bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTLA-4 Protects against Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice
Authors: Amin Hilman Zulkifli , Sasaki Naoto , Yamashita Tomoya , Mizoguchi Taiji , Hayashi Tomohiro , Emoto Takuo , Matsumoto Takuya , Yoshida Naofumi , Tabata Tokiko , Horibe Sayo , Kawauchi Shoji , Rikitake Yoshiyuki , Hirata Ken-ichi 
Published: May 2019

AbstractVascular inflammation via T-cell-mediated immune responses has been shown to be critically involved in the pathogenesis of abdominal aortic aneurysm (AAA). T-cell coinhibitory molecule cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is known to act as a potent negative regulator of immune responses. However, the role of this molecule in the development of AAA remains completely unknown. We determined the effects of CTLA-4 overexpression on experimental AAA. We continuously infused CTLA-4 transgenic (CTLA-4-Tg)/apolipoprotein E–deficient (Apoe−/−) mice or control Apoe−/− mice fed a high-cholesterol diet with angiotensin II by implanting osmotic mini-pumps and evaluated the development of AAA. Ninety percent of angiotensin II-infused mice developed AAA, with 50% mortality because of aneurysm rupture. Overexpression of CTLA-4 significantly reduced the incidence (66%), mortality (26%), and diameter of AAA. These protective effects were associated with a decreased number of effector CD4+ T cells and the downregulated expression of costimulatory molecules CD80 and CD86, ligands for CTLA-4, on CD11c+ dendritic cells in lymphoid tissues. CTLA-4-Tg/Apoe−/− mice had reduced accumulation of macrophages and CD4+ T cells, leading to attenuated aortic inflammation, preserved vessel integrity, and decreased susceptibility to AAA and aortic rupture. Our findings suggest T-cell coinhibitory molecule CTLA-4 as a novel therapeutic target for AAA.
Systematic evaluation and optimization of the experimental steps in RNA G-quadruplex structure sequencing
Authors: Yeung Pui Yan , Zhao Jieyu , Chow Eugene Yui-Ching , Mou Xi , Hong HuiQi , Chen Leilei , Chan Ting-Fung , Kwok Chun Kit 
Published: May 2019

AbstractcDNA library preparation is important for many high-throughput sequencing applications, such as RNA G-quadruplex structure sequencing (rG4-seq). A systematic evaluation of the procedures of the experimental pipeline, however, is lacking. Herein, we perform a comprehensive assessment of the 5 key experimental steps involved in the cDNA library preparation of rG4-seq, and identify better reaction conditions and/or enzymes to carry out each of these key steps. Notably, we apply the improved methods to fragmented cellular RNA, and show reduced RNA input requirement, lower transcript abundance variations between biological replicates, as well as lower transcript coverage bias when compared to prior arts. In addition, the time to perform these steps is substantially reduced to hours. Our method and results can be directly applied in protocols that require cDNA library preparation, and provide insights to the further development of simple and efficient cDNA library preparation for different biological applications.
Volumetric assessment of extracranial carotid artery aneurysms
Authors: de Vries E. E. , van Laarhoven C. J. H. C. M. , Kuijf H. J. , Hazenberg C. E. V. B. , van Herwaarden J. A. , Viergever M. A. , de Borst G. J. 
Published: May 2019

AbstractThe extracranial carotid artery aneurysm (ECAA) is a rare pathology for which clinical treatment guidelines are lacking. In general, symptoms or growth of the aneurysm sac are thought to indicate intervention. ECAAs may present in a large variety of shapes and sizes, and conventional diameter measurements fail to indicate geometrical differences. Therefore, we propose a protocol to measure ECAA size by 3D volumetric assessment. The volumes of 40 ECAAs in computed tomography angiography (CTA) images were measured through manual segmentation, by two independent operators. Volumes of the entire internal carotid artery (ICA) and the ECAA were measured separately. Excellent inter- and intraoperator reliability was found for both ICA and ECAA volumes, with all intraclass correlation coefficients above 0.94. Bland-Altman analysis revealed normal differences for both inter- and intraoperator agreement. For all volumes, similarity of the segmentations was excellent. Outliers were explained by presence of intraluminal ECAA thrombus, which hampered identification of the aneurysm outer wall. These results implicate robustness of our protocol, which is designed as a step-up towards (semi)automatic volumetric measurements to monitor patients with ECAA. Future (semi)automatic volumetric assessments are recommended and such techniques can be developed and validated using the proposed protocol and manual reference segmentations.
Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection
Authors: Zhang Xiaoman , Chen Xianli , Wei Meijuan , Zhang Chunyu , Xu Tao , Liu Liguan , Xu Zhengju 
Published: May 2019

