bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient‐level indirect treatment comparison of lanadelumab versus pdC1‐INH i.v. in hereditary angioedema patients: PATCH study
Authors: Magerl Markus , Schiffhorst Guido , Fanter Lena , Müller Gerrit , Hirche Christoph , Berkemeier Fabian , Aygören Emel 
Published: August 2023

AbstractBackgroundHereditary angioedema (HAE) is an autosomal dominant inherited disease in which patients suffer from local attacks primarily affecting skin and gastrointestinal tract, and sometimes even the upper respiratory tract leading to asphyxiation. Since head‐to‐head trials between authorized treatments are lacking, this study compares efficacy and safety of lanadelumab and intravenous plasma‐derived C1‐esterase inhibitor (pdC1‐INH i.v.) in HAE patients on long‐term prophylaxis by means of an indirect treatment comparison.MethodsEfficacy and safety of lanadelumab against pdC1‐INH i.v. were analyzed in a fully prespecified indirect comparison based on individual patient data (n = 231) from the HELP and CHANGE clinical trials. Primary and secondary efficacy endpoints were compared using a generalized linear model for count data. Confounding variables were identified a priori via systematic literature research and validated by clinical experts. Adjustment of confounders was implemented using a conditional regression model.ResultsLanadelumab showed a statistically significant improvement in reduction of HAE attack rates compared to pdC1‐INH i.v. across multiple endpoints: Monthly attack rate of patients treated with lanadelumab was less than half compared to pdC1‐INH i.v. (Rate ratio: 0.486; 95% CI: 0.253, 0.932). Monthly rate of laryngeal attacks was found to be five times lower for lanadelumab (Rate ratio: 0.2; 95% CI: 0.044, 0.915) and monthly rate of acute treated HAE attacks among lanadelumab patients was about one third of the attack rate of pdC1‐INH i.v. patients (Rate ratio: 0.366; 95% CI: 0.185, 0.727).ConclusionThis study contributes to current knowledge in the treatment of HAE by indicating a statistically significant reduction of HAE attacks under lanadelumab compared to pdC1‐INH i.v.
Birthweight of the subsequent singleton pregnancy following a first twin or singleton pregnancy
Authors: Basnet Prativa , Skjærven Rolv , Harmon Quaker E. , Wilcox Allen J. , Klungsøyr Kari , Sørbye Linn Marie , Morken Nils‐Halvdan , Kvalvik Liv G. 
Published: August 2023

AbstractIntroductionBirthweight is an important pregnancy indicator strongly associated with infant, child, and later adult life health. Previous studies have found that second‐born babies are, on average, heavier than first‐born babies, indicating an independent effect of parity on birthweight. Existing data are mostly based on singleton pregnancies and do not consider higher order pregnancies. We aimed to compare birthweight in singleton pregnancies following a first twin pregnancy relative to a first singleton pregnancy.Material and MethodsThis was a prospective registry‐based cohort study using maternally linked offspring with first and subsequent pregnancies registered in the Medical Birth Registry of Norway between 1967 and 2020. We studied offspring birthweights of 778 975 women, of which 4849 had twins and 774 126 had singletons in their first pregnancy. Associations between twin or singleton status of the first pregnancy and birthweight (grams) in subsequent singleton pregnancies were evaluated by linear regression adjusted for maternal age at first delivery, year of first pregnancy, maternal education, and country of birth. We used plots to visualize the distribution of birthweight in the first and subsequent pregnancies.ResultsMean combined birthweight of first‐born twins was more than 1000 g larger than mean birthweight of first‐born singletons. When comparing mean birthweight of a subsequent singleton baby following first‐born twins with those following first‐born singletons, the adjusted difference was just 21 g (95% confidence interval 5–37 g).ConclusionsBirthweights of the subsequent singleton baby were similar for women with a first twin or a first singleton pregnancy. Although first twin pregnancies contribute a greater combined total offspring birthweight including more extensive uterine expansion, this does not explain the general parity effect seen in birthweight. The physiological reasons for increased birthweight with parity remain to be established.
A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group
Authors: Neunert Cindy , Heitink‐Polle Katja M. J. , Lambert Michele P. 
Published: August 2023

