bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular pathways of calcitonin gene‐related peptide‐induced relaxation of human coronary arteries: A key role for Gβγ subunit instead of cAMP
Authors: de Vries Tessa , Labruijere Sieneke , Rivera‐Mancilla Eduardo , Garrelds Ingrid M. , de Vries René , Schutter Dennis , van den Bogaerdt Antoon , Poyner David R. , Ladds Graham , Danser A. H. Jan , MaassenVanDenBrink Antoinette 
Published: April 2024

AbstractBackground and PurposeCalcitonin gene‐related peptide (CGRP) is a potent vasodilator. While its signalling is assumed to be mediated via increases in cAMP, this study focused on elucidating the actual intracellular signalling pathways involved in CGRP‐induced relaxation of human isolated coronary arteries (HCA).Experimental ApproachHCA were obtained from heart valve donors (27 M, 25 F, age 54 ± 2 years). Concentration–response curves to human α‐CGRP or forskolin were constructed in HCA segments, incubated with different inhibitors of intracellular signalling pathways, and intracellular cAMP levels were measured with and without stimulation.ResultsAdenylyl cyclase (AC) inhibitors SQ22536 + DDA and MDL‐12330A, and PKA inhibitors Rp‐8‐Br‐cAMPs and H89, did not inhibit CGRP‐induced relaxation of HCA, nor did the guanylyl cyclase inhibitor ODQ, PKG inhibitor KT5823, EPAC1/2 inhibitor ESI09, potassium channel blockers TRAM‐34 + apamin, iberiotoxin or glibenclamide, or the Gαq inhibitor YM‐254890. Phosphodiesterase inhibitors induced a concentration‐dependent decrease in the response to KCl but did not potentiate relaxation to CGRP. Relaxation to forskolin was not blocked by PKA or AC inhibitors, although AC inhibitors significantly inhibited the increase in cAMP. Inhibition of Gβγ subunits using gallein significantly inhibited the relaxation to CGRP in human coronary arteries.ConclusionWhile CGRP signalling is generally assumed to act via cAMP, the CGRP‐induced vasodilation in HCA was not inhibited by targeting this intracellular signalling pathway at different levels. Instead, inhibition of Gβγ subunits did inhibit the relaxation to CGRP, suggesting a different mechanism of CGRP‐induced relaxation than generally believed.
Five decades of research on immediate implant therapy: A modern bibliometric network analysis via Altmetric and level of evidence mapping
Authors: Sabri Hamoun , Manouchehri Neshatafarin , Tavelli Lorenzo , Kan Joseph Y. K. , Wang Hom‐Lay , Barootchi Shayan 
Published: April 2024

AbstractAimTo conduct a bibliometric network analysis to explore the research landscape of immediate implant placement (IIP) and provide insights into its trends and contributors.Materials and MethodsThe Scopus database was utilized as the bibliographic source, and a search strategy was implemented to identify relevant research articles. Various bibliometric parameters were extracted, including publication year, journal, authors, citations, and funding. The analysis involved examining authorship patterns, international collaborations, level of evidence, Altmetric data, and funding analysis.ResultsWe identified a steady annual growth rate of 6.49% in IIP research. The top three countries contributing to research output were the USA, Italy, and China. Prolific authors were identified based on publication and citation metrics. International collaborations among different countries were observed. The level of evidence analysis revealed that over 30% of the articles fell into higher levels of evidence (levels 1 and 2). Altmetric data analysis indicated no significant correlations between citation counts and Altmetric Attention Score (AAS), and conversely a significant association with Mendeley readers count. Funding and open access did not significantly impact the bibliometric indices of the papers.ConclusionsThe focus of research on IIP has been evolving as indicated by an exponential growth rate in this study. Only approximately 16% of the articles fit into level 1 evidence, therefore, emphasizing on higher quality level research study shortage in this field. Modern indices can be used as new bibliometric indicators as they also cover social media and online attention scores.
Deciphering the intricate linkage between the gut microbiota and Alzheimer's disease: Elucidating mechanistic pathways promising therapeutic strategies
Authors: Liang Junyi , Wang Yueyang , Liu Bin , Dong Xiaohong , Cai Wenhui , Zhang Ning , Zhang Hong 
Published: April 2024

