bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age‐related carotid extra‐media thickening is associated with increased blood pressure and arterial stiffness
Authors: Carlini Nicholas A. , Harber Matthew P. , Fleenor Bradley S. 
Published: June 2021

AbstractAgeing results in higher blood pressure and arterial stiffening leading to increased cardiovascular disease (CVD) risk. The extra‐media thickness (EMT) is a composite measure of the arterial adventitia, perivascular adipose tissue (PVAT) and the jugular vein, but the association among EMT and ageing, blood pressure and arterial stiffness is largely unknown. We hypothesized that EMT is associated with ageing, blood pressure and arterial stiffness. Fifty (18M/32F, age range 20–79 years.) individuals underwent measures of EMT (media‐adventitia border to jugular lumen interface) via ultrasonography, blood pressure (brachial; carotid), arterial stiffness (carotid beta‐stiffness, distensibility and Young's modulus) and body composition (dual X‐ray absorptiometry). Independent two‐tailed t‐tests compared characteristics between young and middle‐aged/older adults (MA/O). Bivariate correlations assessed the relation between EMT, ageing, blood pressure and arterial stiffness endpoints. Partial correlations were used to adjust for age, sex, body mass index (BMI) and body fat percentage. Compared to young, MA/O adults had higher EMT, blood pressure, arterial stiffness, BMI and BF% (all, p ≤ 0.05). Carotid EMT was positively correlated with age (r = 0.46), brachial SBP (r = 0.32), carotid SBP (r = 0.42), PP (r = 0.42), beta‐stiffness (r = 0.37) and Young's elastic modulus (r = 0.43) (all, p ≤ 0.05), and negatively correlated with carotid distensibility (r = −0.34, p ≤ 0.05). All endpoints correlated with EMT remained after adjusting for BMI, BF% and sex (p ≤ 0.05). These data suggest EMT is a clinically relevant target that may be associated with age‐related CVD risk in humans, yet further investigation is required to elucidate the role of EMT in age‐related increases in blood pressure and arterial stiffness.
A first‐in‐human study of KMRC011, a potential treatment for acute radiation syndrome, to explore tolerability, pharmacokinetics, and pharmacodynamics
Authors: Yang Eunsol , Choi Hyejung , Park Jin‐Sol , Noh Young‐Woock , Choi Chi‐Min , Lee Woo‐Jong , Ko Jae‐Wook , Kim Jungryul 
Published: June 2021

AbstractKMRC011 is a novel Toll‐like receptor 5 agonist under development as a treatment for acute radiation syndrome (ARS). The aim of this first‐in‐human study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of a single intramuscular dose of KMRC011 in healthy subjects. A randomized, single‐blind, placebo‐controlled, single dose‐escalation study was conducted with the starting dose of 5 μg. Eight (4 only for 5 μg cohort) subjects per cohort were randomly assigned to KMRC011 or placebo in a 3:1 ratio. Dose‐limiting toxicity (DLT) was assessed throughout the study. Serum concentrations of KMRC011, granulocyte colony‐stimulating factor (G‐CSF), and interleukin‐6 (IL‐6) were measured up to 48 h postdose. Based on safety review, the dose of KMRC011 escalated up to 20 μg, and consequently, a total of 4 dose levels (5, 10, 15, and 20 μg) were explored. The most common adverse event was injection site reaction, showing no dose‐related trend. Three DLTs (2 cases of hepatic enzyme increased and 1 of pyrexia) were observed; 1 in the 15 μg cohort and 2 in the 20 μg cohort. A developed method could not detect any KMRC011 in serum. KMRC011 15 μg and 20 μg showed significant increases of G‐CSF, IL‐6, and absolute neutrophil counts, compared with the placebo. A single intramuscular administration of KMRC011 ranging from 5 to 15 μg was tolerated in healthy subjects. Doses of KMRC011 equal to or greater than 15 μg exerted TLR5 agonist‐like activities by increasing serum G‐CSF and IL‐6. It suggests that KMRC011 has the potential for a treatment for ARS.
Model‐based assessments of CYP3A‐mediated drug‐drug interaction risk of milademetan
Authors: Hong Ying , Ishizuka Tomoko , Watanabe Akiko , Tachibana Masaya , Lee Mark , Ishizuka Hitoshi , LaCreta Frank , Abutarif Malaz 
Published: June 2021

AbstractMilademetan is a small‐molecule inhibitor of murine double minute 2 (MDM2) that is in clinical development for advanced solid tumors and hematological cancers, including liposarcoma and acute myeloid leukemia. Milademetan is a CYP3A and P‐glycoprotein substrate and moderate CYP3A inhibitor. The current study aims to understand the drug‐drug interaction (DDI) risk of milademetan as a CYP3A substrate during its early clinical development. A clinical DDI study of milademetan (NCT03614455) showed that concomitant administration of single‐dose milademetan with the strong CYP3A inhibitor itraconazole or posaconazole increased milademetan mean area under the curve from zero to infinity (AUCinf) by 2.15‐fold (90% confidence interval [CI], 1.98–2.34) and 2.49‐fold (90% CI, 2.26–2.74), respectively, supporting that the milademetan dose should be reduced by 50% when concomitantly administered with strong CYP3A inhibitors. A physiologically‐based pharmacokinetic (PBPK) model of milademetan was subsequently developed to predict the magnitude of CYP3A‐mediated DDI potential of milademetan with moderate CYP3A inhibitors. The PBPK model predicted an increase in milademetan exposure of 1.72‐fold (90% CI, 1.69–1.76) with fluconazole, 1.91‐fold (90% CI, 1.83–1.99) with erythromycin, and 2.02‐fold (90% CI, 1.93–2.11) with verapamil. In addition, it estimated that milademetan’s original dose (160 mg once daily) could be resumed from its half‐reduced dose 3 days after discontinuation of concomitant strong CYP3A inhibitors. The established PBPK model of milademetan was qualified and considered to be robust enough to support continued development of milademetan.
The impact of postbariatric hypoglycaemia on driving performance: A randomized, single‐blind, two‐period, crossover study in a driving simulator
Authors: Lehmann Vera , Tripyla Afroditi , Herzig David , Meier Jasmin , Banholzer Nicolas , Maritsch Martin , Zehetner Jörg , Giachino Daniel , Nett Philipp , Feuerriegel Stefan , Wortmann Felix , Bally Lia 
Published: June 2021

AbstractPostbariatric hypoglycaemia (PBH) is an increasingly recognized complication of bariatric surgery, but its effect on daily functioning remains unclear. In this randomized, single‐blind, crossover trial we assessed driving performance in patients with PBH. Ten active drivers with PBH (eight females, age 38.2 ± 14.7 years, body mass index 27.2 ± 4.6 kg/m2) received 75 g glucose to induce PBH in the late postprandial period and aspartame to leave glycaemia unchanged, on two different occasions. A simulator was driven during 10 minutes before (D0) and 20 (D1), 80 (D2), 125 (D3) and 140 minutes (D4) after the glucose/aspartame ingestion, reflecting the expected blood glucose (BG) increase (D1), decrease (D2) and hypoglycaemia (D3, D4). Seven driving features indicating impaired driving were integrated in a Bayesian hierarchical regression model to assess the difference in driving performance after glucose/aspartame ingestion. Mean ± standard deviation peak and nadir BG after glucose were 182 ± 24 and 47 ± 14 mg/dL, while BG was stable after aspartame (85 ± 4 mg/dL). Despite the lack of a difference in symptom perception, driving performance was significantly impaired after glucose versus aspartame during D4 (posterior probability 98.2%). Our findings suggest that PBH negatively affects driving performance.
Two healthy lifestyle scores are associated with lower subsequent fatigue risk using inverse probability weighting in an international longitudinal cohort of people with multiple sclerosis
Authors: Weiland Tracey J. , Nag Nupur , De Livera Alysha , Jelinek George A. , Neate Sandra L. , Bevens William , Simpson‐Yap Steve 
Published: June 2021

AbstractBackground and purposeSeveral modifiable lifestyle factors have been associated with the onset and health outcomes of multiple sclerosis (MS), including clinically significant fatigue. A combined lifestyle score approach represents one method of assessing their relationship with clinical outcomes. The aim was to examine the association of two lifestyle scores with clinically significant fatigue and change thereof over 2.5 years' follow‐up using inverse probability treatment weighting (IPTW).MethodsData on sociodemographic, lifestyle, and clinical characteristics surveyed from an international cohort of people with MS at baseline and at 2.5‐year follow‐up were used. Fatigue was defined by the Fatigue Severity Scale (FSS >5) and healthy lifestyle by the Healthy Lifestyle Index Score (HLIS) and the Smoking, Nutrition, Alcohol Consumption and Physical Activity (SNAP) score. Analyses were by IPTW accounting for age, sex, MS type, disability, treated comorbidity number, immunomodulatory medication use, prescription antifatigue medication use, and ongoing relapse symptoms.ResultsIn total, 1268 participants completed the FSS at both time points; approximately 62% had fatigue. Using doubly robust IPTW, high (>11/20) HLIS (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.81–0.98) and high (>3/5) SNAP (OR 0.82, 95% CI 0.73–0.90) were each associated with lower risk of fatigue at follow‐up. Evaluating change in fatigue, a higher SNAP score was associated with a lower risk of fatigue (OR 0.89, 95% CI 0.80–0.97) but the score for HLIS did not reach statistical significance (OR 0.93, 95% CI 0.85–1.01).ConclusionThese results suggest a robust role for key lifestyle factors in preventing clinically significant fatigue and may represent a place for lifestyle modification in improving clinical outcomes in MS.
Brain activity is contingent on neuropsychological function in a functional magnetic resonance imaging study of verbal working memory in amyotrophic lateral sclerosis
Authors: Kobeleva Xenia , Machts Judith , Veit Maria , Vielhaber Stefan , Petri Susanne , Schoenfeld Mircea Ariel 
Published: June 2021

AbstractBackground and purposeAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that causes progressive degeneration of neurons in motor and non‐motor brain regions, affecting multiple cognitive domains such as memory. A functional magnetic resonance imaging (fMRI) study was performed to explore working memory function in ALS.MethodsTo contribute to the growing research field that employs structural and functional neuroimaging to investigate the effect of ALS on different working memory components, the localization and intensity of alterations in neural activity was explored using fMRI. Being the first study to specifically address verbal working memory via fMRI in the context of ALS, the verbal n‐back task with 0‐back and 2‐back conditions was employed.ResultsDespite ALS patients showing unimpaired accuracies (p = 0.724) and reaction times (p = 0.0785), there was significantly increased brain activity of frontotemporal and parietal regions in the 2‐back minus 0‐back contrast in patients compared to controls (using nonparametric statistics with 5000 permutations and a T threshold of 2.5).DiscussionIncreased brain activity of the frontotemporal and parietal regions during working memory performance was largely associated with better neuropsychological function within the ALS group, suggesting a compensatory effect during working memory execution. This study therefore adds to the current knowledge on neural correlates of working memory in ALS and contributes to a more nuanced understanding of hyperactivity during cognitive processes in fMRI studies of ALS.
The long‐term efficacy of cannabidiol in the treatment of refractory epilepsy
Authors: Patel Sandip , Grinspoon Reid , Fleming Bradley , Skirvin Lauren A. , Wade Christina , Wolper Emma , Bruno Patricia L. , Thiele Elizabeth A. 
Published: June 2021

AbstractObjectiveCannabidiol (CBD) has been shown to reduce seizures among patients with refractory epilepsies of various etiologies in recent clinical trials and an expanded access program (EAP). Most studies report efficacy over short time periods (<1 year), with little published on longer term efficacy. Here, we investigate the efficacy of CBD for a treatment period of up to 60 months (median = 45.5 months).MethodsWe conducted a retrospective review of patient‐reported seizure logs and medical records for 54 subjects with refractory epilepsy who enrolled in the Massachusetts General Hospital's open‐label EAP for CBD as a new treatment for epilepsy. We analyzed the effect of CBD on seizure frequencies and concomitant antiepileptic drug (AED) use at 1 year after starting treatment and the most recent study visit.ResultsOur results indicate that CBD maintains its efficacy for controlling seizures from Year 1 to the most recent study visit. The percentage of seizure responders remained similar at these time points (41.7%–42.6%), and the seizure response rate was also maintained (p = .12). Efficacy was also seen over a broad dose range, and up to 50 mg/kg/day. CBD was particularly effective for controlling seizures in the setting of tuberous sclerosis complex and for reducing epileptic spasms and absence seizures. Although CBD use did not lead to an overall decrease in concomitant AEDs, most subjects reduced the dose of at least one concomitant AED compared to baseline. CBD was generally well tolerated, with drowsiness and diarrhea as the primary adverse reactions.SignificanceThis study demonstrates CBD does not lose its efficacy in controlling seizures over a treatment period of up to 60 months. Taken alongside other results on the efficacy and tolerability of CBD in the treatment of refractory epilepsies, our results provide evidence that CBD is an effective, safe, and well‐tolerated AED for long‐term use.
Antioxidant extracts from Dicerocaryum senecioides as active ingredients in semi‐permanents and hair conditioners
Authors: Rambwawasvika Hardlife , Dzomba Pamhidzai , Gwatidzo Luke , Chiririwa Haleden 
Published: June 2021

AbstractBackgroundDifferent hair types respond differently to cosmetic treatments; hence, many options ought to be availed to the consumer. The purpose of this study was to evaluate the use of antioxidant extract from Dicerocaryum senecioides as active alternatives in hair semi‐permanent waving and hair conditioning.MethodsThe antioxidant phytochemicals were first identified and isolated by thin‐layer chromatography (TLC) and spraying with revealing agents. The antioxidant potency was determined by DPPH antiradical scavenging and ferric reducing power methods. The extract was incorporated in two different formulations to make the extract perm (bio‐semi‐permanent) and the antioxidant hair conditioner (AC). The formulations had their performance examined for hair curling and conditioning on Asian and African hair types. Hair damage was assessed by scanning the surface of treated samples on an attenuated total reflectance–Fourier transform infrared spectrometer (ATR‐FTIR) and by quantifying lost protein on ultraviolet visible (UV‐Vis) spectrophotometer.ResultsThe extract antioxidant had an IC50 of 26.54 ± 0.34 µg/ml exhibiting greater antioxidant potency compared to the controls quercetin (38.84 ± 0.12 µg/ml) and ascorbic acid (35.22 ± 0.07 µg/ml). The extract perm had a lower curling ability indicated by a perm set of 85.10 ± 3.92% and 81.35 ± 2.35% for Asian and African hairs, respectively, while commercial product, ammonium thioglycolate (ATG) had 96.05 ± 1.70% and 93.60 ± 2.21% for the same. The curling of hair with extract perm resulted in less oxidative damage with oxidative peak areas of 3.37 ± 0.09 and 3.71 ± 0.03 as well as lower protein losses of 4.72 ± 0.71 µg/mg and 5.62 ± 0.70 µg/mg on Asian and African hair samples, respectively. The application of AC reduced the oxidative damage peak areas of ATG and extract perm treated Asian hair samples by 1.15 and 0.48 units, respectively. AC was also effective in reducing damage caused by UV radiation on ATG‐treated samples by 1.06 units (African hair) and 1.09 units on Asian hair.ConclusionThe results show antioxidant extracts from Dicerocryum senecioides as a promising and safer alternative for hair conditioning and semi‐permanent curling.
Does consumption make company better? An activity and companionship model of experienced utility
Authors: Mora José‐Domingo 
Published: June 2021

AbstractCompanions may enhance the enjoyment of information goods, services, and life in general, but how this enhancement varies over activities and social context remains underexplored. Furthermore, we ignore whether consumption makes company better as compared to non‐consumption. To address these questions, we implement a mixed methods approach. First, we validate a duration‐based measure of experienced utility on survey data; and, second, calibrate an econometric model of this utility measure on secondary data from the American Time Use Survey. Results show that relational proximity of companions reduces experienced utility, suggesting relational costs; whereas numerosity (cumulative number of companions by activity and day) may partly compensate for, or even reverse those costs of relating to others. Moreover, this balance of estimates of proximity and numerosity of companions is positive for non‐consumption but negative for consumption activities. Consumption emerges as a sub‐optimal locus for social interaction, with important implications for theory and practice.
Genetic taste sensitivity and dental caries in children and adolescents: A systematic review and meta‐analysis
Authors: Alkuhl Huda , Morgan Rebecca , Koletsi Despina , Kavvadia Katerina 
Published: June 2021

AbstractBackgroundPROP test (6‐n‐propylthiouracil) for the identification of genetic sensitivity to caries in young individuals has emerged as a useful tool for caries risk assessment.AimTo systematically appraise available evidence on the association between genetic taste sensitivity, as detected by (PROP), and caries.DesignSeven databases, as of March 2020, were searched. Search terms included ‘caries’, ‘taste predisposition’, ‘PROP’. Risk of bias assessment was performed using ROBINS‐I tool, and the quality of evidence was assessed with GRADE. Random‐effects meta‐analyses were conducted to synthesize data, and pooled effects were estimated through standardized mean differences (SMDs) and associated confidence Intervals (95% CIs).ResultsOf 92 articles initially retrieved, 12 were eligible for inclusion. Seven contributed to the meta‐analyses. All were cross‐sectional studies, with moderate‐to‐serious risk of bias. The non‐tasters of PROP exhibited a significantly higher value for the DMFT compared with tasters (SMD: 1.23; 95% CI: 0.90, 1.56; P < .001), whereas the association for the DMFS was SMD: 1.34; 95% CI: 0.66, 2.01; P < .001 (non‐tasters versus super‐tasters). The quality of evidence was very low overall.ConclusionsWithin the limitations of this study, non‐tasters to PROP exhibited higher caries experience, with subsequent clinical implications for follow‐up and management of the ‘high‐susceptibility’ individuals.
Formation of anisotropic grains and modified ferroelectric properties in Cr‐doped Bi5FeTi3O15 thin films
Authors: Zhang Junyan , Song Dongpo , Lee Jung‐Kun 
Published: June 2021

AbstractAurivillius phase Bi5CrxFe1−xTi3O15 (0≤ x ≤1) thin films are prepared by the chemical solution deposition method, and the effect of Cr content on the microstructure, ferroelectric property, and electric transport behavior of Bi5CrxFe1−xTi3O15 films is investigated. X‐ray diffraction analysis shows that all of Bi5CrxFe1−xTi3O15 films are complete solid solution and maintain the Aurivillius structure. The replacement of Fe3+ with smaller Cr3+ decreases anisotropy and lattice aspect ratio in a‐b plane, which is minimized at the composition of Bi5Cr0.5Fe0.5Ti3O15. This changes the grain shape from sphere to plate, and Bi5Cr0.5Fe0.5Ti3O15 film consists of only plate‐like grains. Cr doping increases saturated polarization (Pm) and decreases coercive field (Ec). Cr doping increases Pm of Bi5CrxFe1−xTi3O15 film to 35 μC/cm2, but decreases Ec down to 125 kV/cm. A decrease in the lattice aspect ratio of a‐b plane promotes the alignment of ferroelectric dipoles under electric field. The frequency‐dependent dielectric property and the leakage current show that the plate‐like grains of Cr‐rich Bi5CrxFe1−xTi3O15 films suppress the transport of carriers from grains to grains and prevents a dramatic leakage current increase. The results of this study provide a design rule to control the ferroelectricity of Aurivillius phase Bi5CrxFe1−xTi3O15 thin films by modifying the composition and lattice aspect ratio.
When does being paid an hourly wage make it difficult to be a happy volunteer?
Authors: DeVoe Sanford E. , Pai Jieun 
Published: June 2021

AbstractWhen people willingly volunteer their time, how does the salience of the opportunity costs of their time influence their experience of the activity? Study 1 uses the American Time Use Survey Well‐Being module to examine whether the subjective experience of happiness while volunteering is influenced by how people are paid and the opportunity costs of their time spent volunteering. Among hourly paid workers for whom there is a salient heuristic for the opportunity costs of time, we found that higher opportunity costs of time as indicated by income and duration of the activity were associated with diminished happiness experienced during volunteering. No differences across income and duration emerged among non‐hourly workers for whom there was not a salient heuristic for the opportunity costs of time. Using a student population who all volunteered for the same charity activity, Study 2 tested whether making the opportunity costs salient caused less happiness to be reported from the activity than those in the control condition. These studies contribute to our understanding of the psychological consequences of thinking about time in terms of money and how it may influence the hedonic experience of activities people choose to undertake in the applied context of volunteering.
Ion‐poor water and dietary salt deprivation upregulate the ghrelinergic system in the goldfish (Carassius auratus)
Authors: Lim YouRee , Lee Vivienne , Blanco Ayelen , Kelly Scott P. , Unniappan Suraj 
Published: June 2021

AbstractBecause the ghrelinergic system in teleost fishes is broadly expressed in organs that regulate appetite as well as those that contribute to the regulation of salt and water balance, we hypothesized that manipulating salt and water balance in goldfish (Carassius auratus) would modulate the ghrelinergic system. Goldfish were acclimated to either freshwater (FW) or ion‐poor FW (IPW) and were fed either a control diet containing 1% NaCl or low‐salt diet containing 0.1% NaCl. Endpoints of salt and water balance, i.e., serum Na+ and Cl− levels, muscle moisture content and organ‐specific Na+‐K+‐ATPase (NKA) activity, were examined in conjunction with brain, gill and gut mRNA abundance of preproghrelin and its receptor, growth hormone secretagogue receptor (ghs‐r). Acclimation of fish to IPW reduced serum osmolality and Cl− levels and elevated kidney NKA activity, while FW fish fed a low NaCl diet exhibited a modest reduction in muscle moisture content but otherwise no apparent osmoregulatory disturbance. In contrast, a combined treatment of IPW acclimation and low dietary NaCl content reduced serum osmolality and Cl− levels, elevated muscle moisture content and increased gill, kidney and intestinal NKA activity. This intensified response to the combined effects of water and dietary ion deprivation is consistent with an increased effort to enhance ion acquisition. In association with these latter observations, a significant upregulation of preproghrelin mRNA expression in brain and gut was observed. A significant increase in ghs‐r mRNAs was also observed in the gill of goldfish acclimated to IPW alone but a reduction in dietary NaCl content did not impact the ghrelinergic system of goldfish in FW. The results support the hypothesis that the ghrelinergic system is modulated in response to manipulated salt and water balance. Whether the central and peripheral ghrelinergic system contributes to ionic homeostasis in goldfish currently remains unclear and warrants further research.