bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic connexin 43‐hemichannels aggravate seizures by modulating blood‐brain barrier permeability in temporal lobe epilepsy mice
Authors: Song Honghong , Li Yi , Liu Jiayu , Bai Xianshu , Jiang Li , Li Tingsong 
Published: August 2024

AbstractThe involvement of astrocytic connexin 43 (Cx43) in epileptogenesis has been extensively studied through various approaches, yet the underlying mechanism remains enigmatic. In this study, we explored whether astrocytic Cx43 forms hemichannels (HCs) that contribute to seizure progression in temporal lobe epilepsy (TLE) in mice. We focused on how these HCs influence the permeability of the blood‐brain barrier (BBB), a crucial factor in the pathophysiology of epilepsy. Immunofluorescence staining and western blot analysis were employed to assess Cx43 expression in kainic acid‐induced TLE mice, while BBB permeability was evaluated in TLE mice and those treated with TAT‐Gap19 (an astrocytic Cx43 HC inhibitor) using Evans Blue permeation, serum S100β protein quantification, ZO‐1 expression, and albumin extravasation into brain parenchyma via western blotting. Furthermore, seizure burden was monitored continuously using telemetric electroencephalography (EEG) and video monitoring in epileptic and TAT‐Gap19‐treated mice. Results demonstrated a significant increase in Cx43 content in hippocampal tissue in the TLE group, with a pronounced expression around blood vessels. TAT‐GAP19 treatment alleviated EEG seizures and BBB permeability in TLE mice. These findings suggest that astrocytic Cx43 HCs in the hippocampus play a crucial role in epileptogenesis and seizure progression by regulating BBB permeability. Targeting Cx43‐formed HCs distributed around the neurovascular unit may offer a novel therapeutic approach for epilepsy.
A New Validated Approach for Identifying Childhood Immunizations in Electronic Health Records in the United Kingdom
Authors: Suffel Anne M. , Walker Jemma L. , Campbell Colin , Carreira Helena , Warren‐Gash Charlotte , McDonald Helen I. 
Published: August 2024

ABSTRACTBackgroundRoutinely collected electronic health records (EHR) offer a valuable opportunity to carry out research on immunization uptake, effectiveness, and safety, using large and representative samples of the population. In contrast to other drugs, vaccines do not require electronic prescription in many settings, which may lead to ambiguous coding of vaccination status and timing.MethodologyWe propose a comprehensive algorithm to identifying childhood immunizations in routinely collected EHR. In order to deal with ambiguous coding, over‐recording, and backdating in EHR, we suggest an approach combining a wide range of medical codes in combination to identify vaccination events and using appropriate wash‐out periods and quality checks. We illustrate this approach on a cohort of children born between 2006 and 2014 followed up to the age of five in the Clinical Practice Research Datalink (CPRD) Aurum, a UK primary care dataset of EHR, and validate the results against national estimates of vaccine coverage by NHS Digital and Public Health England.ResultsOur algorithm reproduced estimates of vaccination coverage, which are comparable to official national estimates and allows to approximate the age at vaccination. Electronic prescription data only do not cover vaccination events sufficiently.ConclusionOur new proposed method could be used to provide a more accurate estimation of vaccination coverage and timing of vaccination for researchers and policymakers using EHR. As with all observational research using real‐world data, it is important that researchers understand the context of the used dataset used and the clinical practice of recording.
A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug–Drug Interactions in Women With Epilepsy
Authors: Muschett Matthew R. , Ewig Celeste , Morris Earl , Adkins Lauren E. , Goodin Amie , Brown Joshua 
Published: August 2024

ABSTRACTPurposeConcomitant use of hormonal contraceptive agents (HCAs) and enzyme‐inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs.MethodsRelevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE‐II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs.ResultsA total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long‐acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long‐acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long‐acting injectables and contraceptive implants.ConclusionsTo mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long‐acting injectable contraceptives should be evidence‐based.
Leftover of Amoxicillin Suspension After Use by Children in the Netherlands
Authors: Sadreghaemy Milad , Gamba Magdalena A. , Bloem Lourens T. , Egberts Toine C. G. 
Published: August 2024

