bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Aberrations Uncovered in Barrett's Esophagus and Esophageal Adenocarcinoma Using Whole Transcriptome Sequencing
Authors: Maag Jesper L.V. , Fisher Oliver M. , Levert-Mignon Angelique , Kaczorowski Dominik C. , Thomas Melissa L. , Hussey Damian J. , Watson David I. , Wettstein Antony , Bobryshev Yuri V. , Edwards Melanie , Dinger Marcel E. , Lord Reginald V. 
Published: July 2017

Abstract
Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence of any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is the main risk factor for EAC; however, the mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant Barrett's tissues to better understand this disease. Machine-learning and network analysis methods were applied to discover novel driver genes for EAC development. Identified gene expression signatures for the distinction of EAC from BE were validated in separate datasets. An extensive analysis of the noncoding RNA (ncRNA) landscape was performed to determine the involvement of novel transcriptomic elements in Barrett's disease and EAC. Finally, transcriptomic mutational investigation of genes that are recurrently mutated in EAC was performed. Through these approaches, novel driver genes were discovered for EAC, which involved key cell cycle and DNA repair genes, such as BRCA1 and PRKDC. A novel 4-gene signature (CTSL, COL17A1, KLF4, and E2F3) was identified, externally validated, and shown to provide excellent distinction of EAC from BE. Furthermore, expression changes were observed in 685 long noncoding RNAs (lncRNA) and a systematic dysregulation of repeat elements across different stages of Barrett's disease, with wide-ranging downregulation of Alu elements in EAC. Mutational investigation revealed distinct pathways activated between EAC tissues with or without TP53 mutations compared with Barrett's disease. In summary, transcriptome sequencing revealed altered expression of numerous novel elements, processes, and networks in EAC and premalignant BE.
Implications: This study identified opportunities to improve early detection and treatment of patients with BE and esophageal adenocarcinoma. Mol Cancer Res; 15(11); 1558–69. ©2017 AACR.
CYLD Deubiquitinates Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4 Contributing to Adventitial Remodeling
Authors: Yu Bing , Liu Ziyi , Fu Yi , Wang Yingbao , Zhang Lu , Cai Zeyu , Yu Fang , Wang Xian , Zhou Jun , Kong Wei 
Published: July 2017

Objective—
Transdifferentiation of adventitial fibroblasts (AFs) into myofibroblasts plays a critical role during the vascular remodeling that occurs during atherosclerosis, restenosis, and aortic aneurysm. The ubiquitination/deubiquitination regulatory system is essential for the quality control of proteins. The involvement of ubiquitination/deubiquitination during AF transdifferentiation remains largely unknown. In this study, we determined the role of cylindromatosis (CYLD), a deubiquitinase, in the process of AF differentiation and activation in vitro and in vivo.

Approach and Results—

Transforming growth factor-β1 and homocysteine, 2 known inducers of AF transdifferentiation, greatly upregulated CYLD expression in a time- and dose-dependent manner. The silencing of CYLD significantly inhibited AF transdifferentiation and activation as evidenced by the expression of contractile proteins, the production of the proinflammatory cytokines MCP-1 (monocyte chemotactic protein 1) and IL-6 (interleukin-6), the deposition of extracellular matrix, and cell migration. We further asked whether CYLD mediates AF activation via the regulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) as it is an essential factor during AF transdifferentiation. Indeed, the silencing of CYLD repressed transforming growth factor-β1–induced and homocysteine-induced Nox4 upregulation and reactive oxygen species production, whereas Nox4 overexpression greatly rescued the inhibitory effect on AF activation by CYLD silencing. Most interestingly, transforming growth factor-β1 and homocysteine repressed Nox4 ubiquitination and prolonged the half-life of Nox4. Moreover, Nox4 was deubiquitinated via a direct interaction with the ubiquitin-specific protease domain of CYLD. In accordance, hyperhomocysteinemia significantly increased adventitial CYLD and Nox4 expression, promoted AF transdifferentiation, and aggravated CaPO
4
-induced abdominal aortic aneurysm in mice. These effects were abolished in CYLD
−/−
mice.

