bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics of cannabidiol and the impact of food and formulation on systemic exposure in children with drug‐resistant developmental and epileptic encephalopathies
Authors: Brstilo Lucas , Valenzuela Gabriela Reyes , Ibarra Manuel , Guido Paulo Cáceres , Bressan Ignacio , Marin Nora , Delaven Sandra Fabiana , Agostini Silvana , Montilla Carlos Pérez , López María Emilia , Cresta Araceli , Armeno Marisa , Bournissen Facundo García , Caraballo Roberto , Schaiquevich Paula 
Published: January 2025

AbstractObjectiveIdentifying factors influencing cannabidiol (CBD) exposure can optimize treatment efficacy and safety. We aimed to describe the population pharmacokinetics of CBD in children with drug‐resistant developmental and epileptic encephalopathies (DEEs) and assess the influence of environmental, pharmacological, and clinical characteristics on CBD systemic exposure.MethodsData from two pharmacokinetic studies of patients aged 2–18 years with DEEs were included (N = 48 patients). Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6 h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast. CBD plasma concentrations were also available following administration of a CBD‐enriched formulation. Samples were quantified using a validated liquid chromatography/tandem mass spectrometry assay. A CBD population pharmacokinetic model was developed using nonlinear mixed‐effects modeling. The effects of formulation, concomitant food intake, and demographic, clinical, and pharmacological factors on CBD pharmacokinetics were evaluated. Simulated maximum plasma concentration (Cmax) and area under the concentration–time curve between 0 and 12 h (AUC0‐12) were calculated.ResultsA one‐compartment model with transit compartments and first‐order elimination best described CBD pharmacokinetics. Mean values for CBD apparent clearance (CL/F) and volume of distribution (V/F) were 143.5 L/h and 1892.4 L, respectively. Weight was allometrically scaled for V/F and CL/F, sex was associated with V/F, and both formulation and food condition were associated with F (relative bioavailability). CBD Cmax increased by 41% and AUC0‐12 by 45% when CBD was administered with food compared to fasting. Dose‐normalized AUC0‐12 was approximately 50% lower with CBD‐enriched oil compared to purified CBD.SignificanceIn the present study, we described the effects of food and formulation on CBD exposure in children with DEEs. Increased CBD exposure with food intake and significant changes in drug exposure when switching between CBD formulations should be considered in patient management.
Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy
Authors: Verdoodt Fien , Bhatti Sofie F. M. , Molina Jenifer , Van Ham Luc , Vanhaecke Lynn , Junius Greet , Hemeryck Lieselot Y. , Hesta Myriam 
Published: January 2025

AbstractObjectiveIdiopathic epilepsy (IE) is the most common chronic neurological disease in dogs and an established natural animal model for human epilepsy types with genetic and unknown etiology. However, the metabolic pathways underlying IE remain largely unknown.MethodsPlasma samples of healthy dogs (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 121 known target metabolites) and fingerprinted (n = 1825 untargeted features) using liquid chromatography coupled to mass spectrometry. Dogs with IE were classified as mild phenotype (MP; n = 22) or drug‐resistant (DR; n = 27). All dogs received the same standard adult maintenance diet for a minimum of 20 days (35 ± 11 days) before sampling. Data were analyzed using a combination of univariate (one‐way analysis of variance or Kruskal–Wallis rank sum test), multivariate (limma, orthogonal partial least squares–discriminant analysis), and pathway enrichment statistical analysis.ResultsIn dogs with both DR and MP IE, a distinct plasma metabolic profile and fingerprint compared to healthy dogs was observed. Metabolic pathways involved in these alterations included oxidative stress, inflammation, and amino acid metabolism. Moreover, significantly lower plasma concentrations of vitamin B6 were found in MP (p = .001) and DR (p = .005) compared to healthy dogs.SignificanceOur data provide new insights into the metabolic pathways underlying IE in dogs, further substantiating its potential as a natural animal model for humans with epilepsy, reflected by related metabolic changes in oxidative stress metabolites and vitamin B6. Even more, several metabolites within the uncovered pathways offer promising therapeutic targets for the management of IE, primarily for dogs, and ultimately for humans.
Bridging the health information gap among undergraduate university students: The role of academic libraries
Authors: Kwafoa Paulina Nana Yaa , Filson Christopher K. , Tachie‐Donkor Gloria , Atuase Diana , Nunekpeku Paul 
Published: January 2025