AbstractThis study was performed to analyze the potential resistant mutations within HBV reverse transcriptase (RT) sequences against nucleos(t)ide analogues (NA). HBV DNA RT region spanning from amino acid 169 to 250 was amplified and sequenced from 435 HBV patients who experienced NA treatment. Among study’s cohort, genotypes B and C infected patients were 55.9% and 44.1%, respectively. Mutations were recorded in 54.7% (238/435) patients at 22 positions. Genotype C displayed significant higher frequency of potential NA resistant mutations than genotype B (63.0% vs. 48.1%, P = 0.003). Moreover, eight mutation sites, including 180, 181, 191, 200, 202, 221, 229 and 224, in genotype C showed significant higher frequencies than in genotype B. In contrast, mutation at site 236 was more common in genotype B. Notably, 11 mutations at position 169, 202, 250, 173, 180, 200, 207, 214, 237, 242 and 245 coexisted with M204I or V. Substitutions at nine non-classical mutation sites (191, 207, 213, 218, 221, 224, 229, 238 and 242) were detected in patients with virological breakthrough. Particularly, tenofovir (TDF) resistance was observed in one patient undergoing TDF monotherapy and experienced several NA treatment before. These results might provide clinical useful information under antiviral therapy.
Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status
Authors: Hwang Chi Sang , Park Sang Chul , Cho Hyung-Ju , Park Dong-Joon , Yoon Joo-Heon , Kim Chang-Hoon 
Published: May 2019

AbstractChronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund–Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r  =  0.83, p  < 0.001) regardless of the presence of NPs. Patients with more EETs demonstrated higher Lund–Mackay scores (r  =  0.51, p  = 0.009), blood eosinophilia (r  =  0.80, p  < 0.001), and decreased olfactory function (r  = −0.65, p  < 0.001). No correlation between the extent of EET formation and the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs. Formation of EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS, regardless of NP status.
Retinal Vascular Density as A Novel Biomarker of Acute Renal Injury after Acute Coronary Syndrome
Authors: Alan Guillaume , Guenancia Charles , Arnould Louis , Azemar Arthur , Pitois Stéphane , Maza Maud , Bichat Florence , Zeller Marianne , Gabrielle Pierre-Henri , Bron Alain Marie , Creuzot-Garcher Catherine , Cottin Yves 
Published: May 2019

AbstractIodinated contrast agent (ICA)-induced acute kidney injury (AKI) following acute coronary syndrome (ACS) is a frequent complication, which may lead to chronic kidney disease and increased mortality. Optical coherence tomography angiography (OCT-A) of the retina is new tool delivering a rapid and noninvasive assessment of systemic microvascularization, which is potentially involved in the occurrence of ICA-induced AKI. Between October 2016 and March 2017, 452 ACS patients were admitted to our cardiac intensive care unit. OCT-A was performed within 48 h after the ICA injection. Patients with a history of retinal disease were excluded. The patients included were divided into two groups depending on whether or not AKI occurred after injection of ICA, according to KDIGO criteria. Of the 216 patients included, 21 (10%) presented AKI. AKI was significantly associated with age, Mehran score, GRACE score, and NT-proBNP. AKI patients had significantly lower retinal vascular density (RVD)) and had more frequent low RVD (81% vs 45%, P = 0.002). Adding low RVD to the Mehran score and the NT-proBNP, or to the GRACE score and the NT-proBNP, significantly improved their predictive values, suggesting that systemic microvascular involvement remains incompletely addressed by either standard risk scores or factors known to be associated with ICA-induced AKI.
Lipid-dependent Akt-ivity: where, when, and how
Authors: Siess Katharina M. , Leonard Thomas A. 
Published: May 2019

Abstract
Akt is an essential protein kinase activated downstream of phosphoinositide 3-kinase and frequently hyperactivated in cancer. Canonically, Akt is activated by phosphoinositide-dependent kinase 1 and mechanistic target of rapamycin complex 2, which phosphorylate it on two regulatory residues in its kinase domain upon targeting of Akt to the plasma membrane by PI(3,4,5)P3. Recent evidence, however, has shown that, in addition to phosphorylation, Akt activity is allosterically coupled to the engagement of PI(3,4,5)P3 or PI(3,4)P2 in cellular membranes. Furthermore, the active membrane-bound conformation of Akt is protected from dephosphorylation, and Akt inactivation by phosphatases is rate-limited by its dissociation. Thus, Akt activity is restricted to membranes containing either PI(3,4,5)P3 or PI(3,4)P2. While PI(3,4,5)P3 has long been associated with signaling at the plasma membrane, PI(3,4)P2 is gaining increasing traction as a signaling lipid and has been implicated in controlling Akt activity throughout the endomembrane system. This has clear implications for the phosphorylation of both freely diffusible substrates and those localized to discrete subcellular compartments.
The Utility of High-Resolution Pharyngeal Manometry in Dysphagia Treatment
Authors: Davidson Kate (Humphries) , O'Rourke Ashli K. 
Published: May 2019

PurposeHigh-resolution pharyngeal manometry (HRPM) is an emerging technology that shows promise as both an adjuvant diagnostic and therapeutic tool in oropharyngeal dysphagia management. Advances in manometric technology, including increased number of sensors and topographical pressure plots, enhance the biofeedback potential for the pharynx. This clinical focus article serves as an overview of the utility of HRPM in dysphagia treatment.ConclusionHRPM-facilitated biofeedback aids the patient in the correct implementation of clinical recommendations and also provides the clinician an assessment of the effectiveness and accuracy of those targeted interventions. Topographic pressure plots provide intuitive feedback, allow easier swallow-to-swallow comparisons, and produce visually color-coded pressure information for the patient and clinician in real time. Paired with existing, evidence-based interventions, HRPM biofeedback may facilitate maneuver and strategy planning, exercise training and monitoring, temporal coordination, upper esophageal segment relaxation and duration, swallow mapping (topographic pattern recognition and approximation), fatigue monitoring, dose planning, adherence tracking, and efficacy assessment of selected interventions. Although competency training is needed to effectively utilize HRPM, there are growing opportunities for the speech-language pathologist to acquire and implement this technology for the benefit of patients.
IRAS 23385+6053: an embedded massive cluster in the making
Authors: Cesaroni R. , Beuther H. , Ahmadi A. , Beltrán M. T. , Csengeri T. , Galván-Madrid R. , Gieser C. , Henning T. , Johnston K. G. , Klaassen P. D. , Kuiper R. , Leurini S. , Linz H. , Longmore S. , Lumsden S. L. , Maud L. T. , Moscadelli L. , Mottram J. C. , Palau A. , Peters T. , Pudritz R. E. , Sánchez-Monge Á. , Schilke P. , Semenov D. , Suri S. , Urquhart J. S. , Winters J. M. , Zhang Q. , Zinnecker H. 
Published: May 2019

Context.This study is part of the CORE project, an IRAM/NOEMA large program consisting of observations of the millimeter continuum and molecular line emission towards 20 selected high-mass star-forming regions. The goal of the program is to search for circumstellar accretion disks, study the fragmentation process of molecular clumps, and investigate the chemical composition of the gas in these regions.Aims.We focus on IRAS 23385+6053, which is believed to be the least-evolved source of the CORE sample. This object is characterized by a compact molecular clump that is IR-dark shortward of 24μm and is surrounded by a stellar cluster detected in the near-IR. Our aim is to study the structure and velocity field of the clump.Methods.Observations were performed at ~1.4 mm and employed three configurations of NOEMA and additional single-dish maps, merged with the interferometric data to recover the extended emission. Our correlator setup covered a number of lines from well-known hot core tracers and a few outflow tracers. The angular (~0′′.45–0′′.9) and spectral (0.5 km s−1) resolutions were sufficient to resolve the clump in IRAS 23385+6053 and investigate the existence of large-scale motions due to rotation, infall, or expansion.Results.We find that the clump splits into six distinct cores when observed at sub-arcsecond resolution. These are identified through their 1.4 mm continuum and molecular line emission. We produce maps of the velocity, line width, and rotational temperature from the methanol and methyl cyanide lines, which allow us to investigate the cores and reveal a velocity and temperature gradient in the most massive core. We also find evidence of a bipolar outflow, possibly powered by a low-mass star.Conclusions.We present the tentative detection of a circumstellar self-gravitating disk lying in the most massive core and powering a large-scale outflow previously known in the literature. In our scenario, the star powering the flow is responsible for most of the luminosity of IRAS 23385+6053 (~3000L⊙). The other cores, albeit with masses below the corresponding virial masses, appear to be accreting material from their molecular surroundings and are possibly collapsing or on the verge of collapse. We conclude that we are observing a sample of star-forming cores that is bound to turn into a cluster of massive stars.
Comparing Outcomes for Fasciocutaneous versus Muscle Flaps in Foot and Ankle Free Flap Reconstruction
Authors: Lee Z-Hye , Abdou Salma A. , Daar David A. , Anzai Lavinia , Stranix John T. , Thanik Vishal , Levine Jamie P. , Saadeh Pierre B. 
Published: May 2019

Background The distal lower extremity poses unique reconstructive challenges due to its requirements for durability of the load-bearing plantar surface and for thin, pliable contour in the dorsal foot and ankle region. This study compares outcomes between muscle and fasciocutaneous flaps in patients with foot and ankle defects.
Methods A retrospective review of soft tissue free flaps used for traumatic foot and ankle defects was performed. Outcomes included takebacks, partial flap failure, total flap failure, and wound complications.
Results A total of 165 cases met inclusion criteria, with muscle flaps (n = 110) comprising the majority. Defects involving the non–weight-bearing surface were more common (n = 86) than those of the weight-bearing surface (n = 79). Complications occurred in 56 flaps (33.9%), including 11 partial losses (6.7%) and 6 complete losses (3.6%). There were no differences in take backs, partial flap failure, or total flap failure between muscle and fasciocutaneous flaps; however, fasciocutaneous flaps had significantly fewer wound complications compared with muscle flaps (7.3% vs. 19.1%, p = 0.046). On multivariable regression analysis, defects of the weight-bearing surface had significantly increased risk of wound breakdown compared with those in the non–weight-bearing surface (odds ratio: 5.05, p = 0.004).
Conclusion Compared with fasciocutaneous flaps, muscle flaps demonstrated higher rates of wound complications. While the flap selection in foot and ankle reconstruction depends on the nature of the defect, our findings support the use of fasciocutaneous over muscle flaps in this region.
Why haploinsufficiency persists
Authors: Morrill Summer A. , Amon Angelika 
Published: May 2019

Significance
For most genes, a single copy is enough to support normal growth and development of diploid organisms, but a small subset of genes known as haploinsufficient (HI) genes exhibit extreme sensitivity to decreased gene dosage. Given the relatively high frequency of gene-inactivating mutations over the lifespan of an organism, and cell-to-cell variability in gene expression, haploinsufficiency represents a significant barrier to organismal fitness. Why the expression of these genes has not been modulated over evolutionary time to eliminate their haploinsufficiency remains unexplained. We find that the limit of haploinsufficient genes on organismal fitness cannot be overcome by an increase in expression because haploinsufficient genes also confer a fitness disadvantage when encoded in extra copy, leaving these genes evolutionarily “stuck.”
Torque-dependent remodeling of the bacterial flagellar motor
Authors: Wadhwa Navish , Phillips Rob , Berg Howard C. 
Published: May 2019

