bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental modelling of cardiac pressure overload hypertrophy: Modified technique for precise, reproducible, safe and easy aortic arch banding-debanding in mice
Authors: Merino David , Gil Aritz , Gómez Jenny , Ruiz Luis , Llano Miguel , García Raquel , Hurlé María A. , Nistal J. Francisco 
Published: February 2018

AbstractPressure overload left ventricular hypertrophy is a known precursor of heart failure with ominous prognosis. The development of experimental models that reproduce this phenomenon is instrumental for the advancement in our understanding of its pathophysiology. The gold standard of these models is the controlled constriction of the mid aortic arch in mice according to Rockman’s technique (RT). We developed a modified technique that allows individualized and fully controlled constriction of the aorta, improves efficiency and generates a reproducible stenosis that is technically easy to perform and release. An algorithm calculates, based on the echocardiographic arch diameter, the intended perimeter at the constriction, and a suture is prepared with two knots separated accordingly. The aorta is encircled twice with the suture and the loop is closed with a microclip under both knots. We performed controlled aortic constriction with Rockman’s and the double loop-clip (DLC) techniques in mice. DLC proved superiority in efficiency (mortality and invalid experiments) and more homogeneity of the results (transcoarctational gradients, LV mass, cardiomyocyte hypertrophy, gene expression) than RT. DLC technique optimizes animal use and generates a consistent and customized aortic constriction with homogeneous LV pressure overload morphofunctional, structural, and molecular features.
Insights into the inhibitory mechanisms of NADH on the αγ heterodimer of human NAD-dependent isocitrate dehydrogenase
Authors: Liu Yabing , Hu Lejia , Ma Tengfei , Yang Jun , Ding Jianping 
Published: February 2018

AbstractHuman NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the oxidative decarboxylation of isocitrate in the citric acid cycle. In the α2βγ heterotetramer of NAD-IDH, the γ subunit plays the regulatory role and the β subunit the structural role. Previous biochemical data have shown that mammalian NAD-IDHs can be inhibited by NADH; however, the molecular mechanism is unclear. In this work, we show that the αβ, αγ and α2βγ enzymes of human NAD-IDH can be inhibited by NADH, and further determine the crystal structure of the αγ heterodimer bound with an Mg2+ and an NADH at the active site and an NADH at the allosteric site, which resembles that of the inactive αMgγ heterodimer. The NADH at the active site occupies the binding site for NAD+ and prevents the binding of the cofactor. The NADH at the allosteric site occupies the binding sites for ADP and citrate and blocks the binding of the activators. The biochemical data confirm that the NADH binding competes with the binding of NAD+ and the binding of citrate and ADP, and the two effects together contribute to the NADH inhibition on the activity. These findings provide insights into the inhibitory mechanisms of the αγ heterodimer by NADH.
A Meta-Surface Antenna Array Decoupling (MAAD) Method for Mutual Coupling Reduction in a MIMO Antenna System
Authors: Wang Ziyang , Zhao Luyu , Cai Yuanming , Zheng Shufeng , Yin Yingzeng 
Published: February 2018

AbstractIn this paper, a method to reduce the inevitable mutual coupling between antennas in an extremely closely spaced two-element MIMO antenna array is proposed. A suspended meta-surface composed periodic square split ring resonators (SRRs) is placed above the antenna array for decoupling. The meta-surface is equivalent to a negative permeability medium, along which wave propagation is rejected. By properly designing the rejection frequency band of the SRR unit, the mutual coupling between the antenna elements in the MIMO antenna system can be significantly reduced. Two prototypes of microstrip antenna arrays at 5.8 GHz band with and without the metasurface have been fabricated and measured. The matching bandwidths of antennas with reflection coefficient smaller than −15 dB for the arrays without and with the metasurface are 360 MHz and 900 MHz respectively. Using the meta-surface, the isolation between elements is increased from around 8 dB to more than 27 dB within the band of interest. Meanwhile, the total efficiency and peak gain of each element, the envelope correlation coefficient (ECC) between the two elements are also improved by considerable amounts. All the results demonstrate that the proposed method is very efficient for enhancing the performance of MIMO antenna arrays.
Fermi-LAT observation of nonblazar AGNs
Authors: Sahakyan N. , Baghmanyan V. , Zargaryan D. 
Published: February 2018

