bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of food on the single‐dose pharmacokinetics and tolerability of savolitinib in Chinese healthy volunteers
Authors: Ding Qichen , OU Meixian , Zhu Huijuan , Wang Yijun , Jia Jingying , Sai Yang , Chen Qian , Wang Jian 
Published: May 2021

AbstractThe aim of this study was to investigate the effect of a high‐fat and high‐calorie meal on the single‐dose pharmacokinetics (PK) and tolerability of savolitinib. The study included two phases: safety run‐in phase and food effect assessment phase. In the safety run‐in phase, 9 healthy male volunteers were divided into three groups to be administered a single oral dose of savolitinib tablets at 200, 400, and 600 mg. In the food effect assessment phase, 16 healthy male volunteers received a single 600 mg dose of savolitinib tablets following an overnight fast or a high‐fat and high‐calorie breakfast prior to dosing. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety and tolerability were assessed throughout the study by clinical assessments and adverse events (AEs). A total of 25 healthy male volunteers were enrolled in the study, including 9 in the safety run‐in phase and 16 in the food effect assessment phase. In the food effect assessment phase, the geometric mean ratios (90% confidence interval) for savolitinib dosed under the fed condition compared with that dosed under the fasting condition were 102.7% (84.9%, 124.2%) and 117.1% (103.9%, 131.9%) for Cmax and AUC0‐inf of savolitinib, respectively. The Tmax was delayed significantly (p = 0.023) under fed condition. The most common AEs possibly related to the study drug were dizziness, nausea, and emesis. The study indicated that a high‐fat and high‐calorie meal has no clinically relevant impact on the PK and bioavailability of savolitinib in healthy male volunteers.
A micromechanical loading/unloading constitutive model of fiber‐reinforced ceramic‐matrix composites considering matrix crack closure
Authors: Li Longbiao 
Published: May 2021

AbstractUnder cyclic loading/unloading, hysteresis loops appear due to the internal slip between the fiber and the matrix in the interface debonding regions of fiber‐reinforced ceramic‐matrix composites (CMCs). Hysteresis loops can be used as an effective tool to monitor internal damage evolution inside of CMCs. Within the present study, a micromechanical loading/unloading constitutive model was designed to predict the cyclic hysteresis loops of CMCs based on the matrix crack closure. A correlation was formulated between their hysteresis loops, matrix cracking density, loading/unloading inverse tangent modulus (ITMs), and interface reverse/new slip ratio (IRSR/INSR), as well as their dependence upon the material properties. In addition, different SiC/SiC composites (i.e., mini, unidirectional, cross‐ply, and 2D plain‐woven) were predicted based on the hysteresis loops, ITMs, IRSR, and INSR experimental results. The results indicated identical hysteresis loop peak strains for the samples both with and without matrix crack closure, though those without the matrix crack closure exhibited a lower hysteresis loop residual strain. All in all, the theoretical predicted results with regard to matrix crack closure were in correlation with the experimental data.
Improving fatigue life of 7N01 Al alloy weld by surface spinning strengthening
Authors: Wang Dongqiqiong , Wang Suhuan , Wang Qiang , Hou Jiapeng , Li Xiaowu , Zhang Zhefeng 
Published: May 2021

AbstractThe purpose of this study is to improve the surface microstructure and mechanical properties of 7N01 Al alloy welded joints by surface spinning strengthening (3S), so as to improve the fatigue life at certain stress. Results show that after the 3S treatment, the microhardness of the welded joint increases significantly due to the introduction of some nanoprecipitates and dislocations, and the strength and elongation increase simultaneously. The minimum fatigue life of the welded specimen under the condition of maximum stress of 150 MPa and stress ratio of 0.1 is increased from less than 106 cycles to more than 3 × 106 cycles after the 3S treatment. Fracture surface analysis shows that the crack initiation site of the sample with welded joint is turned from the surface to the subsurface after 3S treatment, which is beneficial to the elimination of surface defect and the improvement of surface strength.
A portfolio of climate‐tailored approaches to advance the design of marine protected areas in the Red Sea
Authors: Gajdzik Laura , DeCarlo Thomas M. , Aylagas Eva , Coker Darren J. , Green Alison L. , Majoris John E. , Saderne Vincent F. , Carvalho Susana , Berumen Michael L. 
Published: May 2021