ABSTRACTPurposeIn clinical practice, a discrepancy may exist between the prescribed amount of a drug and the commercially available pack sizes in the pharmacy, potentially contributing to drug waste. This study aimed—as an example of this phenomena—to quantify leftover of amoxicillin suspension prescribed to children, due to discrepancies between physician‐prescribed and pharmacy‐dispensed amounts.MethodsWe performed a retrospective cohort study including amoxicillin suspension dispensations for patients aged 0–12 years between 2017 and 2019 utilizing the Dutch PHARMO database. Leftover amount of amoxicillin was estimated by assessing the discrepancy between the prescribed and dispensed amounts. Extrapolated amoxicillin weight and economic spillage estimates for the Netherlands were determined. The impact of two theoretical interventions on leftover amount was assessed: (1) introducing vials with half the volume of the current 100 and 30 mL vials and (2) a combination of the first intervention with a maximum of 10% round‐down by the dispensing pharmacy of the prescribed dose.ResultsWe included 79 512 amoxicillin suspension dispensations for 62 252 patients. The mean leftover amount of amoxicillin suspension per dispensing was 27%. The yearly amount of amoxicillin leftover was 49.8 kg in the study cohort, equivalent to yearly 633 kg and €621 000 when extrapolated to the Netherlands. Employing the first theoretical intervention reduced the mean leftover per dispensing to 20%, reducing the yearly leftover to 31.6 kg amoxicillin in the study cohort, and to 400 kg and €400 000 extrapolated. The second theoretical intervention further reduced leftover to 17%, reducing the yearly leftover to 24.3 kg amoxicillin in the study cohort, and to 300 kg and €300 000 extrapolated.ConclusionApproximately a quarter of amoxicillin suspension remains as leftover per dispensing. Applying different theoretical intervention shows the potential for a significant reduction of amoxicillin leftover.
Studying the Impact of European Union Regulatory Interventions for Minimising Risks From Medicines: Lessons Learnt and Recommendations
Authors: Goedecke Thomas , Martirosyan Liana , Gault Nathalie , Seifert Karin , Morales Daniel R. , Bahri Priya , Strassmann Valerie , Huber Martin , Straus Sabine 
Published: August 2024

ABSTRACTPurposeThe European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) launched a strategy to examine the public health impact of major regulatory interventions aimed at minimising risks of medicinal products. We conducted a lessons learnt analysis of impact studies completed between 2015 and 2023.MethodsWe surveyed PRAC Sponsors and (Co‐)Rapporteurs involved in the evaluation of 12 impact studies (10 commissioned by EMA and 2 conducted collaboratively by Member States) to explore how these support regulatory decision‐making. Questions covered achievement of study objectives, risk minimisation effectiveness, added value for regulatory decision‐making, and recommendations for future impact studies. Themes were generated using thematic content analysis.ResultsSurvey responses from 15 PRAC Sponsors and (Co‐)Rapporteurs from 10 European Union Member States were included in the analysis. Among four cross‐sectional surveys and eight drug utilisation studies, 50% achieved all objectives, the other studies partially due to limitations. Two studies concluded that risk minimisation measures were overall effective, two were effective with variation across countries, two were partially effective and four studies showed limited effectiveness. Two studies were deemed inconclusive due to limitations. The reasons for the limited effectiveness of risk minimisation may be explored using mixed‐method approaches. Assessment of study feasibility and a priori discussion of effectiveness measurements is important.ConclusionDespite limitations, impact research adds value to regulatory decision‐making by addressing knowledge gaps and providing additional information on unintended consequences of regulatory interventions. Our recommendations will help to improve planning, conducting and interpretating future impact studies.
The Effect of Sodium Glucose Cotransporter‐2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis
Authors: Wang Tiansheng , Ji Dongze , Stürmer Til , Ismail Sherin , Dong Shujie , Shen Peng , Lin Hongbo , Shi Luwen , Guan Xiaodong , Xu Yang 
Published: August 2024

ABSTRACTPurposeThe role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter‐2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long‐term HbA1c variability.MethodsUsing 2018–2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis.ResultsWith a median follow‐up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64–0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were −16.67% (95% CI: −27.71% to −5.62%) and −1.98% (95% CI: −14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses.ConclusionsCompared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.
Analysis of Longitudinal Patterns and Predictors of Medicine Use in Residential Aged Care Using Group‐Based Trajectory Modeling: The “MEDTRAC‐Cardiovascular” Longitudinal Cohort Study
Authors: Wabe Nasir , Timothy Andrea , Urwin Rachel , Xu Ying , Nguyen Amy , Westbrook Johanna I. 
Published: August 2024

ABSTRACTAimCardiovascular diseases are the leading cause of death globally. Ensuring ongoing use of medicines—medication persistence—is crucial, yet no prior studies have examined this in residential aged care facilities (RACFs). We aimed to identify long‐term trajectories of persistence with cardiovascular medicines and determine predictors of persistence trajectories.MethodA longitudinal cohort study of 2837 newly admitted permanent residents from 30 RACFs in New South Wales, Australia. We monitored weekly exposure to six cardiovascular medicine classes—lipid modifiers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs), beta‐blockers, diuretics, calcium channel blockers (CCB), and cardiac therapy—over 3 years. Group‐based trajectory modeling was employed to determine persistence trajectories for each class.ResultsAt baseline, 76.6% (n = 2172) received at least one cardiovascular medicine with 41.2% receiving lipid modifiers, 31.4% ACEI/ARBs, 30.2% beta‐blockers, 24.4% diuretics, 18.7% CCBs, and 14.8% cardiac therapy. The model identified two persistence trajectories for CCBs and three trajectories for all other classes. Sustained high persistence rates ranged from 68.4% (ACEI/ARBs) to 79.8% (beta‐blockers) while early decline in persistence and subsequent discontinuation rates ranged from 7.6% (cardiac therapy) to 25.3% (CCBs). Logistic regressions identified 11 predictors of a declining persistence across the six medicine classes.ConclusionOur study revealed varied patterns of cardiovascular medicine use in RACFs, with 2–3 distinctive medicine use trajectories across different classes, each exhibiting a unique clinical profile, and up to a quarter of residents discontinuing a medicine class. Future studies should explore the underlying reasons and appropriateness of nonpersistence to aid in identifying areas for improvement.
Nutritional quality of photosynthetically diverse crops under future climates
Authors: Walsh Catherine A. , Lundgren Marjorie R. 
Published: August 2024

SummarySocietal Impact StatementClimate change continues to intensify the challenges of food production as agricultural systems face more variable and extreme weather. Coupled with increasing human population, growers must balance increasing crop yields with nutrient content to prevent global malnutrition. Photosynthetic diversity may permit some crops to tolerate climate change and elevated CO2 whilst maintaining both crop yield quantity and quality. This review examines how photosynthetic diversity interacts with crop production and nutritional stability under elevated CO2 and climate change, and highlights opportunities for photosynthetic diversity to inspire agricultural solutions.SummaryInnovative agricultural solutions are desperately needed to achieve food security for a growing human population amidst the imminent pressures of climate change that threaten more variable and extreme weather, placing additional pressures on already precarious agricultural systems. Not only are crop yields at risk under climate change but rising global atmospheric CO2 concentrations are concurrently driving a carbon dilution effect that threatens to reduce the nutritional quality of our crops to further global malnutrition. Plants using different photosynthetic metabolisms, however, experience these negative impacts to yield and nutrition to different degrees. Thus, photosynthetic diversity may offer solutions to combat malnutrition under climate change and elevated CO2 concentrations, whether that be through targeting existing resilient species for agricultural programmes or applying agricultural biotechnology to engineer photosynthetic diversity into existing crops. Here, we discuss how each major photosynthetic type is predicted to fare under elevated CO2 concentrations and climate change and explore agricultural opportunities to maintain both yield and nutrient stability.
Fuzzy Gravity: Four‐Dimensional Gravity on a Covariant Noncommutative Space and Unification with Internal Interactions
Authors: Roumelioti Danai , Stefas Stelios , Zoupanos George 
Published: August 2024

AbstractIn the present work, an extended description of the covariant noncommutative space is presented, which accommodates the Fuzzy Gravity model constructed previously. It is based on the historical lesson that the use of larger algebras containing all generators of the isometry of the continuous one helped in formulating a fuzzy covariant noncommutative space. Specifically a further enlargement of the isometry group leads the authors, in addition to the construction of the covariant noncommutative space, also to the suggestion of the group that should be gauged on such a space in order to construct a Fuzzy Gravity theory. As a result, two Fuzzy Gravity models are obtained, one in de Sitter and one in anti‐de Sitter space, depending on the extension of the isometry group, and their spontaneous symmetry breaking leading to fuzzy versions of the noncommutative gravity are discussed. In addition, how to introduce fermions in the fuzzy gravity is discussed for the first time, and even more importantly, how to unify the constructed noncommutative‐fuzzy gravity with internal interactions based on or as grand unified theories.
Characterization of an RR‐2 cuticle protein DcCP8 and its potential application based on SPc nanoparticle‐wrapped dsRNA in Diaphorina citri
Authors: Lu Zhan‐Jun , Xia Tao , Zhang Can , He Qing , Zhong Hong , Fu Shang‐Cheng , Yuan Xiao‐Fang , Liu Xiao‐Qiang , Liu Ying‐Xue , Chen Wei , Yi Long , Yu Hai‐Zhong 
Published: August 2024

AbstractBACKGROUNDThe insect cuticle consists of chitin fibers and a protein matrix, which plays an important role in protecting the body from invasion of various pathogens and prevents water loss. Periodic synthesis and degradation of the cuticle is required for the growth and development of insects. Key genes involved in cuticle formation have long been considered a potential target for pest control.RESULTSIn this study, a member of the RR‐2 subfamily of cuticular protein 8 (DcCP8) was identified from the Diaphorina citri genome database. Immunofluorescence analysis suggested that DcCP8 was mainly located in the Diaphorina citri exocuticle and can be induced to up‐regulate 12 h following 20‐hydroxyecdysone (20E) treatment. Silencing of DcCP8 by RNA interference (RNAi) significantly disrupted the metamorphosis to the adult stage, and improved the permeability of the cuticle. Transmission electron microscopy (TEM) analysis revealed that the synthesis of the exocuticle was impressed after silencing of DcCP8. Furthermore, the recombinant DcCP8 protein exhibited chitin‐binding properties in vitro, down‐regulation of DcCP8 significantly inhibited expression levels of chitin metabolism‐related genes. Additionally, a sprayable RNAi method targeting DcCP8 based on star polycation (SPc) nanoparticles‐wrapped double‐stranded RNA (dsRNA) significantly increased Diaphorina citri mortality. Transcriptome sequencing further confirmed that genes associated with the endocytic pathway and immune response were up‐regulated in Diaphorina citri after SPc treatment.CONCLUSIONSThe current study indicated that DcCP8 is critical for the formation of Diaphorina citri exocuticles, and lays a foundation for Diaphorina citri control based on large‐scale dsRNA nanoparticles. © 2024 Society of Chemical Industry.
Spin Polarization Measurement in SERF Comagnetometer Based on Phase‐Frequency Response of Magnetic Field
Authors: Cai Ze , Liu Feng , Du Pengcheng , Zhang Kai , Yuan LinLin , Fan Wenfeng , Lei Xusheng , Quan Wei 
Published: August 2024

AbstractThis work presents an innovative approach for measuring the spin polarizations of coupled atomic ensembles in spin‐exchange relaxation‐free (SERF) comagnetometers, using the phase‐frequency response of the magnetic field. The zero‐phase point in the phase‐frequency response of the magnetic field along the ‐axis is examined to determine the deceleration factor and electronic magnetic field. Ultimately, the spin polarizations of electrons and noble‐gas atoms are calculated. The method is applied to test vapor cells with different parameters under various temperatures and pumping light intensities. The measurement errors caused by transverse electron relaxation of electronic spin polarization and nuclear spin polarization are 5.59% and 1.95% under high polarization, and 8.06% and 2.62% under low polarization. The measurement method features minimal impact on nuclear spin polarization and wide applicability compared to other methods, making it more applicable and suitable for SERF comagnetometers. This method has great significance in better understanding the system state of the SERF comagnetometer and improving its sensitivity.
Effect of processing on protein solubility of Chlorella sorokiniana dispersions
Authors: Li Ruifen , Mejdahl Tove Kristine Byskov , Jørgensen Maria Louise , Corredig Milena , Gregersen Sandra Beyer 
Published: August 2024

AbstractPotential exists in the utilization of Chlorella biomass as a source for food ingredients, due to an increased demands for more environmentally friendly sources of high‐quality proteins. This study investigated the protein solubility of white Chlorella sorokiniana dry powders, containing either whole cells or homogenized cells as a function of pH. The effect of different cell disruption methods was evaluated. The results demonstrated that protein solubility can be improved by resuspending the powder at alkaline pH (pH 8). The highest solubility was achieved for the homogenized powder, which reached approximately 18% protein at pH 8 compared to a value of 8% at its original pH (pH 4.6). High intensity ultrasonication and high‐pressure homogenization increased protein extraction efficiency, while pre‐heating at 40°C did not have any significant effects. Overall, the results demonstrate how the design of the processing can aid in ensuring higher protein solubility, and contribute to facilitating the potential utilization of chlorella biomass as a protein source.