bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoproterozoic copper cycling, and the rise of metazoans
Authors: Parnell J. , Boyce A. J. 
Published: March 2019

AbstractThe rise of animal life is temporally related to the increased availability of oxygen in the hydrosphere and atmosphere during the Neoproterozoic. However, the earliest metazoans probably needed relatively low oxygen concentrations, suggesting additional environmental and/or biochemical developments were involved. Copper was required in the exploitation of oxygen by the evolving animals, through the development of respiratory proteins and the extracellular matrix required for structural support. We synthesize global data demonstrating a marked enrichment of copper in the Earth’s crust that coincided with the biological use of oxygen, and this new biological use of copper. The copper enrichment was likely recycled into the surface environment by weathering of basalt and other magmatic rocks, at copper liberation rates up to 300 times that of typical granitic terrain. The weathering of basalts also triggered the Sturtian glaciation, which accelerated erosion. We postulate that the coincidence of a high availability of copper, along with increased oxygen levels, for the first time during the Neoproterozoic supported the critical advances of respiration and structural support in evolving animals.
AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration
Authors: Sabin Keith Z. , Jiang Peng , Gearhart Micah D. , Stewart Ron , Echeverri Karen 
Published: March 2019

AbstractSalamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Injury induced upregulation of miR-200a in glial cells supresses c-Jun expression in these cells. Inhibition of miR-200a during regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, extracellular matrix remodeling and axon guidance. This work identifies a unique role for miR-200a in inhibiting reactive gliosis in axolotl glial cells during spinal cord regeneration.
Silencing of XRCC4 increases radiosensitivity of triple-negative breast cancer cells
Authors: Wen Yuqing , Dai Gongpeng , Wang Liping , Fu Kanda , Zuo Shuguang 
Published: March 2019

Abstract
Background: Radiotherapy is an important locoregional treatment, and its effect on triple-negative breast cancer (TNBC) needs to be enhanced. The aim of the present study was to investigate the potential effects of XRCC4 on radiosensitivity of TNBC. Methods: The RNAi technique was implemented to establish the TNBC stable cell line with XRCC4 knockdown. MTT assay was used to detect the effect of XRCC4 knockdown on cell proliferation. Western blot and immunohistochemistry assays were employed to identify protein expression. Colony assay was performed to detect the effect of XRCC4 knockdown on the colony formation ability of TNBC cells with radiation treatment. Comet assay was conducted to evaluate the influence of XRCC4 silencing on DNA repair activity in ionizing radiation. In addition, we performed a survival analysis based on data in TCGA database. Results: XRCC4 knockdown by lentivirus-mediated shRNA had no significant effect on proliferation of TNBC cells. Knockdown of XRCC4 could substantially increase the sensitivity of TNBC cells to ionizing radiation. The DNA damage level was detected to be increased in the XRCC4 knockdown group, indicating there was a significant repair delay in the XRCC4-deleted cells. Clinical sample analysis exhibited that there were various XRCC4 expression in different patients with TNBC. Moreover, survival analysis showed that high expression of XRCC4 was significantly associated with poor progression-free survival after radiotherapy in TNBC patients. Conclusion: Our findings suggest that XRCC4 knockdown sensitizes TNBC cells to ionizing radiation, and could be considered as a novel predictor of radiosensitivity and a promising target for TNBC.
Study on the relationship between the pathogenic mutations of SLC26A4 and CT phenotypes of inner ear in patient with sensorineural hearing loss
Authors: Wu Lihua , Liu Yunliang , Wu Jianman , Chen Sheng , Tang Shupin , Jiang Yi , Dai Pu 
Published: March 2019

Abstract
To investigate the possible association of pathogenic mutations of SLC26A4 and computerized tomography (CT) phenotypes of inner ear, and explore the feasibility of using the method of gene sequence analysis. A total of 155 patients with bilateral hearing loss carrying SLC26A4 gene mutations were further subjected to high-resolution temporal bone CT and thyroid B ultrasound tests. The potential relationship between the pathogenic mutations of gene and the CT phenotypes were analyzed. As a result, 65 patients (41.9%, 65/155) carried SLC26A4 gene mutations, and 27 cases were detected with pathogenic mutations of SLC26A4 where IVS7-2A&gt;G (55.6%, 15/27) was the most common pathogenic mutation. Amongst them, 19 patients carrying bi-allelic SLC26A4 mutations were all confirmed to have inner ear malformation by CT scan including four cases of enlarged vestibular aqueduct (EVA) and 15 cases of Mondini dysplasia (MD). However, there was only one in eight cases of single allele pathogenic mutation who was confirmed to have EVA by CT scan. Further, only one patient with EVA was confirmed to be slightly higher of total T3 than normal by thyroid ultrasound scan and thyroid hormone assays. These findings suggested that CT detection and SLC26A4 gene detection are efficient methods to diagnose EVA, which can complement each other. Also, the bi-allelic pathogenic mutations of SLC26A4 are more likely to induce inner ear malformation than single allele pathogenic mutation.
Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p
Authors: Liu Dahai , Wang Jianfeng , Liu Meihan 
Published: March 2019

