bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling changes in the pharmacokinetics of tacrolimus during pregnancy after kidney transplantation: A retrospective cohort study
Authors: Schagen Maaike R. , Ulu Asiye Nur , Francke Marith I. , van de Wetering Jacqueline , van Buren Marleen C. , Schoenmakers Sam , Matic Maja , van Schaik Ron H. N. , Hesselink Dennis A. , de Winter Brenda C. M. 
Published: August 2023

AimsPregnancy after kidney transplantation is realistic but immunosuppressants should be continued to prevent rejection. Tacrolimus is safe during pregnancy and is routinely dosed based on whole‐blood predose concentrations. However, maintaining these concentrations is complicated as physiological changes during pregnancy affect tacrolimus pharmacokinetics. The aim of this study was to describe tacrolimus pharmacokinetics throughout pregnancy and explain the changes by investigating covariates in a population pharmacokinetic model.MethodsData of pregnant women using a twice‐daily tacrolimus formulation following kidney transplantation were retrospectively collected from 6 months before conception, throughout gestation and up to 6 months postpartum. Pharmacokinetic analysis was performed using nonlinear mixed effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. The final model was evaluated using goodness‐of‐fit plots, visual predictive checks and a bootstrap analysis.ResultsA total of 260 whole‐blood tacrolimus predose concentrations from 14 pregnant kidney transplant recipients were included. Clearance increased during pregnancy from 34.5 to 41.7 L/h, by 15, 19 and 21% in the first, second and third trimester, respectively, compared to prior to pregnancy. This indicates a required increase in the tacrolimus dose by the same percentage to maintain the prepregnancy concentration. Haematocrit and gestational age were negatively correlated with tacrolimus clearance (P ≤ 0.01), explaining 18% of interindividual and 85% of interoccasion variability in oral clearance.ConclusionsTacrolimus clearance increases during pregnancy, resulting in decreased exposure to tacrolimus, which is explained by gestational age and haematocrit. To maintain prepregnancy target whole‐blood tacrolimus predose concentrations during pregnancy, increasing the dose is required.
Pharmacokinetics, pharmacodynamics and urinary recovery of oral lysergic acid diethylamide administration in healthy participants
Authors: Holze Friederike , Erne Livio , Duthaler Urs , Liechti Matthias E. 
Published: August 2023

AimsLysergic acid diethylamide (LSD) is currently investigated for several neurological and psychiatric illnesses. Various studies have investigated the pharmacokinetics and the pharmacokinetic–pharmacodynamic relationship of LSD in healthy participants, but data on urinary recovery and confirmatory studies are missing.MethodsThe present study characterized the pharmacokinetics, pharmacokinetic–pharmacodynamic relationship and urinary recovery of LSD at doses of 85 and 170 μg administered orally in 28 healthy participants. The plasma concentrations and subjective effects of LSD were continuously evaluated over a period of 24 h. Urine was collected during 3 time intervals (0–8, 8–16 and 16–24 h after LSD administration). Pharmacokinetic parameters were determined using compartmental modelling. Concentration–subjective effect relationships were described using pharmacokinetic–pharmacodynamic modelling.ResultsMean (95% confidence interval) maximal LSD concentrations were 1.8 ng/mL (1.6–2.0) and 3.4 ng/mL (3.0–3.8) after the administration of 85 and 170 μg LSD, respectively. Maximal concentrations were achieved on average after 1.7 h. Elimination half‐lives were 3.7 h (3.4–4.1) and 4.0 h (3.6–4.4), for 85 and 170 μg LSD, respectively. Only 1% of the administered dose was recovered from urine unchanged within the first 24 h, 16% was eliminated as 2‐oxo‐3‐hydroxy‐LSD. Urinary recovery was dose proportional. Mean (±standard deviation) durations of subjective effects were 9.3 ± 3.2 and 11 ± 3.7 h, and maximal effects (any drug effects) were 77 ± 18% and 87 ± 13% after 85 and 170 μg of LSD, respectively.ConclusionThe present novel study validates previous findings. LSD exhibited dose‐proportional pharmacokinetics and first‐order elimination kinetics and dose‐dependent duration and intensity of subjective effects. LSD is extensively metabolized and shows dose‐proportional urinary recovery.
Effect of lemborexant on pharmacokinetics of clozapine: A potential drug–drug interaction mediated by time‐dependent inhibition of CYP3A4
Authors: Watanabe Kenya , Misaka Shingen , Kanno‐Nozaki Keiko , Chiyoda Takaaki , Suzuki Yuhei , Sato Akiko , Suto Takahiro , Kuroda Junko , Shimomura Kenju , Miura Itaru , Yabe Hirooki 
Published: August 2023

