bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYP2C8*3 and *4 define CYP2C8 phenotype: An approach with the substrate cinitapride
Authors: Campodónico Diana María , Zubiaur Pablo , Soria‐Chacartegui Paula , Casajús Ana , Villapalos‐García Gonzalo , Navares‐Gómez Marcos , Gómez‐Fernández Antía , Parra‐Garcés Raúl , Mejía‐Abril Gina , Román Manuel , Martín‐Vílchez Samuel , Ochoa Dolores , Abad‐Santos Francisco 
Published: September 2022

AbstractCinitapride is a gastrointestinal prokinetic drug, prescribed for the treatment of functional dyspepsia, and as an adjuvant therapy for gastroesophageal reflux disease. In this study, we aimed to explore the impact of relevant variants in CYP3A4 and CYP2C8 and other pharmacogenes, along with demographic characteristics, on cinitapride pharmacokinetics and safety; and to evaluate the impact of CYP2C8 alleles on the enzyme's function. Twenty‐five healthy volunteers participating in a bioequivalence clinical trial consented to participate in the study. Participants were genotyped for 56 variants in 19 genes, including cytochrome P450 (CYP) enzymes (e.g., CYP2C8 or CYP3A4) or transporters (e.g., SLC or ABC), among others. CYP2C8*3 carriers showed a reduction in AUC of 42% and Cmax of 35% compared to *1/*1 subjects (p = 0.003 and p = 0.011, respectively). *4 allele carriers showed a 45% increase in AUC and 63% in Cmax compared to *1/*1 subjects, although these differences did not reach statistical significance. CYP2C8*3 and *4 alleles may be used to infer the following pharmacogenetic phenotypes: ultrarapid (UM) (*3/*3), rapid (RM) (*1/*3), normal (NM) (*1/*1), intermediate (IM) (*1/*4), and poor (PM) metabolizers (*4/*4). In this study, we properly characterized RMs, NMs, and IMs; however, additional studies are required to properly characterize UMs and PMs. These findings should be relevant with respect to cinitapride, but also to numerous CYP2C8 substrates such as imatinib, loperamide, montelukast, ibuprofen, paclitaxel, pioglitazone, repaglinide, or rosiglitazone.
Human radiolabeled mass balance studies supporting the FDA approval of new drugs
Authors: Ramamoorthy Anuradha , Bende Girish , Chow Edwin Chiu Yuen , Dimova Hristina , Hartman Neil , Jean Daphney , Pahwa Sonia , Ren Yunzhao , Shukla Chinmay , Yang Yuching , Doddapaneni Suresh , Danielsen Zhixia Yan 
Published: September 2022

AbstractHuman radiolabeled mass balance studies are an important component of the clinical pharmacology programs supporting the development of new investigational drugs. These studies allow for understanding of the absorption, distribution, metabolism, and excretion of the parent drug and metabolite(s) in the human body. Understanding the drug's disposition as well as metabolite profiling and abundance via mass balance studies can help inform the overall drug development program. A survey of the US Food and Drug Administration (FDA)‐approved new drug applications (NDAs) indicated that about 66% of the drugs had relied on findings from the mass balance studies to help understand the pharmacokinetic characteristics of the drug and to inform the overall drug development program. When such studies were not available in the original NDA, adequate justifications were routinely provided. Of the 104 mass balance studies included in this survey, most of the studies were conducted in healthy volunteers (90%) who were mostly men (>86%). The studies had at least six evaluable participants (66%) and were performed using the final route(s) of administration (98%). Eighty‐five percent of the studies utilized a dose within the pharmacokinetic linearity range with 54% of the studies using a dose the same as the approved dose. Nearly all studies were performed as a single‐dose (97%) study using a fit‐for‐purpose radiolabeled formulation. In this analysis, we summarized the current practices for conducting mass balance studies and highlighted the importance of conducting appropriately designed human radiolabeled mass balance studies and the challenges associated with inadequately designed or untimely studies.
Epicardial adipose tissue thickness is associated with reduced peak oxygen consumption and systolic reserve in patients with type 2 diabetes and normal heart function
Authors: Nesti Lorenzo , Pugliese Nicola Riccardo , Chiriacò Martina , Trico Domenico , Baldi Simona , Natali Andrea 
Published: September 2022

AbstractAimTo investigate the impact of epicardial adipose tissue (EAT) thickness on cardiopulmonary performance in patients with type 2 diabetes (T2D) and normal heart function.Materials and methodsWe analysed EAT thickness in subjects with T2D and normal biventricular systo‐diastolic functions undergoing a maximal cardiopulmonary exercise test combined with stress echocardiography, speckle tracking and pulmonary function assessment, as well as serum N‐terminal pro B‐type natriuretic peptide (NT‐proBNP).ResultsIn the 72 subjects enrolled, those with EAT thickness above the median (> 5 mm) showed higher body fat mass, smaller indexed left ventricular dimensions and marginally reduced diastolic function variables at rest. Higher EAT thickness was associated with lower peak oxygen uptake (VO2peak 17.1 ± 3.6 vs. 21.0 ± 5.7 ml/min/kg, P = .001), reduced systolic reserve (ΔS′ 4.6 ± 1.6 vs. 5.8 ± 2.5 m/s, P = .02) and higher natriuretic peptides (NT‐proBNP 64 [29‐165] vs. 31 [26‐139] pg/ml, P = .04), as well as chronotropic insufficiency and impaired heart rate recovery. Ventilatory variables and peripheral oxygen extraction were not different between groups. EAT was independently associated with VO2peak and linearly and negatively correlated with peak heart rate, heart rate recovery, workload, VO2 at the anaerobic threshold and at peak, and cardiac power output, and was directly correlated with natriuretic peptides.ConclusionHigher EAT thickness in T2D is associated with worse cardiopulmonary performance and multiple traits of subclinical cardiac systolic dysfunction.
Seasonality, body size, and maturation time in the neotropical grasshopper Sphenarium histrio across an altitudinal gradient
Authors: Ramírez‐Delgado Víctor Hugo , Cueva del Castillo Raúl 
Published: September 2022

AbstractIn insects, male mating success and female fecundity usually increase with body size. However, natural selection favors faster maturation, reducing the risk of pre‐reproductive death, when the reproductive season is short in habitats located at high altitudes or far from the equator. Also, if males that mature earlier than females under these conditions increase their mating opportunities, protandry may evolve in their populations. Nonetheless, as body size is strongly correlated with maturation time in insects, faster sexual maturation is reached at the expense of having a small body size. We analyzed the differences in adult body size of males and females of the grasshopper Sphenarium histrio Gerstaecker (Orthoptera: Pyrgomorphidae) in three sites across an altitudinal gradient in southern Mexico. We also evaluated the possibility of protandry in these sampling sites using a common garden experiment. Male and female grasshoppers collected from low altitude sites in the field and reared in the laboratory were larger than those from a high altitude, suggesting genetic differentiation. Grasshoppers from a high altitude hatched earlier, had a shorter development time, presented fewer instars, and were smaller than grasshoppers from the other sampling sites. Moreover, development time in the three sampling sites was shorter in males than in females, suggesting protandry. Interestingly, the males from the three sites showed similar growth rates, but the females from low and high altitudes, respectively, had the fastest and slowest growth rates. In general, the adaptive value of the evolution of protandry has been focused on males. However, it may be that the growth rates of females in these sites could modify the degree of protandry as a response to their risk of pre‐reproductive death and the potential benefits associated with multiple matings.
No‐self and compassion: Nietzsche and Buddhism
Authors: Janaway Christopher 
Published: September 2022

AbstractThe article examines two claims made by Antoine Panaïoti: (1) That both Nietzsche and Buddhists denounce the self as a misleading fiction. (2) That Buddhist compassion is close to a “compassion of strength” that Nietzsche approves. This article agrees with (1) and disagrees with (2). The descriptive metaphysical commitments of Nietzsche and Buddhism are subordinate to their divergent normative projects. Both reject a single, enduring, and independent self; but where Mahāyāna Buddhism advocates care or compassion toward all sentient beings, Nietzsche questions the value of compassion, holding that suffering is not bad in itself. Some recent commentators suggest that a text by the Buddhist philosopher Śāntideva offers an argument from “no‐self” to universal compassion. Nietzsche disputes this connection; and Śāntideva's Madhyamaka position, in which nothing has an intrinsic nature, cannot easily counter Nietzsche's claim that suffering is not intrinsically bad. Nietzsche's privileging of states of “becoming,” “discovering,” or “creating” oneself sets him deeply at odds with Buddhism. For Buddhists the fundamentally problematic attitude is a pre‐theoretical sense of self, “egoism,” or “self‐grasping” which is at the root of human craving. Agreeing with the philosophical claim that there is no self is not sufficient to dispel this pre‐theoretical orientation.
Protocols for cleaning the incisor access cavity contaminated with epoxy resin sealer
Authors: Boderé Pieter‐Jan , Calberson Filip , De Bruyne Mieke , De Moor Roeland , Meire Maarten 
Published: September 2022

AbstractThis study compared different methods for cleaning the sealer‐contaminated access cavity of upper incisors. After standard endodontic access, the canals of 50 extracted maxillary incisors were chemomechanically prepared and obturated with gutta‐percha and epoxy resin sealer. Teeth were randomly assigned to one of five different pulp chamber cleaning protocols (n = 10): air/water spray, ethanol‐saturated cotton pellet (CP), ethanol‐saturated microbrush reaching the root filling (MB), MB + air polishing (PROPHYflex; KaVo), or MB + etching with 37% phosphoric acid. Each tooth was split and the sealer‐covered area of the pulp chamber was determined on images taken before and after cleaning using image analysis software. The sealer‐covered area was compared across groups using one‐way ANOVA. Greatest mean sealer‐covered area reduction was observed for MB + etching (98.0%), MB + air polishing (95.2%), and MB alone (92.8%), yielding a significantly higher sealer‐covered area reduction than after air/water spray (8.3%) and ethanol‐saturated cotton pellet (53.4%). The upper incisor access cavity is best cleaned with an ethanol‐saturated microbrush reaching up to the root filling, followed by air/water spraying and etching. The use of cotton pellets should be discouraged.
A combination of hepatic encephalopathy and body mass index was associated with the point of no return for improving liver functional reserve after sofosbuvir/velpatasvir treatment in patients with hepatitis C virus‐related decompensated cirrhosis
Authors: Sano Tomoya , Amano Keisuke , Ide Tatsuya , Yokoyama Keiji , Noguchi Kazunori , Nakamura Hiroki , Isoda Hiroshi , Ohno Miki , Shirachi Miki , Morita Yasuyo , Yano Yoichi , Sumie Shuji , Kawaguchi Toshihiro , Kuwahara Reiichiro , Arinaga‐Hino Teruko , Takahashi Hirokazu , Shakado Satoshi , Hirai Fumihito , Kawaguchi Takumi 
Published: September 2022

AbstractAimsThe real‐world efficacy of sofosbuvir/velpatasvir treatment for patients with hepatitis C virus‐related decompensated cirrhosis is unclear. We aimed to identify factors that improve liver functional reserve after treatment.MethodsThis was a multicenter retrospective study of 12‐week sofosbuvir/velpatasvir treatment. A total of 48 patients with Child–Pugh (CP) class B or C were enrolled at 11 institutions. We evaluated changes in liver functional reserve at 24 weeks post‐treatment.ResultsAt baseline, 40 and eight patients were CP class B and C, respectively. The overall rate of sustained virologic response 12 weeks post‐treatment was 95.8% (46/48). Serum albumin, alanine aminotransferase and α‐fetoprotein levels, and the FIB‐4 index were significantly improved post‐treatment (P < 0.05). Among patients who achieved sustained virologic response 12 weeks post‐treatment, those with CP class A increased from 0 to 24 patients (56%) at 24 weeks post‐treatment. In multivariate analysis, body mass index (BMI) ≥25 was an independent factor that inhibited CP class improvement (P < 0.05). In decision tree analysis, after treatment, the initial divergent variable for CP class improvement was hepatic encephalopathy, followed by serum sodium level and BMI.ConclusionSofosbuvir/velpatasvir treatment improved the liver functional reserve in patients with hepatitis C virus‐related decompensated cirrhosis at 24 weeks post‐treatment. However, BMI ≥25 inhibited improvement in CP class. Additionally, decision tree analysis revealed that a combination of hepatic encephalopathy, serum sodium levels, and BMI were diversity profiles associated with no improvement in liver functional reserve after the treatment.
The Youth Patient and Public Involvement Café—A youth‐led model for meaningful involvement with children and young people
Authors: Thomson Abigail , Peasgood Edward , Robertson Sam 
Published: September 2022

AbstractIntroductionThere are few meaningful frameworks or toolkits that exist for involvement with young people. Coproduction is a more recent patient and public involvement (PPI) approach that emphasizes the importance of power‐sharing, to set young people as equal partners in the research process. This paper explores the successes and challenges encountered by one coproduced PPI space for young people.MethodsThis paper is written by a team of young people who developed and worked on the Youth PPI Café over a period of 18 months. It explores how we developed a youth‐led space for involvement in research. The authors have reflected on their experiences, providing examples of how youth PPI and coproduction were delivered in the NHS, in practice.ResultsBy working ‘with’ young people, rather than ‘for’ them, we offer insights into the successes and challenges of an entirely youth‐led involvement space. Despite being effective in shaping mental health research for children and young people, we faced challenges with tokenism, resourcing and diversity and inclusion.ConclusionsInvolving youth meaningfully in research has the potential to inform studies at a macro‐ and microlevel, enabling positive change within research and within the systems that support young people.Patient or Public ContributionYoung people aged 16–24 years with lived experience were included at every stage of this project, from formulation to the delivery and development of the group, to the preparation of this manuscript and its dissemination. Sussex Partnership NHS Foundation Trust's charity ‘Heads On’ provided funding for this study.
Calvin's Visual Exegesis of Old Testament Prophecy: Figural Reading and the Sacramental Character of Scripture
Authors: Pak Sujin 
Published: September 2022

AbstractThis article provides a study of John Calvin's treatment of the Old Testament prophets' language, images and metaphors to illuminate the distinctly visual character of his theology. It explores Calvin's theology of Scripture as shaped by the visual theology rooted in his exegesis of the Old Testament prophetic books. The author argues that the Old Testament prophets serve as supreme models for imitation of how to make God's Word come alive through visual images and powerful metaphors. Furthermore, the article draws connections between Calvin's engagement with the prophets' language of ‘painting’, ‘mirror’, ‘vivid representation’ and ‘visible symbol’ and his descriptions of biblical theophanies and the power of sacraments. Bringing these elements side by side, a vivid portrait emerges of Calvin's conception of Scripture as a visual sign. The author argues that this visual sign‐character of Scripture undergirds a deeper commitment of Calvin's – a conviction of Scripture's sacramental character and functions. Consequently, the article argues that the visual features of Calvin's theology – where visual aspects unite his theologies of Scripture and the sacraments – set forth Scripture itself as a sacrament and call students of Calvin to take more seriously the visual and material commitments of his theology.
Tracking the associative boost in infancy
Authors: Plunkett Kim , Delle Luche Claire , Hills Thomas , Floccia Caroline 
Published: September 2022

AbstractDo words that are both associatively and taxonomically related prime each other in the infant mental lexicon? We explore the impact of these semantic relations in the emerging lexicon. Using the head‐turn preference procedure, we show that 18‐month‐old infants have begun to construct a semantic network of associatively and taxonomically related words, such as dog‐cat or apple‐cheese. We demonstrate that priming between words is longer‐lasting when the relationship is both taxonomic and associative, as opposed to purely taxonomic, reflecting the associative boost reported in the adult priming literature. Our results demonstrate that 18‐month‐old infants are able to construct a lexical‐semantic network based on associative and taxonomic relations between words in the network, and that lexical‐semantic links are more robust when they are both associative and taxonomic in character. Furthermore, the manner in which activation is propagated through the emerging lexical‐semantic network appears to depend upon the type of semantic relation between words. We argue that 18‐month‐old infants have a mental lexicon that shares important structural and processing properties with that of the adult system.
Single‐phase (Hf0.84Ta0.16)C solid solution nanowires growth via catalyst‐assisted chemical vapor deposition
Authors: Chen Hui , Zhang Yulei , Fu Yanqin , Zhang Jian , Shuai Kang 
Published: September 2022

AbstractFabricating one‐dimensional (1D) ceramic nanostructure with superior performance is an important approach to broaden their applications. In this paper, the synthesis of single‐phase (Hf0.84Ta0.16)C solid solution nanowires via catalyst‐assisted chemical vapor deposition was proposed for the first time. The [0 1 1̄] growth direction of (Hf0.84Ta0.16)C solid solution nanowires was discussed in detail and its corresponding growth mechanism was identified to be top‐type vapor–liquid–solid mechanism. More impressively, our work could widen the application ranges of ceramic nanowires and propose the new thinking of fabricating ultrahigh melting point nanostructure.
Microbial incubations of 8-phenyloctanoic acid and furan fatty acids in rumen fluid
Authors: Wiedmaier-Czerny Nina , Blumberg Olga , Schulz Tobias , Kemmler Franziska , Titze Natascha , Wild Katharina , Vetter Walter 
Published: September 2022

AbstractAimsThe digestive tract of ruminants is specialized in the digestion of various plant components. One of the largest parts of the stomach is the so-called rumen, which contains a large number of micro-organisms that may degrade or modify fatty acids, for example by β-oxidation, chain elongation and/or hydrogenation.Methods and ResultsHere we performed incubation experiments with less common fatty acids by in vitro incubations with rumen fluid of fistulated cows for 24 h. Sample extracts were analysed by gas chromatography with mass spectrometry. As substrates, we selected one phenyl fatty acid and four furan fatty acids (FuFAs). All studied fatty acids were degraded by β-oxidation (two or three chain-shortening steps) while chain elongation or saturation of the aromatic part (terminal phenyl or central furan moiety) was not observed in any case.ConclusionsThe percentage of β-oxidation products was low, especially in the case of the FuFAs. This could be due to the rather long carbon number of FuFAs (19–22 carbon atoms). In addition, compound-specific differences in the degradation rates were observed in our experiments.Significance and Impact of the StudyOur results produce evidence that FuFAs, which are valuable antioxidants that are known to be present in various feed items of the cow, can be effectively passed on the rumen into the milk.
Do masks affect social interaction?
Authors: Crandall Christian S. , Bahns Angela J. , Gillath Omri 
Published: September 2022

AbstractWearing face masks to prevent the spread of COVID‐19 has proved controversial in many countries; conducting new research on the use of masks would be colored by this controversy. In 2012 (pre‐COVID), we conducted an experiment on the effects of masks on social interaction. College students (N = 250) were assigned to find a previously unknown student in a lecture hall, converse, and evaluate the interaction. Half were assigned to wear a surgical mask, sunglasses, and a hat (all provided); half wore no extra gear. Mask wearing had no effect on the ease, authenticity, friendliness of the conversation, mood, discomfort, or interestingness of the interaction. There were no discernable consequences of political ideology on the partner selection process or the evaluation of the interaction. Mask‐wearing did not disable successful social interaction in this setting.
Use of animal models to understand titin physiology and pathology
Authors: Marcello Matteo , Cetrangolo Viviana , Savarese Marco , Udd Bjarne 
Published: September 2022

AbstractIn recent years, increasing attention has been paid to titin (TTN) and its mutations. Heterozygous TTN truncating variants (TTNtv) increase the risk of a cardiomyopathy. At the same time, TTNtv and few missense variants have been identified in patients with mainly recessive skeletal muscle diseases. The pathogenic mechanisms underlying titin‐related diseases are still partly unknown. Similarly, the titin mechanical and functional role in the muscle contraction are far from being exhaustively clarified. In the last few years, several animal models carrying variants in the titin gene have been developed and characterized to study the structural and mechanical properties of specific titin domains or to mimic patients' mutations. This review describes the main animal models so far characterized, including eight mice models and three fish models (Medaka and Zebrafish) and discusses the useful insights provided by a thorough characterization of the cell‐, tissue‐ and organism‐phenotypes in these models.