Context. Fermi Large Area Telescope (Fermi-LAT) has recently detected γ-ray emission from active galactic nuclei (AGN) that do not show clear evidence for optical blazar characteristics or have jets pointing away from the observer (nonblazar AGNs). These are interesting γ-ray emitters providing an alternative approach to studying high energy emission processes.
Aims. This paper investigates the spectral and temporal properties of γ-ray emission from nonblazar AGNs using the recent Fermi-LAT observational data.
Methods. The data collected by Fermi-LAT during 2008–2015, from the observations of 26 nonblazar AGNs, including 11 Fanaroff–Riley Type I (FRI) and ten FRII radio galaxies and steep spectrum radio quasars (SSRQs) and five narrow line seyfert 1s (NLSy1s) are analysed using the new PASS 8 event selection and instrument response function. Possible spectral changes above GeV energies are investigated with a detailed spectral analysis. Light curves generated with normal and adaptive time bins are used to study the γ-ray flux variability.
Results. Non-blazar AGNs have a γ-ray photon index in the range of 1.84–2.86 and a flux varying from a few times 10−9 photon cm−2 s−1 to 10−7 photon cm−2 s−1. Over long time periods, the power law provides an adequate description of the γ-ray spectra of almost all sources. Significant curvature is observed in the γ-ray spectra of NGC 1275, NGC 6251, SBS 0846 + 513, and PMN J0948 + 0022 and their spectra are better described by log parabola or by the power law with exponential cut-off models. The γ-ray spectra of PKS 0625-25 and 3C 380 show a possible deviation from a simple power-law shape, indicating a spectral cut-off around the observed photon energy of Ecut = 131.2 ± 88.04 GeV and Ecut = 55.57 ± 50.74 GeV, respectively. Our analysis confirms the previous finding of an unusual spectral turnover in the γ-ray spectrum of Cen A: the photon index changes from Γ = 2.75 ± 0.02 to 2.31 ± 0.1 at 2.35 ± 0.08 GeV. In the Γ−Lγ plane, the luminosity of nonblazar AGNs is spread in the range of (1041–1047) erg s−1, where those with the lowest luminosity are FRI radio galaxies (but typically appear with a harder photon index) and those with the highest luminosity have are SSRQs/NLSY1s (with softer photon indexes). We confirm the previously reported short-timescale flux variability of NGC 1275 and 3C 120. The γ-ray emission from NLSY1s, 1H 0323 + 342, SBS 0846 + 513, and PMN J0948 + 0022 is variable, showing flares in short scales sometimes accompanied by a moderate hardening of their spectra (e.g., for MJD 56146.8 the γ-ray photon index of SBS 0846 + 513 was Γ = 1.73 ± 0.14). Non-blazar AGNs 3C 111, Cen A core, 3C 207, 3C 275.1, 3C 380, 4C + 39.23B, PKS 1502 + 036, and PKS 2004-447 show a long-timescale flux variability in the γ-ray band.
Airway Inflammation and Inflammatory Biomarkers
Authors: Lim Hui , Nair Parameswaran 
Published: February 2018

AbstractSevere asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a “Th2 endotype” is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E. Individually or in combination, they may help to identify, for example, if the dominant effector protein is interleukin (IL) 5, IL13, or IgE. There is no reliable marker of a “non-Th2 endotype” although sputum neutrophil may provide some indication. The unbiased systems biology approach to severe asthma endotyping which integrates omics signatures and clinical data using large cohort studies may provide more comprehensive information than simple cellular measurements. Novel imaging techniques, such as hyperpolarized noble gas magnetic resonance imaging and computed tomography parametric response maps and metabolomics profiling in breath and other body fluids are also being evaluated as potential biomarkers to guide therapy and to assess prognosis.
Diagnosis and Management of Severe Asthma
Authors: Chung Kian Fan 
Published: February 2018

