bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs
Authors: Patti Giuseppe , Cavallari Ilaria , Andreotti Felicita , Calabrò Paolo , Cirillo Plinio , Denas Gentian , Galli Mattia , Golia Enrica , Maddaloni Ernesto , Marcucci Rossella , Parato Vito Maurizio , Pengo Vittorio , Prisco Domenico , Ricottini Elisabetta , Renda Giulia , Santilli Francesca , Simeone Paola , De Caterina Raffaele ,   on behalf of the Working Group on Thrombosis of the Italian Society of Cardiology
Published: September 2018

AbstractDiabetes mellitus is an important risk factor for a first cardiovascular event and for worse outcomes after a cardiovascular event has occurred. This situation might be caused, at least in part, by the prothrombotic status observed in patients with diabetes. Therefore, contemporary antithrombotic strategies, including more potent agents or drug combinations, might provide greater clinical benefit in patients with diabetes than in those without diabetes. In this Consensus Statement, our Working Group explores the mechanisms of platelet and coagulation activity, the current debate on antiplatelet therapy in primary cardiovascular disease prevention, and the benefit of various antithrombotic approaches in secondary prevention of cardiovascular disease in patients with diabetes. While acknowledging that current data are often derived from underpowered, observational studies or subgroup analyses of larger trials, we propose antithrombotic strategies for patients with diabetes in various cardiovascular settings (primary prevention, stable coronary artery disease, acute coronary syndromes, ischaemic stroke and transient ischaemic attack, peripheral artery disease, atrial fibrillation, and venous thromboembolism). Finally, we summarize the improvements in cardiovascular outcomes observed with the latest glucose-lowering drugs, and on the basis of the available evidence, we expand and integrate current guideline recommendations on antithrombotic strategies in patients with diabetes for both primary and secondary prevention of cardiovascular disease.
Differentiation enhances Zika virus infection of neuronal brain cells
Authors: Sánchez-San Martín Claudia , Li Tony , Bouquet Jerome , Streithorst Jessica , Yu Guixia , Paranjpe Aditi , Chiu Charles Y. 
Published: September 2018

AbstractZika virus (ZIKV) is an emerging, mosquito-borne pathogen associated with a widespread 2015–2016 epidemic in the Western Hemisphere and a proven cause of microcephaly and other fetal brain defects in infants born to infected mothers. ZIKV infections have been also linked to other neurological illnesses in infected adults and children, including Guillain-Barré syndrome (GBS), acute flaccid paralysis (AFP) and meningoencephalitis, but the viral pathophysiology behind those conditions remains poorly understood. Here we investigated ZIKV infectivity in neuroblastoma SH-SY5Y cells, both undifferentiated and following differentiation with retinoic acid. We found that multiple ZIKV strains, representing both the prototype African and contemporary Asian epidemic lineages, were able to replicate in SH-SY5Y cells. Differentiation with resultant expression of mature neuron markers increased infectivity in these cells, and the extent of infectivity correlated with degree of differentiation. New viral particles in infected cells were visualized by electron microscopy and found to be primarily situated inside vesicles; overt damage to the Golgi apparatus was also observed. Enhanced ZIKV infectivity in a neural cell line following differentiation may contribute to viral neuropathogenesis in the developing or mature central nervous system.
Yes-associated protein promotes the abnormal proliferation of psoriatic keratinocytes via an amphiregulin dependent pathway
Authors: Jia Jinjing , Li Changji , Yang Jiao , Wang Xin , Li Ruilian , Luo Suju , Li Zhengxiao , Liu Jiankang , Liu Zhi , Zheng Yan 
Published: September 2018

AbstractPsoriasis is a chronic inflammatory skin disease with high morbidity, poor treatment methods and high rates of relapse. Keratinocyte hyperproliferation and shortened cell cycles are important pathophysiological features of psoriasis. As a known oncogene, Yes-associated protein (YAP) plays a role in promoting cell proliferation and inhibiting cell apoptosis; however, whether YAP is involved in the pathogenesis of psoriasis remains to be determined. Amphiregulin (AREG), a transcriptional target of YAP, was found to be upregulated in psoriasis, and overexpression of AREG promoted keratinocyte proliferation. In the present study, immunohistochemistry showed that YAP expression was elevated in the skin of psoriasis patients and in the Imiquimod (IMQ) mouse model of psoriasis. Knockdown of YAP in HaCaT cells inhibited cell proliferation, caused cell cycle arrest in G0/G1 phase and promoted apoptosis. These changes in YAP-knockdown HaCaT cells were related to changes in AREG expression. We concluded that YAP may play an important role in the regulation of abnormal keratinocyte proliferation via an AREG-dependent pathway and that YAP could be a new target in the treatment of psoriasis.
The Vapour-Vapour Interface Observation and Appraisement of a Gas-Condensate/Supercritical CO2 System
Authors: Jia Ying , Shi Yunqing , Huang Lei , Yan Jin , Zheng Rongchen , Sun Lei 
Published: September 2018

