bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Dystonia‐Parkinsonism: Chorea and Ataxia with ATP1A3 Mutations
Authors: de Gusmao Claudio M. , Dy Marisela , Sharma Nutan 
Published: January 2016

AbstractMutations in the ATP1A3 gene (the α‐3 subunit of the Na+/K+ ATPase) are associated with rapid‐onset dystonia‐parkinsonism; alternating hemiplegia of childhood; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome). The authors report 3 cases with pleiotropic movement disorders, including a novel mutation in a patient who presented with ataxia and dysphagia. Case 1 had a history of attention deficit hyperactivity disorder and developed dysphagia, chorea, and limb dystonia after a febrile illness at age 12 years. Case 2 presented with limb dystonia at age 26 years and dysarthia and dysphagia after a febrile illness. Case 3 had a history of learning disability and developed progressive ataxia with cerebellar atrophy at age 20 years. In all cases, deleterious mutations were identified in ATP1A3. They illustrate wide phenotypic variability, including chorea and ataxia. New cases are likely to be diagnosed as knowledge about the phenotypic spectrum expands.
Rate of convergence of the Bézier variant of an operator involving Laguerre polynomials
Authors: Öksüzer Özlem , Karsli Harun , Yeşildal Fatma Taşdelen 
Published: January 2016

In the present paper, we consider the Bézier variant of an operator involving Laguerre polynomials of degree k, with α≥1, for bounded functions f defined on the interval [0,1]. In particular, by using the Chanturia modulus of variation, we estimate the rate of pointwise convergence of (Pn,αf)(x,t) at those points x∈(0,1) at which the one‐sided limits f(x+),f(x−) exist. To prove our main result, we have used some methods and techniques of probability theory. Our result extends and generalizes the very recent results of very recent results of the authors to more general classes of functions. Copyright © 2016 John Wiley & Sons, Ltd.
Early cleavages influence the molecular and the metabolic pattern of individually cultured bovine blastocysts
Authors: Milazzotto Marcella Pecora , Goissis Marcelo Demarchi , Chitwood James Lee , Annes Kelly , Soares Carlos Alexandre , Ispada Jéssica , Assumpção Mayra Elena Ortiz Ávila , Ross Pablo Juan 
Published: January 2016

SUMMARYEmbryo morphokinetics suggests that the timing of the first embryonic cell divisions may predict the developmental potential of an embryo; however, correlations between embryonic morphokinetics and physiology are not clear. Here, we used RNA sequencing to determine the gene expression profile of in vitro‐produced early‐ and late‐dividing bovine embryos and their respective blastocysts, and compared these profiles to in vivo‐produced blastocysts to identify differentially expressed genes (DEGs). Principal component analysis revealed that fast‐ and slow‐dividing embryos possess similar transcript abundance over the first cleavages. By the blastocyst stage, however, more DEGs were observed between the fast‐ and slow‐dividing embryo groups, whereas blastocysts from the slow‐dividing group were more similar to in vivo‐produced blastocysts. Gene ontology enrichment analysis showed that the slow‐dividing and in vivo‐produced blastocysts shared biological processes related to groups of up‐ or down‐regulated genes when compared to the fast‐dividing blastocysts. Based on these DEG results, we characterized the relationship between developmental kinetics and energy metabolism of in vitro‐produced bovine embryos. Embryos from fast‐ and slow‐dividing groups exhibited different pyruvate and lactate metabolism at 22 hr post‐in vitro culture (hpc), glucose consumption at 96 hpc, and glutamate metabolism at 168 hpc. Glycogen storage was similar between cleavage‐stage and morulae groups, but was higher in the blastocysts of the slow‐dividing group. On the other hand, blastocysts of the fast‐dividing group had a higher concentration of lipids. Taken together, these data identify transcriptomic and metabolic differences between embryos with different morphokinetics, suggesting that sorting embryos based on cleavage speed may select for different metabolic patterns. Mol. Reprod. Dev. 83: 324–336, 2016. © 2016 Wiley Periodicals, Inc.
Bias and precision analysis of diffusional kurtosis imaging for different acquisition schemes
Authors: Sprenger Tim , Sperl Jonathan I. , Fernandez Brice , Golkov Vladimir , Eidner Ines , Sämann Philipp G. , Czisch Michael , Tan Ek T. , Hardy Christopher J. , Marinelli Luca , Haase Axel , Menzel Marion I. 
Published: January 2016

