bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically Based Pharmacokinetic Modeling of Cannabidiol, Delta‐9‐Tetrahydrocannabinol, and Their Metabolites in Healthy Adults After Administration by Multiple Routes
Authors: Qian Lixuan , Zhang Tao , Dinh Jean , Paine Mary F. , Zhou Zhu 
Published: January 2025

ABSTRACTThe two most extensively studied cannabinoids, cannabidiol (CBD) and delta‐9‐tetrahydrocannabinol (THC), are used for myriad conditions. THC is predominantly eliminated via the cytochromes P450 (CYPs), whereas CBD is eliminated through both CYPs and UDP‐glucuronosyltransferases (UGTs). The fractional contributions of these enzymes to cannabinoid metabolism have shown conflicting results among studies. Physiologically based pharmacokinetic (PBPK) models for CBD and THC and for drug–drug interaction studies involving CBD or THC as object drugs were developed and verified to improve estimates of these contributions. First, physicochemical and pharmacokinetic parameters for CBD, THC, and their metabolites (7‐OH‐CBD, 11‐OH‐THC, and 11‐COOH‐THC) were obtained from the literature or optimized. Second, PBPK base models were developed for CBD and THC after intravenous administration. Third, beginning with the intravenous models, absorption models were developed for CBD after oral and oromucosal spray administration and for THC after oral, inhalation, and oromucosal spray administration. The full models well‐captured the area under the concentration–time curve (AUC) and peak concentration (Cmax) of CBD and THC from the verification dataset. Predicted AUC and Cmax for CBD and 7‐OH‐CBD were within two‐fold of the observed data. For THC, 11‐OH‐THC, and 11‐COOH‐THC, 100%, 100%, and 83% of the predicted AUC values were within two‐fold, respectively, of the observed values; 100%, 92%, and 94% of the predicted Cmax values, respectively, were within two‐fold of the observed values. The verified models could be used to help address critical public health needs, including assessing potential drug interaction risks involving CBD and THC.
Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting
Authors: Jiang Xu , Cha Jun Seok , Jin Byung Hak , Kim Choon Ok , Chae Dongwoo 
Published: January 2025

ABSTRACTGranulocyte colony‐stimulating factor (G‐CSF) mobilizes peripheral blood (PB) progenitor cells from bone marrow (BM) into circulation for PB stem cell transplantation (PBSCT). This study aimed to develop a population pharmacokinetic–pharmacodynamic (PK‐PD) model of filgrastim in healthy subjects to optimize PB CD34+ cell collection. Plasma filgrastim concentrations and CD34+ cell count data were obtained from a clinical study involving healthy Korean subjects. A total of 1378 plasma concentration measurements and 982 CD34+ cell count data collected from 53 subjects were used in the PK‐PD model. Filgrastim PKs were adequately described by a one‐compartment linear disposition model with an additional transit compartment for absorption. Log‐transformed body weight was the only significant covariate affecting the volume of distribution and clearance. CD34+ cell mobilization was best captured by a modified Friberg model, assuming continual entry of proliferating BM stem cells into PB via a single transit compartment. Simulation results suggested that the 5 μg/kg twice‐daily dosing regimen may yield higher CD34+ cell counts compared to the 10 μg/kg once‐daily regimen for achieving target CD34+ cell counts of 20/μL and 50/μL. We successfully developed a robust PK‐PD model of G‐CSF that optimizes the yield of CD34+ cells during allogeneic PBSCT. This model can guide the efficient determination of optimal G‐CSF dosing regimens and CD34+ cell harvesting strategies.
A Patient With Concurrent Hidradenitis Suppurativa and Porokeratosis Palmaris et Plantaris Disseminata: Case Report and Review of Autoinflammatory Keratinization Diseases
Authors: Rogers Meredith C. , Ash Mark , Hernandez Amanda , Hosler Gregory A. 
Published: January 2025

