bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of published population pharmacokinetic models to inform tacrolimus dosing in adult heart transplant recipients
Authors: Kirubakaran Ranita , Hennig Stefanie , Maslen Ben , Day Richard O. , Carland Jane E. , Stocker Sophie L. 
Published: September 2021

Background and AimIdentification of the most appropriate population pharmacokinetic model‐based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially, necessitating dose adjustments.MethodsPopulation pharmacokinetic models of tacrolimus were selected (n = 17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate‐release formulation of tacrolimus (Prograf) were obtained up to 391 days post‐transplant. The performance of each model was evaluated using: (i) prediction‐based assessment (bias and imprecision) of the individual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL = 0, FOCE‐I) from 1–3 prior dosing occasions; and (ii) simulation‐based assessment (prediction‐corrected visual predictive check). Both assessments were stratified based on concomitant azole antifungal use.ResultsRegardless of the number of prior dosing occasions (1–3) and concomitant azole antifungal use, all models demonstrated unacceptable individual predicted tacrolimus concentration of the fourth dosing occasion (n = 152). The prediction‐corrected visual predictive check graphics indicated that these models inadequately predicted observed tacrolimus concentrations.ConclusionAll models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.
Retrospective analyses of other iatrogenic immunodeficiency‐associated lymphoproliferative disorders in patients with rheumatic diseases
Authors: Kaji Daisuke , Kusakabe Manabu , Sakata‐Yanagimoto Mamiko , Makishima Kenichi , Suehara Yasuhito , Hattori Keiichiro , Ota Yasunori , Mitsuki Takashi , Yuasa Mitsuhiro , Kageyama Kosei , Taya Yuki , Nishida Aya , Ishiwata Kazuya , Takagi Shinsuke , Yamamoto Hisashi , Asano‐Mori Yuki , Ubara Yoshifumi , Izutsu Koji , Uchida Naoyuki , Wake Atsushi , Taniguchi Shuichi , Yamamoto Go , Chiba Shigeru 
Published: September 2021

SummaryOther iatrogenic immunodeficiency‐associated lymphoproliferative disorders (OIIA‐LPDs) occur in patients receiving immunosuppressive drugs for autoimmune diseases; however, their clinicopathological and genetic features remain unknown. In the present study, we analysed 67 patients with OIIA‐LPDs, including 36 with diffuse large B‐cell lymphoma (DLBCL)‐type and 19 with Hodgkin lymphoma (HL)‐type. After discontinuation of immunosuppressive drugs, regression without relapse was achieved in 22 of 58 patients. Spontaneous regression was associated with Epstein–Barr virus positivity in DLBCL‐type (P = 0·013). The 2‐year overall survival and progression‐free survival (PFS) at a median follow‐up of 32·4 months were 92·7% and 72·1% respectively. Furthermore, a significant difference in the 2‐year PFS was seen between patients with DLBCL‐type and HL‐type OIIA‐LPDs (81·0% vs. 40·9% respectively, P = 0·021). In targeted sequencing of 47 genes in tumour‐derived DNA from 20 DLBCL‐type OIIA‐LPD samples, histone‐lysine N‐methyltransferase 2D (KMT2D; eight, 40%) and tumour necrosis factor receptor superfamily member 14 (TNFRSF14; six, 30%) were the most frequently mutated genes. TNF alpha‐induced protein 3 (TNFAIP3) mutations were present in four patients (20%) with DLBCL‐type OIIA‐LPD. Cases with DLBCL‐type OIIA‐LPD harbouring TNFAIP3 mutations had shorter PFS and required early initiation of first chemotherapy. There were no significant factors for spontaneous regression or response rates according to the presence of mutations. Overall, OIIA‐LPDs, especially DLBCL‐types, showed favourable prognoses.
Empagliflozin and uric acid metabolism in diabetes: A post hoc analysis of the EMPA‐REG OUTCOME trial
Authors: Ferreira João Pedro , Inzucchi Silvio E. , Mattheus Michaela , Meinicke Thomas , Steubl Dominik , Wanner Christoph , Zinman Bernard 
Published: September 2021