PurposeDiffusional kurtosis imaging (DKI) is an approach to characterizing the non‐Gaussian fraction of water diffusion in biological tissue. However, DKI is highly susceptible to the low signal‐to‐noise ratio of diffusion‐weighted images, causing low precision and a significant bias due to Rician noise distribution. Here, we evaluate precision and bias using weighted linear least squares fitting of different acquisition schemes including several multishell schemes, a diffusion spectrum imaging (DSI) scheme, as well as a compressed sensing reconstruction of undersampled DSI scheme.MethodsMonte Carlo simulations were performed to study the three‐dimensional distribution of the apparent kurtosis coefficient (AKC). Experimental data were acquired from one healthy volunteer with multiple repetitions, using the same acquisition schemes as for the simulations.ResultsThe angular distribution of the bias and precision were very inhomogeneous. While axial kurtosis was significantly overestimated, radial kurtosis was underestimated. The precision of radial kurtosis was up to 10‐fold lower than axial kurtosis.ConclusionThe noise bias behavior of DKI is highly complex and can cause overestimation as well as underestimation of the AKC even within one voxel. The acquisition scheme with three shells, suggested by Poot et al, provided overall the best performance. Magn Reson Med 76:1684–1696, 2016. © 2016 International Society for Magnetic Resonance in Medicine
ISMRM Raw data format: A proposed standard for MRI raw datasets
Authors: Inati Souheil J. , Naegele Joseph D. , Zwart Nicholas R. , Roopchansingh Vinai , Lizak Martin J. , Hansen David C. , Liu Chia‐Ying , Atkinson David , Kellman Peter , Kozerke Sebastian , Xue Hui , Campbell‐Washburn Adrienne E. , Sørensen Thomas S. , Hansen Michael S. 
Published: January 2016

PurposeThis work proposes the ISMRM Raw Data format as a common MR raw data format, which promotes algorithm and data sharing.MethodsA file format consisting of a flexible header and tagged frames of k‐space data was designed. Application Programming Interfaces were implemented in C/C++, MATLAB, and Python. Converters for Bruker, General Electric, Philips, and Siemens proprietary file formats were implemented in C++. Raw data were collected using magnetic resonance imaging scanners from four vendors, converted to ISMRM Raw Data format, and reconstructed using software implemented in three programming languages (C++, MATLAB, Python).ResultsImages were obtained by reconstructing the raw data from all vendors. The source code, raw data, and images comprising this work are shared online, serving as an example of an image reconstruction project following a paradigm of reproducible research.ConclusionThe proposed raw data format solves a practical problem for the magnetic resonance imaging community. It may serve as a foundation for reproducible research and collaborations. The ISMRM Raw Data format is a completely open and community‐driven format, and the scientific community is invited (including commercial vendors) to participate either as users or developers. Magn Reson Med 77:411–421, 2017. © 2016 Wiley Periodicals, Inc.
The importance of correcting for signal drift in diffusion MRI
Authors: Vos Sjoerd B. , Tax Chantal M. W. , Luijten Peter R. , Ourselin Sebastien , Leemans Alexander , Froeling Martijn 
Published: January 2016

PurposeTo investigate previously unreported effects of signal drift as a result of temporal scanner instability on diffusion MRI data analysis and to propose a method to correct this signal drift.MethodsWe investigated the signal magnitude of non‐diffusion‐weighted EPI volumes in a series of diffusion‐weighted imaging experiments to determine whether signal magnitude changes over time. Different scan protocols and scanners from multiple vendors were used to verify this on phantom data, and the effects on diffusion kurtosis tensor estimation in phantom and in vivo data were quantified. Scalar metrics (eigenvalues, fractional anisotropy, mean diffusivity, mean kurtosis) and directional information (first eigenvectors and tractography) were investigated.ResultsSignal drift, a global signal decrease with subsequently acquired images in the scan, was observed in phantom data on all three scanners, with varying magnitudes up to 5% in a 15‐min scan. The signal drift has a noticeable effect on the estimation of diffusion parameters. All investigated quantitative parameters as well as tractography were affected by this artifactual signal decrease during the scan.ConclusionBy interspersing the non‐diffusion‐weighted images throughout the session, the signal decrease can be estimated and compensated for before data analysis; minimizing the detrimental effects on subsequent MRI analyses. Magn Reson Med 77:285–299, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.
Placebo effects of caffeine on maximal voluntary concentric force of the knee flexors and extensors
Authors: Tallis Jason , Muhammad Bilal , Islam Mohammed , Duncan Michael J. 
Published: January 2016

