bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot implementation of an electronic diagnostic support tool (AiD‐DST) designed to identify the cause(s) of delirium
Authors: Leong Elizabeth , Chang Stephane , Yearwood Kristi , Eeles Eamonn , Yerkovich Stephanie , Ling Carolina , Teodorczuk Andrew , Dissanayaka Nadeeka 
Published: February 2025

AbstractObjective(s)The identification of cause(s) of delirium remains a clinical challenge within medicine. Our group have previously successfully developed and tested the Aetiology in Delirium—Decision Support Tool (AiD‐DST). The AiD‐DST is designed to help medical professionals close the gap on the detection of cause(s) of delirium. Here, we report on use of AiD‐DST in the real‐world setting.MethodsA real‐world implementation study of the AiD‐DST within a general medical ward of a metropolitan hospital was conducted over a 10‐week period. A mixed method evaluation was performed based upon the RE‐AIM Framework that incorporates reach, effectiveness, adoption, implementation and maintenance of an intervention.ResultsReach: fifty‐three out of 87 (61%) eligible doctors consented to participation in the study. Effectiveness: A mean of 4.3 diagnoses were generated per patient with no difference in frequency when compared with historical control (z = 1.36; p = .17). Average usability score was 5.86 (SD = 1.15) on a 7‐point scale, with 93% of respondents being satisfied with the AiD‐DST. Free text feedback comprised themes of accessibility, ergonomics, diagnostic accuracy and applicability of AiD‐DST to related conditions. Implementation: Instrument completion rate was 98% (n = 49/50), with a median completion time of 90 s. Maintenance: Sixty‐seven % of uses of AiD‐DST occurred in the second half of the study (p = .3). Following the initiation period there was an increase in use (r = .79; p = 02).ConclusionProof of principle was demonstrated for local implementation of a diagnostic support tool (AiD‐DST).
The Role of Medical Student Quality Improvement Projects in Health Care: A Scoping Review
Authors: Stubbs Casey , Ward Bernadette 
Published: February 2025

ABSTRACTIntroductionAcross Australia, there is considerable variation in the quality of health care and the risk of associated complications. Hence, many patients are receiving poor‐quality care. This may be exacerbated in rural and remote areas where the availability of health care is relatively limited. Addressing this requires a multipronged approach that supports the workforce. Involving medical practitioners in medical students' quality improvement (QI) scholarly projects may be one strategy to assist with bridging this gap. The aim of this review was to synthesise the evidence relating to medical students' compulsory curriculum‐based quality improvement projects and associated practice outcomes.MethodScoping review of peer‐reviewed literature (January 2000–June 2024).ResultsOf the 239 articles, six empirical studies from Australia, New Zealand, the UK and the USA were included. Half of these were based in community settings and the rest in hospitals. Only one was in a rural setting. The time allocated to projects was between 5 and 12 weeks. Five of the six studies reported that student project recommendations had been implemented. One study reported that the process enhanced doctors' adherence to best practice guidelines.DiscussionMuch of the research about the outcomes of medical student curriculum‐based projects focuses on research outputs. These relatively short student QI projects are one strategy to improve evidence‐based practice while upskilling clinicians. Further work is needed to examine their impact, particularly in rural areas.ConclusionIntegrating medical students into ‘real‐world’ QI health service projects can enhance the quality of health care whilst building the skills of the medical workforce.
Is No difference a good outcome? Equity evaluation of the general surgery prioritization tool
Authors: Wood Douglas , Findlay Nohoana , Kim Alice Hyun Min , Behar Kfyr‐Eyal , Lin Anthony 
Published: February 2025