AbstractAimTo evaluate the effect of empagliflozin on uric acid (UA) levels, antigout medication and gout episodes in the EMPA‐REG OUTCOME trial (NCT01131676).Materials and methodsA total of 7020 patients with type 2 diabetes (T2D) were randomized to either empagliflozin (10 or 25 mg) or placebo. The effects of empagliflozin versus placebo on UA concentration were assessed using mixed linear models. A composite outcome of new prescription of antigout medication or gout episode was studied with Cox proportional hazards models.ResultsEmpagliflozin reduced serum UA levels versus placebo: week 52 adjusted mean treatment difference = −0.37 (95% confidence interval [CI] −0.42, −0.31) mg/dL; this was more pronounced in patients with baseline UA ≥ 7.0 mg/dL versus <7.0 mg/dL: week 52 adjusted mean treatment difference = −0.56 (95% CI −0.68, −0.43) and −0.30 (95% CI −0.37, −0.24) mg/dL, respectively. Among 6607 patients not taking antigout medications at baseline, 5.2% had a gout episode or initiated antigout treatment versus 3.6% in the placebo and empagliflozin groups, respectively: hazard ratio 0.67 (95% CI 0.53, 0.85; P = 0.001). Both components of the composite outcome contributed to the reduction with empagliflozin in the composite. Risk reduction was similar with both empagliflozin doses.ConclusionsEmpagliflozin reduced UA levels and the composite of gout episodes or prescription of antigout medication. These clinically important findings expand the utility of empagliflozin as a potential antigout treatment in patients with T2D, beyond its well‐established cardio‐renal benefits.
Prediction of chemical components of urinary stones through colour Doppler ultrasound twinkling artefacts under optimized space composite algorithm
Authors: Zhang Aiwei , Wang Junwei , Zhang Cunming , Gu Lingzhu 
Published: September 2021

AbstractThe study focused on the application value of the space compounding algorithm‐based colour Doppler ultrasound twinkling artefacts in predicting chemical components of urinary tract stones. Specifically, the minimum variance method was used to optimize the space‐compounding algorithm to improve the quality of colour Doppler ultrasound artefacts. Then, the urinary system stone model was built to quantitatively analyse the influence of stone components on colour Doppler twinkling artefacts. The results showed that no notable differences were noted in the twinkling artefact intensity (TAI), the width of twinkling artefact (TAW), and the length of twinkling artefact (TAL) between the oxalic acid monohydrate, hydroxyapatite, uric acid, and cystine stone models (p < 0.01). The area under the curve (AUC) of the TAI for the diagnosis of calcium‐free calculus models was 0.978, that of TAW was 0.9462, and that of TAL was 0.9315. The diagnostic sensitivity and specificity of TAI were 89% and 96%, respectively, the diagnostic sensitivity and specificity of TAW were 86% and 80%, respectively, and the diagnostic sensitivity and specificity of TAL were 78% and 97%, respectively. The ability of TAL (AUC of 0.953) to distinguish between hydroxyapatite stone model and cystine stone was better than TAI (AUC of 0.702) and TAW (AUC of 0.657) (p < 0.01); and TAL and TAW were positively correlated with TAI (R2 was 0.79 and 0.68, respectively, p < 0.01). In conclusion, the space compounding algorithm based on minimum variance method can improve the quality of colour Doppler ultrasound twinkling artefacts, and colour Doppler ultrasound twinkling artefacts can predict the chemical components of urinary stones, which can be used as a criterion for clinical diagnosis.
Retained austenite stability on rolling contact fatigue performance of 8620 case‐carburized steel
Authors: Morris Dallin , Sadeghi Farshid 
Published: September 2021