SummaryImmune thrombocytopenia (ITP) in children is a relatively mild and self‐limited disorder with the majority of children demonstrating normalization of platelet count by 12 months from diagnosis. Because of this, many children with ITP can be observed without the need for treatment. When needed, treatment with either intravenous immunoglobulin (IVIG) or corticosteroids is highly effective (>80% IVIG and >95% corticosteroids). For those children who require second‐line therapies, response rates of >60% are seen with both the thrombopoietin‐receptor agonists and rituximab. Despite this, some children will have ‘refractory’ ITP (rITP) with poor or transient responses to platelet‐raising therapies. Here, we review the clinical features of rITP in children, outline proposed classifications and explore potential predictors for children with rITP.
Licorice metabolite 18β‐glycyrrhetinic acid activates G protein‐gated inwardly rectifying K+ channels
Authors: Chen I‐Shan , Yasuda Jumpei , Notomi Takuya , Nakamura Tomoe Y. 
Published: August 2023

Background and PurposeLicorice (liquorice) is a common food additive and is used in Chinese medicine. Excess licorice intake can induce atrial fibrillation. Patients with atrial fibrillation possess constitutively activated G protein‐gated inwardly rectifying K+ (GIRK) channels. Whether licorice affects GIRK channel activity is unknown. We aimed to clarify the effects of licorice ingredients on GIRK current and the mechanism of action.Experimental ApproachA major component of licorice, glycyrrhizic acid (GA), and its metabolite, 18β‐glycyrrhetinic acid (18β‐GA), were tested. We performed electrophysiological recordings in Xenopus oocytes to examine the effects of GA and 18β‐GA on various GIRK subunits (Kir3.1–Kir3.4), mutagenesis analyses to identify the crucial residues for drug action and motion analysis in cultured rat atrial myocytes to clarify effects of 18β‐GA on atrial functions.Key ResultsGA inhibited Kir3.1‐containing channels, while 18β‐GA activated all Kir3.x subunits. A pore helix residue Phe137 in Kir3.1 was critical for GA‐mediated inhibition, and the corresponding Ser148 in Kir3.2 was critical for 18β‐GA‐mediated activation. 18β‐GA activated GIRK channel in a Gβγ‐independent manner, whereas phosphatidylinositol 4,5‐bisphosphate (PIP2) was essential for activation. Glu236 located at the cytoplasmic pore of Kir3.2 appeared to be important to interactions with 18β‐GA. In rat atrial myocytes, 18β‐GA suppressed spontaneous beating via activation of GIRK channels.Conclusion and ImplicationsGA acts as a novel GIRK inhibitor, and 18β‐GA acts as a novel GIRK activator. 18β‐GA alters atrial function via activation of GIRK channels. This study elucidates the pharmacological activity of licorice ingredients and provides information for drug design.
Identification of Fangji Huangqi Tang as a potential herbal formula for Sjogren syndrome treatment via network pharmacology and experimental validation
Authors: Shao Yanxiong , Hu Jun , Wang Shaohai , Jiang Hua , Miao Guojun , Li Chaoran , Zhang Jie , Xu Yubo 
Published: August 2023

AbstractFangji Huangqi Tang (FHT) is a well‐known Chinese herbal formula that is prescribed as treatment for rheumatoid diseases. In this study, we aimed to investigate the potential therapeutic targets, efficacy, and safety of FHT in the treatment of Sjogren's syndrome (SS). The Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in SS. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential biological functions of the DEGs. Subsequently, an FHT‐herb‐active compound‐target network was constructed to identify the relationship between the active compounds in FHT and the related targets. Then, enrichment analysis involving the DEGs and protein–protein interaction (PPI) network analysis were performed to analyze the biological functions of potential targets and screen hub genes. Further, molecular docking was employed to verify the binding affinity between the active compounds and the hub targets, and in vivo experiments involving NOD/LtJ mice were conducted to verify the therapeutic effects of FHT on SS‐like symptoms. Finally, inhibition of PIK3CK/Akt pathway by FHT was validated by WB and rt‐qPCR. A total of 1836 DEGs were identified in SS based on the GSE159574 dataset, and 114 targets of the active compounds in FHT were screened. Further, via network pharmacology analysis and molecular docking, six active compounds and five hub targets were obtained, and enrichment analysis showed that the anti‐SS effect of FHT was predominantly associated with immune cells, such as T cells and neutrophils. In vivo, FHT effectively reduced lymphocyte infiltration foci, increased saliva flow rate, and inhibited increases in the levels of SS‐related autoantibodies (anti‐SSA and anti‐SSB). Furthermore, the biosafety of FHT was verified via the serological examination of liver and kidney function. WB and rt‐qPCR analysis confirmed that FHT could inhibit the expression of PIK3CG and the activation of PIK3CG/Akt pathway. Via network pharmacological analysis, molecular docking, and in vivo verification, we demonstrated the multicomponent and multitarget characteristics of FHT in SS treatment, thereby providing novel insights into the pathogenesis of SS and the therapeutic targets of FHT for SS.
Inflammasomes NLRP3 and AIM2 in peri‐implantitis: A cross‐sectional study
Authors: Galindo‐Moreno Pablo , Montalvo‐Acosta Saray , Martín‐Morales Natividad , Carrillo‐Gálvez Ana Belén , González‐Rey Elena , O'Valle Francisco , Padial‐Molina Miguel 
Published: August 2023