ABSTRACTIntroduction: We examined the placebo effect of caffeine and the combined effect of caffeine and caffeine expectancy on maximal voluntary strength. Methods: Fourteen men completed 4 randomized, single‐blind experimental trials: (1) told caffeine, given caffeine (5 mg/kg) (CC); (2) told caffeine, given placebo (CP); (3) told placebo, given placebo (PP); and (4) told placebo, given caffeine (PC). Maximal voluntary concentric force and fatigue resistance of the knee flexors and extensors were measured using isokinetic dynamometry. Results: A significant and equal improvement in peak concentric force was found in the CC and PC trials. Despite participants believing caffeine would evoke a performance benefit, there was no effect of CP. Conclusion: Caffeine caused an improvement in some aspects of muscle strength, but there was no additional effect of expectancy. Performance was poorer in participants who believed caffeine would have the greatest benefit, which highlights a link between expected ergogenicity, motivation, and personality characteristics. Muscle Nerve 54: 479–486, 2016
Non‐invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies by relative haplotype dosage
Authors: Parks Michael , Court Samantha , Cleary Siobhan , Clokie Samuel , Hewitt Julie , Williams Denise , Cole Trevor , MacDonald Fiona , Griffiths Mike , Allen Stephanie 
Published: January 2016

AbstractObjectiveDevelopment of an accurate and affordable test for the non‐invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies (DMD/BMD) to implement in clinical practice.MethodCell‐free DNA was extracted from maternal blood and prepared for massively parallel sequencing on an Illumina MiSeq by targeted capture enrichment of single nucleotide polymorphisms (SNPs) across the dystrophin gene on chromosome X. Sequencing data were analysed by relative haplotype dosage.ResultsSeven healthy pregnant donors and two pregnant DMD carriers all bearing a male fetus were recruited through the non‐invasive prenatal diagnosis for single gene disorders study. Non‐invasive prenatal diagnosis testing was conducted by relative haplotype dosage analysis for X‐linked disorders where the genomic DNA from the chorionic villus sampling (for healthy pregnant donors) or from the proband (for pregnant DMD carriers) was used to identify the reference haplotype. Results for all patients showed a test accuracy of 100%, when the calculated fetal fraction was >4% and correlated with known outcomes. A recombination event was also detected in a DMD patient.ConclusionOur new test for NIPD of DMD/BMD has been shown to be accurate and reliable during initial stages of validation. It is also feasible for implementation into clinical service. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
One‐year mortality associated with COPD treatment: a comparison of tiotropium and long‐acting beta2‐agonists in three Italian regions: results from the OUTPUL study
Authors: Kirchmayer Ursula , Cascini Silvia , Agabiti Nera , Di Martino Mirko , Bauleo Lisa , Formoso Giulio , Voci Claudio , Pistelli Riccardo , Patorno Elisabetta , Davoli Marina ,   on behalf of the OUTPUL study group
Published: January 2016

AbstractPurposeLong‐acting bronchodilators, i.e. beta‐2‐agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one‐year mortality associated to treatment with tiotropium versus LABA.MethodsA population‐based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006–2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium). We used ‘intention to treat’ (ITT) and ‘as treated’ (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group.ResultsAmong the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person‐years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94–1.20) at the ITT analysis and 1.00 (95%CI: 0.93–1.08) at the AT analysis. Results were robust in sensitivity analysis.ConclusionsIn this real‐world study use of tiotropium was not associated with an increased risk of one‐year mortality compared with LABA. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
Pharmacodynamic Effects of Low‐Dose Pioglitazone in Patients with the Metabolic Syndrome without Diabetes Mellitus
Authors: Vu Anh , Kosmiski Lisa A. , Beitelshees Amber L. , Prigeon Ronald , Sidhom Maha S. , Bredbeck Brooke , Predhomme Julie , Deininger Kimberly M. , Aquilante Christina L. 
Published: January 2016

Study ObjectiveTo determine the effects of low‐dose pioglitazone on plasma adipocyte‐derived cytokines, high‐sensitivity C‐reactive protein (hs‐CRP), and components of the metabolic syndrome in adults with the metabolic syndrome without diabetes mellitus.DesignProspective, randomized, double‐blind, placebo‐controlled study.SettingUniversity of Colorado Clinical and Translational Research Center.PatientsThirty‐two men and women, aged 30–60 years, without diabetes who had a clinical diagnosis of the metabolic syndrome, as defined by the American Heart Association/National Heart, Lung, and Blood Institute criteria.InterventionPatients were randomly assigned to receive oral pioglitazone 7.5 mg daily or matching placebo for 8 weeks.Measurements and Main ResultsThe primary end point was the change in plasma high‐molecular‐weight (HMW) adiponectin level from baseline to week 8. Other end points were changes in plasma total adiponectin, omentin, and hs‐CRP levels, and changes in components of the metabolic syndrome (e.g., insulin sensitivity) from baseline to week 8. Pioglitazone was associated with a significant increase in plasma HMW adiponectin from baseline to week 8 compared with placebo (+47% vs −10%, p<0.001). Insulin sensitivity increased significantly from baseline to week 8 in the pioglitazone group (+88%, p=0.02) but not in the placebo group (+15%, p=0.14). Change in HMW adiponectin was significantly correlated with the change in insulin sensitivity in the pioglitazone group (r= 0.784, p=0.003). No significant differences in mean percentage changes in plasma total adiponectin, omentin, and hs‐CRP levels were observed between the pioglitazone and placebo groups. Likewise, changes in body weight, insulin sensitivity, glucose, lipids, and blood pressure did not differ significantly between the groups.ConclusionLow‐dose pioglitazone favorably modulates plasma HMW adiponectin, which was associated with an improvement in insulin sensitivity, in patients with the metabolic syndrome without diabetes.
PD‐1 Pathway Inhibitors: Immuno‐Oncology Agents for Restoring Antitumor Immune Responses
Authors: Medina Patrick J. , Adams Val R. 
Published: January 2016

Immune checkpoint inhibitors are designed to restore a patient's own antitumor immune response that has been suppressed during tumor development. The first monoclonal antibodies against the immune checkpoint programmed death 1 (PD‐1) receptor, nivolumab and pembrolizumab, are now approved for clinical use. Both agents are indicated for the treatment of advanced melanoma, as well as for the treatment of metastatic non–small cell lung cancer (NSCLC). Nivolumab is also approved for the treatment of advanced renal cell carcinoma. In patients with melanoma, these agents result in objective response rates of ~25–40%, with durable responses lasting more than 2 years in some cases. Results from phase III trials have shown improved survival with nivolumab versus standard‐of‐care chemotherapy in both patients with advanced melanoma and those with advanced NSCLC. In patients with advanced melanoma, both PD‐1 inhibitors (nivolumab and pembrolizumab) have shown improved survival versus ipilimumab. PD‐1 inhibitors are associated with adverse events that have immune etiologies, with grade greater than 3 adverse events typically reported in 16% or less of patients. However, most immune‐mediated adverse events (including grade 3–4 adverse events) can be managed by using published management algorithms without permanent discontinuation of the agent. As nivolumab and pembrolizumab enter the clinic, and with more PD‐1 pathway agents in development for a range of tumor types, this review aims to provide pharmacists with a basic understanding of the role of PD‐1 in modulating the immune system and their use in the cancer treatment. The most recent clinical efficacy and safety data are discussed, highlighting the response characteristics distinctive to immune checkpoint inhibitors, along with pharmacokinetic and pharmacodynamic data and cost considerations.
Flexible Cu(In,Ga)Se2 solar cell on stainless steel substrate deposited by multi‐layer precursor method: its photovoltaic performance and deep‐level defects
Authors: Chantana Jakapan , Hironiwa Daisuke , Watanabe Taichi , Teraji Seiki , Minemoto Takashi 
Published: January 2016