AbstractClozapine (CLZ) is extensively used for treatment‐resistant schizophrenia (TRS) with caution to avoid serious adverse events such as agranulocytosis and drug–drug interactions (DDIs). In the current report, we present a case of a 35‐year‐old male non‐smoking TRS patient whose steady‐state plasma trough concentrations (Ctrough) of CLZ and its active metabolite, N‐desmethylclozapine (NDMC), were significantly increased after initiating oral administration of lemborexant (LEM), a dual orexin receptor antagonist, for the treatment of insomnia. The patient experienced oversedation with sleepiness and fatigue while maintaining high levels of Ctrough of CLZ. The increased concentrations of CLZ returned to normal ranges after the discontinuation of LEM dosing, implying a pharmacokinetic DDI between CLZ and LEM. To gain insight into possible mechanisms, we performed in vitro assays of CYP1A2‐ and CYP3A4‐mediated CLZ metabolism by measuring the formations of NDMC and clozapine N‐oxide (CNO). In accordance with previous studies, the incubation of CLZ with each enzyme resulted in the production of both metabolites. LEM had only a weak inhibitory effect on CYP1A2‐ and CYP3A4‐mediated CLZ metabolism. However, the preincubation of LEM with CYP3A4 in the presence of NADPH showed a significant enhancement of inhibitory effects on CLZ metabolism with IC50 values for the formations of CNO and NDMC of 2.8 μM and 4.1 μM, respectively, suggesting that LEM exerts as a potent time‐dependent inhibitor for CYP3A4. Taken together, the results of the current study indicate that co‐medication of CLZ with LEM may lead to increase in exposure to CLZ and risks of CLZ‐related adverse events.
Climate change and business accountability, empirical evidence on the roles of environmental strategy and environmental accounting
Authors: Omran Mohammed S. Y. , Yaaqbeh Mohammad N. S. 
Published: August 2023

AbstractThis study examines the roles of environmental strategy and accounting in corporate carbon performance, as measured by the Greenhouse Gas (GHG) Protocol. A novel interaction model is developed based on legitimacy theory and natural‐resource dependence theory to capture the interaction between environmental strategy and accounting. An international sample of 3322 firms from 73 countries is used in the analysis, based on a panel data design for 17 years (2005–2022). The empirical findings reveal an overall reactive role of these environmental initiatives in relation to carbon performance. The marginal effect analysis shows that environmental accounting favourably moderates the effect of environmental strategic functions on carbon performance, indicating that the former facilitates the translation of the latter into practice. Similarly, environmental strategic initiatives improve the impact of environmental accounting information on carbon performance. The main contribution of this study stems from methodologically demonstrating how the synergy between environmental strategic initiatives and environmental information mechanisms can translate into improved carbon performance. This finding has multiple societal, practical and research implications. The interaction effect evidence can be viewed as consistent with recent trends of integrated approaches to thinking and reporting, where interrelated phenomena are integrated into operational and reporting contexts to improve efficiency. This can be of interest to policymakers, investors, corporate managers and providers of assurance services related to carbon performance.
No clitting! We need to talk about clitoris transplantation
Authors: Campo‐Engelstein Lisa 
Published: August 2023