AbstractBackgroundInflammasome components NLRP3 and AIM2 contribute to inflammation development by the activation of caspase‐1 and IL‐1β. They have not been yet evaluated in samples from patients with active peri‐implantitis. Thus, the aim of the present study is to analyze the expression of inflammasomes NLRP3 and AIM2 and subsequent caspase 1 and IL‐1β assessing the microenvironment of leukocyte subsets in samples from patients with active peri‐implantitis.MethodsBiopsies were collected from 33 implants in 21 patients being treated for peri‐implantitis. Biopsies from gingival tissues from 15 patients with healthy periodontium were also collected for control. These tissues were evaluated through conventional histological stainings. Then, immunohistochemical detection was performed to analyze NLRP3, AIM2, caspase‐1, and IL‐1β and markers of different leukocyte subsets. PCR for inflammasomes and related genes was also done.ResultsThis manuscript reveals a high immunohistochemical and mRNA expression of NLRP3 and AIM2 inflammasomes, caspase‐1, and IL‐1β in biopsies collected from human peri‐implantitis. The expression of the tested markers was significantly correlated with the increase in inflammatory infiltrate, probing depth, presence of biofilm, and bleeding on probing. In these peri‐implantitis lesions, the area of biopsy tissue occupied by inflammatory infiltrate was intense while the area occupied by collagen was significantly lower. In comparison with periodontal healthy tissues, the inflammatory infiltrate was statistically significantly higher in the peri‐implantitis biopsies and was mainly composed of plasma cells, followed by T and B lymphocytes.ConclusionIn human peri‐implantitis, chronic inflammation can be explained in part by the action of IL‐1β/caspase 1 induced through NLRP3 and AIM2 inflammasome activation.
Corticospinal excitability changes during muscle relaxation and contraction in motor imagery
Authors: Takenaka Yuma , Matsumoto Hitomi , Suzuki Tomotaka , Sugawara Kenichi 
Published: August 2023

AbstractTo enhance smooth muscle contraction and relaxation during rehabilitation and sports activities, a comprehensive understanding of the motor control mechanisms within the central nervous system is necessary. However, current knowledge on these aspects is insufficient. Therefore, this study aimed to deepen our understanding of motor controls, by investigating the alterations in corticospinal excitability within cortical motor areas related to muscle contraction and relaxation using motor imagery with a reaction time task paradigm. Transcranial magnetic stimulation was used to measure the motor‐evoked potentials in the first dorsal interosseous muscle of the right hand after the ‘go’ signal. Static weak muscle contraction (Experiment 1: 18 healthy participants) and resting state (Experiment 2: 16 healthy participants) were applied as background factors, and a trial without motor imagery was performed as a control. Muscle contraction was maintained in the background in the contraction motor imagery. A decrease in excitability in the relaxation motor imagery task occurred compared with the control. When the muscles were at rest, an increase in excitability in the contraction motor imagery and a transient increase in excitability in the relaxation motor imagery occurred compared with the control condition. Hence, the excitability of contraction and relaxation motor imagery is characterized by a continuous increase in excitability, transient increase and subsequent decrease in excitability, respectively. These results suggest that muscle contraction sensory information in the background condition may be necessary for muscle relaxation. Matching the background conditions may be crucial when utilizing motor imagery for rehabilitation or sports training.
Impact of nitrogen and phosphorus additions on soil gross nitrogen transformations in a temperate desert steppe
Authors: Yue Ping , Zhang Jinbo , Zhu Gaodi , Yin Xiaoyue , Zhang Xiaoxue , Wang Shaokun , Müller Christoph , Misselbrook Tom , Zuo Xiaoan 
Published: August 2023

AbstractNutrient addition has a significant impact on plant growth and nutrient cycling. Yet, the understanding of how the addition of nitrogen (N) or phosphorus (P) significantly affects soil gross N transformations and N availability in temperate desert steppes is still limited. Therefore, a 15N tracing experiment was conducted to study these processes and their underlying mechanism in a desert steppe soil that had been supplemented with N and P for 4 years in northwestern China. Soil N mineralization was increased significantly by P addition, and N and P additions significantly promoted soil autotrophic nitrification, rather than NH4+‐N immobilization. The addition of N promoted dissimilatory NO3− reduction to NH4+, while that of P inhibited it. Soil NO3−‐N production was greatly increased by N added alone and by that of N and P combined, while net NH4+‐N production was decreased by these treatments. Soil N mineralization was primarily mediated by pH, P content or organic carbon, while soil NH4+‐N content regulated autotrophic nitrification mainly, and this process was mainly controlled by ammonia‐oxidizing bacteria rather than archaea and comammox. NH4+‐N immobilization was mainly affected by functional microorganisms, the abundance of narG gene and comammox Ntsp‐amoA. In conclusion, gross N transformations in the temperate desert steppe largely depended on soil inorganic N, P contents and related functional microorganisms. Soil acidification plays a more key role in N mineralization than other environmental factors or functional microorganisms.
Load‐bearing capacity and wear characteristics of short fiber‐reinforced composite and glass ceramic fixed partial dentures
Authors: Mangoush Enas , Garoushi Sufyan , Vallittu Pekka , Lassila Lippo 
Published: August 2023

AbstractThe aim of this study was to evaluate load‐bearing capacity and wear performance of experimental short fiber‐reinforced composite (SFRC) and conventional lithium‐disilicate CAD/CAM fabricated fixed partial dentures (FPDs). Two groups (n = 12/group) of three‐unit CAD/CAM fabricated posterior FPDs were made. The first group used experimental SFRC blocks, and the second group fabricated from lithium‐disilicate (IPS e.max CAD). All FPDs were luted on a zirconia testing jig with dual‐curing resin cement. Half of FPDs per group were quasi‐statically loaded until fracture. The other half experienced cyclic fatigue aging (100.000 cycles, Fmax = 500 N) before loading quasi‐statically until fracture. Fracture mode was examined using SEM. Wear test was performed using 15,000 loading cycles. Both material type and aging had a significant effect on the load‐bearing capacity of FPDs. Experimental SFRC CAD without fatigue aging had significantly the highest load‐bearing capacity (2096 ± 149N). Cyclic fatigue aging decreased the load‐bearing capacity of the SFRC group (1709 ± 188N) but increased it for the lithium‐disilicate group (1546 ± 155N). Wear depth values of SFRC CAD (29.3μm) were significantly lower compared to lithium‐disilicate (54.2μm). Experimental SFRC CAD demonstrated the highest load‐bearing capacity before and after cyclic fatigue aging, and superior wear behavior compared to the control material.
Thromboelastometry and prediction of in‐hospital mortality in neonates with sepsis
Authors: Sokou Rozeta , Tsantes Andreas G. , Lampridou Maria , Tsante Konstantina A. , Houhoula Dimitra , Piovani Daniele , Bonovas Stefanos , Boutsikou Theodora , Iliodromiti Zoi , Iacovidou Nicoletta , Tsantes Argirios E. , Konstantinidi Aikaterini 
Published: August 2023

AbstractIntroductionThis study aimed at evaluating the role of rotational thromboelastometry (ROTEM) assays in the prediction of in‐hospital mortality of neonates with sepsis.MethodsOver a 6‐year period, 129 neonates with confirmed sepsis, hospitalized in our neonatal intensive care unit (NICU) were included in the study. Demographics, clinical, and laboratory data were recorded at the sepsis onset and ROTEM assays were performed. Modified neonatal multiple organ dysfunction (NEOMOD) and neonatal sequential organ failure assessment (nSOFA) were calculated simultaneously. Mortality during in‐hospital stay was the main outcome measure.ResultsIn‐hospital mortality was associated with patient intense hypocoagulability expressed by lower ROTEM MCF in the INTEM assay. The INTEM MCF demonstrated the best prognostic performance for NICU mortality in septic neonates among the other ROTEM parameters but without statistical significance (area under the curve [AUC] = 0.731; 95% confidence interval [CI]: 0.593–0.869).ConclusionOur results indicate that ROTEM INTEM MCF parameter has good predictive capacity for in‐hospital mortality of septic neonates, similar to that of modified NEOMOD score, nSOFA score, and platelet count, highlighting the integral role of coagulation in sepsis pathophysiology. Hence, ROTEM could serve as a valuable monitoring tool to identify neonates at risk.
Effect of intramedullary fixation and plate fixation on postoperative wound complications in clavicle fractures: A meta‐analysis
Authors: Lin Shangce , Huang Jin , Lamin Bangura Mohamed , Zeng Teng , Tian Yaqin , Liu Lian , Luo Huasong 
Published: August 2023