AbstractBackgroundThe general surgery prioritization tool (GSPT) was implemented in 2018 to equitably prioritize non‐cancer elective general surgery waitlists. It combines patient‐reported Impact On Life (IOL) scores and clinician‐reported values for a total score which determines access to the waitlist. In New Zealand there are inequities in surgical access and outcomes, particularly for Māori, and this study evaluates whether the GSPT may contribute.MethodA retrospective review of general surgery prioritization events at Capital & Coast District Health Board, New Zealand, between May 2018 and August 2022 was conducted. The patient‐reported IOL score (6–36), total score (0–100), waitlist access, and time to surgery in days were recorded and analyzed for ethnic, age and gender differences.Results4527 events were included. Median IOL score and total score were 20 and 68. 4231 (90.8%) met the waitlist threshold with a median time to surgery of 99 days. Higher average IOL scores were associated with being female (P = 0.005), Pacific Peoples (P = 0.007) and Other Ethnicity (P = 0.006). The average total score for Māori was 1.13 points higher than Europeans (P = 0.013). There was no evidence of associations between the odds of surgery booking and patient age, ethnicity and gender when adjusted for deprivation and procedure type.ConclusionThis study shows that despite differences in the IOL and total scores across ethnicity, no evidence of difference was found in the odds of surgical booking based on patient ethnicity, age or gender. Amendments to weighting of IOL scores and ethnicity score adjustment could be considered to remedy this.
How I treat iron‐refractory iron deficiency anaemia—An expert opinion‐based treatment guidance for children and adults
Authors: Hoving V. , Donker A. E. , Schols S. E. M. , Swinkels D. W. 
Published: February 2025

SummaryIron‐refractory iron deficiency anaemia (IRIDA) is a rare hereditary microcytic anaemia characterized by partial or complete resistance to oral iron supplementation, caused by elevated plasma hepcidin levels resulting from pathogenic variants in the TMPRSS6 gene. Although intravenous iron supplementation is often effective, patient responses can vary significantly due to various factors, and potential side effects of this treatment remain unclear. Additionally, evidence‐based international guidelines for diagnosing and managing IRIDA are lacking. This review aims to provide patient‐tailored treatment strategies, informed by case studies and expert opinion, to address the specific therapeutic needs of both children and adults with IRIDA.
Stratigraphic Controls on CO2 Migration at Sleipner: An Example From a Basin‐Floor Fan of the Utsira Formation
Authors: Warchoł Michał Jakub , Pontén Anna , Furre Anne‐Kari 
Published: February 2025

ABSTRACTFor nearly three decades, Equinor's Sleipner Carbon Capture and Storage project has demonstrated how the application of geological principles, modelling techniques and analysis of repeated time‐lapse (4D) seismic data has helped to characterise the CO2 plume migration within the late Miocene–early Pliocene Utsira Formation. However, the influence of stratigraphic complexity on fluid migration has been rather poorly understood. This has resulted in a significant degree of uncertainty in the geological characterisation of the storage formation, including the distribution of mudstone‐rich elements, which may serve as baffles and barriers for migration of fluid, and elements that allow for their bypass. Our study, utilising high‐quality 3D seismic data integrated with wireline‐logs, time‐lapse seismic and regional contextual information, has shown that the Utsira Formation in the South Viking Graben represents a confined, channelized submarine fan system characterised by a complex stratigraphic architecture. The study has highlighted that the intricate interplay between fan lobes, channel erosion, channel infill and draping of lobes, lobe‐complexes and channel incision surfaces by mud‐rich layers, provides a first‐order control on CO2 storage compartments and exerts a substantial influence on vertical and lateral fluid flow pathways. The latter is well expressed by the morphology of several mapped CO2‐filled layers. Both generally discontinuous channel‐base mud‐rich drapes and more continuous lobe‐complex and fan mudstone drapes have been locally compromised by processes linked to channel erosion and sand injection, in some cases combined with faulting and fracturing. This complex stratigraphic pattern has probably been exacerbated by post‐depositional deformation that triggered fluid and sediment expulsion from the Utsira Formation and the underlying early‐Miocene Skade Formation. These factors allowed for increased vertical connectivity between originally disconnected sandstone bodies and fluid migration from deeper to shallower layers, prior to injection of CO2, thus serving as preferred pathways post‐injection.
Integrating early response biomarkers in pharmacokinetic models: A novel method to individualize the initial infliximab dose in patients with Crohn's disease
Authors: Samuels Abigail , Irie Kei , Mizuno Tomoyuki , Reifenberg Jack , Punt Nieko , Vinks Alexander A. , Minar Phillip 
Published: February 2025

AbstractThe use of model‐informed precision dosing to personalize infliximab has been shown to improve both the acquisition of concentration targets and clinical outcomes during maintenance. Current iterations of infliximab pharmacokinetic models include time‐varying covariates of drug clearance, however, not accounting for the expected improvements in the covariates can lead to indiscriminate use of higher infliximab doses and imprecise drug exposure. The aim was to identify changes in the four biomarkers associated with infliximab clearance (Xiong et al. model) and determine if integration of these dynamic changes would improve model performance during induction and early maintenance. We analyzed two cohorts of children receiving infliximab for Crohn's Disease. The Emax method was used to assess time‐varying changes in covariates. Model performance (observed vs. predicted infliximab concentrations) was evaluated using median percentage error (bias) and median absolute percentage error (precision). The combined cohorts included 239 Crohn's disease patients. We found from baseline to dose 4, the maximum changes in weight, albumin, erythrocyte sedimentation rate, and neutrophil CD64 were 4.7%, +11.7%, −62.4%, and −26.5%, respectively. We also found the use of baseline covariates alone to forecast future trough concentration was inferior to the Emax time‐varying method with a significant improvement observed in bias (doses 2, 3, and 4) and precision (doses 2 and 4). The integration of the four time‐varying biomarkers of drug clearance with pharmacokinetic modeling improved the accuracy and precision of the predictions. This novel strategy may be key to improving drug exposure, minimizing indiscriminate dosing strategies, and reducing healthcare costs.
The epilepsy–autism phenotype associated with developmental and epileptic encephalopathies: New mechanism‐based therapeutic options
Authors: Specchio Nicola , Di Micco Valentina , Aronica Eleonora , Auvin Stéphane , Balestrini Simona , Brunklaus Andreas , Gardella Elena , Scheper Mirte , Taglialatela Maurizio , Trivisano Marina , Curatolo Paolo 
Published: February 2025

AbstractEpilepsy and autism often co‐occur in genetic developmental and epileptic encephalopathies (DEEs), but their underlying neurobiological processes remain poorly understood, complicating treatment. Advances in molecular genetics and understanding the neurodevelopmental pathogenesis of the epilepsy–autism phenotype may lead to mechanism‐based treatments for children with DEEs and autism. Several genes, including the newly reported PPFIA3, MYCBP2, DHX9, TMEM63B, and RELN, are linked to various neurodevelopmental and epileptic disorders, intellectual disabilities, and autistic features. These findings underscore the clinical heterogeneity of genetic DEEs and suggest diverse neurobiological mechanisms influenced by genetic, epigenetic, and environmental factors. Mechanisms linking epilepsy and autism include γ‐aminobutyric acidergic (GABAergic) signaling dysregulation, synaptic plasticity, disrupted functional connectivity, and neuroinflammatory responses. GABA system abnormalities, critical for inhibitory neurotransmission, contribute to both conditions. Dysregulation of the mechanistic target of rapamycin (mTOR) pathway and neuroinflammation are also pivotal, affecting seizure generation, drug resistance, and neuropsychiatric comorbidities. Abnormal synaptic function and connectivity further underscore the epilepsy–autism phenotype. New treatment options targeting specific mechanisms linked to the epilepsy–autism phenotype are emerging. Genetic variants in potassium channel genes like KCNQ2 and KCNT1 are frequent causes of early onset DEEs. Personalized treatments like retigabine and quinidine have been explored with heterogeneous responses. Efforts are ongoing to develop more effective KCNQ activators and KCNT1 blockers. SCN1A genetic variants, particularly in Dravet syndrome, show potential for treatment of autistic symptoms with low‐dose clonazepam, fenfluramine, and cannabidiol, although human trials have yet to consistently replicate animal model successes. Early intervention before the age of 3 years, particularly in SCN1A‐ and tuberous sclerosis complex‐related DEEs, is crucial. Additionally, targeting the mTOR pathway shows promise for seizure control and managing epilepsy‐associated comorbidities. Understanding the distinct autism spectrum disorder phenotype in DEEs and implementing early behavioral interventions are essential for improving outcomes. Despite genetic advances, significant challenges persist in diagnosing and treating DEE‐associated epilepsy–autism phenotypes. Future clinical trials should adopt precision health approaches to improve neurodevelopmental outcomes.
Pharmacokinetic variability and use of therapeutic drug monitoring of cannabidiol in patients with refractory epilepsy
Authors: Johannessen Landmark Cecilie , Sætre Johan , Gottås André , Wolden Martha , McQuade Tao Angell‐Petersen , Kjeldsen Signe Flood , Våtevik Anne , Sætre Erik , Svendsen Torleiv , Burns Margrete Larsen , Øiestad Elisabeth Leere , Johannessen Svein I. 
Published: February 2025

AbstractObjectiveCannabidiol (CBD) (Epidyolex) is a new antiseizure medication (ASM) for rare and severe epileptic syndromes. We aimed to investigate the pharmacokinetic variability of CBD to elucidate relationships between doses, serum concentrations, metabolites, and biochemical markers of toxicity by using therapeutic drug monitoring (TDM) data.MethodsData on serum concentrations of all ASMs, CBD, and the active metabolite 7‐hydroxy‐cannabidiol (7‐OH‐CBD) were collected (January 2022 to June 2023) at the Section for Clinical Pharmacology, National Centre for Epilepsy, Oslo University Hospital.ResultsData from 52 patients were included: 122 serum concentration measurements (1–7 per patient); 48% female, mean age 23 (range 3–55) years. At maintenance (n = 34), the mean daily dose was 535 (SD 224) mg, that is, 10.03 (standard deviation [SD] .49) mg/kg/day, serum concentration .26 (SD .14) for CBD and .13 (SD .10) μmol/L for 7‐OH‐CBD. Reference ranges of .15–.50 μmol/L for CBD and .04–.25 μmol/L for 7‐OH‐CBD are proposed, which included 80% of measurements. There was a linear correlation between CBD dose to concentration and CBD to CBD‐7‐OH concentrations (r2 = .39 and .38) (p < .05). The hepatic marker alanine aminotransferase (ALT) increased on average 37%, demonstrating a moderate effect on liver function. Intra‐individual coefficients of variation (CVs) were 32% (SD 17) for CBD and 48% (SD 24) for 7‐OH‐CBD (n = 15, ≥3 measurements). Twenty different ASMs were used: clobazam (n = 24), valproate (n = 17), and stiripentol (n = 8) were most common. The mean concentration ratio of desmethyl‐clobazam/clobazam increased by 140% (7.29–17.5; p < .05) but was variable, pointing to enzyme inhibition by CBD.SignificanceThis observational study with TDM data revealed extensive pharmacokinetic variability of CBD in patients with refractory epilepsy. The results demonstrate the need for close follow‐up and use of TDM, including biochemical markers of toxicity, for individualized treatment with CBD.
Enlarged perivascular space in the temporal lobe as a prognostic marker in temporal lobe epilepsy with hippocampal sclerosis
Authors: Cho Soomi , Song Seungwon , Yum Jungyon , Kim Eun Hwa , Roh Yun Ho , Kim Won‐Joo , Heo Kyoung , Na Han Kyu , Kim Kyung Min 
Published: February 2025

AbstractObjectiveThis study was undertaken to investigate the regional burden of enlarged perivascular spaces (EPVSs) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS) and explore its prognostic relevance.MethodsIn this retrospective observational study, EPVSs in the temporal lobe (T‐EPVS), centrum semiovale (CS‐EPVS), basal ganglia (BG‐EPVS), midbrain, and hippocampus were visually rated in 68 treatment‐naïve patients with TLE‐HS. Regional EPVS burden was dichotomized into high and low degrees (cutoff: >10 for BG‐EPVS/T‐EPVS; >20 for CS‐EPVS). Cox proportional hazards models were used to determine the potential predictors of seizure freedom (SF; no seizure for >1 year) and delayed SF (SF achieved >6 months after initiating antiseizure medication [ASM]). Multivariate logistic regression using stepwise variable selection based on the Akaike information criterion was performed to investigate whether EPVS burden was associated with medical refractoriness (never achieving SF).ResultsOf the 68 patients, 20 were classified into the refractory group (29.4%). The high T‐EPVS group had an older epilepsy onset (37.3 ± 12.3 vs. 26.5 ± 13.0 years, p = .005), higher pretreatment seizure density (median = 12.0, interquartile range [IQR] = 5.0–20.0 vs. 4.0, IQR = 2.0–10.5, p = .008), and lower focal to bilateral tonic–clonic seizure prevalence (13.3% vs. 73.6%, p < .001) than the low T‐EPVS group. High T‐EPVS burden (odds ratio [OR] = 10.908, 95% confidence interval [CI] = 1.895–62.789) was an independent predictor of medial refractoriness, along with female sex (OR = 12.906, 95% CI = 2.214–75.220) and ASM treatment duration (OR = .985, 95% CI = .971–.999). The low T‐EPVS group had higher probability of achieving delayed SF than the high T‐EPVS group (pLog‐rank = .030, pCox regression = .038), whereas the probability of achieving SF was comparable between the two groups (pLog‐rank = .053, pCox regression = .146).SignificanceIncreased T‐EPVS burden may serve as an imaging marker of unfavorable prognosis in patients with TLE‐HS, underscoring the potential role of perivascular dysfunction in diminished ASM response.
The Role of Fibroblasts in Chronic Inflammatory and Proliferative Skin Diseases
Authors: Zang Rui , Xu Chen‐Chen , Fan Zhu , Wang Qing‐Nan , Guo Zi‐Jian , Liu Li , Cui Bing‐Nan , Huang Yuan‐Yuan , Yang Jiao 
Published: February 2025

ABSTRACTFibroblasts (FBs) are crucial mesenchymal cells that preserve the skin's natural structure and physiological processes. They can build dense connective tissue by remodelling the extracellular matrix (ECM) and control immunological activity by secreting cytokines. This indicates that the development of chronic inflammatory and proliferative skin disorders is significantly influenced by fibroblasts. In order to provide new ideas for clinical research and treatment with a clearer perspective, this study thoroughly compiles the involvement of fibroblasts in various chronic inflammatory and proliferative skin diseases such as psoriasis, hypertrophic scar (HS), keloid, atopic dermatitis (AD), oral lichen planus (OLP), chronic eczema, and rosacea.
Study on laser ablation quality and removal mechanism of SiCf/SiC composites by wavelength and thermal effect equation
Authors: Song Juan , Wang Bangfu , Jiang Qingyang , Hao Xiaohong 
Published: February 2025

AbstractSiCf/SiC composites exhibit exceptional material properties, rendering them ubiquitous in aerospace, high‐end automotive, and other advanced applications. However, these composites pose processing challenges due to their high hardness, brittleness, anisotropy, as well as heterogeneity. To investigate the material removal mechanisms and processing quality during picosecond laser ablation of SiCf/SiC composites, this study conducted linear scanning ablation experiments employing picosecond pulse lasers. The experiments were followed by a detailed analysis of the surface morphology, and elemental composition of the grooves under varying laser parameters. The findings reveal that laser power, scanning speed, repetition rate, and scanning duration exert a profound influence on the postablation groove characteristics. Specifically, as laser power increases, the groove width and depth broaden, accompanied by an expansion in both the ablation area and the heat‐affected zone. During laser irradiation of SiCf/SiC composites, the chemical bonds within the matrix and fibers undergo disruption, initiating oxidation reactions, and the formation of oxides. The oxides primarily manifest as solid SiO, SiO2, and gaseous CO and CO2. Furthermore, this article introduces a graphical model that elucidates the material removal mechanism by using laser. Collectively, this research provides a theoretical foundation and technical guidance to achieve high performance cutting of SiCf/SiC composites.
Impact of heat treatment on microstructure and tensile strength of monofilaments and bundles of aluminosilicate fibers
Authors: Liu Yang , Wu Yadan , Chen Xiaofei , Sun Xun , Liu Haitao 
Published: February 2025

AbstractContinuous alumina fiber serves as the reinforcement phase within the Al2O3/oxide composite system, and its behavior at elevated temperatures significantly influences the mechanical properties of the composite. This study focuses on a novel type of continuous aluminosilicate fiber (AF18) to investigate the effects of heat treatment temperature (ranging from 1100°C to 1400°C) and duration (2/4/8 h) on the microstructure and mechanical properties of the monofilament. Acknowledging that fibers typically exist in bundles within the composite material, the study further examines the changes in tensile strength of these bundles following heat treatment at various temperatures. The findings indicate that both the heat treatment temperature and duration contribute to an increase in grain size and an enhancement in the surface roughness of the fiber, with the temperature having a more pronounced effect than the duration. The tensile strength of the original fiber monofilament is measured at 2.08 GPa, while the tensile strength of the tow exhibits a reduction of approximately 10% compared to the monofilament, with the degree of attenuation correlating with the heat treatment conditions. Notably, with 8 h of heat treatment at 1200°C, the fiber retains approximately 70% of its tensile strength, demonstrating its capacity for long‐term temperature resistance.