AbstractInjecting supercritical CO2 into gas reservoir is a novel trial to improve condensate gas recovery and decrease the hydrocarbon liquid dropout. A good understanding of the effect of supercritical CO2 on the phase behavior properties of these hydrocarbons is essential for accurately forecasting the displacing performance and storing process of the reservoirs with numerical simulators. This paper presents novel phase behavior experimental procedures and phase equilibrium evaluation methodology for gas-condensate phase system mixed with supercritical CO2 over a wide range of temperatures and pressures. A unique phase behavior phenomena was also reported. The mass transfer between two vapour phases was also measured. In order to interpret and identify the interface property between condensate gas and supercritical CO2, a multiphase thermodynamic VLV equilibrium model was established. Finally, taken YKL condensate gas in Northwest China as an example, the region where the conditions in terms of pressure, temperature and CO2 concentration can yield VLV equilibrium was found. The calculation results of multiphase thermodynamic model for condensate-CO2 system in this paper are close to the experimental data and can truthfully reflect the phase behavior of interface between CO2 and condensate gas. The research results indicate that it is the existence of the interface between CO2 and condensate gas that makes CO2 possible be an attractive option to successfully displace condensate gas and decrease CO2 emissions.
The influence of acoustic startle probes on fear learning in humans
Authors: de Haan Michelle I. C. , van Well Sonja , Visser Renée M. , Scholte H. Steven , van Wingen Guido A. , Kindt Merel 
Published: September 2018

AbstractEven though human fear-conditioning involves affective learning as well as expectancy learning, most studies assess only one of the two distinct processes. Commonly used read-outs of associative fear learning are the fear-potentiated startle reflex (FPS), pupil dilation and US-expectancy ratings. FPS is thought to reflect the affective aspect of fear learning, while pupil dilation reflects a general arousal response. However, in order to measure FPS, aversively loud acoustic probes are presented during conditioning, which might in itself exert an effect on fear learning. Here we tested the effect of startle probes on fear learning by comparing brain activation (fMRI), pupil dilation and US-expectancy ratings with and without acoustic startle probes within subjects. Regardless of startle probes, fear conditioning resulted in enhanced dACC, insula and ventral striatum activation. Interaction analyses showed that startle probes diminished differential pupil dilation between CS+ and CS− due to increased pupil responses to CS−. A trend significant interaction effect was observed for US-expectancy and amygdala activation. Startle probes affect differential fear learning by impeding safety learning, as measured with pupil dilation, a read-out of the cognitive component of fear learning. However, we observed no significant effect of acoustic startle probes on other measures of fear learning.
New Experimental Equipment Recreating Geo-Reservoir Conditions in Large, Fractured, Porous Samples to Investigate Coupled Thermal, Hydraulic and Polyaxial Stress Processes
Authors: McDermott C. I. , Fraser-Harris A. , Sauter M. , Couples G. D. , Edlmann K. , Kolditz O. , Lightbody A. , Somerville J. , Wang W. 
Published: September 2018

AbstractUse of the subsurface for energy resources (enhanced geothermal systems, conventional and unconventional hydrocarbons), or for storage of waste (CO2, radioactive), requires the prediction of how fluids and the fractured porous rock mass interact. The GREAT cell (Geo-Reservoir Experimental Analogue Technology) is designed to recreate subsurface conditions in the laboratory to a depth of 3.5 km on 200 mm diameter rock samples containing fracture networks, thereby enabling these predictions to be validated. The cell represents an important new development in experimental technology, uniquely creating a truly polyaxial rotatable stress field, facilitating fluid flow through samples, and employing state of the art fibre optic strain sensing, capable of thousands of detailed measurements per hour. The cell’s mechanical and hydraulic operation is demonstrated by applying multiple continuous orientations of principal stress to a homogeneous benchmark sample, and to a fractured sample with a dipole borehole fluid fracture flow experiment, with backpressure. Sample strain for multiple stress orientations is compared to numerical simulations validating the operation of the cell. Fracture permeability as a function of the direction and magnitude of the stress field is presented. Such experiments were not possible to date using current state of the art geotechnical equipment.
IFITM proteins inhibit HIV-1 protein synthesis
Authors: Lee Wing-Yiu Jason , Fu Rebecca Menhua , Liang Chen , Sloan Richard D. 
Published: September 2018

AbstractInterferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.
The lipid mediator lysophosphatidic acid induces folding of disordered peptides with basic amphipathic character into rare conformations
Authors: Juhász Tünde , Mihály Judith , Kohut Gergely , Németh Csaba , Liliom Károly , Beke-Somfai Tamás 
Published: September 2018