AbstractBackgroundAlthough university students are young and seem generally healthy, they do have health information needs that affect their academic work. Some university healthcare services and academic libraries collaborated during the COVID‐19 pandemic to provide health information to students.Aims/ObjectivesThe study explored the health information gap among undergraduate students in universities in Ghana.MethodologyThe study involved 382 students from the University of Cape Coast, the University of Ghana, and Kwame Nkrumah University of Science and Technology, including nine librarians and six university health professionals. Respondents for the study were chosen using stratified sampling and purposeful sampling techniques. A questionnaire and a semi‐structured interview guide were used to collect the data.ResultsThe study revealed limited access to health information for undergraduate students. Male and female students had similar high priorities (personal hygiene, disease prevention, healthy living, mental health) but reproductive health information was mostly a priority for female students.DiscussionInadequate access to health information among undergraduate students may pose a threat to avoidable health risks and academic productivity.ConclusionBased on the findings, a functional Collaborative Health Information Model for Academic Libraries and University Healthcare Systems is proposed to address undergraduate students' health information needs.
Temporal Trends in Respiratory Infection Epidemics Among Pediatric Inpatients Throughout the Course of the COVID‐19 Pandemic From 2018 to 2023 in Fukushima Prefecture, Japan
Authors: Kume Yohei , Hashimoto Koichi , Okabe Hisao , Norito Sakurako , Suwa Reiko , Kawase Miyuki , Mochizuki Izumi , Mashiyama Fumi , Ishibashi Naohisa , Suzuki Shigeo , Sakuma Hiroko , Shirato Kazuya , Hosoya Mitsuaki , Go Hayato 
Published: January 2025

ABSTRACTBackgroundNonpharmaceutical interventions for coronavirus disease (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2, during the pandemic altered the epidemiology of respiratory viruses. This study aimed to determine the changes in respiratory viruses among children hospitalized from 2018 to 2023.MethodsNasopharyngeal specimens were collected from children aged under 15 years with fever and/or respiratory symptoms admitted to a medical institution in Fukushima Prefecture between January 2018 and December 2023. Eighteen respiratory viruses were detected using real‐time reverse transcription‐polymerase chain reaction.ResultsOverall, 1933 patients were included. Viruses were detected in 1377 (71.2%); of these, a single virus was detected in 906 (46.9%) and multiple viruses in 471 (24.3%). Among the viruses whose epidemics were temporarily suppressed, the epidemics of respiratory syncytial virus A and human parainfluenza virus type 3 (HPIV3) started earlier, and the epidemics of human metapneumovirus, HPIV1, and influenza A and C viruses resumed as behavioral restrictions for preventing COVID‐19 eased. The median age of children with airway infection was significantly higher in the postpandemic group than in the prepandemic group (18.0 months vs. 21.0 months, p < 0.01). The median age of children infected with HPIV3 and human rhinovirus was significantly higher in the postpandemic group than in the prepandemic group.ConclusionsStrengthening of nonpharmaceutical interventions changed the epidemic dynamics of pediatric infectious diseases, with a trend toward older hospitalized children. Continuous monitoring of pediatric infectious disease outbreaks in hospitalized children can help prepare for the emergence of future viruses and pandemics.
A Design School for Social Innovation: Reflections on a Pilot Case in Japan
Authors: Akasaka Fumiya , Oura Fuko , Watanabe Kentaro 
Published: January 2025

AbstractThe paradigm of design must drastically change to promote sustainable social development that considers not only economic growth but also human well‐being and environmental sustainability. Some scholars argue that the central paradigm of design should focus more on the societal perspective. This article refers to such a socially oriented design approach as design for social innovation (DfSI). Our study identified key insights for designing and promoting a DfSI education programme by investigating and analysing a Japanese pilot case, the Design School at National Institute of Advanced Industrial Science and Technology (AIST‐DS). Based on an analysis of in‐depth interviews that we conducted with the AIST‐DS programme managers and learners, we clarified the effectiveness and challenges of the programme. Furthermore, this article presents relevant design considerations for better planning and promotion of the DfSI education programme. Our case study findings are derived from a deep and detailed analysis, with practical implications for educators and researchers. Simultaneously, from an academic perspective, we hope that these findings will constitute a foothold for accumulating knowledge on DfSI education in the future.
ERK1/2 gene expression and hypomethylation of Alu and LINE1 elements in patients with type 2 diabetes with and without cataract: Impact of hyperglycemia‐induced oxidative stress
Authors: Zeinali Nia Elham , Najjar Sadeghi Ruhollah , Ebadi Mostafa , Faghihi Mohammad 
Published: January 2025