ABSTRACTThe term autoinflammatory keratinization diseases (AIKDs) was recently proposed as a unifying concept for diseases characterized by inflammation in the epidermis and upper dermis which leads to hyperkeratosis, caused by genetic perturbations of the innate immune system. We present a case of a patient with hidradenitis suppurativa and porokeratosis, two AIKDs, followed by a review of these conditions as well as other AIKDs. This case was distinguished by hypertrophic porokeratoses involving cystic hair follicles, showing histopathologic features of both conditions within single biopsy specimens. The patient's course was additionally complicated by SCC arising within a porokeratosis. Our case demonstrates a rare overlap of two AIKDs, occurring not only within the same patient but also within the same lesions.
The cardio‐metabolic protein profile is associated with development of type 2 diabetes at long term follow‐up after gestational diabetes mellitus: Results from the OGFUS study
Authors: Hallig Simone J. , Aalders Jori , Christensen Maria H. , Andersen Marianne S. , Vinter Christina A. , Dunne Fidelma , Højlund Kurt , Jensen Dorte M. , Overgaard Martin 
Published: January 2025

AbstractAimsWomen with previous gestational diabetes mellitus (GDM) have an increased risk for later development of type 2 diabetes. During pregnancy, GDM affects the cardio‐metabolic protein profile; however, it is unknown how GDM affects the cardio‐metabolic protein profile in the long term and if it is associated with type 2 diabetes after GDM. We hypothesise that the cardio‐metabolic protein profile is affected long term and is associated with the development of type 2 diabetes after GDM.Materials and MethodsA case–control follow‐up study based on the Odense GDM Follow‐Up Study (OGFUS) cohort, which included women with previous GDM (n = 128) and matched controls without previous GDM (n = 70). Blood samples from a follow‐up assessment 8–10 years after delivery were analysed using a 29‐plex panel of apolipoproteins, transport and inflammation/immune proteins using multiple‐reaction‐monitoring mass spectrometry.ResultsApolipoprotein A‐I, D and M were significantly lower in women with previous GDM compared to controls (all p < 0.001), while apolipoprotein L‐I, H, vitamin D binding protein, CRP, vitronectin, transthyretin and complement factors 3 and B were significantly higher (p = 0.008, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, respectively). All associations remained significant after adjustment for multiple testing except CRP, whereas apolipoprotein D, vitronectin and complement factors 3 and B were associated with the development of type 2 diabetes in women with previous GDM (p = 0.02, p = 0.001, p < 0.001, p = 0.004, respectively).ConclusionsThe cardio‐metabolic protein profile 8–10 years after pregnancy is altered in women with previous GDM. Apolipoprotein D, vitronectin and complement factors 3 and B are candidate risk markers of type 2 diabetes after GDM pregnancy.
Understanding Happiness Amidst COVID‐19: Exploring Relations, Religion and Trust
Authors: Ruberto Matteo A. , Gioeli Giulia , Rizzolli Matteo , Maruotti Antonello 
Published: January 2025

ABSTRACTIn recent literature, various social implications arising from the COVID‐19 pandemic have been extensively deliberated upon. In this study, we introduce an ordinal random effects model designed to explore the changes in individual perceived happiness during periods of lockdown. We delve into the impact of diverse factors such as social and family relationships, spirituality, religiosity, and trust in institutions, alongside a range of demographic and economic variables. Our data set comprises responses from 1212 individuals in the United States gathered between March and April 2020. The findings reveal an anticipated decline in overall happiness during the COVID‐19 crisis, particularly noticeable within specific demographic and behavioural segments: social connections, trust, and religiosity exhibit nuanced variations, contingent upon the level of spirituality and the specific institutions under consideration.
Inoculation and conservation of the biocontrol agent European earwig in Washington pear orchards
Authors: Orpet Robert J. , Curtiss R. T. , Catron Katlyn A. , DuPont S. Tianna , Beers Elizabeth H. , Nottingham Louis B. 
Published: January 2025