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.
Does Donor Age of Nonirradiated Achilles Tendon Allograft Influence Mid-Term Results of Revision ACL Reconstruction?
Authors: Zaffagnini Stefano , Roberti di Sarsina Tommaso , Bonanzinga Tommaso , Nitri Marco , Macchiarola Luca , Stefanelli Federico , Lucidi Gianandrea , Grassi Alberto 
Published: February 2018

Purpose The purpose of the present study was to investigate if the donor age of nonirradiated Achilles tendon allograft could influence the clinical results of revision anterior cruciate ligament (ACL) reconstruction.
Methods All patients that underwent ACL revision between 2004 and 2008 with at least 4 years of follow-up were included. For all the patients that met the inclusion criteria, the age of the graft donor was obtained from the tissue bank. Lysholm score was administered to patients that met inclusion criteria. In addition, patients were divided in two groups based on the donor age (<45 years vs. ≥45 years), and the baseline characteristics and outcomes were compared.
Results Fifty-two patients were evaluated at a mean 4.8 ± 0.8 years follow-up with Lysholm score. The Lysholm significantly improved from 62.3 ± 6.6 at preoperative status to 84.4 ± 12.3 at final follow-up. The mean donor age was 48.7 ± 8.4 years; a significant difference in Lysholm score was noted between patients that received an allograft with a donor age <45 years (14 patients; 27%) and those receiving an allograft with a donor age ≥45 years (38; 73%) (89.5 ± 3.2 vs. 80.1 ± 11.1, respectively; p = 0.0469). The multiple regression model showed the donor age, the final follow-up, and the preoperative Lysholm score as significant predictors of postoperative Lysholm score (p < 0.0002).
Conclusion Donor age of nonirradiated Achilles tendon allograft influenced the mid-term results of revision ACL reconstruction, thus advising the use of grafts from young donors.
Level of Evidence Level III, retrospective comparative study.
Survival Analysis after Core Decompression in Association with Platelet-Rich Plasma, Mesenchymal Stem Cells, and Synthetic Bone Graft in Patients with Osteonecrosis of the Femoral Head
Authors: D'Ambrosi Riccardo , Biancardi Elena , Massari Giulia , Ragone Vincenza , Facchini Renato 
Published: February 2018

Purpose The aim of this study was to report the rate of survivorship in patients with osteonecrosis of the femoral head treated with core decompression in association with mesenchymal stem cells (MSCs) implantation, platelet-rich plasma (PRP) injection, and synthetic bone graft.
Methods We evaluated 24 hips in 16 patients, according to Ficat classification, treated by core decompression, injection of PRP and MSCs, and backfilling of the core tract with synthetic bone graft. Survivorship was estimated using Kaplan–Meier curves.
Results The survivorship of core decompression in association with the procedure is 50% at 75 months of follow-up. The survival rate was 80% for patients in early stage and 28.6% for patients in advanced stage at 75 months. When we compared Kaplan–Meier survival curves of patients in stage III + IV and patients in stage I + II, we noticed that the survival functions are statistically different (p < 0.05, log-rank test), particularly in stage I + II where we had a greater surviving core decompression, in comparison to patients in stage III + IV.
Conclusion This technique is safe and good preliminary results were obtained in patients with early stages of the disease with no reported complications.
Level of Evidence Level IV, therapeutic case series.
CX3CR1/CX3CL1 Axis Mediates Platelet–Leukocyte Adhesion to Arterial Endothelium in Younger Patients with a History of Idiopathic Deep Vein Thrombosis
Authors: Furio Elena , García-Fuster Maria , Redon Josep , Marques Patrice , Ortega Rebeca , Sanz Maria , Piqueras Laura 
Published: February 2018

AbstractMechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CX3CR1/CX3CL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) with a history of idiopathic DVT and without known cardiovascular risk factors and 23 aged-matched control subjects (age: 34 ± 7.8 years). Flow cytometry was used to evaluate peripheral markers of platelet activation, leukocyte immunophenotypes and CX3CR1/CX3CL1 expression in both groups. A flow chamber assay was employed to measure leukocyte arrest under dynamic conditions. Platelet activation and the percentage of circulating CX3CR1-expressing platelets, CX3CR1-expressing platelet-bound monocytes and CD8+ lymphocytes were higher in patients with DVT than in controls. Additionally, patients with DVT had increased plasma levels of CX3CL1, soluble P-selectin and platelet factor 4/CXCL4. Interestingly, this correlated with enhanced platelet–leukocyte interaction and leukocyte adhesion to TNFα-stimulated arterial endothelial cells, which was partly dependent on endothelial CX3CL1 upregulation and increased CX3CR1 expression on platelets, monocytes and lymphocytes. In conclusion, increased CX3CR1 expression on circulating platelets may constitute a prognostic marker for long-term adverse cardiovascular events in patients with DVT. Blockade of CX3CL1/CX3CR1 axis may represent a new therapeutic strategy for the prevention of cardiovascular comorbidities associated with DVT.
Evaluation of the Antibacterial, Antioxidant and α-Glucosidase Inhibitory Activities of Withanolides from Physalis gracilis
Authors: Padierna Gerardo , Pérez-Castorena Ana , Martínez Mahinda , Nieto-Camacho Antonio , Morales-Jiménez Jesús , Maldonado Emma 
Published: February 2018

AbstractA chemical investigation of the leaves, flowers, and stems of Physalis gracilis led to the isolation of three withanolides identified as withanolide D (1), 24,25-dihydrowithanolide D (2), and withaphysacarpin (3). The structures of these compounds were determined by analyses of their spectroscopic data, including 1D and 2D NMR. The antibacterial, antioxidant, and α-glucosidase inhibitory activities of compounds 1 and 3 and derivatives 4 and 5 were evaluated. None of the compounds showed antioxidant or glucosidase inhibitory activity. Also, they were inactive against gram-negative bacteria. However, compound 3 was found active against Bacillus subtilis (MIC=65.5 µM) and compound 5 against Staphylococcus aureus (MIC=27.9 µM).
Antimicrobial Constituents from Leaves of Dolichandrone spathacea and Their Relevance to Traditional Use
Authors: Nguyen Phuc-Dam , Abedini Amin , Gangloff Sophie , Lavaud Catherine 
Published: February 2018

AbstractFive new compounds, three iridoid glycosides (1-3) and two triterpenoid saponins (4, 5), along with thirty-two known compounds were isolated from the methanolic extract of the leaves of Dolichandrone spathacea. This traditional medicinal plant is widely used in Asia and India as antiseptic, for bronchitis and thrush treatment, and the methanolic extract has been shown to possess antibacterial activity against methicillin-resistant Staphylococcus aureus. The new iridoids were esterified derivatives of 6-ajugol and 6-catalpol, and the new saponins were glucosides of two polyhydroxy triterpenes with ursan skeleton. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments and HR-ESI-MS analysis, and from comparison with the literature. This study aimed at investigating extracts and isolated compounds for their antimicrobial activities against bacterial and yeast strains, in order to validate the uses of the plant in folk medicine. The 6-O-esterified iridoids had weaker antibacterial activity; verbascoside and p-methoxycinnamic acid, the major compounds of the methanol extract, possessed strong antibacterial activity, which could account for the traditional antiseptic and anti-infectious uses of the leaves of D. spathacea.
Balloon-assisted endoscopy facilitates endoscopic submucosal dissection of difficult superficial proximal colon tumors
Authors: Yamashina Takeshi , Hayashi Yoshikazu , Sakamoto Hirotsugu , Yano Tomonori , Miura Yoshimasa , Shinozaki Satoshi , Sunada Keijiro , Kawarai Lefor Alan , Yamamoto Hironori 
Published: February 2018

Abstract
Background Colorectal endoscopic submucosal dissection (ESD) can be technically difficult in some situations, such as paradoxical movement of the proximal colon. The double-balloon endoscope provides stable endoscopic maneuvering, even in the small intestine. The aim of this study was to assess the outcomes of balloon-assisted endoscopic submucosal dissection (BAESD) of colonoscopically difficult superficial proximal colon tumors.
Methods We retrospectively reviewed the records of patients who underwent BAESD of superficial proximal colon tumors where colonoscopic difficulties were encountered, from January 2011 to September 2016. Difficulties were defined as a previous incomplete colonoscopy using a conventional colonoscope or unstable endoscopic maneuverability around the tumor with a conventional colonoscope. A propensity score model was used as a secondary analysis to compare outcomes of the BAESD group with those of a non-BAESD group.
Results BAESD was performed on 63 tumors in 63 patients. En bloc resection was achieved for 62 tumors (98 %) and an R0 resection was achieved for 55 tumors (87 %). Propensity score matching analysis created 59 matched pairs from the BAESD and non-BAESD groups. There were no statistically significant differences between the two groups in en bloc resection (100 % vs. 100 %; P > 0.99), R0 resection (90 % vs. 93 %; P = 0.74), perforation (0 % vs. 2 %; P > 0.99) or postoperative bleeding (3 % vs. 0 %; P = 0.50).
Conclusion Balloon-assisted endoscopy achieved safe and reliable ESD of colonoscopically difficult superficial proximal colon tumors.
Spatial patterns of tree yield explained by endogenous forces through a correspondence between the Ising model and ecology
Authors: Noble Andrew E. , Rosenstock Todd S. , Brown Patrick H. , Machta Jonathan , Hastings Alan 
Published: February 2018

SignificanceExplaining correlations across space of cyclic dynamics in ecology is a fundamental challenge. We apply ideas from statistical physics, originally used to explain the behavior of magnets, to a dataset on yield from pistachio trees, obtaining a robust description and potential explanation for the generation of spatial correlations in cyclic dynamics. These results suggest looking for mechanistic underpinnings at the level of interactions between neighboring trees that lead to spatial correlations in dynamics and a surprising correspondence between the descriptions of physical phenomena, magnetization, and ecological dynamics. This work demonstrates with data, and not just models, that correlations in cyclic dynamics can be generated from local interactions and dynamics even in a very noisy ecological system.
Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events
Authors: Hämmerer Dorothea , Callaghan Martina F. , Hopkins Alexandra , Kosciessa Julian , Betts Matthew , Cardenas-Blanco Arturo , Kanowski Martin , Weiskopf Nikolaus , Dayan Peter , Dolan Raymond J. , Düzel Emrah 
Published: February 2018

Significance
Locus coeruleus (LC) integrity in cognitively normal older adults is a potentially important preclinical marker in dementia. Our study establishes a link between variability in LC integrity and cognitive decline related to noradrenergic modulation in old age. We find that in older adults, reduced LC integrity explains lower memory performance. This effect was more pronounced for memory related to negative events, and accompanied by increased pupil diameter size in response to negative events. The study provides a strong motivation for future research investigating the role of LC integrity in healthy, as well as in pathological, aging.
Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity
Authors: Davenport A. J. , Cross R. S. , Watson K. A. , Liao Y. , Shi W. , Prince H. M. , Beavis P. A. , Trapani J. A. , Kershaw M. H. , Ritchie D. S. , Darcy P. K. , Neeson P. J. , Jenkins M. R. 
Published: February 2018

SignificanceDavenport et al. discovered that the chimeric antigen receptor (CAR) immune synapse structure is different from the T cell receptor (TCR) synapse. The CAR immune synapse formed a disorganized pattern of Lck and more rapidly recruited lytic granules compared with the TCR. The differing immune synapse correlated with faster killing of tumor target cells and detachment from dying tumor cells by CAR-T cells. These findings provide a mechanism whereby CAR-T cells can effectively reduce large tumor burden in patients. This study will form a basis upon which to compare future receptor design to modulate signaling and programming of cytotoxic CAR-T cells to improve treatment of solid cancers.