Abstract
Background: Long non-coding RNA taurine up-regulated gene 1 (TUG1) was reportedly involved in initiation and development of several cancers. However, its function and molecular mechanisms in multiple myeloma (MM) are still unclear. The present study aimed to determine the expression status, biological function, and potential mechanisms of TUG1 in the progression of MM.
Materials and methods: The expression levels of TUG1 were examined in MM samples and cell lines by real-time quantitative PCR. The effects of TUG1 on MM cells proliferation and apoptosis were assessed using Cell Counting Kit-8 assay and flow cytometry respectively. MiRNAs-targeted sites in TUG1 were screened by Starbase2.0 and were identified by RNA immunoprecipitation assay combined with luciferase reporter assay.
Results: The expression levels of TUG1 were markedly increased in MM samples and cell lines. Knockdown of TUG1 significantly suppressed the proliferation, induced cell cycle arrest at G1/G0 phase, and promoted apoptosis of MM cells. In exploring the regulatory mechanism, miR-29b-3p was confirmed to be a direct target of TUG1, and repression of miR-29b-3p could partially rescue the effect TUG1 knockdown on MM cell proliferation, cycle, and apoptosis. In addition, TUG1 positively modulated histone deacetylases 4 (HDAC4, a target of miR-29b-3p) expression through sponging of miR-29b-3p in MM cells.
Conclusion: These findings suggested that TUG1 exerted an oncogenic role in MM by acting as a competing endogenous RNA of miR-29b-3p, and implied the potential application of TUG1 in treatment for MM.
Launch of a CME-associated eruptive prominence as observed with IRIS and ancillary instruments
Authors: Zhang P. , Buchlin É. , Vial J.-C. 
Published: March 2019

Aims. In this paper we focus on the possible observational signatures of the processes which have been put forward for explaining eruptive prominences. We also try to understand the variations in the physical conditions of eruptive prominences and estimate the masses leaving the Sun versus the masses returning to the Sun during eruptive prominences.Methods. As far as velocities are concerned, we combined an optical flow method on the Atmospheric Imaging Assembly (AIA) 304 Å and Interface Region Imaging Spectrograph (IRIS). Mg IIh&k observations in order to derive the plane-of-sky velocities in the prominence, and a Doppler technique on the IRIS Mg IIh&k profiles to compute the line-of-sight velocities. As far as densities are concerned, we compared the absolute observed intensities with values derived from non-local thermodynamic equilibrium radiative transfer computations to derive the total (hydrogen) density and consequently compute the mass flows.Results. The derived electron densities range from 1.3 × 109to 6.0 × 1010cm−3and the derived total hydrogen densities range from 1.5 × 109to 2.4 × 1011cm−3in different regions of the prominence. The mean temperature is around 1.1 × 104K, which is higher than in quiescent prominences. The ionization degree is in the range of 0.1–10. The total (hydrogen) mass is in the range of 1.3 × 1014–3.2 × 1014g. The total mass drainage from the prominence to the solar surface during the whole observation time of IRIS is about one order of magnitude smaller than the total mass of the prominence.
Relative magnetic field line helicity
Authors: Moraitis K. , Pariat E. , Valori G. , Dalmasse K. 
Published: March 2019

Context. Magnetic helicity is an important quantity in studies of magnetized plasmas as it provides a measure of the geometrical complexity of the magnetic field in a given volume. A more detailed description of the spatial distribution of magnetic helicity is given by the field line helicity, which expresses the amount of helicity associated to individual field lines rather than in the full analysed volume.
Aims. Magnetic helicity is not a gauge-invariant quantity in general, unless it is computed with respect to a reference field, yielding the so-called relative magnetic helicity. The field line helicity corresponding to the relative magnetic helicity has only been examined under specific conditions so far. This work aims to define the field line helicity corresponding to relative magnetic helicity in the most general way. In addition to its general form, we provide the expression for the relative magnetic field line helicity in a few commonly used gauges, and reproduce known results as a limit of our general formulation.
Methods. By starting from the definition of relative magnetic helicity, we derived the corresponding field line helicity, and we noted the assumptions on which it is based.
Results. We checked that the developed quantity reproduces relative magnetic helicity by using three different numerical simulations. For these cases we also show the morphology of field line helicity in the volume, and on the photospheric plane. As an application to solar situations, we compared the morphology of field line helicity on the photosphere with that of the connectivity-based helicity flux density in two reconstructions of an active region’s magnetic field. We discuss how the derived relative magnetic field line helicity has a wide range of applications, notably in solar physics and magnetic reconnection studies.
A persistent quiet-Sun small-scale tornado
Authors: Tziotziou K. , Tsiropoula G. , Kontogiannis I. 
Published: March 2019

