bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta
Authors: Machín Cynthia , Corripio-Miyar Yolanda , Hernández Julia N. , Pérez-Hernández Tara , Hayward Adam D. , Wright Harry W. , Price Daniel R. G. , Matthews Jacqueline B. , McNeilly Tom N. , Nisbet Alasdair J. , González Jorge F. 
Published: June 2021

AbstractDue to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.
Ulam–Hyers–Mittag-Leffler stability for tripled system of weighted fractional operator with TIME delay
Authors: Almalahi Mohammed A. , Panchal Satish K. , Jarad Fahd , Abdeljawad Thabet 
Published: June 2021

AbstractThis study is aimed to investigate the sufficient conditions of the existence of unique solutions and the Ulam–Hyers–Mittag-Leffler (UHML) stability for a tripled system of weighted generalized Caputo fractional derivatives investigated by Jarad et al. (Fractals 28:2040011 2020) in the frame of Chebyshev and Bielecki norms with time delay. The acquired results are obtained by using Banach fixed point theorems and the Picard operator (PO) method. Finally, a pertinent example of the results obtained is demonstrated.
Aggressive infantile myofibromatosis with intestinal involvement
Authors: Römer Tristan , Wagner Norbert , Braunschweig Till , Meyer Robert , Elbracht Miriam , Kontny Udo , Moser Olga 
Published: June 2021

Abstract
Background
Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations in PDGFRB have been identified as the most common molecular defect in familial IM.

Case presentation
We here describe an infant with PDGFRB-driven IM with multiple tumors at different sites, including intestinal polyposis with hematochezia, necessitating temporary chemotherapy.

Conclusions
PDGFRB-driven IM is clinically challenging due to its fluctuating course and multiple organ involvement in the first years of life. Early molecular genetic analysis is necessary to consider tyrosine kinase inhibitor treatment in case of aggressive visceral lesions.
SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma
Authors: Wu Jian , Zhang Min , Faruq Omar , Zacksenhaus Eldad , Chen Wenming , Liu Aijun , Chang Hong 
Published: June 2021

Abstract
Background
SMAD1, a central mediator in TGF-β signaling, is involved in a broad range of biological activities including cell growth, apoptosis, development and immune response, and is implicated in diverse type of malignancies. Whether SMAD1 plays an important role in multiple myeloma (MM) pathogenesis and can serve as a therapeutic target are largely unknown.

Methods
Myeloma cell lines and primary MM samples were used. Cell culture, cytotoxicity and apoptosis assay, siRNA transfection, Western blot, RT-PCR, Soft-agar colony formation, and migration assay, Chromatin immunoprecipitation (Chip), animal xenograft model studies and statistical analysis were applied in this study.

Results
We demonstrate that SMAD1 is highly expressed in myeloma cells of MM patients with advanced stages or relapsed disease, and is associated with significantly shorter progression-free and overall survivals. Mechanistically, we show that SMAD1 is required for TGFβ-mediated proliferation in MM via an ID1/p21/p27 pathway. TGF-β also enhanced TNFα-Induced protein 8 (TNFAIP8) expression and inhibited apoptosis through SMAD1-mediated induction of NF-κB1. Accordingly, depletion of SMAD1 led to downregulation of NF-κB1 and TNFAIP8, resulting in caspase-8-induced apoptosis. In turn, inhibition of NF-κB1 suppressed SMAD1 and ID1 expression uncovering an autoregulatory loop. Dorsomorphin (DM), a SMAD1 inhibitor, exerted a dose-dependent cytotoxic effect on drug-resistant MM cells with minimal cytotoxicity to normal hematopoietic cells, and further synergized with the proteasomal-inhibitor bortezomib to effectively kill drug-resistant MM cells in vitro and in a myeloma xenograft model.