AbstractVarying levels of retained austenite (RA) were achieved through varying undercooling severity in uniformly treated case carburized 8620 steel. Specimens were characterized via XRD and EBSD techniques to determine RA volume fraction and material characteristics prior to rolling contact fatigue (RCF). Higher RA volume fractions did not lead to improvement in RCF lives. XRD measurements after RCF testing indicated that little RA decomposition had occurred during RCF. A continuum damage mechanics (CDM) finite element model (FEM) was then developed to investigate the effects of RA stability on RCF. The results obtained from the CDM FEM captured similar behavior observed in the experimental results. Utilizing the CDM FEM, a parametric study was undertaken to examine the effects of RA quantity, RA stability, and applied pressure on RCF performance. The study demonstrates that the energy requirements to transform the RA phase are critical to RCF performance.
Association between dipeptidyl peptidase‐4 inhibitors and increased risk for bullous pemphigoid within 3 months from first use: A 5‐year population‐based cohort study using the Japanese National Database
Authors: Kuwata Hirohito , Nishioka Yuichi , Noda Tatsuya , Kubo Shinichiro , Myojin Tomoya , Higashino Tsuneyuki , Takahashi Yutaka , Ishii Hitoshi , Imamura Tomoaki 
Published: September 2021

AbstractAims/IntroductionWe assessed the association between dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and bullous pemphigoid (BP) and time‐dependent changes in the risk for developing BP after DPP‐4i initiation.Materials and MethodsThe present population‐based, real‐world study was carried out using the Japanese National Database dataset collected between 2013 and 2018. To assess independent correlations between DPP‐4is and the development of BP, the self‐controlled case series method was used.ResultsAmong the cohort followed up for a median of 1,540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person‐years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person‐years, whereas that in patients with type 2 diabetes who did and did not use DPP‐4is was 40.7 and 30.0/100,000 person‐years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP‐4i use showed a risk ratio of 2.15 (95% confidence interval [CI] 1.75–2.63), 1.70 (95% CI 1.37–2.11), 1.44 (95% CI 1.15–1.82), 1.25 (95% CI 0.98–1.59), 0.84 (95% CI 0.63–1.10), 0.84 (95% CI 0.64–1.11) and 1.05 (95% CI 0.92–1.20), for the risk period of ≤30, 31–60, 61–90, 91–120, 121–150, 151–180 and 181–365 days, respectively.ConclusionsAlthough DPP‐4is were associated with increased risk for BP, the risk was particularly significant within 3 months from first use.
Effects of multimedia‐based fall prevention education on the knowledge, attitudes, or behaviors of patients
Authors: Wang Su‐Ching , Lee De‐Chih , Lee Yi‐Hua , Chang Yuan‐Ping , Chu I‐Lien 
Published: September 2021

AbstractObjectivesPatient safety is regarded as a critical quality monitoring indicator for medical institutions. The effects of a multimedia‐based patient education intervention on knowledge, attitudes, and behaviors regarding fall prevention were observed.MethodsThe study had a quasi‐experimental research design and enrolled 140 participants. Seventy participants in the experimental group received multimedia‐based patient education and a health education leaflet, while those in the control group received only the health education leaflet. A structured questionnaire was used for data collection at baseline, and a posttest was applied after the intervention.ResultsThe participants were predominantly treated in the gastroenterology department (45.7%), followed by the pulmonology department (33.6%). A total of 86.4% of patients had not experienced a fall within 3 months. After the intervention, the average scores for all variables in the experimental group were higher than those in the control group. The results indicate that attitudes, knowledge, and behaviors regarding fall prevention among patients in the pulmonology department were higher than those among patients in the gastroenterology department; the differences were statistically significant.ConclusionThe individualized health education content was of substantial significance for patients with different disease backgrounds and facilitated changes in their knowledge, attitudes, and behaviors regarding falls.Relevance to clinical practiceMultimedia‐based patient education influenced inpatients' knowledge, attitudes, and behaviors for preventing falls.
Beyond the beak: Brain size and allometry in avian craniofacial evolution
Authors: Marugán‐Lobón Jesús , Nebreda Sergio M. , Navalón Guillermo , Benson Roger B. J. 
Published: September 2021