Significance
The molecular machines that carry out important biological functions in living cells are often made from smaller units that self-assemble inside the cell. Despite decades of research into the function of assembled molecular complexes, little is known about how their assembly itself is regulated to accommodate varying environmental conditions. We measure how the assembly of the bacterial flagellar motor depends on its operational parameters, such as speed and torque. Based on these measurements, we use tools from statistical physics to construct a model for the regulated self-assembly, which largely captures the observed kinetics. This work advances our understanding of how interactions between protein subunits can be tuned by external stimuli to functionally control the formation of macromolecular assemblies.
Estimating power plant CO2 emission using OCO-2 XCO2 and high resolution WRF-Chem simulations
Authors: Zheng Tao , Nassar Ray , Baxter Martin 
Published: May 2019

Abstract
Anthropogenic CO2 emission from fossil fuel combustion has major impacts on the global climate. The Orbiting Carbon Observatory 2 (OCO-2) observations have previously been used to estimate individual power plant emissions with a Gaussian plume model assuming constant wind fields. The present work assesses the feasibility of estimating power plant CO2 emission using high resolution chemistry transport model simulations with OCO-2 observation data. In the new framework, 1.33 km Weather Research and Forecasting-Chem (WRF)-Chem simulation results are used to calculate the Jacobian matrix, which is then used with the OCO-2 XCO2 data to obtain power plant daily mean emission rates, through a maximum likelihood estimation. We applied the framework to the seven OCO-2 observations of near mid-to-large coal burning power plants identified in Nassar et al (2017 Geophys. Res. Lett. 44, 10045–53). Our estimation results closely match the reported emission rates at the Westar power plant (Kansas, USA), with a reported value of 26.67 ktCO2/day, and our estimated value at 25.82–26.47 ktCO2/day using OCO-2 v8 data, and 22.09–22.80 ktCO2/day using v9 data. At Ghent, KY, USA, our estimations using three versions (v7, v8, and v9) range from 9.84–20.40 ktCO2/day, which are substantially lower than the reported value (29.17 ktCO2/day). We attribute this difference to diminished WRF-Chem wind field simulation accuracy. The results from the seven cases indicate that accurate estimation requires accurate meteorological simulations and high quality XCO2 data. In addition, the strength and orientation (relative to the OCO-2 ground track) of the XCO2 enhancement are important for accurate and reliable estimation. Compared with the Gaussian plume model based approach, the high resolution WRF-Chem simulation based approach provides a framework for addressing varying wind fields, and possible expansion to city level emission estimation.
Disaster Risk Assessment of Transmission Lines Based on TOPSIS
Authors: Chen Taowei , Zhu Ling , Xia Qiao , Deng Honglei , Zhou Chen 
Published: May 2019

Abstract
It is of great significance to ensure the safe and reliable operation of the power grid by effectively evaluating the disaster risk of the power grid lines and arranging the sequence of line guard reasonably. A disaster risk assessment method of transmission lines based on TOPSIS is proposed in this paper where six typical natural disasters of the line are considered, the comprehensive risk values of different lines under different disasters combined with the hazards of line accidents is determined, the risk assessment of multiple transmission lines are realized, and its feasibility is verified by applying it to multiple transmission lines in a certain area of China Southern power grid.
Research on Distributed Protection in Switch Stations Based on GOOSE
Authors: Jiang Xin , Yun Baoji 
Published: May 2019

Abstract
The application of IEC61850 standard and the development of smart terminal unit (STU) technology provide a powerful platform for secondary protection research of distribution network. Aiming at the problems of override trip in the protection of the incoming line and feeders on traditional 10kV switching stations, a scheme combining distributed voltage loss protection and overcurrent protection is proposed. The smart terminal unit collects and processes the operation data, realizes data exchange through GOOSE network communication, and cooperates to realize the protection function of the switch stations. In this paper, a protection logic diagram based on the GOOSE mechanism is constructed, which realizes the protection function of feeder lines fault lockout incoming line breakers and the bus line fault lockout busbar automatic transfer switch.