AbstractCu(In,Ga)Se2 (CIGS) films on soda‐lime glass and stainless steel (SUS) substrates with several [Ga]/([Ga] + [In]), GGI, and Fe concentrations are fabricated by so‐called “multi‐layer precursor method”. From optical deep‐level transient spectroscopy, deep‐level defect located at 0.8 eV from valence band maximum (EV) is observed. This defect becomes recombination center when GGI is over 0.4, thereby decreasing cell performances. Fe‐related deep‐level defect is moreover detected in CIGS film on SUS substrate situated at 0.45 eV from EV. Its density is consistent with Fe concentration in CIGS films. According to SCAPS simulation and experimental results, Fe concentration of above threshold (1.0 × 1016 atom/cm3) decreases carrier lifetime and carrier density and has more harmful influence on cell performances with GGI of above 0.4. On the other hand, Fe concentration of below threshold (1.0 × 1016 atom/cm3) has no detrimental impact on cell performances. Namely, conversion efficiency (η) is slightly changed by below 2%. CIGS solar cell on SUS substrate with η of 17.5% is fabricated by decreasing Fe concentration to approximately 5.2 × 1016 atom/cm3 although higher than the threshold value. Copyright © 2016 John Wiley & Sons, Ltd.
Why reinvent the wheel? Building new proteins based on ready‐made parts
Authors: Khersonsky Olga , Fleishman Sarel J. 
Published: January 2016

AbstractWe protein engineers are ambivalent about evolution: on the one hand, evolution inspires us with myriad examples of biomolecular binders, sensors, and catalysts; on the other hand, these examples are seldom well‐adapted to the engineering tasks we have in mind. Protein engineers have therefore modified natural proteins by point substitutions and fragment exchanges in an effort to generate new functions. A counterpoint to such design efforts, which is being pursued now with greater success, is to completely eschew the starting materials provided by nature and to design new protein functions from scratch by using de novo molecular modeling and design. While important progress has been made in both directions, some areas of protein design are still beyond reach. To this end, we advocate a synthesis of these two strategies: by using design calculations to both recombine and optimize fragments from natural proteins, we can build stable and as of yet un‐sampled structures, thereby granting access to an expanded repertoire of conformations and desired functions. We propose that future methods that combine phylogenetic analysis, structure and sequence bioinformatics, and atomistic modeling may well succeed where any one of these approaches has failed on its own.
Insecticidal potency of RNAi‐based catalase knockdown in Rhynchophorus ferrugineus (Oliver) (Coleoptera: Curculionidae)
Authors: Al‐Ayedh Hassan , Rizwan‐ul‐Haq Muhammad , Hussain Abid , Aljabr Ahmed M 
Published: January 2016

AbstractBACKGROUNDPalm trees around the world are prone to notorious Rhynchophorus ferrugineus, which causes heavy losses of palm plantations. In Middle Eastern countries, this pest is a major threat to date palm orchards. Conventional pest control measures with the major share of synthetic insecticides have resulted in insect resistance and environmental issues. Therefore, in order to explore better alternatives, the RNAi approach was employed to knock down the catalase gene in fifth and tenth larval instars with different dsRNA application methods, and their insecticidal potency was studied.RESULTSdsRNA of 444 bp was prepared to knock down catalase in R. ferrugineus. Out of the three dsRNA application methods, dsRNA injection into larvae was the most effective, followed by dsRNA application by artificial feeding. Both methods resulted in significant catalase knockdown in various tissues, especially the midgut. As a result, the highest growth inhibition of 123.49 and 103.47% and larval mortality of 80 and 40% were observed in fifth‐instar larvae, whereas larval growth inhibition remained at 86.83 and 69.08% with larval mortality at 30 and 10% in tenth‐instar larvae after dsRNA injection and artificial diet treatment. The topical application method was the least efficient, with the lowest larval growth inhibition of 57.23 and 45.61% and 0% mortality in fifth‐ and tenth‐instar larvae. Generally, better results were noted at the high dsRNA dose of 5 µL.CONCLUSIONCatalase enzyme is found in most insect body tissues, and thus its dsRNA can cause broad‐scale gene knockdown within the insect body, depending upon the application method. Significant larval mortality and growth inhibition after catalase knockdown in R. ferrugineus confirms its insecticidal potency and suggests a bright future for RNAi‐based bioinsecticides in pest control. © 2016 Society of Chemical Industry