AbstractIntensified coastal development is compromising the health and functioning of marine ecosystems. A key example of this is the Red Sea, a biodiversity hotspot subjected to increasing local human pressures. While some marine‐protected areas (MPAs) were placed to alleviate these stressors, it is unclear whether these MPAs are managed or enforced, thus providing limited protection. Yet, most importantly, MPAs in the Red Sea were not designed using climate considerations, likely diminishing their effectiveness against global stressors. Here, we propose to tailor the design of MPAs in the Red Sea by integrating approaches to enhance climate change mitigation and adaptation. First, including coral bleaching susceptibility could produce a more resilient network of MPAs by safeguarding reefs from different thermal regions that vary in spatiotemporal bleaching responses, reducing the risk that all protected reefs will bleach simultaneously. Second, preserving the basin‐wide genetic connectivity patterns that are assisted by mesoscale eddies could further ensure recovery of sensitive populations and maintain species potential to adapt to environmental changes. Finally, protecting mangrove forests in the northern and southern Red Sea that act as major carbon sinks could help offset greenhouse gas emissions. If implemented with multinational cooperation and concerted effort among stakeholders, our portfolio of climate‐tailored approaches may help build a network of MPAs in the Red Sea that protects more effectively its coastal resources against escalating coastal development and climate instability. Beyond the Red Sea, we anticipate this study to serve as an example of how to improve the utility of tropical MPAs as climate‐informed conservation tools.
Matching‐adjusted indirect comparisons of oral rimegepant versus placebo, erenumab, and galcanezumab examining monthly migraine days and health‐related quality of life in the treatment of migraine
Authors: Popoff Evan , Johnston Karissa , Croop Robert , Thiry Alexandra , Harris Linda , Powell Lauren , Coric Vladimir , L’Italien Gilbert , Moren James 
Published: May 2021

AbstractObjectiveRimegepant is an orally administered small‐molecule calcitonin gene‐related peptide (CGRP) receptor antagonist, with demonstrated efficacy in the acute treatment of migraine. Recent estimates from a single‐arm trial (BHV3000‐201) have also shown evidence of long‐term preventive effects in monthly migraine days (MMDs) and health‐related quality of life (HRQoL). This study aimed to compare MMDs and HRQoL data for oral rimegepant to those obtained in placebo‐controlled trials for injectable anti‐CGRP monoclonal antibodies (mAbs) galcanezumab and erenumab.MethodsMatching‐adjusted indirect comparisons (MAICs) were conducted using rimegepant subject‐level data and published aggregate‐level results from mAb trials. Rimegepant baseline characteristics were matched to the pooled subject characteristics from EVOLVE‐I/II (galcanezumab vs. placebo;n = 1773) and STRIVE (ereumab vs. placebo;n = 955) by reweighting the rimegepant subjects to more closely match the distributions observed in these trials. To align with inclusion criteria of the mAb trials, only the subset of rimegepant subjects with a history of 4–14 MMDs were included (n = 257). Weighted mean differences were used to calculate adjusted change in MMDs, Migraine Disability Assessment Test (MIDAS) score, and Migraine‐Specific Quality of Life Questionnaire version 2 (MSQv2) scores from baseline to week 12.ResultsWhen matched to the EVOLVE trials, rimegepant was superior to placebo with a mean difference in MMD change from baseline [95% confidence interval] of −1.16 [−1.80, −0.52] and was not statistically significantly different from galcanezumab 0.59 [−0.13, 1.32]. When matched to the STRIVE trial, rimegepant was superior to placebo −1.59 [−2.15, −1.03] and was not statistically significantly different from erenumab −0.06 [−0.61, 0.50]. Rimegepant showed superior MIDAS and MSQv2 results compared with placebo in both EVOLVE trials and in the STRIVE trial, no statistically significant differences from galcanezumab and erenumab regarding MIDAS, and favorable results compared with erenumab across all MSQv2 domains, while being generally similar to galcanezumab across all MSQv2 domains.ConclusionsWhen adjustments were made to reflect baseline characteristics in published literature, supporting data from BHV3000‐201 suggest that rimegepant every other day is an effective therapy in reducing disability and MMDs and enhancing migraine‐specific HRQoL. These data support the preventive benefit observed in randomized trials of rimegepant and further validate its efficacy for both acute and preventive treatment of migraine.
Post‐rift stress history of Southwest Japan inferred from early to middle Miocene intrusions and meso‐scale faults in the Tajima–Myokensan area
Authors: Haji Toshiki , Yamaji Atsushi 
Published: May 2021