AbstractMembrane-active, basic amphipathic peptides represent a class of biomolecules with diverse functions. Sequentially close protein segments also show similar behaviour in several ways. Here we investigated the effect of the lipid mediator lysophosphatidic acid (LPA) on the conformation of structurally disordered peptides including extracellular antimicrobial peptides (AMPs), and calmodulin-binding motifs derived from cytosolic and membrane target proteins. The interaction with associated LPA resulted in gain of ordered secondary structure elements, which for most cases were previously uncharacteristic of the particular peptide. Results revealed mechanism of the LPA-peptide interactions with regulation of the lipid on peptide conformation and oligomerization in a concentration-dependent manner involving (1) relocation of tryptophan residues into the lipid cluster, (2) multiple contacts between the binding partners dictated by complex driving forces, (3) multiple peptide binding to LPA associates with an affinity in the low micromolar range, and (4) selectivity for LPA compared with structurally related lipids. In line with recent findings showing endogenous molecules inducing structural changes in AMPs, we propose that accumulation of LPA in signalling or pathological processes might modulate host-defense activity or trigger certain processes by direct interaction with cationic amphipathic peptide sequences.
Sensitivity to CT-optimal, Affective Touch Depends on Adult Attachment Style
Authors: Krahé Charlotte , von Mohr Mariana , Gentsch Antje , Guy Lisette , Vari Chiara , Nolte Tobias , Fotopoulou Aikaterini 
Published: September 2018

AbstractAffective touch supports affiliative bonds and social cognition. In particular, gentle, stroking touch, which has recently been associated with the C Tactile (CT) system, is typically perceived as pleasant and prosocial. However, it remains unknown whether pre-existing models of social relating influence the perception of CT-optimal touch. In this study (N = 44 adults), we examined how individual differences in attachment styles relate to the perception of CT-optimal touch, as well as to a different modality of interoception, namely heartbeat perception. Using the gold-standard assessment of attachment (Adult Attachment Interview), we found that insecure attachment was associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Acknowledging the different traditions in measuring attachment, we also used a well-validated self-report questionnaire that pertains to explicit representations of current close relationships. Using this measure, we found that higher scores in attachment anxiety (but not attachment avoidance) were associated with reduced pleasantness discrimination between CT-optimal vs. non-CT optimal touch. Attachment patterns (in both measures) were not related to cardiac perception accuracy. These results corroborate and extend previous literature on CT-optimal touch and its relation with affiliative bonds and social cognition. Given that attachment was not related to perceived cardiac accuracy, these findings point to the specificity of the relationship between CT-optimal touch and attachment.
Three-Dimensional Retinal Organoids Facilitate the Investigation of Retinal Ganglion Cell Development, Organization and Neurite Outgrowth from Human Pluripotent Stem Cells
Authors: Fligor Clarisse M. , Langer Kirstin B. , Sridhar Akshayalakshmi , Ren Yuan , Shields Priya K. , Edler Michael C. , Ohlemacher Sarah K. , Sluch Valentin M. , Zack Donald J. , Zhang Chi , Suter Daniel M. , Meyer Jason S. 
Published: September 2018

AbstractRetinal organoids are three-dimensional structures derived from human pluripotent stem cells (hPSCs) which recapitulate the spatial and temporal differentiation of the retina, serving as effective in vitro models of retinal development. However, a lack of emphasis has been placed upon the development and organization of retinal ganglion cells (RGCs) within retinal organoids. Thus, initial efforts were made to characterize RGC differentiation throughout early stages of organoid development, with a clearly defined RGC layer developing in a temporally-appropriate manner expressing a complement of RGC-associated markers. Beyond studies of RGC development, retinal organoids may also prove useful for cellular replacement in which extensive axonal outgrowth is necessary to reach post-synaptic targets. Organoid-derived RGCs could help to elucidate factors promoting axonal outgrowth, thereby identifying approaches to circumvent a formidable obstacle to RGC replacement. As such, additional efforts demonstrated significant enhancement of neurite outgrowth through modulation of both substrate composition and growth factor signaling. Additionally, organoid-derived RGCs exhibited diverse phenotypes, extending elaborate growth cones and expressing numerous guidance receptors. Collectively, these results establish retinal organoids as a valuable tool for studies of RGC development, and demonstrate the utility of organoid-derived RGCs as an effective platform to study factors influencing neurite outgrowth from organoid-derived RGCs.
Cooperation in the spatial prisoner’s dilemma game with probabilistic abstention
Authors: Cardinot Marcos , Griffith Josephine , O’Riordan Colm , Perc Matjaž 
Published: September 2018