Conclusions—
CYLD contributes to the transdifferentiation of AFs via deubiquitinating Nox4 and may play a role in vascular remodeling.
Kinetics of Circulating MicroRNAs in Response to Cardiac Stress in Patients With Coronary Artery Disease
Authors: Jansen Felix , Schäfer Lisa , Wang Han , Schmitz Theresa , Flender Anna , Schueler Robert , Hammerstingl Christoph , Nickenig Georg , Sinning Jan‐Malte , Werner Nikos 
Published: July 2017

Background

Circulating micro
RNA
s (mi
RNA
s/miRs) are regulated in patients with coronary artery disease. The impact of transient coronary ischemia on circulating mi
RNA
levels is unknown. We aimed to investigate circulating mi
RNA
kinetics in response to cardiac stress in patients with or without significant coronary stenosis.

Methods and Results

Eighty of 105 screened patients with stable coronary artery disease underwent dobutamine stress echocardiography before coronary angiography. Nine circulating vascular mi
RNA
s (mi
RNA
‐21, mi
RNA
‐26, mi
RNA
‐27a, mi
RNA
‐92a, mi
RNA
‐126‐3p, mi
RNA
‐133a, mi
RNA
‐222, mi
RNA
‐223, and mi
RNA
‐199‐5p) were quantified in plasma by reverse transcription polymerase chain reaction before, immediately after, and 4 and 24 hours after dobutamine stress echocardiography. Quantitative polymerase chain reaction revealed increased mi
RNA
‐21, miRNA‐126‐3p, and miRNA‐222 levels at 24 hours after dobutamine stress echocardiography in all patients. On coronary angiography, significant coronary artery stenoses (>80% diameter stenosis) were found in 41 patients. Stratifying patients according to the prevalence of significant stenoses, patients with stenosis showed an increase of circulating mi
RNA
‐21, mi
RNA
‐126‐3p, and mi
RNA
‐222 in response to cardiac stress. In patients without significant stenoses (<50% diameter stenosis), mi
RNA
‐92a levels gradually increased in response to cardiac stress.

Conclusions

mi
RNA
s are distinctly released into the circulation in response to cardiac stress depending on the prevalence of significant coronary stenoses.
The Impact of Cryoballoon Versus Radiofrequency Ablation for Paroxysmal Atrial Fibrillation on Healthcare Utilization and Costs: An Economic Analysis From the FIRE AND ICE Trial
Authors: Chun K. R. Julian , Brugada Josep , Elvan Arif , Gellér Laszlo , Busch Matthias , Barrera Alberto , Schilling Richard J. , Reynolds Matthew R. , Hokanson Robert B. , Holbrook Reece , Brown Benedict , Schlüter Michael , Kuck Karl‐Heinz ,   for the FIRE AND ICE Investigators
Published: July 2017

Background

This study sought to assess payer costs following cryoballoon or radiofrequency current (
RFC
) catheter ablation of paroxysmal atrial fibrillation in the randomized
FIRE AND ICE
trial.

Methods and Results

A trial period analysis of healthcare costs evaluated the impact of ablation modality (cryoballoon versus
RFC
) on differences in resource use and associated payer costs. Analyses were based on repeat interventions, rehospitalizations, and cardioversions during the trial, with unit costs based on 3 national healthcare systems (Germany [€], the United Kingdom [£], and the United States [

$

]). Total payer costs were calculated by applying standard unit costs to hospital stays, using
International Classification of Diseases, 10th Revision
diagnoses and procedure codes that were mapped to country‐specific diagnosis‐related groups. Patients (N=750) randomized 1:1 to cryoballoon (n=374) or
RFC
(n=376) ablation were followed for a mean of 1.5 years. Resource use was lower in the cryoballoon than the
RFC
group (205 hospitalizations and/or interventions in 122 patients versus 268 events in 154 patients). The cost differences per patient in mean total payer costs during follow‐up were €640, £364, and

$

925 in favor of cryoballoon ablation (
P
=0.012, 0.013, and 0.016, respectively). This resulted in trial period total cost savings of €245 000, £140 000, and

$

355 000.