AbstractEuropean earwig, Forficula auricularia L. sensu lato (Dermaptera: Forficulidae), is a univoltine, resident, omnivorous species and a beneficial predator in pome fruit orchards. Here, three methods were used to investigate pear (Pyrus communis L., Rosaceae) orchard inoculation with European earwig for biocontrol of pear psylla, Cacopsylla pyricola (Foerster) (Hemiptera: Psyllidae), in Washington State, USA. The first method was earwig inoculation experiments. In a first experiment (2019–2020), each of three orchards had one inoculation and one control plot. In a second experiment (2020–2021), there were four inoculation and four control plots in each of the same three orchards. In both experiments, earwigs persisted during the year of inoculation, but earwigs were nearly absent the following season at two orchards that used conventional broad‐spectrum pesticides. At the third orchard, which excluded broad‐spectrum pesticides under an integrated pest management (IPM) program, earwigs became abundant in year two of the second experiment. The second method was case studies. In the first of two case studies, during 2016, 2017, 2022, and 2023, in half of the integrated orchard from above, conventional broad‐spectrum sprays were used. Earwig populations became low in the conventional half. In the second case study, earwigs became abundant after inoculation of an integrated orchard by the grower. Earwigs spread to the edge of the orchard in year two and spilled into a neighboring orchard in years three and four. The third method was an observational study of 36 pear orchards over 5 years. Earwigs were rarely found in conventionally sprayed orchards, and earwigs increased each additional year integrated management was used. The findings suggest conventional pear spray programs in Washington nearly eradicate earwigs, but populations can recover under integrated management with natural dispersal from refuges or with inoculative releases.
Carotid endarterectomy and the risk of perioperative stroke: The importance of chronic ischaemic lesions and small vessel disease
Authors: Törmänen Henrietta , Koskinen Suvi , Nuotio Krista , Vikatmaa Pirkka , Kovanen Petri T. , Soinne Lauri , Lindsberg Perttu J. , Ijäs Petra 
Published: January 2025

AbstractBackground and purposePerioperative stroke is a well‐recognized complication of carotid endarterectomy (CEA), but well‐performing prediction models do not exist for it. Our aim was to identify novel predictors for perioperative ischaemic cerebrovascular events (iCVEs), emphasizing cerebrovascular imaging and potential biomarkers for stroke in carotid stenosis (CS) patients in a well‐characterized prospective CS cohort.MethodsHelsinki Carotid Endarterectomy Study 2 is an observational prospective and consecutive cohort study of CS patients subjected to CEA during 2012–2015. The associations between perioperative stroke and transient ischaemic attack (iCVEs) and potential predictive factors were evaluated by univariate and Cox regression analyses.ResultsOf 488 operated CS patients, 33 (7%) sustained an iCVE including 21 (4%) ischaemic strokes. In univariate analysis, moderate ipsilateral CS (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.08–4.23), covert or chronic ipsilateral brain infarct in imaging (HR 2.27, 95% CI 1.09–4.76) and severe cerebral small vessel disease (HR 3.36, 95% CI 1.04–10.88) appeared as novel risk factors for perioperative iCVE. In Cox proportional hazards regression modelling, female gender (HR 3.03, 95% CI 1.30–7.04), a history of coronary heart disease (HR 3.59, 95% CI 1.52–8.47), covert or chronic ipsilateral infarct (HR 2.32, 95% CI 1.01–5.34) and severe small vessel disease (HR 2.63, 95% CI 1.07–6.47) were the strongest independent predictors of perioperative iCVE.ConclusionsIn addition to the previously reported clinical risk factors, it was found that imaging markers of past cerebrovascular disease, covert or chronic ipsilateral infarct and severe small vessel disease, and moderate ipsilateral stenosis are associated with perioperative iCVEs.
Are my learners advanced?: Using measures of complexity and accuracy to analyze L2 Spanish writing
Authors: Mangold Marie 
Published: January 2025

AbstractOne of the critiques of proficiency as defined by scales, such as that of ACTFL, is its lack of grounding in linguistic realities. Measures of complexity, accuracy, and fluency provide a route in which proficiency can be quantitatively measured by identifying linguistic correlates (see Brown et al., 2017; Long et al., 2012). This project aimed to identify the linguistic correlates that distinguish L2 Spanish writing at intermediate‐high and advanced‐low proficiency levels as defined by the Language Ability Self‐Evaluation Resource. Forty writing samples comprised the data. Measures of lexical complexity (density and diversity), syntactic complexity (mean length of T‐unit, number of clauses per T‐unit, average length of error‐free T‐unit), and accuracy (ratio of error‐free T‐unit, number of errors per 100 words) were used to analyze the samples. Findings suggest that accuracy is the linguistic feature that best distinguishes intermediate from advanced proficiency in L2 Spanish writing. The implications of these findings for research and pedagogy are examined.
Z‐Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis
Authors: Mishra Sanchita , Dey Ayushi Amin , Kesavardhana Sannula 
Published: January 2025

ABSTRACTZ‐nucleic acid binding protein 1 (ZBP1) is an innate immune sensor recognizing nucleic acids in Z‐conformation. Upon Z‐nucleic acid sensing, ZBP1 triggers innate immune activation, inflammation, and programmed cell death during viral infections, mice development, and inflammation‐associated diseases. The Zα domains of ZBP1 sense Z‐nucleic acids and promote RIP‐homotypic interaction motif (RHIM)‐dependent signaling complex assembly to mount cell death and inflammation. The studies on ZBP1 spurred an understanding of the role of Z‐form RNA and DNA in cellular and physiological functions. In particular, short viral genomic segments, endogenous retroviral elements, and 3′UTR regions are likely sources of Z‐RNAs that orchestrate ZBP1 functions. Recent seminal studies identify an intriguing association of ZBP1 with adenosine deaminase acting on RNA‐1 (ADAR1), and cyclic GMP‐AMP synthase (cGAS) in regulating aberrant nucleic acid sensing, chronic inflammation, and cancer. Thus, ZBP1 is an attractive target to aid the development of specific therapeutic regimes for disease biology. Here, we discuss the role of ZBP1 in Z‐RNA sensing, activation of programmed cell death, and inflammation. Also, we discuss how ZBP1 coordinates intracellular perturbations in homeostasis, and Z‐nucleic acid formation to regulate chronic diseases and cancer.
Leaving no one behind: Gender inequality, economic inequality, and organizational entrenchment of nurses in remote areas of Egypt
Authors: Eweida Rasha Salah , Mohamed Hamad Nagwa Ibrahim , Abdelrahman Mahitab Mohamed , Shalhoub Abdullah Abdulrahman Bin , Elsmalosy Mohamed Farag Awad , Othman Ahmed Abdellah , Atta Mohamed Hussein Ramadan 
Published: January 2025

AbstractAimThis study investigates the association between gender inequality, economic inequality, and organizational entrenchment among nurses serving in remote areas.BackgroundEgypt ranks low in gender equity across the Middle East and North Africa (MENA) region. In the culture of nursing, gender‐based discrimination is among the factors that can further hamper nurses' economic advancement and adversely affect organizational entrenchment.MethodsA multicenter cross‐sectional correlational design followed the “Improving the reporting of observational studies in epidemiology” (STROBE) checklist. The nurses' personal characteristics data sheet, perceived economic inequality scale, workplace gender discrimination scale, and career entrenchment scale were used to gather data from 760 nurses' who participated voluntarily in this study.ResultsPerceived economic inequality and workplace gender discrimination were both negatively associated with career entrenchment, with perceived economic inequality (B = –0.517, Beta = –0.155, p < 0.001) and workplace gender discrimination (B = –0.798, Beta = –0.180, p < 0.001). Additionally, workplace gender discrimination was positively related to perceived economic inequality (B = 0.770, Beta = 0.580, p < 0.001). The correlations between the variables were strong, with workplace gender discrimination and perceived economic inequality showing a significant positive correlation (r = 0.580, p < 0.01). At the same time, both had negative correlations with career entrenchment (r = –0.270, p < 0.01 for workplace gender discrimination and r = –0.259, p < 0.01 for perceived economic inequality).ConclusionGender discrimination and economic inequality are significant risk factors for decreased career entrenchment.
Effect of 2‐Way Social Support and Social Networks on the General Well‐Being of Older Adults: A Latent Profile Analysis
Authors: Tao Jingrui , Dai Shimeng , Xu Qiongying , Zhang Yao , Chen Xuewei , Dong Chaoqun 
Published: January 2025