AbstractResearch has shown that the addition of abstention as an option transforms social dilemmas to rock-paper-scissor type games, where defectors dominate cooperators, cooperators dominate abstainers (loners), and abstainers (loners), in turn, dominate defectors. In this way, abstention can sustain cooperation even under adverse conditions, although defection also persists due to cyclic dominance. However, to abstain or to act as a loner has, to date, always been considered as an independent, third strategy to complement traditional cooperation and defection. Here we consider probabilistic abstention, where each player is assigned a probability to abstain in a particular instance of the game. In the two limiting cases, the studied game reverts to the prisoner’s dilemma game without loners or to the optional prisoner’s dilemma game. For intermediate probabilities, we have a new hybrid game, which turns out to be most favorable for the successful evolution of cooperation. We hope this novel hybrid game provides a more realistic view of the dilemma of optional/voluntary participation.
Utility of 15(S)-HETE as a Serological Marker for Eosinophilic Esophagitis
Authors: Lu Shaolei , Herzlinger Michael , Cao Weibiao , Noble Lelia , Yang Dongfang , Shapiro Jason , Kurtis Jonathan , LeLeiko Neal , Resnick Murray 
Published: September 2018

AbstractThe pathogenesis of eosinophilic esophagitis (EoE) involves Th2-mediated eosinophil recruitment and degranulation into the esophagus. However, measuring serum Th2 cytokines, eosinophils, and eosinophil-derived products does not reliably distinguish EoE from control populations. Non-invasive methods to diagnose EoE are lacking. We evaluated the diagnostic value of a novel candidate biomarker of EoE: 15(S)-hydroxyeicosatetraenoic acid (HETE). We used immunoassay to measure 15(S)-HETE and cytokine profiles in patients undergoing endoscopy with known or suspected EoE. 31 subjects were enrolled, 16 with EoE, and 15 with an alternate diagnosis. 15(S)-HETE was elevated in the EoE group compared to non-EoE group. The sensitivity and specificity of 15(S)-HETE to be used as a non-invasive marker is 50% and 80%, respectively. 15(S)-HETE may aid in the diagnosis of EoE.
Variable importance for sustaining macrophyte presence via random forests: data imputation and model settings
Authors: Van Echelpoel Wout , Goethals Peter L. M. 
Published: September 2018

AbstractData sets plagued with missing data and performance-affecting model parameters represent recurrent issues within the field of data mining. Via random forests, the influence of data reduction, outlier and correlated variable removal and missing data imputation technique on the performance of habitat suitability models for three macrophytes (Lemna minor, Spirodela polyrhiza and Nuphar lutea) was assessed. Higher performances (Cohen’s kappa values around 0.2–0.3) were obtained for a high degree of data reduction, without outlier or correlated variable removal and with imputation of the median value. Moreover, the influence of model parameter settings on the performance of random forest trained on this data set was investigated along a range of individual trees (ntree), while the number of variables to be considered (mtry), was fixed at two. Altering the number of individual trees did not have a uniform effect on model performance, but clearly changed the required computation time. Combining both criteria provided an ntree value of 100, with the overall effect of ntree on performance being relatively limited. Temperature, pH and conductivity remained as variables and showed to affect the likelihood of L. minor, S. polyrhiza and N. lutea being present. Generally, high likelihood values were obtained when temperature is high (>20 °C), conductivity is intermediately low (50–200 mS m−1) or pH is intermediate (6.9–8), thereby also highlighting that a multivariate management approach for supporting macrophyte presence remains recommended. Yet, as our conclusions are only based on a single freshwater data set, they should be further tested for other data sets.
Doxorubicin induces caspase-mediated proteolysis of KV7.1
Authors: Strigli Anne , Raab Christian , Hessler Sabine , Huth Tobias , Schuldt Adam J. T. , Alzheimer Christian , Friedrich Thomas , Burridge Paul W. , Luedde Mark , Schwake Michael 
Published: September 2018

AbstractKv7.1 (KCNQ1) coassembles with KCNE1 to generate the cardiac IKs-channel. Gain- and loss-of-function mutations in KCNQ1 are associated with cardiac arrhthymias, highlighting the importance of modulating IKs activity for cardiac function. Here, we report proteolysis of Kv7.1 as an irreversible posttranslational modification. The identification of two C-terminal fragments of Kv7.1 led us to identify an aspartate critical for the generation of one of the fragments and caspases as responsible for mediating proteolysis. Activating caspases reduces Kv7.1/KCNE1 currents, which is abrogated in cells expressing caspase-resistant channels. Enhanced cleavage of Kv7.1 can be detected for the LQT mutation G460S, which is located adjacent to the cleavage site, whereas a calmodulin-binding-deficient mutation impairs cleavage. Application of apoptotic stimuli or doxorubicin-induced cardiotoxicity provokes caspase-mediated cleavage of endogenous IKs in human cardiomyocytes. In summary, caspases are novel regulatory components of IKs channels that may have important implications for the molecular mechanism of doxorubicin-induced cardiotoxicity.