Conclusions

When compared with
RFC
ablation, cryoballoon ablation was associated with a reduction in resource use and payer costs. In all 3 national healthcare systems analyzed, this reduction resulted in substantial trial period cost savings, primarily attributable to fewer repeat ablations and a reduction in cardiovascular rehospitalizations with cryoballoon ablation.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Identifier: NCT01490814.
Just Say No: Explaining the Lack of International Mediation in Kashmir
Authors: Biswas Bidisha 
Published: July 2017

AbstractThe dispute between India and Pakistan over Kashmir is one of the world’s most protracted and potentially dangerous conflicts. While the international community has strong interest in limiting violent conflagration between the two states, third party action aimed at amelioration has been very limited. This contrasts with overall global mediation efforts, which have increased in the post-Cold War period. Using archival research, this study explores the reasons for the Government of India’s implacable opposition to any external intervention in the conflict. We argue that both strategic and ideational motivations have influenced its decisions. In particular, India’s strict adherence to the principle of strategic autonomy precludes the possibility of accepting external mediation. By exploring how and why strategic and ideational motivations intersect to become a formidable barrier to third party intervention, this article contributes to our understanding of why certain countries develop resistance to mediation.
A Third-Law Isentropic Analysis of a Simulated Hurricane
Authors: Marquet Pascal 
Published: July 2017

Abstract
The moist-air entropy can be used to analyze and better understand the general circulation of the atmosphere or convective motions. Isentropic analyses are commonly based on studies of different equivalent potential temperatures, all of which are assumed to fully represent the entropy of moist air. It is, however, possible to rely either on statistical physics or the third law of thermodynamics when defining and computing the absolute entropy of moist air and to study the corresponding third-law potential temperature, which is different from the previous ones. The third law assumes that the entropy for the most stable crystalline state of all substances is zero when approaching absolute zero temperature.
This paper shows that the way all these moist-air potential temperatures are defined has a large impact on (i) the plotting of the isentropes for a simulation of Hurricane Dumile, (ii) the changes in moist-air entropy computed for a steam cycle defined for this hurricane, (iii) the analyses of isentropic streamfunctions computed for this hurricane, and (iv) the computations of the heat input, the work function, and the efficiency defined for this steam cycle.
The moist-air entropy is a state function and the isentropic analyses must be completely determined by the local moist-air conditions. The large differences observed between the different formulations of moist-air entropy are interpreted as proof that the isentropic analyses of moist-air atmospheric motions must be achieved by using the third-law potential temperature defined from general thermodynamics.
The Response of the Southern Hemisphere Middle Atmosphere to the Madden–Julian Oscillation during Austral Winter Using the Specified-Dynamics Whole Atmosphere Community Climate Model
Authors: Yang Chengyun , Li Tao , Smith Anne K. , Dou Xiankang 
Published: July 2017

Abstract
Using the specified-dynamics (SD) Whole Atmosphere Community Climate Model (SD-WACCM), the effects of the Madden–Julian oscillation (MJO) on the midwinter stratosphere and mesosphere in the Southern Hemisphere (SH) are investigated. The most significant responses of the SH polar cap temperature to the MJO are found about 30 days after MJO phase 1 (P1) and about 10 days after MJO phase 5 (P5) in both the ERA-Interim data and the SD-WACCM simulation. The 200- and 500-hPa geopotential height anomalies in the SH reveal that wave trains emanate from the Indian and Pacific Oceans when the MJO convection is enhanced in the eastern Indian Ocean and the western Pacific. As a result, the upward propagation and dissipation of planetary waves (PWs) in the middle and high latitudes of the SH stratosphere is significantly enhanced, the Brewer–Dobson (BD) circulation in the SH stratosphere strengthens, and temperatures in the SH polar stratosphere increase. Wavenumber 1 in the stratosphere is the dominant component of the PW perturbation induced by the MJO convection. In the SH mesosphere, the MJO leads to enhancement of the dissipation and breaking of gravity waves (GWs) propagating as a result of wind-filtering change in the SH extratropics and causes anomalous downwelling in the middle and high latitudes of the mesosphere. The circulation thus changes significantly, resulting in anomalous cooling in the mesosphere in response to MJO P1 and P5 at lags of 10 and 30 days, respectively.
Assessment of the SMAP Level-4 Surface and Root-Zone Soil Moisture Product Using In Situ Measurements
Authors: Reichle Rolf H. , De Lannoy Gabrielle J. M. , Liu Qing , Ardizzone Joseph V. , Colliander Andreas , Conaty Austin , Crow Wade , Jackson Thomas J. , Jones Lucas A. , Kimball John S. , Koster Randal D. , Mahanama Sarith P. , Smith Edmond B. , Berg Aaron , Bircher Simone , Bosch David , Caldwell Todd G. , Cosh Michael , González-Zamora Ángel , Holifield Collins Chandra D. , Jensen Karsten H. , Livingston Stan , Lopez-Baeza Ernesto , Martínez-Fernández José , McNairn Heather , Moghaddam Mahta , Pacheco Anna , Pellarin Thierry , Prueger John , Rowlandson Tracy , Seyfried Mark , Starks Patrick , Su Zhongbo , Thibeault Marc , van der Velde Rogier , Walker Jeffrey , Wu Xiaoling , Zeng Yijian 
Published: July 2017