Context. Recently, the appearance, characteristics, and dynamics of a persistent 1.7 h vortex flow, resembling a small-scale tornado, have been investigated with observations both from the ground and from space in a quiet-Sun region in several lines and channels and for the first time in the Hα line centre. The vortex flow showed significant substructure in the form of several intermittent chromospheric swirls.
Aims. We investigate the oscillatory behaviour of various physical parameters in the vortex area in an attempt to better understand the physics of the reported vortex flow. This is the first analysis of this extent.
Methods. We used the same data set of high spatial and temporal resolution CRisp Imaging SpectroPolarimeter (CRISP) observations in several wavelengths along the Hα and Ca II 8542 Å line profiles, as well as Doppler velocities and full-width at half-maximum (FWHM) derived from the Hα line profiles. The spectral analysis of oscillations is based on a two-dimensional wavelet analysis performed within the vortex flow area and in a quiet-Sun region (used for comparison), as well as along line and circular slices.
Results. The vortex flow shows significant oscillatory power in the range of 3–5 min, peaking around 4 min. This power behaves differently than the reference quiet-Sun region. The derived oscillations reflect the cumulative action of different components such as swaying motions, rotation, and waves. The derived periods for swaying motions are in the range of 200–220 s, and the rotation periods are ∼270 s for Hα and ∼215 s for Ca II 8542 Å. Periods increase with atmospheric height and seem to decrease with radial distance from the vortex centre, suggesting a deviation from a rigid rotation. The behaviour of power within the vortex flow as a function of period and height implies the existence of evanescent waves. Moreover, considerable power is obtained even for periods as long as 10 min, not only at photospheric but also at chromospheric heights, while the formation of vortexes is related to turbulent convection or to twisting motions exercised in the magnetic field concentrations. These imply that different types of waves may be excited, such as magnetoacoustic (e.g. kink) or Alfvén waves.
Conclusions. The vortex flow seems to be dominated by two motions: a transverse (swaying) motion, and a rotational motion. The obtained oscillations point to the propagation of waves within it. Nearby fibril-like flows could play an important role in the rotational modulation of the vortex flow. There also exists indirect evidence that the structure is magnetically supported, and one of the swirls, close to its centre, seems to be acting as a “central engine” to the vortex flow.
Timely Data for Targeted Quality Improvement Interventions: Use of a Visual Analytics Dashboard for Bronchiolitis
Authors: Hester Gabrielle , Lang Tom , Madsen Laura , Tambyraja Rabindra , Zenker Paul 
Published: March 2019

Background Standard methods for obtaining data may delay quality improvement (QI) interventions including for bronchiolitis, a common cause of childhood hospitalization.
Objective To describe the use of a dashboard in the context of a multifaceted QI intervention aimed at reducing the use of chest radiographs, bronchodilators, antibiotics, steroids, and viral testing in patients with bronchiolitis.
Methods This QI initiative took place at Children's Minnesota, a large, not-for-profit children's health care organization. A multidisciplinary bronchiolitis workgroup developed a local clinical guideline and order-set. Delays in obtaining baseline data prompted a pediatric hospitalist and information technology specialist to modify a vendor's dashboard to display data related to bronchiolitis guideline metrics. Patients 2 months to 2 years old with a bronchiolitis emergency department (ED)/inpatient encounter in the period October 1, 2014 to April 30, 2018 were included. The primary outcome was a functioning dashboard; a process measure was the percentage of ED clinician logins. Outcome measures included the percent use of guideline metrics (e.g., bronchodilators) displayed on statistical process control charts (ED vs. inpatient). Balancing measures included length of stay, charge ratios, and hospital revisits.
Results A workgroup (formed October 2015) implemented a bronchiolitis order-set and guideline (February 2016) followed by a bronchiolitis dashboard (August 2016) consolidating disparate data sources loaded within 2 to 4 days of discharge. In total, 35% of ED clinicians logged in. Leaders used the dashboard to target and track interventions such as a bronchodilator order alert. There were improvements in most outcome metrics; however, timing did not suggest direct dashboard impact. ED balancing measures were lower after implementation.
Conclusion We described use of a dashboard to support a multifaceted QI initiative for bronchiolitis. Leaders used the dashboard for targeted interventions but the dashboard did not directly impact the observed improvements. Future studies should assess reasons for low individual dashboard use.
Dual Antiplatelet or Dual Antithrombotic Therapy for Secondary Prevention in High-Risk Patients with Stable Coronary Artery Disease?
Authors: Sumaya Wael , Geisler Tobias , Kristensen Steen D. , Storey Robert F. 
Published: March 2019

AbstractAntithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.
Improvement of pulmonary arterial hypertension, inflammatory response, and epithelium injury by dual activation of cAMP/cGMP pathway in a rat model of monocrotaline-induced pulmonary hypertension
Authors: Muraki Yo , Naito Takako , Tohyama Kimio , Shibata Sachio , Kuniyeda Kanako , Nio Yasunori , Hazama Masatoshi , Matsuo Takanori 
Published: March 2019

ABSTRACT
Pulmonary hypertension (PH) is a life-threatening lung disease. PH with concomitant lung diseases, e.g., idiopathic pulmonary fibrosis, is associated with poor prognosis. Development of novel therapeutic vasodilators for treatment of these patients is a key imperative. We evaluated the efficacy of dual activation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using an active, small-molecule phosphodiesterase (PDE4)/PDE5 dual inhibitor (Compound A). Compound A increased both cAMP and cGMP levels in WI-38 lung fibroblasts and suppressed the expressions of type-1 collagen α1 chain and fibronectin. Additionally, compound A reduced right ventricular weight/left ventricular weight+septal weight ratio, brain natriuretic peptide expression levels in right ventricle, C─C motif chemokine ligand 2 expression levels in lung, and plasma surfactant protein D. Our data indicate that dual activation of cAMP/cGMP pathways may be a novel treatment strategy for PH.
Radiographic and clinical outcomes following etanercept monotherapy in Japanese methotrexate-naïve patients with active rheumatoid arthritis
Authors: Takeuchi Tsutomu , Miyasaka Nobuyuki , Pedersen Ron , Sugiyama Noriko , Hirose Tomohiro 
Published: March 2019

Abstract
Objectives: Compare outcomes with methotrexate (MTX) or etanercept (ETN) monotherapy in Japanese patients with active rheumatoid arthritis (RA) who were MTX-naïve or with intolerance or inadequate response to prior MTX (MTX-IR).
Methods: Post hoc analysis of a phase 3 study comparing MTX, ETN 10 mg twice weekly, and ETN 25 mg twice weekly in Japanese patients with RA. Disease activity was evaluated using American College of Rheumatology (ACR) scores and 28-joint Disease Activity Score (DAS28), radiographic progression evaluated using van der Heijde’s modified Total Sharp Score (mTSS), and functional status evaluated using Health Assessment Questionnaire Disability Index (HAQ-DI).
Results: Among MTX-naïve and MTX-IR patients, greater proportions of those randomized to either ETN group achieved ACR20, ACR50, ACR70, DAS28 ≤3.2 or &lt;2.6, clinically relevant inhibition of mTSS changes, and reductions in HAQ-DI compared with MTX at the majority of time points. There were very few clinically meaningful differences between ETN groups for any of the variables evaluated.
Conclusion: ETN monotherapy was more effective than MTX in both MTX-naïve and MTX-IR patients, with very few clinically meaningful differences between ETN 10 mg and ETN 25 mg when given twice weekly. The relative benefits of ETN were greater in MTX-naïve patients than MTX-IR patients.
ClinicalTrials.gov identifier
NCT00445770
A review of global-local-global linkages in economic land-use/cover change models
Authors: Hertel Thomas W , West Thales A P , Börner Jan , Villoria Nelson B 
Published: March 2019

Abstract
Global change drivers of land-use/cover change (LUCC) like population dynamics, economic development, and climate change are increasingly important to local sustainability studies, and can only be properly analyzed at fine-scales that capture local biophysical and socio-economic conditions. When sufficiently widespread, local feedback to stresses originating from global drivers can have regional, national, and even global impacts. A multiscale, global-to-local-to-global (GLG) framework is thus needed for comprehensive analyses of LUCC and leakage. The number of GLG-LUCC studies has grown substantially over the past years, but no reviews of this literature and their contributions have been completed so far. In fact, the largest body of literature pertains to global-to-local impacts exclusively, whereas research on local feedback to regional, national, and global spheres remain scarce, and are almost solely undertaken within large modeling institutes. As such, those are rarely readily accessible for modification and extension by outside contributors. This review of the recent GLG-LUCC studies calls for more open-source modeling and availability of data, arguing that the latter is the real constraint to more widespread analyses of GLG-LUCC impacts. Progress in this field will require contributions from hundreds of researchers around the world and from a wide variety of disciplines.