AbstractBirds exhibit an enormous variety of beak shapes. Such remarkable variation, however, has distracted research from other important aspects of their skull evolution, the nature of which has been little explored. Key aspects of avian skull variation appear to be qualitatively similar to those of mammals, encompassing variation in the degree of cranial vaulting, cranial base flexure, and the proportions and orientations of the occipital and facial regions. The evolution of these traits has been studied intensively in mammals under the Spatial Packing Hypothesis (SPH), an architectural constraint so‐called because the general anatomical organization and development of such skull parts makes them evolve predictably in response to changes in relative brain size. Such SPH predictions account for the different appearances of skull configurations across species, either in having longer or shorter faces, and caudally or ventrally oriented occiputs, respectively. This pattern has been morphometrically and experimentally proven in mammals but has not been examined in birds or other tetrapods, and so its generality remains unknown. We explored the SPH in an interspecific sample of birds using three‐dimensional geometric morphometrics. Our results show that the dominant trend of evolutionary variation in the skull of crown‐group birds can be predicted by the SPH, involving concomitant changes in the face, the cranial vault and the basicranium, and with striking similarities to craniofacial variation among mammals. Although craniofacial variation is significantly affected by allometry, these allometric effects are independent of the influence of the SPH on skull morphology, as are any effects of volumetric encephalization. Our results, therefore, validate the hypothesis that a general architectural constraint underlies skull homoplasy evolution of cranial morphology among avian clades, and possibly between birds and mammals, but they downplay encephalization and allometry as the only factors involved.
Pathological personality, situations, and their joint influences on daily emotional symptoms
Authors: Hong Ryan Y. , Sheng Dan , Yee Wan Qi 
Published: September 2021

AbstractObjectiveThe present research aims to advance current understanding on how individuals with pathological personality traits construe their day‐to‐day situational experiences.MethodCollege students (N = 231) completed a measure of personality pathology, followed by six assessments of everyday situations and anxiety/depression symptoms over two weeks.ResultsMultilevel analyses indicated that personality pathology was meaningfully associated with situational experiences. Major findings suggested that situations that entailed aggravations and interpersonal confrontations were associated with negative affectivity, antagonism, and psychoticism. Detached individuals were less likely to experience pleasant and social situations. Exploratory analyses suggested an amplification effect where individuals high on personality pathology were more anxious or depressed when they perceived certain situational features, compared to their low trait counterparts. However, such cross‐level interactions constituted a small minority; most personality traits and situations exerted additive effects on symptoms.ConclusionSituational experiences appear to be driven in part by personality pathology. The exacerbation of daily negative symptoms can be attributed to the joint (largely additive) influence of the trigger situations and pathological personality traits.
Social groups constrain the spatiotemporal dynamics of wild sifaka gut microbiomes
Authors: Perofsky Amanda C. , Ancel Meyers Lauren , Abondano Laura A. , Di Fiore Anthony , Lewis Rebecca J. 
Published: September 2021

AbstractPrimates acquire gut microbiota from conspecifics through direct social contact and shared environmental exposures. Host behaviour is a prominent force in structuring gut microbial communities, yet the extent to which group or individual‐level forces shape the long‐term dynamics of gut microbiota is poorly understood. We investigated the effects of three aspects of host sociality (social groupings, dyadic interactions, and individual dispersal between groups) on gut microbiome composition and plasticity in 58 wild Verreaux's sifaka (Propithecus verreauxi) from six social groups. Over the course of three dry seasons in a 5‐year period, the six social groups maintained distinct gut microbial signatures, with the taxonomic composition of individual communities changing in tandem among coresiding group members. Samples collected from group members during each season were more similar than samples collected from single individuals across different years. In addition, new immigrants and individuals with less stable social ties exhibited elevated rates of microbiome turnover across seasons. Our results suggest that permanent social groupings shape the changing composition of commensal and mutualistic gut microbial communities and thus may be important drivers of health and resilience in wild primate populations.
Metatheories of disagreement: Introduction
Authors: Hartl Péter , Gyarmathy Ákos 
Published: September 2021