Abstract
The Soil Moisture Active Passive (SMAP) mission Level-4 Surface and Root-Zone Soil Moisture (L4_SM) data product is generated by assimilating SMAP L-band brightness temperature observations into the NASA Catchment land surface model. The L4_SM product is available from 31 March 2015 to present (within 3 days from real time) and provides 3-hourly, global, 9-km resolution estimates of surface (0–5 cm) and root-zone (0–100 cm) soil moisture and land surface conditions. This study presents an overview of the L4_SM algorithm, validation approach, and product assessment versus in situ measurements. Core validation sites provide spatially averaged surface (root zone) soil moisture measurements for 43 (17) “reference pixels” at 9- and 36-km gridcell scales located in 17 (7) distinct watersheds. Sparse networks provide point-scale measurements of surface (root zone) soil moisture at 406 (311) locations. Core validation site results indicate that the L4_SM product meets its soil moisture accuracy requirement, specified as an unbiased RMSE (ubRMSE, or standard deviation of the error) of 0.04 m3 m−3 or better. The ubRMSE for L4_SM surface (root zone) soil moisture is 0.038 m3 m−3 (0.030 m3 m−3) at the 9-km scale and 0.035 m3 m−3 (0.026 m3 m−3) at the 36-km scale. The L4_SM estimates improve (significantly at the 5% level for surface soil moisture) over model-only estimates, which do not benefit from the assimilation of SMAP brightness temperature observations and have a 9-km surface (root zone) ubRMSE of 0.042 m3 m−3 (0.032 m3 m−3). Time series correlations exhibit similar relative performance. The sparse network results corroborate these findings over a greater variety of climate and land cover conditions.
Initiation of spreading depression by synaptic and network hyperactivity: Insights into trigger mechanisms of migraine aura
Authors: Vinogradova Lyudmila V 
Published: July 2017

Background Cortical spreading depression (SD) is thought to underlie migraine aura but mechanisms of triggering SD in the structurally normal, well-nourished cortex of migraine patients remain unknown. Synaptic and network dysfunctions appear to underlie episodic neurological disorders, including migraine. The narrative review summarizes old and recent experimental evidence for triggering SD by synaptic/network mechanisms and discusses the relevance of the data to migraine pathogenesis. Our hypothesis is that under some conditions synaptic/network hyperactivity may reliably ignite SD, and this mechanism may underlie triggering migraine aura in patients. Findings High-frequency tetanic stimulation of the cortex reliably triggers SD in synaptically connected regions; SD is a reliable cortical response to acute hyperexcitability (epileptic seizures), though chronic epilepsy prevents triggering SD; in the hyperexcitable cortex, SD may be triggered by sensory stimulation; compromised glutamatergic transmission plays the critical role in triggering SD. Conclusion SD may be triggered by dynamic network instability produced by dysfunction of calcium-dependent glutamate release. Synaptic drive from subcortical sensory processing structures (brainstem and/or thalamocortical networks) is able to evoke depolarization of hyperexcitable cortical neurons sufficient to initiate the regenerative SD process. Studying SD initiation by synaptic/network hyperexcitability may provide insights into basic mechanisms underlying SD generation in migraine brain.
Relationship between perceived organizational justice and moral distress in intensive care unit nurses
Authors: Haghighinezhad Ghazaleh , Atashzadeh-Shoorideh Foroozan , Ashktorab Tahereh , Mohtashami Jamileh , Barkhordari-Sharifabad Maasoumeh 
Published: July 2017

Background: The nature of the nursing profession pays more attention to ethics of healthcare than its therapeutic dimension. One of the prevalent moral issues in this profession is moral distress. Moral distress appears more in intensive care units due to the widespread need for moral decision-making regarding treatment and care in emergency situations. In this connection, organizational justice is of high importance and, as a significant motivational tool, leaves important impacts upon attitude and behavior of personnel. Aim/objective: This study aimed at investigation of the relationship between perceived organizational justice and moral distress in intensive care unit nurses. Research design: This is a descriptive-correlational research which examined the relationship between perceived organizational justice and moral distress in intensive care unit nurses. Participants and research context: A total of 284 intensive care unit nurses were selected via census sampling. The data were collected through questionnaires and then were analyzed via SPSS-20 using Pearson and Spearman correlation tests. Ethical considerations: This study was approved by the Committee of Ethics in Medical Research. Completion of informed consent form, guarantee of the confidentiality of information, explanation on purposes of the research, and voluntary participation in the study were moral considerations observed in this study. Findings: There was a statistically significant negative correlation between the total perceived organizational justice and the total moral distress (p = 0.024, r = −0.137) and also between “procedural and interactional justice and errors” and “not respecting the ethics principles.” Meanwhile, no relationship was found by the findings between distributive justice and dimensions of moral distress. Conclusion: According to the results of the study, there was a reverse significant relationship between moral distress and perceived organizational justice; therefore, the head nurses are expected to contribute to reduce moral distress and to increase perceived organizational justice in nurses.
Case Report: Diagnosis of a Rare Plaque-Like Dermal Fibroma Successfully Treated With Mohs Surgery
Authors: Gill Pavandeep , Arlette John , Shiau Carolyn J. , Abi Daoud Marie S. 
Published: July 2017

Background: CD34-positive plaque-like dermal fibroma (PDF) is a poorly characterised benign dermal neoplasm that has a wide differential diagnosis. It can be mistaken for other entities on superficial biopsy and be overtreated, leading to unnecessary worry and extensive surgery. Objective: To report on an uncommon presentation of this entity, the histopathologic differential diagnosis of PDF, and a novel treatment method. Methods: Clinical and histopathological information was obtained for a PDF lesion on a 75-year-old man. Results: On superficial biopsy, the PDF lesion was misinterpreted as a possible neurothekeoma. Successful Mohs surgery and genetic testing confirmed the diagnosis of PDF, and the patient received appropriate tissue-sparing surgical management. Conclusion: This case adds to our current knowledge about PDF and highlights the importance of early recognition of these lesions to direct appropriate diagnostic testing (full-thickness biopsy) and management. This case confirms successful management with Mohs surgery.
The Xenopus tadpole: An in vivo model to screen drugs favoring remyelination
Authors: Mannioui Abdelkrim , Vauzanges Quentin , Fini Jean Baptiste , Henriet Esther , Sekizar Somya , Azoyan Loris , Thomas Jean Léon , Pasquier David Du , Giovannangeli Carine , Demeneix Barbara , Lubetzki Catherine , Zalc Bernard 
Published: July 2017

Background: In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely. Objective: A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules. Methods: In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced demyelinating responses. As tadpoles are transparent, these events can be monitored in vivo and quantified. At the end of metronidazole-induced demyelination, tadpoles were screened in water containing the compounds tested. After 72 h, remyelination was assayed by counting numbers of oligodendrocytes per optic nerve. Results: Among a battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring remyelination. Crispr/cas9 gene editing showed that the promyelinating effect of siponimod involves the sphingosine-1-phosphate receptor 5. Conclusion: This Xenopus transgenic line constitutes a simple in vivo screening platform for myelin repair therapeutics. We validated several known promyelinating compounds and demonstrated that the strong remyelinating efficacy of siponimod implicates the sphingosine-1-phosphate receptor 5.