bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel NF‐κB Inhibitor, Edasalonexent (CAT‐1004), in Development as a Disease‐Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects
Authors: Donovan Joanne M. , Zimmer Michael , Offman Elliot , Grant Toni , Jirousek Michael 
Published: January 2017

AbstractIn Duchenne muscular dystrophy (DMD), NF‐κB is activated in skeletal muscle from infancy regardless of the underlying dystrophin mutation and drives inflammation and muscle degeneration while inhibiting muscle regeneration. Edasalonexent (CAT‐1004) is a bifunctional orally administered small molecule that covalently links 2 compounds known to inhibit NF‐κB, salicylic acid and docosahexaenoic acid (DHA). Edasalonexent is designed to inhibit activated NF‐κB upon intracellular cleavage to these bioactive components. Preclinical data demonstrate disease‐modifying activity in DMD animal models. Three placebo‐controlled studies in adult subjects assessed the safety, pharmacokinetics, and pharmacodynamics of single or multiple edasalonexent doses up to 6000 mg. Seventy‐nine adult subjects received edasalonexent, and 25 received placebo. Pharmacokinetic results were consistent with the intracellular cleavage of edasalonexent to its active components. Food increased plasma exposures of edasalonexent and salicyluric acid, an intracellularly formed metabolite of salicylic acid. The NF‐κB pathway and proteosome gene expression profiles in peripheral mononuclear cells were significantly decreased (P = .02 and P = .002, respectively) after 2 weeks of edasalonexent treatment. NF‐κB activity was inhibited following a single dose of edasalonexent but not by equimolar doses of salicylic acid and DHA. Edasalonexent was well tolerated, and the most common adverse events were mild diarrhea and headache. In first‐in‐human studies, edasalonexent was safe, well tolerated, and inhibited activated NF‐κB pathways, suggesting potential therapeutic utility in DMD regardless of the causative dystrophin mutation, as well as other NF‐κB–mediated diseases.
Gene Ages, Nomenclatures, and Functional Diversification of the Methuselah/Methuselah‐Like GPCR Family in Drosophila and Tribolium
Authors: Friedrich Markus , Jones Jeffery W. 
Published: January 2017

ABSTRACTAffecting lifespan regulation and oxidative stress resistance, the G‐protein coupled receptor (GPCR) gene methuselah (mth) plays important roles in the life history of Drosophila melanogaster. Substantial progress has been made in elucidating the molecular pathways by which mth affects these traits, yet conflicting ideas exist as to how old these genetic interactions are as well as how old the mth gene itself is. Root to these issues is the complex gene family history of the Mth/Mthl GPCR family, which experienced independent expansions in a variety of animal clades, leading to at least six subfamilies in insects. Within insects, drosophilid flies stand out by possessing up to three times more Mth/Mthl receptors due to the expansion of a single subfamily, the mth superclade subfamily, which contains an even younger subfamily introduced here as the melanogaster subgroup subfamily. As a result, most of the 16 Mth/Mthl receptors of D. melanogaster are characterized by n:1 orthology relationships to singleton mth superclade homologs in nondrosophilid species. This challenge is exacerbated by the inconsistent naming of Mth/Mthl orthologs across species. To consolidate this situation, we review established ortholog relationships among insect Mth/Mthl receptors, clarify the gene nomenclatures in two important satellite model species, the fruit fly relative D. virilis and the red flour beetle Tribolium castaneum, and discuss the genetic and functional evolution of the D. melanogaster Mth GPCR.
Standardized fluoroscopy‐based technique to measure intraoperative cup anteversion
Authors: Zingg Matthieu , Boudabbous Sana , Hannouche Didier , Montet Xavier , Boettner Friedrich 
Published: January 2017