AbstractIn the last two decades, genital transplants have emerged as another type of quality‐of‐life transplants. Successful allogenic transplantations of the uterus, ovary, testicle, and penis have all been reported. Yet, there is no discussion of clitoris transplantation in the medical literature, mass media, and everywhere else I searched. This surgery could be used for cisgender women who have a clitoral injury or disease or who have undergone female genital cutting. I examine the gender norms regarding sexuality and reproduction to show how they shape surgical advancements. My point in this paper is not to take a normative position on status of current genital transplantations. Rather, I highlight that their existence is due, at least in part, because they align with dominant gender norms: penis and testicle transplantations reinforce the importance of men's virility and the existence of “normal” male genitalia, whereas uterus and ovary transplantations uphold the conflation of women and reproduction and the strong valuing of women's fertility. That medical advances reflect cultural values is not a new claim. What is new in this paper is the discussion of how sexism norms—regarding the invisibility of the clitoris and the devaluing of women's sexual pleasure— has engendered various types of genital transplants, but not clitoris transplantation.
Histiocytic neoplasms: Going, going, but not quite gone
Authors: Collin Matthew 
Published: August 2023

BRAF and MEK inhibitors have revolutionised the treatment of patients with high‐risk histiocytic neoplasms but does a complete response mean that treatment can be withdrawn?Commentary on: Reiner et al. Outcomes after interruption of targeted therapy in patients with histiocytic neoplasms. Br J Haematol 2023;203:389–394.
ETS1 phosphorylation at threonine 38 is associated with the cell of origin of diffuse large B cell lymphoma and sustains the growth of tumour cells
Authors: Chung Elaine Y. L. , Sartori Giulio , Ponzoni Maurilio , Cascione Luciano , Priebe Valdemar , Xu‐Monette Zijun Y. , Fang Xiaosheng , Zhang Mingzhi , Visco Carlo , Tzankov Alexandar , Rinaldi Andrea , Sgrignani Jacopo , Zucca Emanuele , Rossi Davide , Cavalli Andrea , Inghirami Giorgio , Scott David W. , Young Ken H. , Bertoni Francesco 
Published: August 2023

SummaryThe transcriptional factor ETS1 is upregulated in 25% of diffuse large B cell lymphoma (DLBCL). Here, we studied the role of ETS1 phosphorylation at threonine 38, a marker for ETS1 activation, in DLBCL cellular models and clinical specimens. p‐ETS1 was detected in activated B cell‐like DLBCL (ABC), not in germinal centre B‐cell‐like DLBCL (GCB) cell lines and, accordingly, it was more common in ABC than GCB DLBCL diagnostic biopsies. MEK inhibition decreased both baseline and IgM stimulation‐induced p‐ETS1 levels. Genetic inhibition of phosphorylation of ETS1 at threonine 38 affected the growth and the BCR‐mediated transcriptome program in DLBCL cell lines. Our data demonstrate that ETS1 phosphorylation at threonine 38 is important for the growth of DLBCL cells and its pharmacological inhibition could benefit lymphoma patients.
Tumour‐derived exosomes promote the induction of monocytic myeloid‐derived suppressor cells from peripheral blood mononuclear cells by delivering miR‐106a‐5p and miR‐146a‐5p in multiple myeloma
Authors: Mizuhara Kentaro , Shimura Yuji , Tsukamoto Taku , Kanai Akinori , Kuwahara‐Ota Saeko , Yamaguchi Junko , Muramatsu Ayako , Okamoto Haruya , Taminishi‐Katsuragawa Yoko , Kawaji‐Kanayama Yuka , Isa Reiko , Mizutani Shinsuke , Inaba Toshiya , Kuroda Junya 
Published: August 2023

SummaryThe shift of the tumour immune microenvironment to a suppressive state promotes not only the development and progression of the disease in multiple myeloma (MM) but also the development of resistance to immunotherapy. We previously demonstrated that myeloma cells can induce monocytic myeloid‐derived suppressor cells (M‐MDSCs) from healthy peripheral blood mononuclear cells (PBMCs) via the concomitant secretion of CC motif chemokine ligand 5 (CCL5) and macrophage migration inhibitory factor (MIF), but an unknown mediator also promotes M‐MDSC induction. This study demonstrates that miR‐106a‐5p and miR‐146a‐5p delivered by tumour‐derived exosomes (TEXs) from myeloma cells play essential roles in M‐MDSC induction in MM. MiR‐106a‐5p and miR‐146a‐5p upregulate various immunosuppressive/inflammatory molecules in PBMCs, such as IDO1, CD38, programmed death‐ligand 1, CCL5 or MYD88, which are involved in interferon (IFN)‐α response, IFN‐γ response, inflammatory response, tumour necrosis factor‐α signalling and Interleukin‐6‐JAK–STAT3 signalling. These molecular features mirror the increases in myeloid cellular compartments of PBMCs when co‐cultured with myeloma cells. MiR‐106a‐5p and miR‐146a‐5p have a compensatory relationship, and these two miRNAs collaborate with CCL5 and MIF to promote M‐MDSC induction. Collectively, novel therapeutic candidates may be involved in TEX‐mediated sequential cellular and molecular events underlying M‐MDSC induction, potentially improving the efficacy of immunotherapy.
Irish mothers' experiences of providing support in decision‐making to adults with intellectual disabilities: A qualitative study
Authors: Casey Hannah , Desmond Deirdre , Coffey Laura 
Published: August 2023