ABSTRACTAimsTo examine the profiles of general well‐being in older adults and their related sociodemographic characteristics and to explore the association of these profiles with 2‐way social support and social networks.DesignThis was a cross‐sectional study.MethodsIn total, 411 older adults were recruited through convenience sampling from Zhejiang Province, southeast China. Each completed questionnaires on Sociodemographic Characteristics, General Well‐being Schedule, Brief 2‐Way Social Support Scale, and Lubben Social Network Scale. Latent profile analysis was used to categorise participants into distinct subgroups based on their general well‐being. Chi‐square and t‐tests were used for univariate analysis, and binary logistic regression was used to identify influencing factors.ResultsThe latent profile analysis identified two distinct profiles of well‐being in older adults: a low general well‐being group and a high general well‐being group. Binary logistic regression revealed that living arrangements, physical activity, number of chronic diseases, provision of instrumental support and friend networks significantly impact the general well‐being of older adults.ConclusionHeterogeneity in general well‐being levels exists among older adults, necessitating targeted intervention measures tailored to the different characteristics of each subgroup to enhance their support resources and well‐being.Implications for the Profession and/or Patient CareCommunity nurses should identify general well‐being disparities among older adults and craft targeted strategies as educators, providers, counsellors and managers to boost and equalise this demographic's general well‐being.ImpactDistinct profiles of general well‐being among older adults, coupled with the positive effects of friend networks and the provision of social support, highlight the importance of mutual social support and networks in promoting healthy ageing. This may encourage community nurses to develop specific initiatives and programmes aimed at enhancing social engagement among older adults.Reporting MethodThe study followed the STROBE guidelines for cross‐sectional studies.Patient or Public ContributionNo patient or public contribution.
Imaging malaria parasites across scales and time
Authors: Guizetti Julien 
Published: January 2025

AbstractThe idea that disease is caused at the cellular level is so fundamental to us that we might forget the critical role microscopy played in generating and developing this insight. Visually identifying diseased or infected cells lays the foundation for any effort to curb human pathology. Since the discovery of the Plasmodium‐infected red blood cells, which cause malaria, microscopy has undergone an impressive development now literally resolving individual molecules. This review explores the expansive field of light microscopy, focusing on its application to malaria research. Imaging technologies have transformed our understanding of biological systems, yet navigating the complex and ever‐growing landscape of techniques can be daunting. This review offers a guide for researchers, especially those working on malaria, by providing historical context as well as practical advice on selecting the right imaging approach. The review advocates an integrated methodology that prioritises the research question while considering key factors like sample preparation, fluorophore choice, imaging modality, and data analysis. In addition to presenting seminal studies and innovative applications of microscopy, the review highlights a broad range of topics, from traditional techniques like white light microscopy to advanced methods such as superresolution microscopy and time‐lapse imaging. It addresses the emerging challenges of microscopy, including phototoxicity and trade‐offs in resolution and speed, and offers insights into future technologies that might impact malaria research. This review offers a mix of historical perspective, technological progress, and practical guidance that appeal to novice and advanced microscopists alike. It aims to inspire malaria researchers to explore imaging techniques that could enrich their studies, thus advancing the field through enhanced visual exploration of the parasite across scales and time.
Changes in Youth Mental Health Following a School Lockdown due to Violent and Firearm‐Related Threats
Authors: Hullenaar Keith L. , Fisher Benjamin W. , Zatzick Douglas F. , Rivara Frederick P. 
Published: January 2025

ABSTRACTBackgroundSchool shooting events and lockdowns have increased in the United States, raising concerns about their impact on youth mental health.MethodThis study assessed the association between school lockdowns and changes in youth mental health in 10,049 children who participated in the Adolescent Brain and Cognitive Development study. The exposure was school lockdowns related to violence and shooting incidents, and the outcomes were Child Behavior Checklist scores on five mental health disorders.ResultsApproximately 20.3% of children reported ever experiencing a school lockdown with 39.3% of these lockdowns occurring in the past year. Past‐year lockdown exposure (versus no lockdown exposure) was associated with increased symptoms of anxiety disorders (β = 0.20, 95% CI: 0.01, 0.38), somatic disorders (β = 0.23, 95% CI: 0.09, 0.38), and stress problems (β = 0.30, 95% CI: 0.05, 0.56). Among children who reported a past‐year lockdown, those indicating clinical ranges of ADHD (OR = 2.23, 95% CI: 1.17, 4.25) or stress problems (OR = 2.75, 95% CI: 1.05, 7.25) had higher odds than their counterparts of reporting that the lockdown had a lot/some impact (versus little/no impact).Implications for School Health Policy, Practice, and EquityEmergency preparedness in schools should prioritize mental health support post‐lockdowns.ConclusionsResearch and funding are needed to understand the nature, frequency, and consequences of school lockdowns.