ABSTRACTAimsThis study aimed to delineate the effect of hyperglycemia on the Alu/LINE‐1 hypomethylation and in ERK1/2 genes expression in type 2 diabetes with and without cataract.MethodsThis study included 58 diabetic patients without cataracts, 50 diabetic patients with cataracts, and 36 healthy controls. After DNA extraction and bisulfite treatment, LINE‐1 and Alu methylation levels were assessed using Real‐time MSP. ERK1/2 gene expression was analyzed through real‐time PCR. Total antioxidant capacity (TAC), and fasting plasma glucose (FPG) were measured using colorimetric methods. Statistical analysis was performed with SPSS23, setting the significance level at P < 0.05.ResultsThe TAC levels were significantly lower for cataract and diabetic groups than controls (259.31 ± 122.99, 312.43 ± 145.46, 372.58 ± 132.95 nanomole of Trolox equivalent) with a significant correlation between FPG and TAC levels in both the cataract and diabetic groups (P < 0.05). Alu and LINE‐1 sequences were found to be statistically hypomethylated in diabetic and cataract patients compared to controls. In these groups, TAC levels were directly correlated with Alu methylation (P < 0.05) but not LINE‐1. ERK1/2 gene expression was significantly higher in diabetic and cataract patients, showing increases of 2.41‐fold and 1.43‐fold for ERK1, and 1.27‐fold and 1.5 for ERK2, respectively. ERK1 expression correlated significantly with FPG levels. A reverse correlation was observed between TAC levels and ERK1/2 expression.ConclusionsOur findings indicate that hyperglycemia‐induced oxidative stress may alter ERK1/2 gene expression patterns and induce aberrant hypomethylation in Alu and LINE‐1 sequences. These aberrant changes may play a contributing role in diabetic complications such as cataracts.
Identification of Novel and Rare GNAS Mutations in Craniofacial Fibrous Dysplasia
Authors: Xue Jiang , Zhang Jianyun , Ma Ming , Li Xuefen , Sun Lisha , Shi Ruirui , Li Tiejun 
Published: January 2025

ABSTRACTBackgroundFibrous dysplasia (FD), caused by activating mutations of GNAS, is a skeletal disorder with considerable clinicopathological heterogeneity. Although prevalent mutations such as R201C and R201H dominate in FD, a limited number of rare mutations, including R201S, R201G, and Q227L, have been documented. The scarcity of information concerning these uncommon mutations motivates our investigation, seeking to enhance comprehension of this less‐explored subgroup within FD.MethodsThis study introduces three cases of craniofacial FD exhibiting rare GNAS mutations. Employing DNA sequencing on fresh frozen lesion tissues, we conducted a thorough analysis of clinical, radiological, and pathological features, delving into genotypic and phenotypic correlations. A comparative assessment with our previous series was also conducted.ResultsIn the subset of patients subjected to DNA sequencing, a novel GNAS missense mutation (Q227E) was identified in one case, while a rare GNAS mutation (R201S) in exon 8 was found in the other two patients. Although no apparent phenotypic distinctions were observed among those with GNAS hotspot mutations (R201C, R201H), a more severe phenotype was discerned in the case featuring the novel GNAS mutation Q227E.ConclusionsThis study marks the first report of the Q227E mutation in the GNAS gene associated with bone disease, enriching our understanding of FD's genetic basis and shedding light on the clinicopathological heterogeneity of craniofacial FD.
Incidence and Risk Factors of Peri‐Implantitis Over Time—A Prospective Cohort Study
Authors: Romandini Mario , Lima Cristina , Banaco Diogo , Azevedo Rita , Sanz Mariano 
Published: January 2025