ABSTRACTDirect anterior approach (DAA) with the patient lying supine has facilitated the use of intraoperative fluoroscopy and allows for standardized positioning of the patient. The current study presents a new technique to measure acetabular component anteversion using intraoperative fluoroscopy. The current paper describes a mathematical formula to calculate true acetabular component anteversion based on the acetabular component abduction angle and the c‐arm tilt angle (CaT). The CaT is determined by tilting the c‐arm until an external pelvic oblique radiograph with the equatorial plane of the acetabular component perpendicular to the fluoroscopy receptor is obtained. CaT is determined by direct reading on the C‐arm device. The technique was validated using a radiopaque synbone model comparing the described technique to computed tomography anteversion measurement. The experiment was repeated 25 times. The difference in anteversion between the two measuring techniques was on average 0.2° (range −3.0–3.1). The linear regression coefficients evaluating the agreement between the experimental and control methods were 0.99 (95%CI 0.88–1.10, p < 0.001) and 0.33 (95%CI −1.53–2.20, p = 0.713) for the slope and intercept, respectively. The current study confirms that the described three‐step c‐arm acetabular cup measuring technique can reproducibly and reliably assess acetabular component anteversion in the supine position, as compared to CT‐imaging. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2307–2312, 2017.
Raman spectroscopic investigation on pure D2O/H2O from 303 to 573 K: interpretation and implications for water structure
Authors: Hu Qingcheng , Ouyang Shunli , Li Jie , Cao Zhao 
Published: January 2017

D2O and H2O structure are investigated by Raman spectroscopy from 303 to 573 K at saturated vapor pressures in a fused silica capillary tube. As temperature increases to 573 K, Raman peak of D2O is blue‐shifted by 93 cm−1, lower than that of H2O by 128 cm−1, but the two Raman shoulders of D2O/H2O nearly remain unchanged in wavenumber. By fitting the spectra into five Gaussian components assigned to water molecules with different hydrogen bonding (HB) environments, these spectral features are interpreted by a mechanism that D2O and H2O have equal types of water molecules with similar HB degrees – fully hydrogen‐bonded H2O/D2O (FHW/D) and partially hydrogen‐bonded H2O/D2O (PHW/D) but distinct HB configurations that O…D–O is more symmetric and stronger than O…H–O. Much smaller values but slightly weaker temperature dependence of full widths at half maxima for D2O spectra ((FWHM)D2O) than (FWHM)H2O are primarily due to much weaker but slightly less temperature‐dependent intermolecular couplings in D2O than in H2O. Enthalpy change (ΔH) and entropy change (ΔS) on transition from FHW/D to PHW/D are determined based on Gaussian fitting. At low temperatures, a higher ΔHD2O (8.62 ± 0.06 kJ mol−1) than ΔHH2O (7.19 ± 0.05 kJ mol−1) further indicates that O…D–O is about 20% stronger than O…H–O. However, difference between O…D–O strength and O…H–O strength tends to diminish above 434 K, suggested by the rather close ΔHD2O and ΔHH2O, and same value of ΔSD2O and ΔSH2O. Copyright © 2017 John Wiley & Sons, Ltd.
Risk of bias in overviews of reviews: a scoping review of methodological guidance and four‐item checklist
Authors: Ballard Madeleine , Montgomery Paul 
Published: January 2017

ObjectiveTo assess the conditions under which employing an overview of systematic reviews is likely to lead to a high risk of bias.Study DesignTo synthesise existing guidance concerning overview practice, a scoping review was conducted. Four electronic databases were searched with a pre‐specified strategy (PROSPERO 2015:CRD42015027592) ending October 2015. Included studies needed to describe or develop overview methodology. Data were narratively synthesised to delineate areas highlighted as outstanding challenges or where methodological recommendations conflict.ResultsTwenty‐four papers met the inclusion criteria. There is emerging debate regarding overlapping systematic reviews; systematic review scope; quality of included research; updating; and synthesizing and reporting results. While three functions for overviews have been proposed—identify gaps, explore heterogeneity, summarize evidence—overviews cannot perform the first; are unlikely to achieve the second and third simultaneously; and can only perform the third under specific circumstances. Namely, when identified systematic reviews meet the following four conditions: (1) include primary trials that do not substantially overlap, (2) match overview scope, (3) are of high methodological quality, and (4) are up‐to‐date.ConclusionConsidering the intended function of proposed overviews with the corresponding methodological conditions may improve the quality of this burgeoning publication type. Copyright © 2017 John Wiley & Sons, Ltd.
Aridity and Overgrazing Have Convergent Effects on Ecosystem Structure and Functioning in Patagonian Rangelands
Authors: Gaitán Juan J. , Bran Donaldo E. , Oliva Gabriel E. , Aguiar Martín R. , Buono Gustavo G. , Ferrante Daniela , Nakamatsu Viviana , Ciari Georgina , Salomone Jorge M. , Massara Virginia , Martínez Guillermo García , Maestre Fernando T. 
Published: January 2017