AbstractMiocene igneous dikes older and younger than 15 Ma in Southwest Japan are thought to be oriented parallel and perpendicular to the arc, respectively. This difference of orientations was referred to as significant evidence for termination of the opening of the Japan Sea at 15 Ma. The tightest constraint comes from ~60 dikes in the Tajima–Myokensan area, northern Hyogo Prefecture. Here we present orientations of 716 planar intrusive bodies and the directions of 143 meso‐scale faults, obtained using the latest stress inversion techniques from the lower to middle Miocene Hokutan Group in the Tajima–Myokensan area. The results contradict the 15 Ma hypothesis for the end of the opening of the Japan Sea. We find that intrusive bodies cannot be separated into two groups by their orientations as reported previously. Rather, the orientations of their poles comprise a horizontal girdle and a vertical cluster. The former indicates NE‐SW extensional stress, and the latter NW‐SE compression. However, the latter are interpreted as not representative of regional stress, based on common sill intrusions (the formation of which was not influenced by regional stress) in the well‐stratified Muraoka Formation resulting in the vertical cluster of pole orientations from which compression was recognized. The results of fault‐slip analysis are consistent with the extensional stress. Fission‐track and U–Pb ages of zircons were obtained from seven intrusive bodies. These and previously published ages suggest that the area underwent NW‐SE extension both before and after 15 Ma. In the main part of Southwest Japan, the weak extension was kept after 16 Ma when intra‐arc rifting was terminated. This is consistent with the hypothesis that the Japan Sea continued to open until 13.5 Ma.
Apical pressures generated by several canal irrigation methods: A laboratory study in a maxillary central incisor with an open apex
Authors: Magni Eva , Jäggi Marco , Eggmann Florin , Weiger Roland , Connert Thomas 
Published: May 2021

AbstractAimA laboratory study to determine the apical pressure generated by seven canal irrigation methods in an anterior tooth with an open apex.MethodologyCanal irrigation was performed on a 3D‐printed central maxillary incisor with an open apex (maximum diameter of 2.1 mm). Ultrasonically activated irrigation (UAI), sonic activation (EDDY), negative pressure irrigation (EndoVac), the self‐adjusting file (SAF) and the XP‐endo Finisher were employed at tooth length (TL), TL—1 mm, TL—2 mm and TL—3 mm. UAI was tested at three intensity levels additionally. Hydrodynamic irrigation with RinsEndo was performed in the pulp chamber, at the canal orifice, the coronal third, the middle of the canal and at TL. Er:YAG laser activation, at four frequency settings, was performed in the pulp chamber and at the orifice of the canal. The pressure of the fluid towards the canal terminus generated by activation was directly transferred to a pressure sensor with a range of 0 to 120 mmHg and a response time of ≤0.5 ms. The critical threshold for apical extrusion of the irrigant was set at 5.73 mmHg (lower limit of the central venous pressure: 5.88 ± 0.15 mmHg). Each experiment was repeated ten times. The tests were followed by descriptive analyses (maximum, mean, standard deviation, 95% confidence interval).ResultsEndoVac, the SAF, the XP‐endo Finisher, and UAI never exceeded the critical threshold at any insertion depth or intensity level. Er:YAG laser activation exceeded the critical threshold exclusively at frequency settings that varied from the manufacturer's recommendation. EDDY at TL and RinsEndo at any insertion depth exceeded the critical threshold in 100% of the measurements. EDDY at TL—1,—2, and—3 mm crossed the critical threshold in 30%, 10%, and 20% of the measurements, respectively.ConclusionsIn a simulated maxillary central incisor with an open apex, irrigation with EndoVac, Er:YAG laser activation, UAI, the SAF, and the XP‐endo Finisher generated apical pressures below the critical threshold of 5.73 mmHg. By contrast, using EDDY and RinsEndo for irrigation produced higher apical pressures that exceeded the critical threshold.
DISPUTE SETTLEMENT WITH SECOND‐ORDER UNCERTAINTY
Authors: Beshkar Mostafa , Park Jee‐Hyeong 
Published: May 2021