AbstractThis article introducesMetaphilosophy'sspecial issue on metatheories of disagreement, with the aim of promoting discussion on the nature of disagreement on a metatheoretical level. The contributions to this issue cover the following key topics related to disagreement: faultless disagreement, metaontological disagreement, metalinguistic disagreement, responses to peer disagreement in philosophy, hinge epistemology and deep disagreement, disagreement asymmetry, factual and nonfactual disagreement, and defining disagreement or verbal dispute. This introduction also provides general background on four major topics in order to contextualize the contributions to the special issue: first, the problem of characterizing the subject matter of disagreements; second, the most prominent accounts of deep disagreement, disagreement asymmetry and hinges; third, the notion of faultless disagreement; and finally, the problem of offering different approaches on what disagreements are.
Taking a social perspective on moral disgust
Authors: Gert Joshua 
Published: September 2021

AbstractResearch on moral disgust suffers from a methodological bias. The bulk of such investigation focuses almost exclusively on the operation of moral disgust within the psychology of a single individual, or as involving an interaction between two people. This leads to certain questions being salient, while other phenomena, which emerge only at the level of an entire community or society, are largely hidden from view. The present paper explains and defends a perspective that emphasizes the role of moral disgust within a community. It also illustrates the usefulness of this perspective by applying it to three quite distinct accounts of moral disgust: Alexandra Plakias’s response model of moral disgust, David Pizarro’s idea that moral disgust is part of a behavioral immune system, and Jesse Prinz’s self‐consciously simple form of moral sentimentalism.
The Arabidopsis thaliana LysM‐containing Receptor‐Like Kinase 2 is required for elicitor‐induced resistance to pathogens
Authors: Giovannoni Moira , Lironi Damiano , Marti Lucia , Paparella Chiara , Vecchi Valeria , Gust Andrea A. , De Lorenzo Giulia , Nürnberger Thorsten , Ferrari Simone 
Published: September 2021

AbstractIn Arabidopsis thaliana, perception of chitin from fungal cell walls is mediated by three LysM‐containing Receptor‐Like Kinases (LYKs): CERK1, which is absolutely required for chitin perception, and LYK4 and LYK5, which act redundantly. The role in plant innate immunity of a fourth LYK protein, LYK2, is currently not known. Here we show that CERK1, LYK2 and LYK5 are dispensable for basal susceptibility to B. cinerea but are necessary for chitin‐induced resistance to this pathogen. LYK2 is dispensable for chitin perception and early signalling events, though it contributes to callose deposition induced by this elicitor. Notably, LYK2 is also necessary for enhanced resistance to B. cinerea and Pseudomonas syringae induced by flagellin and for elicitor‐induced priming of defence gene expression during fungal infection. Consistently, overexpression of LYK2 enhances resistance to B. cinerea and P. syringae and results in increased expression of defence‐related genes during fungal infection. LYK2 appears to be required to establish a primed state in plants exposed to biotic elicitors, ensuring a robust resistance to subsequent pathogen infections.
Material perception for philosophers
Authors: Ritchie J. Brendan , Paulun Vivian C. , Storrs Katherine R. , Fleming Roland W. 
Published: September 2021

AbstractCommon everyday materials such as textiles, foodstuffs, soil or skin can have complex, mutable and varied appearances. Under typical viewing conditions, most observers can visually recognize materials effortlessly, and determine many of their properties without touching them. Visual material perception raises many fascinating questions for vision researchers, neuroscientists and philosophers, yet has received little attention compared to the perception of color or shape. Here we discuss some of the challenges that material perception raises and argue that further philosophical thought should be directed to how we see materials.