AbstractOver 65% of drylands are used for grazing of managed livestock. Understanding what drives grazing effects on the structure and functioning of rangelands is critical for achieving their sustainability. We studied a network of 239 sites across Patagonian rangelands (Argentina), which constitute one of the world's largest rangeland area. We aimed to (i) evaluate how aridity and grazing affect ecosystem structure and functioning and (ii) test the usefulness of the landscape function analysis (LFA) indices (stability, infiltration and nutrient cycling) as surrogates of soil functioning. Aridity decreased species richness and the cover of palatable grasses but increased the cover of palatable shrubs. Grazing pressure negatively impacted the cover of palatable grasses and species richness but did not affect the cover of shrubs. Aridity had direct and indirect negative relationships with the LFA indices. Grazing pressure had no direct effects on the LFA indices but had an indirect negative effect on them by affecting vegetation structure. The LFA indices were positively and negatively correlated with soil organic carbon and sand contents, respectively, suggesting that these indices are useful proxies of soil functional processes in Patagonian rangelands. Our findings indicate that aridity and overgrazing have convergent effects on the structure and functioning of ecosystems, as both promoted reductions in species richness, the cover of palatable grasses and soil functioning. Rangeland management activities should aim to enhance species richness and the cover of palatable grasses, as these actions could contribute to offset adverse effects of ongoing increases in aridity on drylands. Copyright © 2017 John Wiley & Sons, Ltd.
Respiratory motion prediction and prospective correction for free‐breathing arterial spin‐labeled perfusion MRI of the kidneys
Authors: Song Hao , Ruan Dan , Liu Wenyang , Stenger V. Andrew , Pohmann Rolf , Fernández‐Seara Maria A. , Nair Tejas , Jung Sungkyu , Luo Jingqin , Motai Yuichi , Ma Jingfei , Hazle John D. , Gach H. Michael 
Published: January 2017

PurposeRespiratory motion prediction using an artificial neural network (ANN) was integrated with pseudocontinuous arterial spin labeling (pCASL) MRI to allow free‐breathing perfusion measurements in the kidney. In this study, we evaluated the performance of the ANN to accurately predict the location of the kidneys during image acquisition.MethodsA pencil‐beam navigator was integrated with a pCASL sequence to measure lung/diaphragm motion during ANN training and the pCASL transit delay. The ANN algorithm ran concurrently in the background to predict organ location during the 0.7‐s 15‐slice acquisition based on the navigator data. The predictions were supplied to the pulse sequence to prospectively adjust the axial slice acquisition to match the predicted organ location. Additional navigators were acquired immediately after the multislice acquisition to assess the performance and accuracy of the ANN. The technique was tested in eight healthy volunteers.ResultsThe root‐mean‐square error (RMSE) and mean absolute error (MAE) for the eight volunteers were 1.91 ± 0.17 mm and 1.43 ± 0.17 mm, respectively, for the ANN. The RMSE increased with transit delay. The MAE typically increased from the first to last prediction in the image acquisition. The overshoot was 23.58% ± 3.05% using the target prediction accuracy of ± 1 mm.ConclusionRespiratory motion prediction with prospective motion correction was successfully demonstrated for free‐breathing perfusion MRI of the kidney. The method serves as an alternative to multiple breathholds and requires minimal effort from the patient.
Comparison of respiratory motion suppression techniques for 4D flow MRI
Authors: Dyverfeldt Petter , Ebbers Tino 
Published: January 2017