AbstractThe literature on pretrial dispute settlement has focused on the effect of first‐order uncertainty on bargaining, while assuming common knowledge about higher‐order beliefs. We study the effect of higher‐order uncertainty and show that the existence of such uncertainty improves the efficiency of settlement bargaining by expanding the set of strategies implementable in the equilibrium. We introduce uncertainty about higher‐order beliefs by assuming that one player privately observes an imperfect signal of the other player's type. We show that such signals could improve the efficiency only if they are privately observed: The signal's informational value disappears if it is publicly observable.
MAKE YOURSELVES SCARCE: THE EFFECT OF DEMOGRAPHIC CHANGE ON THE RELATIVE WAGES AND EMPLOYMENT RATES OF EXPERIENCED WORKERS
Authors: Böhm Michael J. , Siegel Christian 
Published: May 2021

AbstractThis article studies the impact of demographic change on experienced workers' relative wages and employment rates. We investigate empirical predictions from a framework of supply and demand for experience skill, using variation across U.S. local labor markets (LLMs) over the last decades and instrumenting experience skill supply by the LLMs' age structures a decade earlier. We find that aging substantially reduces experienced workers' relative wages and full‐time employment rates, and also their labor market participation rates. Our results imply that the effect of demographic change on labor markets might be more severe than previously recognized, as it reaches beyond wages.
WHY DO AMERICANS SPEND SO MUCH MORE ON HEALTH CARE THAN EUROPEANS?
Authors: He Hui , Huang Kevin X.D. , Ning Lei 
Published: May 2021

AbstractEmpirical evidence shows that both leisure and medical care are important in maintaining health and taxation may affect the allocation of these two inputs. We highlight this point using an analytical setting whose implications conform to micro‐ and macro‐data. We then quantify these implications using a life‐cycle overlapping generations model where taxation and relative health‐care price are key determinants of the composition of the two inputs in the endogenous accumulation of health capital. We find that differences in taxation alone explain 44.7% of U.S.–EU differences in health expenditure–GDP ratio and more than 70% of their differences in time allocation.
Morphology of alumina granules obtained by spray freeze drying with twin‐fluid atomization
Authors: Kuzmin Ruslan , Veselov Sergey , Cherkasova Nina , Bataev Vladimir 
Published: May 2021

AbstractThis study presents the results of the morphological dependence of alumina granules obtained by spray freeze drying (SFD) with twin‐fluid atomization. It is shown that the introduction of 1‐, 2‐ and 4‐wt.% polyvinyl alcohol (PVA) as a binder in an alumina suspension leads to the formation of irregular granules. Depending on atomization conditions, spherical, “tadpole‐like,” granule‐satellite and granule aggregates may form during SFD. Increasing the flight time of droplets before the fixing of their shape when they come in contact with liquid nitrogen effectively contributes to the spheroidization of alumina granules. Compacting PVA‐free SFD granules leads to the formation of diagonal flaws in a green‐body structure. Adding PVA prevents the abovementioned defects by increasing the strength of alumina granules. Increasing the amount of PVA leads to an increase in “tadpole‐like” granule content and, consequently, a decrease in a green‐body density.
They are a different breed aren’t they? Exploring how experts by experience influence students through mental health education
Authors: Happell Brenda , O'Donovan Aine , Sharrock Julie , Warner Terri , Gordon Sarah 
Published: May 2021