AbstractBackgroundThe gut microbiome is composed of various microorganisms such as bacteria, fungi, and protozoa, and constitutes an important part of the human gut. Its composition is closely related to human health and disease. Alzheimer's disease (AD) is a neurodegenerative disease whose underlying mechanism has not been fully elucidated. Recent research has shown that there are significant differences in the gut microbiota between AD patients and healthy individuals. Changes in the composition of gut microbiota may lead to the development of harmful factors associated with AD. In addition, the gut microbiota may play a role in the development and progression of AD through the gut–brain axis. However, the exact nature of this relationship has not been fully understood.AimsThis review will elucidate the types and functions of gut microbiota and their relationship with AD and explore in depth the potential mechanisms of gut microbiota in the occurrence of AD and the prospects for treatment strategies.MethodsReviewed literature from PubMed and Web of Science using key terminologies related to AD and the gut microbiome.ResultsResearch indicates that the gut microbiota can directly or indirectly influence the occurrence and progression of AD through metabolites, endotoxins, and the vagus nerve.DiscussionThis review discusses the future challenges and research directions regarding the gut microbiota in AD.ConclusionWhile many unresolved issues remain regarding the gut microbiota and AD, the feasibility and immense potential of treating AD by modulating the gut microbiota are evident.
Point‐of‐care β‐hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG‐PET/CT
Authors: Hartikainen Suvi , Tompuri Tuomo , Laitinen Tiina , Laitinen Tomi 
Published: April 2024

AbstractAimsThe aims of our study were to evaluate whether point‐of‐care β‐hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac [18F]‐fluoro‐2‐deoxy‐d‐glucose‐positron emission tomography with computerized tomography (FDG‐PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging.Methods and ResultsWe recruited 193 patients with any clinical indication for whole body [18F]‐FDG‐PET/CT. BHB level was measured with a point‐of‐care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point‐of‐care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography were measured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut‐off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319).ConclusionsBHB level measured with a point‐of‐care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed.
Sleep duration and association with cardiometabolic health in adolescents and adults with type 1 diabetes: Results from the BCQR‐T1D study
Authors: Simon Stacey L. , Snell‐Bergeon Janet K. , Schäfer Michal , Barker Alex J. , Browne Lorna P. , Truong Uyen , Tell Shoshana S. , Vigers Timothy , Baumgartner Amy D. , Lyon Ellen , Polsky Sarit , Schauer Irene E. , Nadeau Kristen J. 
Published: April 2024

AbstractAimType 1 diabetes (T1D) increases the risk of morbidity and mortality from cardiovascular disease, and insufficient sleep is prevalent. Emerging evidence suggests a link between sleep and cardiometabolic health, but this has not been examined across the lifespan in individuals with T1D. We aimed to examine associations between sleep and cardiometabolic health in adolescents and adults with T1D in a secondary analysis of data from a 4‐week double‐blind, random‐order, placebo‐controlled crossover trial of bromocriptine quick release (BCQR) therapy with a 4‐week washout in between conditions.Materials and MethodsForty‐two adults (19‐60 years) and 42 adolescents (12‐18 years) with T1D >9 months completed 1 week of home monitoring with wrist‐worn actigraphy to estimate sleep duration and continuous glucose monitoring, anthropometrics, arterial stiffness, magnetic resonance imaging (adolescents only), and fasting laboratory testing at each treatment phase.ResultsSixty‐two per cent of adolescents and 74% of adults obtained <7 h of sleep per night at baseline. After adjustment for age, sex and diabetes duration, baseline sleep <7 h per night was associated with a higher body mass index, a higher waist circumference, a higher systolic blood pressure, worse arterial stiffness and a lower estimated insulin sensitivity (all p < .05). When examined by age group, associations between sleep duration and cardiometabolic health outcomes remained significant, predominantly for adolescents. In adolescents only, wake time was significantly later (p = .027) and time in bed was significantly longer with BCQR versus placebo (p = .049).ConclusionsObjectively measured sleep <7 h per night was prevalent in adolescents and adults with T1D and associated with poorer cardiometabolic health markers. Small changes in sleep were seen following BCQR treatment in adolescents only. Sleep may be an important and novel target for improving cardiometabolic health in individuals with T1D.
Fertility and long‐term economic growth
Authors: Huang Kaixing 
Published: April 2024

AbstractEmpirical studies have generally found that higher fertility has a negative or insignificant effect on economic growth. This article argues that this is because existing studies have failed to capture the long‐term lagged effects of fertility. By estimating a long‐term lagged panel model using data from 137 countries, I find that higher fertility first reduces and then increases economic growth, and the long‐term average effect is significantly positive. This finding is robust when focusing on countries at different development levels, exploiting exogenous fertility shocks from global family planning campaigns, and capitalizing on within‐country fertility variation resulting from China's one‐child policy.
Real‐life effectiveness 1 year after switching to avalglucosidase alfa in late‐onset Pompe disease patients worsening on alglucosidase alfa therapy: A French cohort study
Authors: Tard Céline , Bouhour Françoise , Michaud Maud , Beltran Stephane , Fournier Maxime , Demurger Florence , Lagrange Emmeline , Nollet Sylvain , Sacconi Sabrina , Noury Jean‐Baptiste , Magot Armelle , Cintas Pascal , Renard Dimitri , Deibener‐Kaminsky Joëlle , Lefeuvre Claire , Davion Jean‐Baptiste , Salort‐Campana Emmanuelle , Arrassi Azzeddine , Taouagh Nadjib , Spinazzi Marco ,   Pompe Study Group, Attarian Shahram , Laforêt Pascal 
Published: April 2024

AbstractIntroductionLate‐onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α‐glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long‐term treatment results vary. Avalglucosidase alfa demonstrated non‐inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.MethodsData from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow‐up. Respiratory (forced vital capacity [FVC]) and motor functions (Six‐Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.ResultsTwenty‐nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.DiscussionAt the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.ConclusionSwitching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.
Identification of a mosaic MTOR variant in purified neuronal DNA in a patient with focal cortical dysplasia using a novel depth electrode harvesting technique
Authors: Klein Karl Martin , Mascarenhas Rumika , Merrikh Daria , Khanbabaei Maryam , Maroilley Tatiana , Kaur Navprabhjot , Liu Yiping , Soule Tyler , Manalo Minette , Tamura Goichiro , Jacobs Julia , Hader Walter , Pfeffer Gerald , Tarailo‐Graovac Maja 
Published: April 2024

AbstractObjectiveRecent studies have identified brain somatic variants as a cause of focal epilepsy. These studies relied on resected tissue from epilepsy surgery, which is not available in most patients. The use of trace tissue adherent to depth electrodes used for stereo electroencephalography (EEG) has been proposed as an alternative but is hampered by the low cell quality and contamination by nonbrain cells. Here, we use our improved depth electrode harvesting technique that purifies neuronal nuclei to achieve molecular diagnosis in a patient with focal cortical dysplasia (FCD).MethodsDepth electrode tips were collected, pooled by brain region and seizure onset zone, and nuclei were isolated and sorted using fluorescence‐activated nuclei sorting (FANS). Somatic DNA was amplified from neuronal and astrocyte nuclei using primary template amplification followed by exome sequencing of neuronal DNA from the affected pool, unaffected pool, and saliva. The identified variant was validated using droplet digital polymerase chain reaction (PCR).ResultsAn 11‐year‐old male with drug‐resistant genetic–structural epilepsy due to left anterior insula FCD had seizures from age 3 years. Stereo EEG confirmed seizure onset in the left anterior insula. The two anterior insula electrodes were combined as the affected pool and three frontal electrodes as the unaffected pool. FANS isolated 140 neuronal nuclei from the affected and 245 neuronal nuclei from the unaffected pool. A novel somatic missense MTOR variant (p.Leu489Met, CADD score 23.7) was identified in the affected neuronal sample. Droplet digital PCR confirmed a mosaic gradient (variant allele frequency = .78% in affected neuronal sample; variant was absent in all other samples).SignificanceOur findings confirm that harvesting neuronal DNA from depth electrodes followed by molecular analysis to identify brain somatic variants is feasible. Our novel method represents a significant improvement compared to the previous method by focusing the analysis on high‐quality cells of the cell type of interest.
Horse owner experiences and observations with the use of SGLT2i for the management of equine metabolic syndrome and hyperinsulinaemia‐associated laminitis
Authors: Sundra Tania , Kelty Erin , Rossi Gabriele , Lester Guy , Rendle David 
Published: April 2024

SummaryBackgroundSodium‐glucose cotransporter 2 inhibitors (SGLT2i) are being used increasingly in equine practice. While there is emerging clinical evidence of the safety and efficacy of these drugs, there are currently no reports to document owner experiences with treatment.ObjectiveThe objective of the study was to report owner experiences and observations following treatment with SGLT2i in horses.Study designA cross‐sectional online survey.MethodsHorse owners were recruited via social media, online forums and their veterinarians to participate in an anonymous online survey to document their experiences and observations when treating their horses with SGLT2i.ResultsThree hundred forty‐two responses met the inclusion criteria. Ertugliflozin was the most commonly prescribed SGLT2i (79.8%), and the most common reasons for treatment were high insulin concentrations (84.2%) and active laminitis (59.7%). 85.3% of owners reported their horses had an improved quality of life after commencing treatment, while 9.4% reported no change and 5.3% reported a worsening of clinical signs. Of owners who had considered euthanasia prior to treatment (n = 77), 80.5% reported their horse's level of pain to be either mild or absent after 30 days of treatment and 94.8% reported their horse's quality of life to be improved. Most owners (n = 220, 64.7%) reported they were either extremely satisfied or somewhat satisfied (n = 72, 21.2%) with treatment. Treatment concerns included safety/side effects, medication cost, availability and long‐term efficacy. 114 owners (33.3%) reported one or more initial adverse effects upon induction onto the medication, particularly excessive urination (n = 70, 20.5%), excessive drinking (n = 38, 11.1%), excessive weight loss (n = 34, 9.9%) and dullness (n = 26, 7.6%).Main limitationSampling bias through social media and veterinary practices and reliance on subjective owner reports.ConclusionThe use of SGLT2i in horses was associated with excellent rates of owner satisfaction and owner‐reported improved quality of life for the horse; however, some adverse effects were observed.
Condylar fracture location is correlated to exercise history in Thoroughbred racehorses
Authors: Bergstrom Thomas C. , Spriet Mathieu , Carpenter Ryan S. , Jacques Kevin L. , Stover Susan M. 
Published: April 2024