ABSTRACTAimThis prospective cohort study aimed to evaluate the incidence and risk/protective factors of peri‐implantitis over time.MethodsA university‐representative cohort was evaluated at baseline and after a mean follow‐up time of 3.9 years. The main outcome was the incidence of peri‐implantitis, defined as bone loss > 1 mm between the two examinations in implants showing bleeding on probing. Putative risk/protective factors assessed at baseline were tested through multilevel (mixed‐effects) logistic regression analyses.ResultsA total of 73 patients with 322 implants were included. During the follow‐up period, 14 implants (4.3%) were lost in 9 patients (12.3%). Incidence of peri‐implantitis was observed in 22.2% of patients and 9.4% of implants. In the final multilevel multiple logistic regression model, the following factors were associated with occurrence of peri‐implantitis: periodontitis severity (stage IV periodontitis: OR = 41.29; 95% CI: 4.10–415.54), periodontal bone loss/age ratio (> 1: OR = 8.87; 95% CI: 1.47–53.73), smoking (current smokers: OR = 7.84; 95% CI: 1.83–33.50), sleep duration (> 7 h: OR = 19.97; 95% CI: 1.69–236.39), implant location (incisor: OR = 60.60; 95% CI: 4.04–908.33), restoration type (full‐arch fixed restorations: OR = 89.84; 95% CI: 3.66–2202.97), and restoration margin location (juxta‐marginal: OR = 14.17; 95% CI: 1.20–166.76). Keratinized tissue width assessed at baseline was not associated with incidence of peri‐implantitis.ConclusionApproximately one in five patients and one in 10 implants experienced incident peri‐implantitis over a nearly four‐year period. Periodontitis (Stage IV and Grade C), lifestyles (smoking and sleep duration), implant location, and prosthetic factors (restoration type and margin location) emerged as risk factors for peri‐implantitis.
Retrospective analysis of the incidence and clinicopathological findings associated with ammonium urate urolithiasis in dogs with congenital portosystemic shunts: 363 cases (2010‐2023)
Authors: Walton‐Clark M. , Travail V. , Sparks T. , Eiras‐Diaz A. , Davenport A. , Holmes A. , Kent A. , Prior C. , Stilwell Breakspear C. , Dye C. , Good C. , Motta C. , Valls Sanchez F. , Pilati F. , McLauchlan G. , Ruiz G. , Brás I. , Scott J. , Clarke K. , Peak K. , Goonan L. , Ots M. , Rossell Garcia M. , Lau N. , Mansbridge N. , Garcia Dominguez P. , Conway S. , Keyte S. , Chapman T. , Conley T. , Black V. , Coates V. , DiBella A. 
Published: January 2025

ObjectivesTo assess the incidence and clinical findings associated with the presence of ammonium urate urolithiasis in dogs with congenital portosystemic shunts.Materials and MethodsA retrospective review of dogs diagnosed with extrahepatic portosystemic shunts or intrahepatic portosystemic shunts in 15 referral hospitals between 2010 and 2023. Data including signalment, clinical signs, physical examination findings and clinicopathologic test results at the time of the diagnosis were collected, and the presence of ammonium urate urolithiasis was recorded.ResultsA total of 363 dogs were included. The overall incidence of ammonium urate urolithiasis was 19.3%. Dogs with extrahepatic portosystemic shunts were more likely to have urolithiasis compared to those with intrahepatic portosystemic shunts (32.2% vs. 8.0%). Dogs with urolithiasis were older (median 40 vs. 8 months) and more likely to be neutered males (51.4% vs. 9.8%). Ammonia was significantly lower in dogs with urolithiasis. Dogs with urolithiasis were more likely to have haematuria on dipstick analysis and sediment examination.Clinical SignificanceDogs with extrahepatic portosystemic shunts were more likely to have urolithiasis when compared to dogs with intrahepatic portosystemic shunts. Dogs with higher ammonia levels were less likely to have ammonium urate urolithiasis, and older dogs, neutered males, or those with evidence of haematuria had an increased incidence of urolithiasis.
High‐Frequency Instruments and Identification‐Robust Inference for Stochastic Volatility Models
Authors: Ahsan Md. Nazmul , Dufour Jean‐Marie 
Published: January 2025

