bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refining the therapeutic range of posaconazole and isavuconazole for efficient therapeutic drug monitoring using a bioassay approach
Authors: Willeman Théo , Tonini Julia , Garnaud Cécile , Bailly Sébastien , Gandia Peggy , Stanke‐Labesque Françoise , Maubon Danièle , Gautier‐Veyret Elodie 
Published: September 2019

AbstractTherapeutic drug monitoring (TDM) of antifungal triazole was recommended, except for isavuconazole (ISA) whose target trough concentrations (Cmin) need to be specified. Concerning posaconazole (POS), tablet formulation results in higher exposure but no upper Cmin threshold has been yet proposed. We aimed to investigate the pharmacokinetic–pharmacodynamic relationship of POS and ISA, using a bioassay approach as surrogate marker of antifungal activity, in order to refine the therapeutic Cmin of both antifungals. A bioassay using a cellulose disk diffusion method was performed to determine the growth inhibition zone (GIZ) of POS and ISA on Aspergillus fumigatus and Candida parapsilosis (ISA only). GIZs of plasma from patients undergoing TDM for POS (n = 136) or ISA (n = 40) were determined. GIZs of plasma patients and antifungal Cmin were highly correlated for ISA (A. fumigatus: ρ = 0.942, P < 0.0001; C. parapsilosis: ρ = 0.949, P < 0.0001) and POS (ρ = 0.922, P < 0.0001), and these relationships were represented with a Michaelis–Menten model. Based on this modeling, the recommended thresholds of 0.7, 1, and 1.25 mg/L for the POS Cmin corresponded to 50.1, 55.2, and 59.1% of the maximal GIZ, respectively. We propose an upper threshold of 4.8 mg/L for the POS Cmin and a lower threshold of 2.0 mg/L for the Cmin of ISA, as they respectively corresponded to concentrations leading to 90% and 50% of the maximal GIZ on A. fumigatus. The determination of antifungal activity using this bioassay allowed refining target Cmin of POS and ISA, especially the upper threshold of POS (4.8 mg/L) and the lower threshold of ISA (2.0 mg/L).
Influence of the annealing and defects on the VHCF behavior of an SLM AlSi10Mg alloy
Authors: Tridello Andrea , Fiocchi Jacopo , Biffi Carlo A. , Chiandussi Giorgio , Rossetto Massimo , Tuissi Ausonio , Paolino Davide S. 
Published: September 2019

AbstractIn the paper, the influence of the annealing temperature on the Very High Cycle Fatigue (VHCF) of AlSi10Mg specimens produced through selective laser melting (SLM) is experimentally assessed. VHCF tests at 20 kHz are carried out on Gaussian specimens subjected to a heat treatment suggested by the system supplier (heating for 2 hours to 320°C and air cooling) and to a heat treatment proposed by the authors (heating for 2 hours to 244°C and air cooling). The defects originating failure and the conditional P‐S‐N curves are compared. Experimental results show that an annealing temperature of 320 ° C induces the spheroidization of the Si network, which enhances the ductility but has a negative effect on the VHCF response. On the contrary, by reducing the heating temperature to 244 ° C, the original as‐built microstructure is not altered and the minimization of the residual stresses permits to enhance the VHCF response.
The effect of canopy openness of European beech (Fagus sylvatica) forests on ground‐dwelling spider communities
Authors: Černecká Ľudmila , Mihál Ivan , Gajdoš Peter , Jarčuška Benjamín 
Published: September 2019

Abstract
The composition of spider communities in forests is affected by habitat characteristics, such as canopy openness, vegetation cover or tree species diversity; therefore, we assume that the effect of canopy will differ among tree species.
As research in European beech forests has not been conducted, we studied the effect of understory environmental characteristics associated with a gradient of overstory canopy openness in beech forest on ground‐dwelling spider richness, abundance and guild composition in the Western Carpathians, Slovakia. Canopy openness, the cover of understory vegetation and litter, litter thickness and variability and soil reaction were recorded. In total, 17 332 individuals of 174 spider species were trapped during 518 days. We used Generalised Linear Models to explain the effect of environmental characteristics on the assemblages of ground‐dwelling spiders; the unique and shared contributions of the predictors were calculated using variation partitioning.
The association of canopy openness with spider species richness was hump‐shaped and displayed positive linear relationship with abundance. Abundance was also affected by soil pH.
The composition of spider communities was significantly affected by canopy openness and understory characteristics; a major part of this variation was shared between all variables. The guild composition of the assemblages interacted with canopy openness, as sheet‐web weavers were dominant under the most closed canopy, that below 20% of canopy openness, while ground hunters dominated in the rest of the canopy gradient.
The gradient of beech forest canopy openness affected spider species richness, abundance and guild composition and supported distinct assemblages.
Direct and indirect measurement of large electrocaloric effect in barium strontium titanate ceramics
Authors: Dai Guangzhou , Wang Shibin , Huang Guanhua , Chen Guirong , Lu Biao , Li Dandan , Tao Tao , Yao Yingbang , Liang Bo , Lu Sheng‐Guo 
Published: September 2019

AbstractBarium strontium titanate (Ba1‐xSrxTiO3‐BST) ceramics, where x = 0.05, 0.15, 0.25, and 0.35, was prepared via a solid‐state reaction method. The lattice structures and morphologies of the ceramic samples were analyzed using X‐ray diffraction and scanning electron microscopy technologies. The dielectric and ferroelectric properties of the BST ceramics were characterized using a precision impedance analyzer and a ferroelectric polarization‐electric field (P‐E) hysteresis loop tester, respectively. The electrocaloric effect was indirectly calculated using the Maxwell relations and P‐E loops as a function of temperature and electrical field, and also directly measured using a computer‐controlled thermocouple and high‐voltage power supply. An adiabatic temperature change of 1.82 K was procured, indicating a promising potential in the applications as cooling devices.
Global employment and decent jobs, 2010–2030: The forces of demography and automation
Authors: Bloom David E. , McKenna Mathew J. , Prettner Klaus 
Published: September 2019

AbstractGlobally, an estimated 734 million jobs will be required between 2010 and 2030 to accommodate recent and ongoing demographic shifts, account for plausible changes in labour force participation rates, and achieve target unemployment rates of at or below 4 per cent for adults and at or below 8 per cent for youth. The facts that most new jobs will be required in countries where “decent” jobs are less prevalent and workers in many occupations are increasingly subject to risks of automation further compound the challenge of job creation, which is already quite sizable in historical perspective. Failure to create the jobs that are needed through 2030 would put currently operative social security systems under pressure and undermine efforts to guarantee the national social protection floors enshrined in the Sustainable Development Goals (SDGs).
Relationship between time‐to‐isolation and freeze duration: Computational modeling of dosing for Arctic Front Advance and Arctic Front Advance Pro cryoballoons
Authors: Getman Michael K. , Wissner Erik , Ranjan Ravi , Lalonde Jean‐Pierre 
Published: September 2019

AbstractBackgroundPreclinical and clinical studies have utilized periprocedural parameters to optimize cryoballoon ablation dosing, including acute time‐to‐isolation (TTI) of the pulmonary vein, balloon rate of freezing, balloon nadir temperature, and balloon‐thawing time. This study sought to predict the Arctic Front Advance (AFA) vs Arctic Front Advance Pro (AFA Pro) ablation durations required for transmural pulmonary vein isolation at varied tissue depths.MethodsA cardiac‐specific, three‐dimensional computational model that incorporates structural characteristics, temperature‐dependent cellular responses, and thermal‐conductive properties was designed to predict the propagation of cold isotherms through tissue. The model assumed complete cryoballoon‐to‐pulmonary vein (PV) circumferential contact. Using known temperature thresholds of cardiac cellular electrical dormancy (at 23°C) and cellular nonviability (at −20°C), transmural time‐to‐isolation electrical dormancy (TTIED) and cellular nonviability (TTINV) were simulated.ResultsFor cardiac thickness of 0.5, 1.25, 2.0, 3.0, 4.0, and 5.0 mm, the 23°C isotherm passed transmurally in 33, 38, 46, 62, 80, and 95 seconds during cryoablation utilizing AFA and 33, 38, 46, 63, 80, and 95 seconds with AFA Pro. Using the same cardiac thicknesses, the −20°C isotherm passed transmurally in 40, 55, 78, 161, 354, and 696 seconds during cryoablation with AFA and 40, 54, 78, 160, 352, and 722 seconds with AFA Pro.ConclusionThis model predicted a minimum duration of cryoballoon ablation (TTINV) to obtain a transmural lesion when acute TTI of the PV was observed (TTIED). Consequently, the model is a useful tool for characterizing CBA dosing, which may guide future cryoablation dosing strategies.
Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation
Authors: Ahn Jinhee , Shin Seung Yong , Shim Jaemin , Kim Young‐Hoon , Han Sang‐Jin , Choi Eue‐Keun , Oh Seil , Shin Ji Yeon , Choe Jeong Cheon , Park Jin Sup , Lee Hye Won , Oh Jun‐Hyok , Choi Jung Hyun , Lee Han‐Cheol , Cha Kwang Soo , Hong Taek Jong , Lip Gregory Y. H. , Lim Hong Euy 
Published: September 2019

AbstractIntroductionRisk factors of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated especially among the Asian subjects, particularly regarding epicardial adipose tissue (EAT) in cardiac imaging. We aimed to assess the incidence of ES during a long‐term follow‐up period after AF ablation and to identify the risk factors associated with postablation ES, specifically focusing on EAT.Methods and ResultsWe enrolled patients who experienced postablation ES and control subjects from a consortium of AF ablation registries from three institutes in Korea. EAT was assessed using multislice computed tomography before AF ablation. A total of 3464 patients who underwent AF ablation were recruited and followed‐up. During a follow‐up of 47.2 ± 36.4 months, ES occurred in 47 patients (1.36%) with a CHA2DS2‐VASc score of 1.48 ± 1.39 and the overall annual incidence of ES was 0.34%. Compared with the control group (n = 190), the ES group showed significantly higher prior thromboembolism (TE) and AF recurrence rates, larger left atrium size, lower creatinine clearance rate (CCr), and greater total and peri‐atrial EAT volume. Multivariate regression analysis demonstrated larger peri‐atrial EAT volume (hazards ratio, 1.065; 95% confidence interval, 1.005‐1.128), in addition to a prior history of TE and lower CCr, was independently associated with postablation ES. When a cut‐off value of peri‐atrial EAT volume of ≥20.15 mL was applied, patients with smaller peri‐atrial EAT volume showed significantly higher ES‐free survival.ConclusionLarger peri‐atrial EAT volume, in addition to prior TE and lower CCr, was independently associated with postablation ES regardless of AF recurrence and CHA2DS2‐VASc score. (ClinicalTrials.gov number, NCT03479073).
Right ventricular outflow tract low‐voltage areas identify the site of origin of idiopathic ventricular arrhythmias: A high‐density mapping study
Authors: Letsas Konstantinos P. , Efremidis Michael , Vlachos Konstantinos , Asvestas Dimitrios , Takigawa Masateru , Bazoukis George , Frontera Antonio , Giannopoulos George , Saplaouras Athanasios , Sakellaropoulou Antigoni , Mililis Panagiotis , Dragasis Stylianos , Megarisiotou Athanasia , Valkanas Kosmas , Tse Gary , Liu Tong , Deftereos Spyridon , Sideris Antonios , Baranchuk Adrian , Jais Pierre 
Published: September 2019

AbstractIntroductionElectronatomical mapping allows direct and accurate visualization of myocardial abnormalities. This study investigated whether high‐density endocardial bipolar voltage mapping of the right ventricular outflow tract (RVOT) during sinus rhythm may guide catheter ablation of idiopathic ventricular arrhythmias (VAs).Methods and ResultsForty‐four patients (18 males, mean age: 38.1 ± 13.8 years) with idiopathic RVOT VAs and negative cardiac magnetic resonance imaging underwent a stepwise mapping approach for the identification of the site of origin (SOO). High‐density electronatomical mapping (1096.6 ± 322.3 points) was performed during sinus rhythm and identified at least two low bipolar voltage areas less than 1 mV (mean amplitude of 0.20 ± 0.10 mV) in 39 of 44 patients. The mean low‐voltage surface area was 1.4 ± 0.8 cm2. Group 1 consisted of 28 patients exhibiting low‐voltage areas and high‐arrhythmia burden during the procedure. Pace match to the clinical VAs was produced in one of these low‐voltage areas. Activation mapping established the SOO at these sites in 27 of 28 cases. Group 2 comprised 11 patients exhibiting abnormal electroanatomical mapping, but very low‐arrhythmia burden during the procedure. Pace mapping produced a near‐perfect or perfect match to the clinical VAs in one of these areas in 9 of 11 patients which was marked as potential SOO and targeted for ablation. During the follow‐up period, 25 of 28 patients from group 1 (89%) and 7 of 9 patients from group 2 (78%) were free from VAs.ConclusionsSmall but detectable very low‐voltage areas during mapping in sinus rhythm characterize the arrhythmogenic substrate of idiopathic RVOT VAs and may guide successful catheter ablation.
MCU Up‐regulation contributes to myocardial ischemia‐reperfusion Injury through calpain/OPA‐1–mediated mitochondrial fusion/mitophagy Inhibition
Authors: Guan Lichun , Che Zhimei , Meng Xiangdong , Yu Yong , Li Minghui , Yu Ziqin , Shi Hui , Yang Dicheng , Yu Min 
Published: September 2019

AbstractMitochondrial dynamic disorder is involved in myocardial ischemia/reperfusion (I/R) injury. To explore the effect of mitochondrial calcium uniporter (MCU) on mitochondrial dynamic imbalance under I/R and its related signal pathways, a mouse myocardial I/R model and hypoxia/reoxygenation model of mouse cardiomyocytes were established. The expression of MCU during I/R increased and related to myocardial injury, enhancement of mitochondrial fission, inhibition of mitochondrial fusion and mitophagy. Suppressing MCU functions by Ru360 during I/R could reduce myocardial infarction area and cardiomyocyte apoptosis, alleviate mitochondrial fission and restore mitochondrial fusion and mitophagy. However, spermine administration, which could enhance MCU function, deteriorated the above‐mentioned myocardial cell injury and mitochondrial dynamic imbalanced. In addition, up‐regulation of MCU promoted the expression and activation of calpain‐1/2 and down‐regulated the expression of Optic atrophy type 1 (OPA1). Meantime, in transgenic mice (overexpression calpastatin, the endogenous inhibitor of calpain) I/R model and OPA1 knock‐down cultured cell. In I/R models of transgenic mice over‐expressing calpastatin, which is the endogenous inhibitor of calpain, and in H/R models with siOPA1 transfection, inhibition of calpains could enhance mitochondrial fusion and mitophagy, and inhibit excessive mitochondrion fission and apoptosis through OPA1. Therefore, we conclude that during I/R, MCU up‐regulation induces calpain activation, which down‐regulates OPA1, consequently leading to mitochondrial dynamic imbalance.
Tail Risk Networks of Insurers Around the Globe: An Empirical Examination of Systemic Risk for G‐SIIs vs Non‐G‐SIIs
Authors: Chen Hua , Sun Tao 
Published: September 2019

AbstractIn this article, we investigate systemic risk of 157 insurers around the globe. We construct tail risk networks among these insurers using a single‐index model for quantile regressions with a variable selection technique. We develop a new network‐based systemic risk indices, taking into account expected tail losses of insurers, direct and indirect contagion effects, and the time‐varying strength of tail risk spillover. Our systemic risk indices successfully recognize global systemically important insurers (G‐SIIs). We find that on average G‐SIIs are more systemically relevant than non‐G‐SIIs, particularly during the recent U.S. financial crisis. We also find a small group of non‐G‐SIIs that are more important than G‐SIIs. Our results have significant implications for systemic risk regulation.
Time‐dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct‐acting antiviral therapy of chronic hepatitis C
Authors: Laursen Tea Lund , Siggaard Cecilie Brøckner , Kazankov Konstantin , Sandahl Thomas Damgaard , Møller Holger Jon , Tarp Britta , Kristensen Lena Hagelskjær , Laursen Alex Lund , Leutscher Peter , Grønbæk Henning 
Published: September 2019

AbstractSofosbuvir‐based direct‐acting antiviral (DAA) therapy generally cures chronic hepatitis C (CHC) infections, however, the effects on the underlying liver disease and the potential rate of recovery are unclear. We aimed to investigate the effects of DAA therapy on liver inflammation, fibrosis, metabolic function and cognitive function and the time course in CHC patients with advanced liver disease. Seventy‐one CHC patients with advanced liver disease were studied before, during and one year after successful sofosbuvir‐based DAA therapy. Liver inflammation was assessed by plasma sCD163 and sMR levels (ELISA), fibrosis by liver stiffness (transient elastography), function by galactose elimination capacity (GEC) and cognitive performance by continuous reaction time (CRT). During DAA therapy, we observed a rapid sCD163 decline from baseline to end of treatment (6.9 vs 3.8 mg/L, P < .0001), whereas the change in sMR was more subtle (0.37 vs 0.30 mg/L, P < .0001). Liver stiffness decreased by 20% at end of treatment (17.8 vs 14.3 kPa, P < .0001), together suggesting rapid resolution of liver inflammation. One year after treatment, liver stiffness decreased by an additional 15% (P < .0001), suggestive of fibrosis regression. The GEC improved at follow‐up (all: 1.74 vs 1.98 mmol/min), mainly at 12 weeks post‐treatment, both in patients with cirrhosis (n = 56) and those with advanced liver fibrosis (n = 15) (P < .001). The CRT improved at one‐year follow‐up (1.86 vs 2.09, P = .04). In conclusion, successful DAA therapy of CHC proves beneficial in advanced liver disease, with an initial rapid resolution of liver inflammation and a subsequent gradual but steady improvement in liver fibrosis, metabolic liver function and reaction time.
The Bacillus subtilis endospore crust: protein interaction network, architecture and glycosylation state of a potential glycoprotein layer
Authors: Bartels Julia , Blüher Anja , López Castellanos Sebastián , Richter Marcus , Günther Markus , Mascher Thorsten 
Published: September 2019

SummaryThe endospore of Bacillus subtilis is formed intracellularly upon nutrient starvation and is encased by proteinaceous shells. The outermost layer, the crust, is a postulated glycoprotein layer that is composed of six proteins: CotV, W, X, Y, Z and CgeA. Despite some insight into protein interactions and the identification of players in glycosylation, a clear picture of its architecture is still missing. Here, we report a comprehensive mutational analysis that confirms CotZ as the anchor of the crust, while the crust structure is provided by CotV, CotX and CotY. CotY seems to be the major structural component, while CotV and CotX are polar and co‐depend on each other and partially on CotW. CotW is independent of other crust proteins, instead depending on outer coat proteins, indicating a role at the interface of crust and coat. CgeA is co‐expressed with putative glycosyltransferases (CgeB and CgeD) and implicated in crust glycosylation. In accordance, we provide evidence that CgeB, CgeCDE, SpsA‐L, SpsM and SpsNOPQR (formerly YfnHGFED) contribute to the glycosylation state of the spore. The crust polysaccharide layer consists of functionally linked rhamnose‐ and galactose‐related variants and could contain rare sugars. It may therefore protect the crust against biological degradation and scavenging.
COLONIAL, POPULAR, AND SCIENTIFIC? TheExposition du Sahara(1934) and the Formation of the Musée de l'Homme
Authors: Bernasek Lisa 
Published: September 2019

AbstractThis article explores the collection and exhibition practices surrounding theExposition du Sahara(1934), an exhibit organized at a key moment in the transformation of the Musée d'Ethnographie du Trocadéro into France's modernized anthropological museum, the Musée de l'Homme. Through an analysis of archival material and exhibit publications, the article traces how the institutionalization of ethnographic collecting practices was shaped by interactions between museum personnel and collectors on the ground, and by the organizers’ desire to make theExposition du Sahara, and the Musée d'Ethnographie itself, simultaneously scientific, popular, and a successful colonial institution. The account also tells the story of some of the objects from North Africa now housed at the Musée du Quai Branly, where very different modes of interpretation have been applied.
Mating system variation in hybrid zones: facilitation, barriers and asymmetries to gene flow
Authors: Pickup Melinda , Brandvain Yaniv , Fraïsse Christelle , Yakimowski Sarah , Barton Nicholas H. , Dixit Tanmay , Lexer Christian , Cereghetti Eva , Field David L. 
Published: September 2019

SummaryPlant mating systems play a key role in structuring genetic variation both within and between species. In hybrid zones, the outcomes and dynamics of hybridization are usually interpreted as the balance between gene flow and selection against hybrids. Yet, mating systems can introduce selective forces that alter these expectations; with diverse outcomes for the level and direction of gene flow depending on variation in outcrossing and whether the mating systems of the species pair are the same or divergent. We present a survey of hybridization in 133 species pairs from 41 plant families and examine how patterns of hybridization vary with mating system. We examine if hybrid zone mode, level of gene flow, asymmetries in gene flow and the frequency of reproductive isolating barriers vary in relation to mating system/s of the species pair. We combine these results with a simulation model and examples from the literature to address two general themes: (1) the two‐way interaction between introgression and the evolution of reproductive systems, and (2) how mating system can facilitate or restrict interspecific gene flow. We conclude that examining mating system with hybridization provides unique opportunities to understand divergence and the processes underlying reproductive isolation.