AbstractBackgroundCondylar fractures are a major cause of morbidity and mortality in Thoroughbred racehorses. Condylar fractures have a variety of fracture configurations that suggest there may be differences in aetiopathogenesis.ObjectiveTo determine if exercise history differs with condylar fracture location in a population of Thoroughbred racehorses.Study designRetrospective analysis of clinical and exercise data.MethodsExercise history of Thoroughbred racehorses that had condylar fracture repair between 1 January 2018 and 28 February 2021 was compared between racehorses that had fractures located radiographically either within the parasagittal groove (PSG) or abaxial to the PSG (non‐PSG). Age, sex, and last event (race, timed work) matched control groups were compared between the PSG and non‐PSG groups. Additionally, exercise history variables of both groups were each compared with a group‐specific control population, each consisting of three control racehorses of equivalent age and sex matched to each affected racehorse by last event (race or official timed work) before fracture.ResultsEighty‐two horses with 84 fractures (45 PSG, 39 non‐PSG) met inclusion criteria. Age was not different between groups (PSG: 3.4 ± 1.3 years [mean ± SD], non‐PSG: 3.7 ± 1.3, p = 0.3). Number of races (PSG: 5.3 ± 7.1, non‐PSG: 11.4 ± 8.9, p < 0.001), total race furlongs (PSG: 38.2 ± 54.7, non‐PSG: 79.2 ± 64, p = 0.003), and number of active days (PSG: 304 ± 224, non‐PSG: 488 ± 314, p = 0.003) before fracture were greater; while mean number of layups was fewer (PSG: 1.0 ± 1.2, non‐PSG: 0.5 ± 0.7, p = 0.02) in horses with non‐PSG fracture. Horses with non‐PSG fracture had more differences compared with their respective control group than horses with PSG fractures. Outcomes following fracture repair were not different between groups.Main limitationsRetrospective study, one regional racehorse population, two‐dimensional imaging and potential inherent bias for fracture localisation, low statistical power for return to performance analysis.ConclusionsThoroughbred racehorses with non‐PSG condylar fractures have a more extensive exercise history than horses with PSG condylar fractures, suggesting differences in fracture aetiopathogenesis.
Microwave dielectric properties of V2O5/CeO2 doped (Mg0.95Ca0.05)TiO3‐MgO and their application to a dielectric filter
Authors: Shan Yiting , Lu Yang , Guo Xiang , Zhou Hongqing 
Published: April 2024

AbstractThe phase composition, microstructure, sintering characteristics, and microwave dielectric properties of nonstoichiometric MgTiO3‐CaTiO3 ceramics containing an additional 0.2 mol MgO, compositely doped with various amounts of V2O5 and CeO2 additives, were studied. The results revealed that adding an optimum amount of V2O5 and CeO2 could effectively impede second‐phase formation in Mg0.95Ca0.05TiO3‐MgO. High amounts of Mg2+ can react with MgTi2O5 to reduce the content of the secondary phase. The addition facilitated the densification of the microstructure and reduction of sintering temperature. Moreover, the dielectric performances of the material were significantly influenced by V2O5 and CeO2. Mg0.95Ca0.05TiO3‐MgO doped with 0.75 wt% CeO2 exhibited excellent frequency and temperature stabilities. In particular, when co‐doped with 0.5 wt% V2O5 and 0.75 wt% CeO2, Mg0.95Ca0.05TiO3‐MgO exhibited optimum properties after sintering at 1300°C for 2 h; a dielectric constant εr ∼ 19.92 (7 GHz),a Q×f value ∼ 65,236 GHz, and a τf value ∼ −2.03 ppm/°C. This indicates the potential of the material for microwave communication applications. Finally, a dielectric filter with a center frequency of 11.55 GHz was successfully designed and fabricated using a Mg0.95Ca0.05TiO3‐MgO sample co‐doped with 0.5 wt% V2O5 and 0.75 wt% CeO2.The filter exhibited excellent performance with a bandwidth of less than 1.5 is about 40 MHz, the loss at the center frequency point was 0.7 dB, and the 3‐dB bandwidth exceeded 200 MHz, which holds a significant practical value.