bluuebunny/crossref_metadata_2025_split huggingface dataset:
More than BOLD: Dual‐spin populations create functional contrast
Authors: Taylor Amanda J. , Kim Jung H. , Singh Vimal , Halfen Elizabeth J. , Pfeuffer Josef , Ress David 
Published: August 2019

PurposeFunctional MRI contrast has generally been associated with changes in transverse relaxivity caused by blood oxygen concentration, the so‐called blood oxygen level dependent contrast. However, this interpretation of fMRI contrast has been called into question by several recent experiments at high spatial resolution. Experiments were conducted to examine contrast dependencies that cannot be explained only by differences in relaxivity in a single‐spin population.MethodsMeasurements of functional signal and contrast were obtained in human early visual cortex during a high‐contrast visual stimulation over a large range of TEs and for several flip angles. Small voxels (1.5 mm) were used to restrict the measurements to cortical gray matter in early visual areas identified using retinotopic mapping procedures.ResultsMeasurements were consistent with models that include 2 spin populations. The dominant population has a relatively short transverse lifetime that is strongly modulated by activation. However, functional contrast is also affected by volume changes between this short‐lived population and the longer‐lived population.ConclusionSome of the previously observed “nonclassical” behaviors of functional contrast can be explained by these interacting dual‐spin populations.
Feasibility of neurochemically profiling mouse embryonic brain and its development in utero using 1H MRS at 14.1 T
Authors: Lei Hongxia , Montessuit Sylvie , Herzig Sébastien , Martinou Jean‐Claude 
Published: August 2019

We aimed to evaluate the feasibility of neurochemical profiling of embryonic mouse brain developments in utero and to seek potential in vivo evidence of an energy shift in a mitochondrial pyruvate carrier 1 (MPC1) deficient mouse model. C57BL/6 embryonic mouse brains were studied in utero by anatomical MRI and short echo localized proton (1H) MRS at 14.1 T. Two embryonic stages were studied, the energy shift (e.g., embryonic day 12.5–13, E12.5–13) and close to the birth (E17.5–18). In addition, embryonic brains devoid of MPC1 were studied at E12.5–13. The MRI provided sufficient anatomical contrasts for visualization of embryonic brain. Localized 1H MRS offered abundant metabolites through the embryonic development from E12.5 and close to the birth, e.g., E17.5 and beyond. The abundant neurochemical information at E12.5 provided metabolic status and processes relating to cellular development at this stage, i.e., the energy shift from glycolysis to oxidative phosphorylation, evidenced by accumulation of lactate in E12.5–13 embryonic brain devoid of MPC1. The further evolution of the neurochemical profile of embryonic brains at E17.5–18 is consistent with cellular and metabolic processes towards the birth. Localized 1H MRS study of embryonic brain development in utero is feasible, and longitudinal neurochemical profiling of embryonic brains offers valuable insight into early brain development.
Repurposing an anti‐cancer agent for the treatment of hypertrophic heart disease
Authors: Dukinfield Matthew , Maniati Eleni , Reynolds Louise E , Aubdool Aisah , Baliga Reshma S , D'Amico Gabriela , Maiques Oscar , Wang Jun , Bedi Kenneth C , Margulies Kenneth B , Sanz‐Moreno Victoria , Hobbs Adrian , Hodivala‐Dilke Kairbaan 
Published: August 2019

AbstractCoronary microvascular dysfunction combined with maladaptive cardiomyocyte morphology and energetics is a major contributor to heart failure advancement. Thus, dually enhancing cardiac angiogenesis and targeting cardiomyocyte function to slow, or reverse, the development of heart failure is a logical step towards improved therapy. We present evidence for the potential to repurpose a former anti‐cancer Arg‐Gly‐Asp (RGD)‐mimetic pentapeptide, cilengitide, here used at low doses. Cilengitide targets αvβ3 integrin and this protein is upregulated in human dilated and ischaemic cardiomyopathies. Treatment of mice after abdominal aortic constriction (AAC) surgery with low‐dose cilengitide (ldCil) enhances coronary angiogenesis and directly affects cardiomyocyte hypertrophy with an associated reduction in disease severity. At a molecular level, ldCil treatment has a direct effect on cardiac endothelial cell transcriptomic profiles, with a significant enhancement of pro‐angiogenic signalling pathways, corroborating the enhanced angiogenic phenotype after ldCil treatment. Moreover, ldCil treatment of Angiotensin II‐stimulated AngII‐stimulated cardiomyocytes significantly restores transcriptomic profiles similar to those found in normal human heart. The significance of this finding is enhanced by transcriptional similarities between AngII‐treated cardiomyocytes and failing human hearts. Taken together, our data provide evidence supporting a possible new strategy for improved heart failure treatment using low‐dose RGD‐mimetics with relevance to human disease. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Clinical significance of the bronchodilator response in children with severe asthma
Authors: Coverstone Andrea M. , Bacharier Leonard B. , Wilson Bradley S. , Fitzpatrick Anne M. , Teague William Gerald , Phipatanakul Wanda , Wenzel Sally E. , Gaston Benjamin M. , Bleecker Eugene R. , Moore Wendy C. , Ramratnam Sima , Jarjour Nizar N. , Ly Ngoc P. , Fahy John V. , Mauger David T. , Schechtman Kenneth B. , Yin‐DeClue Huiqing , Boomer Jonathan S. , Castro Mario 
Published: August 2019

AbstractBackgroundOur objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP).MethodsWe performed a cross‐sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility.ResultsWe evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05‐4.13), second‐hand smoke exposure (OR, 2.81, 95%CI, 1.23‐6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35‐2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1% predicted (OR, 0.91, 95%CI, 0.88‐0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1% predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1‐year follow‐up though less decline in lung function over 1 year compared to those without reversibility.ConclusionsLung function, that is FEV1% predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.
Management of Tamm–Horsfall Protein for Reliable Urinary Analytics
Authors: Xu Xiaomeng , Barreiro Karina , Musante Luca , Kretz Oliver , Lin Hanfei , Zou Hequn , Huber Tobias B. , Holthofer Harry 
Published: August 2019

PurposeUrinary extracellular vesicles (uEVs) are a novel source of biomarkers. However, urinary Tamm–Horsfall Protein (THP; uromodulin) interferes with all vesicle isolation attempts, precipitates with normal urinary proteins, thus, representing an unwanted “contaminant” in urinary assays. Thus, the aim is to develop a simple method to manage THP efficiently.Experimental designThe uEVs are isolated by hydrostatic filtration dialysis (HFD) and treated with a defined solution of urea to optimize release of uEVs from sample. Presence of uEVs is confirmed by transmission electron microscopy, Western blotting, and proteomic profiling in MS.ResultsUsing HFD with urea treatment for uEV isolation reduces sample complexity to a great extent. The novel simplified uEV isolation protocol allows comprehensive vesicle proteomics analysis and should be part of any urine analytics to release all sample constituents from THP trap.Conclusions and clinical relevanceThe method brings a quick and easy protocol for THP management during uEV isolation, providing major benefits for comprehensive sample analytics.
VHH characterization. Comparison of recombinant with chemically synthesized anti‐HER2 VHH
Authors: Hartmann Lucie , Botzanowski Thomas , Galibert Mathieu , Jullian Magali , Chabrol Eric , Zeder‐Lutz Gabrielle , Kugler Valérie , Stojko Johann , Strub Jean‐Marc , Ferry Gilles , Frankiewicz Lukasz , Puget Karine , Wagner Renaud , Cianférani Sarah , Boutin Jean A. 
Published: August 2019

AbstractIn the continuous exploration of the VHH chemistry, biochemistry and therapeutic future use, we investigated two different production strategies of this small antibody‐like protein, using an anti‐HER2 VHH as a model. The total chemical synthesis of the 125 amino‐acid peptide was performed with reasonable yield, even if optimization will be necessary to upgrade this kind of production. In parallel, we expressed the same sequence in two different hosts: Escherichia coli and Pichia pastoris. Both productions were successful and led to a fair amount of VHHs. The integrity and conformation of the VHH were characterized by complementary mass spectrometry approaches, while surface plasmon resonance experiments were used to assess the VHH recognition capacity and affinity toward its “antigen.” Using this combination of orthogonal techniques, it was possible to show that the three VHHs—whether synthetic or recombinant ones—were properly and similarly folded and recognized the “antigen” HER2 with similar affinities, in the nanomolar range. This opens a route toward further exploration of modified VHH with unnatural amino acids and subsequently, VHH‐drug conjugates.
Visible LED‐Assisted Effective Charge Separation in Ruthenium‐Doped ZnS System for Efficient Photodegradation of Organic Dye
Authors: Mandal Sujoy K. , Karmakar Devdas , Ghosal Supriya , Paul Sumana , Jana Debnarayan 
Published: August 2019

AbstractHarvesting solar light efficiently and effective photo‐induced charge separated photocatalysts becoming an immense demand for environment salvation. Herein, the one‐step solvothermal method has been employed to synthesize Zn1–xRuxS nanoparticles (NPs). A systematic study for the photocatalytic degradation of Methylene blue (MB) for the first time in Ru doped ZnS system has been carried out with visible light (LED) irradiation. Density functional theory has been employed to study the structural, electronic properties and charge transfer mechanism throughout the Ru doped ZnS system. Theoretical results and UV‐Vis spectra suggest a reduction of bandgap as a function of Ru concentration. Bader charge analysis for both the structures as well as photoluminescence quenching has shown Ru acts as a charge center in the charge transfer process. The optimum photodegradation efficiency is achieved in case of 1% Ru doped ZnS NPs. Thus Ru doping in ZnS NPs has a significant role in showing effective photocatalytic behaviour.
Recent Advances and Prospects in the Chemistry of o‐Benzoquinones
Authors: Radhika Sankaran , Saranya Salim , Harry Nissy Ann , Anilkumar Gopinathan 
Published: August 2019

AbstractOrtho‐benzoquinones play a vital role as reactive intermediate having high electrophilic character. Sterically crowded 1,2‐benzoquinones and their derivatives exhibiting divergent functionality have marked attraction in organic synthesis. Their intermolecular Diels‐Alder reactions reflect wide versatile applications. They act as a powerful tool towards the synthesis of biologically active complex heterocyclic ligands. This review focuses on the various novel advancements in the synthesis, reactions and applications of 1,2‐benzoquinones that have been achieved recently.
Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation
Authors: Wang Zhenming , Zhao Jin , Tang Wanze , Hu Liqiu , Chen Xin , Su Yiping , Zou Chang , Wang Jianhong , Lu William W. , Zhen Wanxin , Zhang Ronghua , Yang Dazhi , Peng Songlin 
Published: August 2019

AbstractTissue‐engineered hydrogels have received extensive attention as their mechanical properties, chemical compositions, and biological signals can be dynamically modified for mimicking extracellular matrices (ECM). Herein, the synthesis of novel double network (DN) hydrogels with tunable mechanical properties using combinatorial screening methods is reported. Furthermore, nanoengineered (NE) hydrogels are constructed by addition of ultrathin 2D black phosphorus (BP) nanosheets to the DN hydrogels with multiple functions for mimicking the ECM microenvironment to induce tissue regeneration. Notably, it is found that the BP nanosheets exhibit intrinsic properties for induced CaP crystal particle formation and therefore improve the mineralization ability of NE hydrogels. Finally, in vitro and in vivo data demonstrate that the BP nanosheets, mineralized CaP crystal nanoparticles, and excellent mechanical properties provide a favorable ECM microenvironment to mediate greater osteogenic cell differentiation and bone regeneration. Consequently, the combination of bioactive chemical materials and excellent mechanical stimuli of NE hydrogels inspire novel engineering strategies for bone‐tissue regeneration.
Watch out for this commit! A study of influential software changes
Authors: Li Daoyuan , Li Li , Kim Dongsun , Bissyandé Tegawendé F. , Lo David , Le Traon Yves 
Published: August 2019

AbstractOne single code change can significantly influence a wide range of software systems and their users. For example, (a) adding a new feature can spread defects in several modules, while (b) changing an API method can improve the performance of all client programs. Unfortunately, developers often may not clearly know whether code changes are influential at commit time. This paper investigates influential software changes and proposes an approach to identify them immediately when they are applied. Our goals are to (a) identify existing influential changes (ICs) in software projects, (b) understand their characteristics, and (c) build a classification model of ICs to help developers find and address them early. We first conduct a post‐mortem analysis to discover existing influential changes by using intuitions (eg, changes referred by other changes). Then, we re‐categorize all identified changes through an open‐card sorting process. Subsequently, we conduct a survey with about 100 developers to finalize a taxonomy. Finally, from our ground truth, we extract features, including metrics such as the complexity of changes and file centrality in co‐change graphs to build machine learning classifiers. The experiment results show that our classification model with random samples achieves 86.8% precision, 74% recall, and 80.4% F‐measure, respectively.
Energy dissipation and self‐centering capacities of posttensioning precast segmental ultra‐high performance concrete bridge columns
Authors: Wang Zhen , Wang Jingquan , Zhu Junzheng , Zhao Guotang , Zhang Jian 
Published: August 2019

AbstractThe research aims to better balance energy dissipation (ED) and self‐centering capacities of posttensioning (PT) precast segmental ultra‐high performance concrete bridge columns by adjusting common design parameters. A numerical model is established based on the equivalent plastic hinge model and validated by the cyclic loading test. The validated model is used to conduct a parametric study to investigate the effects of seven common design parameters on ED and self‐centering capacities. The results show the proposed numerical model can accurately predict ED and self‐centering capacities of the proposed bridge columns. The effect of the strength‐yield ratio can be neglected when it is more than 1.2. The lower aspect ratio can first weaken and then improve the equivalent viscous damping ratio with drift ratio up, while the lower aspect ratio can reduce the residual drift ratio. With larger ED bar ratio, smaller unbonded length of ED bars and lower PT tendon ratio, the equivalent viscous damping ratio, and the residual drift ratio are significantly increased. It is not a perfect way to improve ED capacity by increasing the ED bar ratio, which can significantly magnify the residual drift ratio and limitedly enhance the equivalent viscous damping ratio, besides economical considering. Improving the gravity loading ratio and the initial PT stress are deemed to be effective ways to reduce the residual drift ratio because they not only have little influence on the equivalent viscous damping ratio but also result in no more costs.
Electrochemically Induced Diels‐Alder Reaction: An Overview
Authors: Heravi Majid M. , Zadsirjan Vahideh , Kouhestanian Elham , AlimadadiJani Behnoush 
Published: August 2019

AbstractOne of the most important name reactions in organic chemistry, is the Diels‐Alder cycloaddition reaction. It is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile to construct a substituted cyclohexene derivative. It is the stereotypical example of a pericyclic reaction with a concerted mechanism. In synthesis, the use of electricity instead of stoichiometric amounts of oxidant or reducing agents is definitely appealing for economic, ecological and selective, reasons. In this review, we try to underscore the combination of the electrosynthesis with Diels‐Alder cycloaddition reaction to establish of a powerful synthetic tool which may encourage synthetic organic chemists to use it in the future.
Cytotoxic potentials of S. cumini methanolic seed kernel extract in human hepatoma HepG2 cells
Authors: Solai Prakash Ashwin Kumar , Devaraj Ezhilarasan 
Published: August 2019

AbstractSyzygium cumini (Myrtaceae) is commonly called as Jamun or Jambolan. It has antidiabetic, anti‐inflammatory, antipyretic, and antioxidant activities. Hepatocellular carcinoma is the most frequent and deadliest cancers worldwide. We investigated the cytotoxic potentials of S. cumini methanolic seed kernel extract against human hepatoma HepG2 cells. HepG2 cells were treated with 10, 20, and 40 μg/mL of seed kernel extract for 24 hours and cytotoxic analysis was performed by MTT assay. S. cumini induced apoptosis related morphological changes in HepG2 cells were analyzed by annexin V and propidium iodide double staining. Nuclear fragmentation and chromatin condensation were analyzed by Hoechst nuclear staining. Mitochondrial membrane potential (MMP) was investigated by 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimidazolyl‐carbocyanine iodide (JC‐1) staining. Protein expressions of hepatocyte nuclear factor‐1α (HFN‐1α) was performed using western blotting. S. cumini treatments caused a significant and a concentration‐dependent increase in the cytotoxicity of HepG2 cells. S. cumini treatments increased the percentage of cells in an early and late apoptosis stage. This treatment also caused chromatin condensation and nuclear fragmentation. Further, S. cumini treatments decreased MMP and also caused a significant downregulation of HFN‐1α protein expression. The present study demonstrated that S. cumini seed extract induced apoptosis in HepG2 cells through decrease in MMP and downregulation of HFN‐1α.
Preparation and application of bagasse‐based adsorbent for highly efficient removal of mercury ions
Authors: Ma Nianfang , Li Jinrong , Zeng Jian , Liang Lei , Zhang Jiayong 
Published: August 2019

AbstractA high‐performance bagasse‐based adsorbent was prepared from agricultural waste bagasse by grafting of acrylamide and aminating with diethylenetriamine. Effects of catalyst dosage, acrylamide concentration, reaction temperature, and bath ratio on the grafting yield were investigated. The adsorption performances for mercury ions were evaluated by batch adsorption experiments and kinetic experiments. The results show that the adsorbent has high adsorption capacity for mercury in a wide range of pH values. The adsorption capacity could be as high as 813.0 mg/g, and the removal percentage for mercury ions can reach 99.9%. The kinetic adsorption experiments show it can achieve adsorption equilibrium rapidly, which implies that the adsorbent has a strong ability to capture mercury ions. Besides, the bagasse‐based adsorbent showed promising regeneration performance, and its adsorption amount of regenerated adsorbent only slightly decreased after five recycling.Practitioner pointsAn amino‐rich adsorbent was prepared from bagasse.The adsorbent possesses high adsorption capacity and high removal efficiency for mercury.The aminated bagasse adsorbs mercury rapidly.The adsorbent functionalized with amino possesses strong affinity toward mercury.
HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study
Authors: Viscusi E. , Minkowitz H. , Winkle P. , Ramamoorthy S. , Hu J. , Singla N. 
Published: August 2019

Abstract

Purpose
Currently available local anesthetics have not demonstrated sufficient analgesia beyond 12–24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl).

Methods
A phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure.

Results
The study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p < 0.001) and by 21% versus bupivacaine HCl (p < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo (p < 0.001) and 25% versus bupivacaine HCl (p = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [p < 0.001] and 40% for bupivacaine HCl [p = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity.

Conclusions
HTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.