AbstractBackgroundSupported decision‐making may increase self‐determination among adults with intellectual disabilities by encouraging and empowering them to make decisions about their lives to the greatest extent possible. The aim of this study was to explore the perceptions and experiences of mothers of adults with intellectual disabilities in Ireland of providing support in decision‐making.MethodsSemi‐structured interviews were conducted with seven mothers who had an adult son or daughter with an intellectual disability; transcripts were thematically analysed.FindingsThree main themes were identified: support (family, services and routine), decision‐making (importance, ability and Capacity Act) and challenges (conflict, time, complex and enduring support needs and vulnerability).ConclusionsThe findings indicate that although mothers were supportive of the rights of their adult children with intellectual disabilities to make their own decisions, they were often hesitant to fully relinquish control in an effort to protect and guide them.
Lactobacillus species ameliorate membranous nephropathy through inhibiting the aryl hydrocarbon receptor pathway via tryptophan‐produced indole metabolites
Authors: Miao Hua , Wang Yan‐Ni , Yu Xiao‐Yong , Zou Liang , Guo Yan , Su Wei , Liu Fei , Cao Gang , Zhao Ying‐Yong 
Published: August 2023

AbstractBackground and PurposeMembranous nephropathy (MN) is an immune‐mediated glomerular disease in adults. Antibody‐ and antigen‐bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition‐mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis.Experimental ApproachIn this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)‐induced MN rats and in patients with idiopathic MN (IMN).Key ResultsImpaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan‐produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole‐3‐pyruvic acid, indole‐3‐aldehyde and tryptamine and negatively correlated with increased levels of indole‐3‐lactic acid and indole‐3‐acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down‐regulated cytoplasmic AhR, but up‐regulated nuclear AhR, in MN rats and IMN patients.Conclusion and ImplicationsActivation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors.
Endogenous timing and income inequality in the voluntary provision of public goods: Theory and experiment
Authors: Itaya Jun‐ichi , Mizushima Atsue , Kurosaka Kengo 
Published: August 2023

AbstractThis study theoretically and experimentally investigates the effects of income inequality on donors' decisions regarding timing choices and contributions to public goods when contribution timing is endogenously chosen by contributors. To this end, we use the conventional voluntary provision models of Warr (1983) and Bergstrom, Blume and Varian (1986), with Cobb–Douglas preferences augmented with a two‐stage game of Hamilton and Slutsky (1990). The following results were obtained and experimentally confirmed. First, when the distribution of income is extremely unequal, donors are indifferent between the simultaneous and sequential moves in the contribution game. Second, as income inequality is decreased, the simultaneous‐move contribution game is likely to emerge because every donor prefers to act as a leader. Nevertheless, a higher‐income donor may also prefer to act as a follower without specific social preferences and uncertainty regarding the quality of public goods. Third, most theoretical predictions regarding timing decisions are supported in our laboratory experiment, provided that the participants had enough time to learn the consequences of their timing choices.
A pilot study to develop a participation self‐assessment tool for adolescents: The Social Participation Inventory (SPI)
Authors: Bernard Marie , Hoffmann Laura , Richter Matthias , Völlm Carina , Seyda Miriam , Fink Astrid , Dawal Britta 
Published: August 2023

AbstractObjectiveParticipation is one of the key goals of re/habilitative processes. Since participation impacts adolescents' social–emotional development and overall health, this goal is particularly important for them. However, to date, no German‐speaking self‐assessment tool for participation among adolescents is available. This study sought therefore to develop such a tool and to test its psychometric properties.MethodsBased on a preliminary qualitative study, we developed 133 items for a pilot version of the Social Participation Inventory (SPI). The SPI assesses the objective dimension (i.e., attendance) and the subjective dimension (i.e., involvement and satisfaction) of participation. To test the psychometric properties of the SPI, we conducted a quantitative cross‐sectional survey and applied the SPI to n = 151 adolescents with and without disabilities and/or chronic diseases.ResultsBy using principal component analyses, we examined the SPI's consistency and verified the theoretical considerations regarding the two components of participation (i.e., objective and subjective dimensions). Items that did not load sufficiently on components were removed after careful theoretical‐based consideration. The condensed version of the SPI consists of 39 items that assess participation and 18 items to assess the perceived importance of respective areas of life. The SPI shows very good overall reliability (Cronbach's α = .920) and good validity.ConclusionThis study provides a new psychometrically tested participation self‐assessment scale for adolescence with and without disabilities and/or chronic diseases. Further research is needed to re‐evaluate its psychometric properties and to evaluate the application of the SPI in clinical and scientific contexts.
Learning whom not to trust across early and middle adolescence: A longitudinal neuroimaging study to trusting behavior involving an uncooperative other
Authors: Schreuders E. , van Buuren M. , Walsh R. J. , Sijtsma H. , Hollarek M. , Lee N. C. , Krabbendam L. 
Published: August 2023

AbstractLongitudinal changes in trusting behavior across adolescence and their neural correlates were examined. Neural regions of interest (ROIs) included the medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (dACC), left anterior insula (AI), bilateral ventral striatum (VS), and right dorsal striatum (DS). Participants (wave 1 age: M = 12.90) played the investor in a Trust Game with an uncooperative trustee three times (1‐year interval). Analyses included 77 primarily Dutch participants (33 females). Participants decreased their investments with wave. Furthermore, activity was heightened in mPFC, dACC, and DS during investment and repayment, and in right VS (investment) and AI (repayment). Finally, DS activity during repayment increased with wave. These findings highlight early–middle adolescence as an important period for developing sensitivity to uncooperative behavior.
Who's the winner? Children's math learning in competitive and collaborative scenarios
Authors: Fish Lesenia R. , Hildebrand Lindsey , Chernyak Nadia , Cordes Sara 
Published: August 2023

AbstractGames are frequently used to promote math learning, yet the competitive and collaborative contexts introduced by games may exacerbate gender differences. In this study, 1st and 2nd grade children in the U.S. (ages 5–8; N = 274; 70% White, 15% Asian, 2% Black, 1% Native American, 14% mixed or other race; 17% Hispanic) played either a competitive, collaborative, or solo game to learn about a challenging novel math concept: proportion. Overall, both social contexts boosted perseverance and task attitudes. However, analyses revealed the competitive condition yielded gender differences in attention to proportion in the presence of competing cues, with older boys underperforming in the competition condition. Potential explanations for these findings, as well as implications for classroom math learning, are discussed.
Trajectories of parents' gendered play attitudes during early childhood and implications for children's gender development
Authors: Rogers Adam A. , Shawcroft Jane , Stockdale Laura A. , Coyne Sarah M. , Fraser Ashley M. 
Published: August 2023

AbstractThis study examined associations between parents' gendered attitudes about play and children's gender development. The sample was 501 families from a large US city followed annually for 4 years (501 mothers, 383 fathers; 69% White, 16% Latinx, 8% African American; children Mage = 5.67 months, 53% boys). Latent trajectories examined change in parents' attitudes toward same‐ and other‐gender play during first 4 years of the child's life. On a subsample (n = 252), trajectories were examined in relation to children's later gender‐typed preferences and gender constancy. Parents grew more gender‐flexible in their attitudes, particularly parents of boys. Trajectories reflecting more stereotypic attitudes showed some associations (small in magnitude) with children's gender‐typed preferences and gender constancy by age 4.