PurposeThe purpose of this work was to assess the impact of respiratory motion and to compare methods for suppression of respiratory motion artifacts in 4D Flow MRI.MethodsA numerical 3D aorta phantom was designed based on an aorta velocity field obtained by computational fluid mechanics. Motion‐distorted 4D Flow MRI measurements were simulated and several different motion‐suppression techniques were evaluated: Gating with fixed acceptance window size, gating with different window sizes in inner and outer k‐space, and k‐space reordering. Additionally, different spatial resolutions were simulated.ResultsRespiratory motion reduced the image quality. All motion‐suppression techniques improved the data quality. Flow rate errors of up to 30% without gating could be reduced to less than 2.5% with the most successful motion suppression methods. Weighted gating and gating combined with k‐space reordering were advantageous compared with conventional fixed‐window gating. Spatial resolutions finer than the amount of accepted motion did not lead to improved results.ConclusionRespiratory motion affects 4D Flow MRI data. Several different motion suppression techniques exist that are capable of reducing the errors associated with respiratory motion. Spatial resolutions finer than the degree of accepted respiratory motion do not result in improved data quality. Magn Reson Med 78:1877–1882, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution Non‐Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Imaging and T2 relaxometry of short‐T2 connective tissues in the knee using ultrashort echo‐time double‐echo steady‐state (UTEDESS)
Authors: Chaudhari Akshay S. , Sveinsson Bragi , Moran Catherine J. , McWalter Emily J. , Johnson Ethan M. , Zhang Tao , Gold Garry E. , Hargreaves Brian A. 
Published: January 2017

PurposeTo develop a radial, double‐echo steady‐state (DESS) sequence with ultra‐short echo‐time (UTE) capabilities for T2 measurement of short‐T2 tissues along with simultaneous rapid, signal‐to‐noise ratio (SNR)‐efficient, and high‐isotropic‐resolution morphological knee imaging.MethodsTHe 3D radial UTE readouts were incorporated into DESS, termed UTEDESS. Multiple‐echo‐time UTEDESS was used for performing T2 relaxometry for short‐T2 tendons, ligaments, and menisci; and for Dixon water‐fat imaging. In vivo T2 estimate repeatability and SNR efficiency for UTEDESS and Cartesian DESS were compared. The impact of coil combination methods on short‐T2 measurements was evaluated by means of simulations. UTEDESS T2 measurements were compared with T2 measurements from Cartesian DESS, multi‐echo spin‐echo (MESE), and fast spin‐echo (FSE).ResultsUTEDESS produced isotropic resolution images with high SNR efficiency in all short‐T2 tissues. Simulations and experiments demonstrated that sum‐of‐squares coil combinations overestimated short‐T2 measurements. UTEDESS measurements of meniscal T2 were comparable to DESS, MESE, and FSE measurements while the tendon and ligament measurements were less biased than those from Cartesian DESS. Average UTEDESS T2 repeatability variation was under 10% in all tissues.ConclusionThe T2 measurements of short‐T2 tissues and high‐resolution morphological imaging provided by UTEDESS makes it promising for studying the whole knee, both in routine clinical examinations and longitudinal studies. Magn Reson Med 78:2136–2148, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
The use of intravenous pentamidine for the prophylaxis of Pneumocystis pneumonia in pediatric patients
Authors: Kruizinga Matthijs D. , Bresters Dorine , Smiers Frans J. , Lankester Arjan C. , Bredius Robbert G.M. 
Published: January 2017

AbstractPneumocystis jiroveci pneumonia was common in the immunocompromised host before the widespread use of prophylaxis. When trimethoprim–sulfamethoxazole is not tolerated, prophylaxis with intravenous pentamidine (IVP) may be initiated. We performed a retrospective analysis of all pediatric patients who received IVP regarding efficacy, safety, and reason for initiation. Of 106 patients included in our analysis, one patient tested positive for Pneumocystis DNA. Adverse events were reported in 18% of IVP courses, and main reason for initiation was cytopenia (59%). We found IVP to be effective and safe, and recommend the use of IVP in pediatric patients in whom first‐line prophylaxis is contraindicated.
Molecular and morphological characterization of midblock‐sulfonated styrenic triblock copolymers
Authors: Mineart Kenneth P. , Ryan Justin J. , Lee Byeongdu , Smith Steven D. , Spontak Richard J. 
Published: January 2017

ABSTRACTMidblock‐sulfonated triblock copolymers afford a desirable opportunity to generate network‐forming amphiphilic materials that are suitable for use in a wide range of emerging technologies as fuel‐cell, water‐desalination, ion‐exchange, photovoltaic, or electroactive membranes. Employing a previously reported synthetic strategy wherein poly(p‐tert‐butylstyrene) remains unreactive, we have selectively sulfonated the styrenic midblock of a poly(p‐tert‐butylstyrene‐b‐styrene‐b‐p‐tert‐butylstyrene) (TST) triblock copolymer to different extents. Comparison of the resulting sulfonated copolymers with results from our prior study provides favorable quantitative agreement and suggests that a shortened reaction time is advantageous. An ongoing challenge regarding the morphological development of charged block copolymers is the competition between microphase separation of the incompatible blocks and physical cross‐linking of ionic clusters, with the latter often hindering the former. Here, we expose the sulfonated TST copolymers to solvent‐vapor annealing to promote nanostructural refinement. The effect of such annealing on morphological characteristics, as well as on molecular free volume, is explored. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 490–497
Sensitization predicts asthma development among wheezing toddlers in secondary healthcare
Authors: Boersma Nienke A. , Meijneke Ruud W.H. , Kelder Johannes C. , van der Ent Cornelis K. , Balemans Walter A.F. 
Published: January 2017

SummaryIntroductionSome wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain. Aim: This study examines the predictive value of sensitization to inhalant allergens among wheezing toddlers in secondary healthcare for the development of asthma at school age (≥6 years). Methods: Preschool children (1–3 years) who presented with wheezing in secondary healthcare were screened on asthma at school age with the International Study of Asthma and Allergies in Childhood questionnaire. The positive and negative predictive value (PPV and NPV) of specific IgE to inhalant allergens (cut‐off concentration 0.35 kU/L) and several non‐invasive variables from a child's history (such as hospitalization, eczema, and parental atopy) were calculated. The additional predictive value of sensitization when combined with non‐invasive predictors was examined in multivariate analysis and by ROC curves. Results: Of 116 included children, 63% developed asthma at school age. Sensitization to inhalant allergens was a strong asthma predictor. The odds ratio (OR), PPV and NPV were 7.4%, 86%, and 55%, respectively. Eczema (OR 3.4) and hospital admission (OR 2.6) were significant non‐invasive determinants. Adding sensitization to these non‐invasive predictors in multivariate analysis resulted in a significantly better asthma prediction. The area under the ROC curve increased from 0.70 with only non‐invasive predictors to 0.79 after adding sensitization. Conclusion: Sensitization to inhalant allergens is a strong predictor of school age asthma in secondary healthcare and has added predictive value when combined with non‐invasive determinants. Pediatr Pulmonol. 2017;52:729–736. © 2017 Wiley Periodicals, Inc.
Estimating Value Creation from Revealed Preferences: Application to Value‐based Strategies
Authors: Chatain Olivier , Mindruta Denisa 
Published: January 2017

Research summary: We develop and apply a new set of empirical tools consistent with the tenets of value‐based business strategies, leveraging the principle that “no good deal comes undone” and the methods of revealed preferences, to empirically estimate drivers of value creation. We demonstrate how to use these tools in an analysis of value creation in buyer–supplier relationships in the UK corporate legal market. We show that our approach can uncover evidence of subtle mechanisms that traditional methods cannot easily distinguish from each other. Furthermore, we show how the estimates can be used as parameters of biform games for out‐of‐sample analyses of strategic decisions. With readily available data on relationships between firms, this approach can be applied to many other contexts of interest to strategy researchers.Managerial summary: Managers need to understand the drivers of value creation for customers in order to make competitive positioning decisions and understand when they can capture value under competition. However, estimates of the relative importance of each driver are typically difficult to obtain. In this article, we help remedy this problem by demonstrating a novel method that obtains estimates of the contribution of various drivers of value creation from commonly available data of buyer–supplier relationships. These estimates can then be used to inform the strategy‐making process. Copyright © 2017 John Wiley & Sons, Ltd.