ABSTRACTWe introduce a novel class of stochastic volatility models, which can utilize and relate many high‐frequency realized volatility (RV) measures to latent volatility. Instrumental variable methods provide a unified framework for estimation and testing. We study parameter inference problems in the proposed framework with nonstationary stochastic volatility and exogenous predictors in the latent volatility process. Identification‐robust methods are developed for a joint hypothesis involving the volatility persistence parameter and the autocorrelation parameter of the composite error (or the noise ratio). For inference about the volatility persistence parameter, projection techniques are applied. The proposed tests include Anderson‐Rubin‐type tests and their point‐optimal versions. For distributional theory, we provide finite‐sample tests and confidence sets for Gaussian errors, establish exact Monte Carlo test procedures for non‐Gaussian errors (possibly heavy‐tailed), and show asymptotic validity under weaker assumptions. Simulation results show that the proposed tests outperform the asymptotic test regarding size and exhibit excellent power in empirically realistic settings. The proposed inference methods are applied to IBM's price and option data (2009–2013). We consider 175 different instruments (IVs) spanning 22 classes and analyze their ability to describe the low‐frequency volatility. IVs are compared based on the average length of the proposed identification‐robust confidence intervals. The superior instrument set mostly comprises 5‐min HF realized measures, and these IVs produce confidence sets which show that the volatility process is nearly unit‐root. In addition, we find RVs with higher frequency yield wider confidence intervals than RVs with slightly lower frequency, indicating that these confidence intervals adjust to absorb market microstructure noise. Furthermore, when we consider irrelevant or weak IVs (jumps and signed jumps), the proposed tests produce unbounded confidence intervals. We also find that both RV and BV measures produce almost identical confidence intervals across all 14 subclasses, confirming that our methodology is robust in the presence of jumps. Finally, although jumps contain little information regarding the low‐frequency volatility, we find evidence that there may be a nonlinear relationship between jumps and low‐frequency volatility.
Diving Deep Into the Relationship Between Speech Fluency and Second Language Proficiency: A Meta‐Analysis
Authors: Yan Xun , Lei Yuyun , Pan Yulin 
Published: January 2025

AbstractAbundant research has indicated fluency features as meaningful predictors of second language proficiency. However, the extent to which different fluency dimensions and features can predict proficiency remains underexplored. This meta‐analysis employed a multilevel modeling approach to synthesize fluency–proficiency relationships from 71 empirical studies from 1959–2023. Additionally, we examined several moderator variables, including task type, learning context, age, and proficiency measure. The correlations found were strongly positive for speed (r = .55), moderately positive for productivity (r = .38), moderately negative for breakdown (r = −.33), and weakly negative for repair (r = −.11). Moderator analyses revealed that task, learning context, and proficiency measure influence fluency–proficiency relationships in the repair, productivity, and speed dimensions, respectively. Post hoc analyses also suggested that the operationalization of breakdown features might make a difference in fluency–proficiency relationships. This study has both theoretical and methodological implications for second language fluency research.
Liver Injury due to Intravenous Methylprednisolone in the Drug‐Induced Liver Injury Network
Authors: Ahmad Jawad , Li Yi‐Ju , Phillips Elizabeth , Dellinger Andrew , Hayashi Paul H. , Chalasani Naga , Fontana Robert J. , Kleiner David E. , Barnhart Huiman X. , Hoofnagle Jay H. ,   the Drug‐Induced Liver Injury Network
Published: January 2025

ABSTRACTBackground and AimsShort courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP‐related DILI enrolled in the US DILI Network (DILIN).MethodsDILIN cases with MP as a suspected drug were reviewed. DILIN causality scoring was assigned on a 5‐point scale (definite, highly likely, probable, possible, unlikely). All cases with MP causality scores of definite, highly likely or probable were analysed. HLA data from direct sequencing were analysed.ResultsEleven cases of definite, highly likely, or probable MP DILI were identified. The median age was 48 years; 73% were female; median latency to onset was 30 days; 55% were jaundiced; and all had hepatocellular injury with one patient requiring transplantation. Nine of the 11 cases were in patients with multiple sclerosis (MS). Liver biopsies in 7 cases revealed mild acute hepatitis with/without cholestasis. HLA data demonstrated that HLA‐DRB1*15:01, the primary HLA class II allele associated with MS was over‐represented. HLA‐DQB1*06:02‐HLA‐DQA1*01:02 which is haplotypic with the HLA‐DRB1*15 haplotype was more common in the MP DILI cases compared to other DILI controls (p = 0.03) and to DILI controls exposed to MP (p = 0.04).ConclusionMP DILI is characterised by hepatocellular injury, short latency and generally rapid recovery. There was no independent HLA haplotype associated with MP DILI.