AbstractExperts by Experience (EBE) in mental health are increasingly becoming involved in the education of health professionals. In response, research findings suggest positive attitudinal change towards people who experience mental distress and enhanced appreciation of recovery and person‐centred approaches to practice. However, this growing body of evidence has not resulted in the broad adoption of these roles in academia. The perspectives of academics instrumental in implementing academic positions for EBE (referred to as allies) have not yet been articulated. Acknowledging this gap, the aim of this research was to explore experiences of allies involved in implementing EBE positions in academia regarding the impact of EBE led education on students. Qualitative exploratory methods were used involving in‐depth interviews with allies. Data were analysed thematically. Participants observed significant positive impacts on students, as evidenced through four themes: contextualized learning, enhancing reflection, feedback from the clinical field, and students’ own lived experience. The fifth sub‐theme, Challenging experiences were observed to potentially detract from the student experience in some instances. Overall, participants were very supportive of EBE involvement and were confident this approach produced more person‐centred and recovery‐oriented clinicians, with the skills, knowledge and attitudes needed to work as practitioners. These findings support previous research and suggest positive implications for clinical practice and for students with their own mental health challenges.
The impact of negotiators’ motivation on the use of decision support tools in preparation for negotiations
Authors: Roszkowska Ewa , Kersten Gregory E. , Wachowicz Tomasz 
Published: May 2021

AbstractThorough preparation for a negotiation is considered critical for the achievement of successful relational and substantive results. Careful specification of preferences and determining the negotiation offer scoring systems is one of the most important preparation activities. To facilitate this process, preference elicitation aids have been designed and implemented in decision and negotiation support systems (NSSs). This paper shows that negotiators’ motivation affects the use of simple elicitation aid and elicited preferences. We identify three types of motivations: epistemic, social, identity, and assign the factors that describe them. Then, using the dataset from electronic negotiation experiments, we apply logistic regression to identify those motivations that allow distinguishing negotiators who make errors in the determination of the scoring systems from those who do not make them. The key result allows us to identify relational‐ and learning‐oriented goals of the identity motivation as having a significant and direct impact on the negotiators’ classification. Accommodating and competing approaches of social motivation impact agents' accuracy with the differences observed for gender. Surprisingly, epistemic motivation represented by rationality and experientiality factors does not affect users’ accuracy in the prenegotiation phase. The results obtained can be used to design decision support tools adjusted to the motivational profiles of the NSS users.
Lactobacilli reduce recurrences of vaginal candidiasis in pregnant women: a randomized, double-blind, placebo-controlled study
Authors: Ang X.-Y. , Chung F.-Y.-L. , Lee B.-K. , Azhar S.N.A. , Sany S. , Roslan N.S. , Ahmad N. , Yusof S.M. , Abdullah N. , Nik Ab Rahman N.N. , Abdul Wahid N. , Deris Z.Z. , Oon C.-E. , Wan Adnan W.F. , Liong M.-T. 
Published: May 2021

Abstract

Aims
The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; placebo, n = 39) and the potential benefits on quality of life.

Methods and Results
The lactobacilli putative probiotic (SynForU-HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8-weeks in a randomized, double-blind, placebo-controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week-4 and week-8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week-4 and continued after week-8 (P &lt; 0·05), accompanied by reduced symptoms for burning after week-8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week-4 (P = 0·010) and continued after week-8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week-8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week-4 and week-8 (P &lt; 0·05). Patients consuming lactobacilli showed higher defecation times per week at week-4 (P = 0·010) and week-8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy-induced constipation.

Conclusions
Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC.

Significance and Impact of the Study
The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy.