bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of FEIBA and emicizumab (SAFE): Dose escalation study evaluating the safety of in vivo administration of activated prothrombin complex concentrate in haemophilia A patients on emicizumab
Authors: Kizilocak Hande , Marquez‐Casas Elizabeth , Malvar Jemily , Young Guy 
Published: October 2022

AbstractIntroductionEmicizumab is a humanized bispecific monoclonal antibody licensed for patients with severe haemophilia A. Breakthrough bleeding still occurs in patients on emicizumab and can be managed with recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). Thrombotic events were reported when patients on emicizumab received concomitant aPCC at relatively high doses. We studied the effect of infusing various doses of aPCC to patients on emicizumab.Material and methodsNine patients with severe haemophilia A with inhibitors who are on emicizumab were recruited to participate. Patients were infused with varying doses of aPCC in vivo. Samples were tested with thrombin generation (TG) assay.ResultsIn the current in vivo arm of the study four out of nine patients reached the highest dose, 75 U/kg of aPCC and six out of nine patients were actually eligible for the highest dose. In the previous in vitro arm of the study seven out of eight patients reached the normal plasma with spiking aPCC at a very low concentration equivalent to 5 U/kg.ConclusionThe in vitro portion of the study demonstrated that clinically relevant concentrations of aPCC resulted in excessive TG, however, in vivo administration of aPCC to the same patients demonstrated that most of the patients had normal TG at the approved doses of aPCC. In the management of breakthrough bleeding clinicians should heed the boxed warning for concomitant use of emicizumab and aPCC, however, should also be aware that low doses of aPCC may not result in sufficient TG.
A multicenter, randomized, double‐blind, placebo‐controlled, crossover trial to evaluate the efficacy and safety of zolmitriptan nasal spray for the acute treatment of migraine in patients aged 6 to 11 years, with an open‐label extension
Authors: Yonker Marcy E. , McVige Jennifer , Zeitlin Leonid , Visser Hester 
Published: October 2022

AbstractObjectiveTo evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11 years.BackgroundTriptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable.MethodsThis Phase 3, randomized, double‐blind, placebo‐controlled, multicenter crossover trial with an open‐label extension enrolled patients aged 6 to 11 years with a diagnosis of migraine for ≥6 months and ≥16 headache‐free days/month (N = 373). After a run‐in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50 kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0 mg; those ≥50 kg were randomized 5:1 to ZNS 5.0 or 2.5 mg. Patients had 6 weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6 weeks to treat a second migraine attack. Patients could participate in a subsequent 6‐month outpatient open‐label extension. The primary efficacy endpoint was pain‐free status at 2 h in patients treated with the high dose from each stratum.ResultsThe trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9 years) entered the placebo run‐in period and 186 entered the double‐blind period. Pain‐free status at 2 h postdose was achieved by 45/133 (33.8%) and 30/128 (23.4%) of patients who received high‐dose ZNS and placebo, respectively (p = 0.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment‐related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6‐month open‐label extension.ConclusionThe effect of high‐dose ZNS on the primary endpoint of pain‐free status at 2 h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population.
The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: A prospective case–control study
Authors: Georgiou Athina Christina , Twisk Jos W. R. , Crielaard Wim , Ouwerling Peter , Schoneveld Arjan H. , van der Waal Suzette Veronica 
Published: October 2022

AbstractAimTo explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction.MethodologyThis is a prospective case–control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators was examined longitudinally in all subjects during six visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analysed by linear regression analyses and linear mixed‐model analyses.ResultsA total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, granulocyte colony‐stimulating factor (p < .001), interleukin (IL)‐1β (p = .03) and IL‐4 (p = .01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e. 3 months after the tooth extraction, showed a significant reduction in IL‐10 (p = .03) and IL‐12p70 (p = .01).ConclusionsThe immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low‐grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis.
Regulation of caries‐induced pulp inflammation by NLRP3 inflammasome: A laboratory‐based investigation
Authors: Al Natour Banan , Lundy Fionnuala T. , About Imad , Jeanneau Charlotte , Dombrowski Yvonne , El Karim Ikhlas A. 
Published: October 2022

AbstractAimTo evaluate the expression and function of the nod‐like receptor pyrin domain containing 3 (NLRP3) inflammasome in caries induced pulpitis.MethodologyNLRP3 expression was determined with immunohistochemistry in the dental pulp and qPCR in dental pulp cells (DPCs). THP‐1 macrophages expressing the apoptosis‐related speck‐like protein (ASC) and green fluorescent protein (GFP) fusion protein were used to assess NLRP3 inflammasome activation by live cell imaging, following treatment with lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Caspase I inhibitor was used to confirm inflammasome activation. An ex‐vivo pulpitis model in which the DPCs were co‐cultured with THP‐1 macrophages was used to study the effect of the NLRP3 inflammasome inhibitor (MCC950), and cytokines were measured using ELISA and multiplex array. Data were analysed using the t‐test or anova followed by a Bonferroni post hoc test with the level of significance set at p ≤ .05.ResultsNLRP3 inflammasome was differentially expressed in dental pulp of sound and carious teeth. Treatment of DPCs with LTA significantly upregulates NLRP3 and IL‐1 β‐expression (p < .05) and in induces more ASC specks formation compared to LPS. IL‐β release in response to LTA treatment is significantly reduced with Caspase I inhibitor suggesting inflammasome dependent mechanism (p < .01). NLRP3‐specific inhibitor, MCC950, significantly reduced IL‐1β and IL‐6 in an ex‐vivo pulpitis model (p < .01) but had no effect on IL‐8 or matrix metalloproteinase‐9 (MMP‐9).ConclusionsExpression and upregulation of NLRP3 inflammasome with caries and LTA treatment suggest a role in caries‐induced pulpitis. NLRP3 inhibitor attenuated the release of selective inflammatory cytokines and could be a potential treatment target that merit further investigation.
Effect of wet‐jet milling on the c‐axis orientation of hydroxyapatite ceramics fabricated using a strong magnetic field
Authors: Otsuka Yuki , Yamamoto Isao , Iijima Motoyuki , Tatami Junichi 
Published: October 2022

AbstractControlling the crystal orientation of hydroxyapatite, an inorganic material that is a major component of human hard tissues is important to fabricate better artificial bones and artificial tooth roots. To obtain highly oriented hydroxyapatite ceramics under a strong magnetic field, a good dispersion of the raw materials in the slurry must be obtained. This study investigates the effect of wet‐jet milling of a slurry on the orientation of hydroxyapatite ceramics fabricated using a strong magnetic field. Although the prolonged ball milling with ZrO2 balls of the raw powder fractures the primary particles of hydroxyapatite, wet‐jet milling is used to successfully pulverize agglomerated hydroxyapatite raw powder without changing the morphology of the primary particles. Evidently, ceramics with a highly oriented c‐axis of hydroxyapatite are obtained by molding the wet‐jet milled slurry in a strong rotating magnetic field. They exhibit anisotropy in fracture toughness, and the fracture toughness calculated from the crack length perpendicular to the rotating axis is higher than that calculated from the crack length parallel to it. Furthermore, these values are higher than those of randomly oriented hydroxyapatite ceramics, which may be owing to the crystal orientation dependence of the fracture toughness of the hydroxyapatite grains and grain boundaries.
Relationships between job burnout, ethical climate and organizational citizenship behaviour among registered nurses: A cross‐sectional study
Authors: Wang Lyu , Dong Xiaoyu , An Yan , Chen Cancan , Eckert Marion , Sharplin Greg , Fish Jennifer , Fan Xiuzhen 
Published: October 2022

AbstractAimThis study aimed to investigate the levels of nurses' organizational citizenship behaviour and the associations between job burnout and ethical climate with organizational citizenship behaviour.BackgroundOrganizational citizenship behaviour improves adverse outcomes led by nursing shortage. However, the associations between three dimensions of job burnout and organizational citizenship behaviour are inconsistent, and little is known about whether ethical climate is related to organizational citizenship behaviour in nurses.MethodsIn this cross‐sectional study, 1157 nurses were selected using convenience sampling from April to October 2019. Self‐report surveys assessed nurses' organizational citizenship behaviour, emotional exhaustion, depersonalization, personal accomplishment and perceptions of ethical climate.ResultsMean organizational citizenship behaviour was high among nurses. The regression model showed that job burnout and ethical climate explained an additional 38.6% of the variance in organizational citizenship behaviour over and above sociodemographic factors, with 44.9% of the total variance.ConclusionNurses' organizational citizenship behaviour was at a relatively high level. Depersonalization was negatively associated with organizational citizenship behaviour while personal accomplishment and ethical climate were positively related to organizational citizenship behaviour. Therefore, nurse leaders are encouraged to take measures to help nurses reduce job burnout and create a favourable ethical climate for increasing nurses' organizational citizenship behaviour.
Adolescent overweight and obesity in Ireland—Trends and sociodemographic associations between 1990 and 2020
Authors: Moore Heslin Aoibhín , O'Donnell Aisling , Kehoe Laura , Walton Janette , Flynn Albert , Kearney John , McNulty Breige 
Published: October 2022

SummaryBackgroundOverweight and obesity in adolescence is a growing issue and can have a range of both short‐ and long‐term consequences on health.ObjectivesTo analyse trends in adolescent weight status in Ireland across a 30‐year period and to examine the influence of sociodemographic factors on overweight/obesity in Irish adolescents over time.MethodsBody composition and body mass index weight status of Irish adolescents were compared using data from three nationally representative, cross‐sectional Irish national food consumption surveys from 1990, 2006 and 2020. Adjusted analysis of associations between socio‐demographic factors with the risk of adolescent overweight/obesity at each time point were examined.ResultsThe prevalence of Irish adolescents with overweight/obesity has increased significantly in recent years, with 24% of adolescents living with overweight/obesity in 2020 compared to 18% in 2006 and 13% in 1990 (p < 0.001). Of note is a substantial increase in the prevalence of obesity, with 8% of adolescents living with obesity in 2020 compared to 3% in 2006 and 0.5% in 1990 (p < 0.001). A lower affluence social class was associated with 3.95 increased odds of adolescent overweight/obesity (95%CI 2.06–7.61) (p < 0.001) in 2020 only, with 41% of adolescents from the lowest affluence social class affected by overweight/obesity. Parental education level was inversely associated with the risk of adolescent overweight/obesity in 2006 and 2020, with a stronger effect in 2020.ConclusionThere is an increasing prevalence of adolescents living with overweight/obesity in Ireland, with evidence of a growing socioeconomic gradient of overweight/obesity where adolescents affected by socioeconomic disadvantage are most at risk.
G protein coupled pattern recognition receptors expressed in neutrophils: Recognition, activation/modulation, signaling and receptor regulated functions
Authors: Dahlgren Claes , Lind Simon , Mårtensson Jonas , Björkman Lena , Wu Yanling , Sundqvist Martina , Forsman Huamei 
Published: October 2022

SummaryNeutrophils, the most abundant white blood cell in human blood, express receptors that recognize damage/microbial associated pattern molecules of importance for cell recruitment to sites of inflammation. Many of these receptors belong to the family of G protein coupled receptors (GPCRs). These receptor‐proteins span the plasma membrane in expressing cells seven times and the down‐stream signaling rely in most cases on an activation of heterotrimeric G proteins. The GPCRs expressed in neutrophils recognize a number of structurally diverse ligands (activating agonists, allosteric modulators, and inhibiting antagonists) and share significant sequence homologies. Studies of receptor structure and function have during the last 40 years generated important information on GPCR biology in general; this knowledge aids in the overall understanding of general pharmacological principles, governing regulation of neutrophil function and inflammatory processes, including novel leukocyte receptor activities related to ligand recognition, biased/functional selective signaling, allosteric modulation, desensitization, and reactivation mechanisms as well as communication (receptor transactivation/cross‐talk) between GPCRs. This review summarizes the recent discoveries and pharmacological hallmarks with focus on some of the neutrophil expressed pattern recognition GPCRs. In addition, unmet challenges, including recognition by the receptors of diverse ligands and how biased signaling mediate different biological effects are described/discussed.
Genotype and phenotype correlations in 441 patients with epidermolysis bullosa from China
Authors: Chen Fuying , Wei Ruoqu , Deng Dan , Zhang Xue , Cao Yu , Pan Chaolan , Wang Yumeng , Cao Qiaoyu , Wang Jianbo , Zeng Ming , Huang Linting , Gu Yan , Yao Zhirong , Li Ming 
Published: October 2022

AbstractBackgroundEpidermolysis bullosa (EB) is a heterogeneous group of rare and incurable genetic blistering disorders.ObjectivesThe objective was to analyse the genotype–phenotype correlation in EB among Chinese individuals.MethodsNext‐generation sequencing and Sanger sequencing were performed to genetically confirm clinically diagnosed EB. Reverse transcription‐PCR and splice‐site analysis were used to evaluate the consequences of splicing mutations.ResultsA total of 441 cases (413 families) across 11 genes were included. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, simplex and junctional compound EB accounted for 23.4%, 12.7%, 61.5%, 1.1% and 0.2%, respectively. In 16 probands with presumptive recessive EB, failed to find the second allele, COL7A1 (10), COL17A1 (4), LAMB3 (1) and ITGB4 (1). De novo mutations are common in dominant EB (63.8% in EBS, 27.5% in DEB) but extremely rare in recessive DEB (RDEB; 0.74%). Mosaicism is more common than presumed, with 5.4% of dominant EBS. In JEB, only 45.0% of patients with biallelic premature termination codon (PTC) mutations in laminin 332 genes died within 24 months, with a longer average survival age of 11.1 months. In JEB, unusual phenotypes are frequently observed, notably urinary tract involvement, duodenal atresia and EB nevi. In RDEB, 48.8% of cases with biallelic PTC mutations in COL7A1 exhibited a relatively mild phenotype; they are likely to develop a severe phenotype at 0–4 years old, and the PTC mutations position closer to the N‐terminal, leading to earlier onset. Glycine substitution mutations in DEB have complex genotypic and phenotypic heterogeneity. The rare subtype, dominant and recessive compound DEB, consists of 1.8% of the total DEB.ConclusionsThis study reveals the general rules governing genotype–phenotype correlations, rare phenotypes and complex genotypes. Collectively, mutation analysis in different forms of EB provides the basis for improved subclassification with accurate genetic counselling and for prenatal diagnosis.
Low‐energy electron microscopy intensity–voltage data – Factorization, sparse sampling and classification
Authors: Masia Francesco , Langbein Wolfgang , Fischer Simon , Krisponeit Jon‐Olaf , Falta Jens 
Published: October 2022

AbstractLow‐energy electron microscopy (LEEM) taken as intensity–voltage (I–V) curves provides hyperspectral images of surfaces, which can be used to identify the surface type, but are difficult to analyse. Here, we demonstrate the use of an algorithm for factorizing the data into spectra and concentrations of characteristic components (FSC3) for identifying distinct physical surface phases. Importantly, FSC3 is an unsupervised and fast algorithm. As example data we use experiments on the growth of praseodymium oxide or ruthenium oxide on ruthenium single crystal substrates, both featuring a complex distribution of coexisting surface components, varying in both chemical composition and crystallographic structure. With the factorization result a sparse sampling method is demonstrated, reducing the measurement time by 1–2 orders of magnitude, relevant for dynamic surface studies. The FSC3 concentrations are providing the features for a support vector machine‐based supervised classification of the surface types. Here, specific surface regions which have been identified structurally, via their diffraction pattern, as well as chemically by complementary spectro‐microscopic techniques, are used as training sets. A reliable classification is demonstrated on both example LEEM I–V data sets.
Diagnostic performance of magnetic resonance imaging for degenerative temporomandibular joint disease
Authors: Liu Sha‐sha , Xu Li‐li , Lu Shen‐ji , Mao Meng‐ying , Liu Li‐kun , Cai Bin 
Published: October 2022

AbstractBackgroundDegenerative joint disease (DJD) of the temporomandibular joint (TMJ) is an important type of temporomandibular disorders (TMDs) potentially leading to orofacial pain and jaw dysfunction. Magnetic resonance imaging (MRI) is important in TMD diagnosis; however, its diagnostic ability for DJD remains unknown.ObjectiveTo explore the utility of MRI in diagnosing DJD according to the latest diagnostic criteria for TMD and detecting condylar bone abnormalities and their severity.MethodsOverall, 122 participants were examined using cone‐beam computed tomography (CBCT) and MRI. The sensitivity, specificity and accuracy of MRI for detecting DJD and different types of TMJ condylar bone abnormalities were calculated (considering CBCT as gold standard); in addition, we tested MRI and CBCT's consistency in scoring five types of condylar bone abnormalities.ResultsThe sensitivity and specificity of MRI for DJD were 95.3% and 43.1%, respectively. The MRI sensitivities for condylar flattening, erosion, osteophytes, sclerosis and cysts were 98.6%, 96.2%, 79.4%, 50%, and 79.2% (specificity, 53.6%, 48.3%, 81.6%, 83.3%, and 88.2%, respectively), respectively. The consistency between MRI and CBCT in assessing the severity of condylar bone abnormalities was fair‐to‐moderate (kappa coefficient: 0.278–0.491). The inter‐observer consistency for CBCT was good, whereas for MRI, it was relatively poor.ConclusionMRI can detect DJD and condylar bone abnormalities. However, MRI could not efficiently detect the severity of condylar bone abnormalities.
The impact of crime on firm entry
Authors: Barbieri Nicolò , Rizzo Ugo 
Published: October 2022

AbstractThe article investigates the effect of crime on firm entry rates in Italian provinces over the period 2007–2016. The extant literature focuses mainly on the relationship between crime and the sorting of new businesses. The present paper contributes to this stream of work by estimating the effect of crime on the overall propensity to engage in entrepreneurial activities across a national territory. We measure the extent to which property and violent crime affect firm entry rates using an instrumental variable approach in which the instrument for criminal activity is the effective abortion rate. Our findings suggest that crime has a negative, sizable impact on firm entry. The results are robust to alternative instrumental variables and firm entry indicators. This empirical exercise emphasizes the need to consider loss of new business activities as a downstream effect when computing the social costs of crime.
Left ventricular outflow tract obstruction caused by a congenital accessory mitral valve leaflet and treated by open‐heart surgery in a young dog
Authors: Yaginuma Y. , Matsuura K. , Yamada S. , Yoshida T. , Hasegawa M. 
Published: October 2022

A 3‐month‐old Shetland sheepdog presented with a loud ejection murmur and exercise intolerance. Echocardiography revealed an accessory mitral valve leaflet, characterised by a valve‐like structure separate from the mitral valve seen in the subaortic region of the ventricular septum. The left ventricular outflow tract was partially obstructed with a pressure gradient of 12 mmHg. Accessory mitral valve leaflet resection and mitral valvuloplasty were performed during open‐heart surgery. Histology performed on the membrane‐like structures were indicative of fibrous connective tissues. Postoperative echocardiography confirmed removal of the valve‐like structure with resolution of the left ventricular outflow tract obstruction. The pressure gradient was decreased to 4.6 mmHg. The dog was in good condition and no further treatment was required 5 months after surgery. Both cardiac troponin I and NT‐proBNP were markedly decreased. In this dog, surgical resection combined with mitral valve plasty resolved the left ventricular outflow tract obstruction and the clinical signs.