AbstractMore and more meta‐analyses have been conducted to compare the effects of intramedullary fixation (IF) and plate fixation (PF) on the outcome of midshaft clavicle fractures. It can affect the doctors' treatment decisions. A number of studies have been conducted in order to assist surgeons in selecting optimal operative procedures and to recommend operative treatment of clavicle fractures in accordance with the best available research. Our analysis of the IF and PF of clavicle fractures was done through a search for PubMed, Emabase, Web of Science, and Cochrane Library. Two different researchers analysed the research literature for quality of analysis and data extraction. The analysis of the data was done with RevMan 5.3. The 95% CI and OR models have been computed by means of either fixed‐dose or randomize. In addition, RCT in 114 references have been reviewed and added for further analysis. It is concluded that the application of plate and intramedullary fixation in the middle clavicle operation has remarkable influence on the outcome of post‐operation. There was a lower risk of postoperative wound infection in IF (OR, 5.92; 95% CI, 2.46, 14.27 p < 0.0001), smaller surgical incisions (MD, 6.57; 95% CI, 4.90, 8.25 p < 0.0001), and shorter operative time (MD, 17.09; 95% CI 10.42, 23.77 p < 0.0001), less blood loss (MD, 63.62; 95% CI, 55.84, 71.39 p < 0.0001) and shorter hospital stay (MD, 1.05; 95% CI, 0.84, 1.25 p < 0.0001). However, there is no statistical significance in the incidence of wound dehiscence. Thus, the effect of IF on the incidence of injury is better than that of the inner plate in the middle of the clavicle.
Infrared irradiation to drive phosphate condensation as a route to direct additive manufacturing of oxide ceramics
Authors: Somers Nicolas , Montón Alejandro , Özmen Eren , Losego Mark D. 
Published: August 2023

AbstractThis paper introduces a fast, low‐temperature, pressureless process to chemically bind ceramic parts with the help of infrared (IR) irradiation and phosphate binder condensation. Ceramic components are synthesized from slurries of ceramic powders and Al(H2PO4)3 binder that are irradiated with short‐waved IR light capable of heating the system to 350°C. This irradiation is found to be sufficient to drive phosphate condensation, binding the ceramic powders together within a matter of seconds. The IR‐irradiated components show an increase in density and Vickers hardness. Layer‐by‐layer spraying and irradiation is demonstrated as a route to additive manufacturing using various ceramic chemistries. While further optimization is needed to control desired microstructure, this process of using chemically bonded ceramic binders with IR heating for additive manufacturing shows the potential to find applications in various ceramic systems, including refractories, bone implants, electronics, and thermal barrier coatings.
European Parliament Elections in the Dutch Press and the Mainstreaming of Euroscepticism: Outsiders Becoming Insiders?
Authors: Bijsmans Patrick 
Published: August 2023

AbstractEuroscepticism has become prominent across the European Union, also in countries that were originally seen as pro‐integrationist such as the Netherlands. Based on a qualitative analysis of claims in three major Dutch newspapers, I examine the mainstreaming of Euroscepticism in the Netherlands in the context of the 2009, 2014 and 2019 European Parliament elections. Mainstreaming refers to a process in which an idea becomes an integral part of debates in the public sphere. I examine the mainstreaming of Euroscepticism through a two‐part analysis that centres around a fourfold typology, which distinguishes between supportive, Euroalternative, soft Eurosceptic and hard Eurosceptic claims. I find that Euroscepticism has indeed become mainstream, in debates revolving around arguments for and against the European Union. Furthermore, Euroscepticism has not just become more prominent but has also moved from an outsider to an insider perspective. Yet, it often remains unclear what Euroscepticism actually entails.