platform. To address this challenge, we describe an efficient and high‐yielding route to catechol‐functionalized polyethers, which could allow the effects of polymer architecture, molecular weight, and catechol incorporation on the adhesive properties of surface‐anchored PEO to be studied. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2685–2692
An effective combination of sanger and next generation sequencing in diagnostics of primary ciliary dyskinesia
Authors: Djakow Jana , Kramná Lenka , Dušátková Lenka , Uhlík Jiří , Pursiheimo Juha‐Pekka , Svobodová Tamara , Pohunek Petr , Cinek Ondřej 
Published: July 2015

SummaryBackgroundPrimary ciliary dyskinesia (PCD) is a multigenic autosomal recessive condition affecting respiratory tract and other organs where ciliary motility is required. The extent of its genetic heterogeneity is remarkable. The aim of the study was to develop a cost‐effective pipeline for genetic diagnostics using a combination of Sanger and next generation sequencing (NGS).Materials and MethodsData and samples of 33 families with 38 affected subjects with PCD diagnosed in childhood were collected over the territory of the Czech Republic. A panel of 18 PCD causative or candidate genes was implemented into an Illumina TruSeq Custom Amplicon NGS assay, and three ancestral mutations in SPAG1 were screened by conventional Sanger sequencing, which was also used for the confirmation of the NGS results and for the analysis of familial segregation.ResultsThe causative gene was DNAH5 in 11/33 (33%) probands, SPAG1 in 8/33 (24%), and DNAI1, CCDC40, LRRC6 in one family each. If the high proportion of subjects with bi‐allelic ancestral mutations in SPAG1 is corroborated in other Caucasian populations, a simple Sanger sequencing test for these three mutations may serve as an effective pre‐screening step, being followed by an NGS panel for other, much larger, PCD genes.ConclusionsWe present a combination of Sanger sequencing with an NGS panel for known and candidate PCD genes, implemented in a moderate‐size national collection of patients. This strategy has proven to be cost‐effective, rapid and reliable, and was able to detect the causative gene in two thirds of our PCD patients. Pediatr Pulmonol. 2016;51:498–509. © 2015 Wiley Periodicals, Inc.
Surface damage and mechanical strength of silicon wafers
Authors: Würzner Sindy , Buchwald Rajko , Möller Hans Joachim 
Published: July 2015

AbstractThe fracture strength of silicon wafers used for photovoltaic and microelectronic applications mainly depends on the damage structure, which is introduced on the surface during processing of the wafers. The present paper investigates the formation and development of the damage structure by scratching, which occurs during grinding processes or when sawing with diamond coated wires. The basic scratching process has been studied with a newly developed scratch technique, where test parameters comparable to a real process could be used. Single scratch tests have been performed with diamond particles on monocrystalline silicon wafers with a defined surface orientation and under different applied forces. The resulting microcrack structure, which develops under the surface, has been investigated by confocal laser scanning microscopy, scanning electron microscope and Raman spectroscopy. Details of the shape, depth and distance of the cracks have been obtained by high quality sample cross sections. The orientations of the main microcrack planes are determined. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fragmentation pathways of synthetic and naturally occurring coumarin derivatives by ion trap and quadrupole time‐of‐flight mass spectrometry
Authors: Liang Xianrui , Han Xiaomei 
Published: July 2015

RationaleSynthetic and natural coumarin derivatives possess a wide range of biological activities. Fragmentation pathway studies are important in identifying both naturally occurring coumarins and synthetic coumarins with novel structures and properties.MethodsThe fragmentation pathways of eleven coumarin derivatives are investigated by electrospray ionization (ESI) ion‐trap mass spectrometry (ESI‐ITMSn) and ESI quadrupole time‐of‐flight mass spectrometry (QTOFMS) in positive mode. Compounds 1–9 in this study were newly synthesized in our laboratory. Compounds 10 and 11 were isolated from the root of Zanthoxylum armatum.ResultsThe major fragmentation pathways for 11 coumarin derivatives are greatly affected by the heterocyclic ring structures and the side‐chain substituents. Typical losses of small neutral molecules, such as CH3CH2OH, CH2=CH2, CO, and H2O, are observed for compounds 1–5. Compounds 6–9 share similar fragmentation pathways through losses of CO, aromatic rings, and the coumarin skeleton. The main product ions at m/z 205, 219, and 220 observed for compounds 10 and 11 are produced by the loss of C5H12O2, C4H10O2, and the C4H9O2 radical, respectively.ConclusionsThe fragmentation pathways of 11 coumarin derivatives are elucidated based on ITMSn and QTOFMS spectral data. Differences in the structures of the heterocyclic rings and side‐chain substituents strongly affect the fragmentation pathways of the coumarins. The present results will facilitate further research into the fragmentation pathways and structural characterization of these classes of compounds with diverse structures. Copyright © 2015 John Wiley & Sons, Ltd.
Protonated N‐benzyl‐ and N‐(1‐phenylethyl)tyrosine amides dissociate via ion/neutral complexes
Authors: Paulose Justin , Achuthan Revi P. , Linsha Maria P. L. , Mathai George , Prasanth B. , Kumar Talluri M. V. N. , Srinivas Ragampeta 
Published: July 2015

RationaleThe collisional‐induced dissociations (CID) of the [M+H]+ ions of molecules having benzyl groups attached to N‐atoms have been proposed to involve migration of the benzyl group through the intermediacy of ion/neutral complexes (INCs). We report the investigation of the mechanism of dissociation of protonated N‐benzyl‐ and N‐(1‐phenylethyl)tyrosine amides by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and density functional theory (DFT) calculations.MethodsThe amides were synthesized from the corresponding amino acids and amines. The ESI‐MS/MS spectra were recorded using an Agilent QTOF 6540 mass spectrometer. The DFT calculations were performed by using Gaussian 09 software. The structures of the [M+H]+ ions, intermediates, products and transition states (TS) were optimized at the B3LYP/6‐31G(d,p) level of theory.ResultsCID of the [M+H]+ ions of N‐benzyltyrosine amide yields two product ions due to rearrangements: (i) the [M+H–74]+ ion (m/z 197) due to benzyl migration to the hydroxyphenyl ring and (ii) the [M+H–45]+ ion (m/z 226) due to benzyl migration to the NH2 group. DFT calculations suggest that the rearrangements occur through an INC in which the benzyl cation is the cation partner. The [M+H]+ion of N‐(1‐phenylethyl)tyrosine amide rearranges to an INC of the 1‐phenylethyl cation. Subsequent elimination of styrene occurs by transfer of a proton from the 1‐phenylethyl cation to the neutral partner.ConclusionsThe [M+H]+ ions of both N‐benzyl (1) and N‐(1‐phenylethyl) (2) tyrosine amide rearrange into INCs. The dissociation of [M+H]+ ion of 1 yields the benzyl cation and [M+H–74]+ and [M+H–45]+ due to benzyl migration to the hydroxyphenyl ring and NH2 group, respectively. However, the formation of the [M+H–74]+ ion is not observed when the aromatic ring is deactivated. The [M+H]+ ion of 2 either dissociates to form the 1‐phenylethyl cation or [M+H–styrene]+. Copyright © 2015 John Wiley & Sons, Ltd.