Conclusions
This study identifies SMAD1 regulation of NF-κB1/TNFAIP8 and ID1-p21/p27 as critical axes of MM drug resistance and provides a potentially new therapeutic strategy to treat drug resistance MM through targeted inhibition of SMAD1.
Real-time automatic uncertainty estimation of coseismic single rectangular fault model using GNSS data
Authors: Ohno Keitaro , Ohta Yusaku , Kawamoto Satoshi , Abe Satoshi , Hino Ryota , Koshimura Shunichi , Musa Akihiro , Kobayashi Hiroaki 
Published: June 2021

AbstractRapid estimation of the coseismic fault model for medium-to-large-sized earthquakes is key for disaster response. To estimate the coseismic fault model for large earthquakes, the Geospatial Information Authority of Japan and Tohoku University have jointly developed a real-time GEONET analysis system for rapid deformation monitoring (REGARD). REGARD can estimate the single rectangular fault model and slip distribution along the assumed plate interface. The single rectangular fault model is useful as a first-order approximation of a medium-to-large earthquake. However, in its estimation, it is difficult to obtain accurate results for model parameters due to the strong effect of initial values. To solve this problem, this study proposes a new method to estimate the coseismic fault model and model uncertainties in real time based on the Bayesian inversion approach using the Markov Chain Monte Carlo (MCMC) method. The MCMC approach is computationally expensive and hyperparameters should be defined in advance via trial and error. The sampling efficiency was improved using a parallel tempering method, and an automatic definition method for hyperparameters was developed for real-time use. The calculation time was within 30 s for 1 × 106samples using a typical single LINUX server, which can implement real-time analysis, similar to REGARD. The reliability of the developed method was evaluated using data from recent earthquakes (2016 Kumamoto and 2019 Yamagata-Oki earthquakes). Simulations of the earthquakes in the Sea of Japan were also conducted exhaustively. The results showed an advantage over the maximum likelihood approach with a priori information, which has initial value dependence in nonlinear problems. In terms of application to data with a small signal-to-noise ratio, the results suggest the possibility of using several conjugate fault models. There is a tradeoff between the fault area and slip amount, especially for offshore earthquakes, which means that quantification of the uncertainty enables us to evaluate the reliability of the fault model estimation results in real time.
Experimental validation of absolute SPECT/CT quantification for response monitoring in patients with coronary artery disease
Authors: van de Burgt Alina , Dibbets-Schneider Petra , Slump Cornelis H. , Scholte Arthur J. H. A. , Atsma Douwe E. , de Geus-Oei Lioe-Fee , van Velden Floris H. P. 
Published: June 2021

Abstract
Background
Quantitative SPECT enables absolute quantification of uptake in perfusion defects. The aim of this experimental study is to assess quantitative accuracy and precision of a novel iterative reconstruction technique (Evolution; GE Healthcare) for the potential application of response monitoring using 99mTc-tetrofosmin SPECT/CT in patients with coronary artery disease (CAD).

Methods
Acquisitions of an anthropomorphic torso phantom with cardiac insert containing defects (with varying sizes), filled with 99mTc-pertechnetate, were performed on a SPECT/CT (Discovery 670 Pro, GE Healthcare). Subsequently, volumes of interest of the defects were manually drawn on CT to assess the recovery coefficient (RC). Bull’s eye plots were composed to evaluate the uptake per segment. Finally, 99mTc-tetrofosmin SPECT/CT scans of 10 CAD patients were used to illustrate clinical application.

Results
The phantom study indicated that Evolution showed convergence after 7 iterations and 10 subsets. The average repeatability deviation of all configurations was 2.91% and 3.15% (%SD mean) for filtered (Butterworth) and unfiltered data, respectively. The accuracy after post-filtering was lower compared to the unfiltered data with a mean (SD) RC of 0.63 (0.05) and 0.70 (0.07), respectively (p < 0.05). More artificial defects were found on Bull’s eye plots created with the unfiltered data compared to filtered data. Eight out of ten patients showed significant changes in uptake before and after treatment (p < 0.05).

Conclusion
Quantification of 99mTc-tetrofosmin SPECT/CT seems feasible for CAD patients when 7 iterations (10 subsets), Butterworth post-filtering (cut off frequency 0.52 in cycles/cm, order of 5) and manual CT-delineation are applied. However, future prospective patient studies are required for clinical application.
Development of a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis
Authors: Carswell Claire Elizabeth , Reid Joanne , Walsh Ian , Johnston William , Lee Jenny B. , McAneney Helen , Mullan Robert , Nelson Hugh , Matthews Michael , Weatherup Elizabeth , Spencer Andrea , Michelo Jean , Quail Anne , Kielty Grainne , Mackenzie Alistair , Elliott Jenny , Noble Helen 
Published: June 2021

Abstract
Background
Patients with end-stage kidney disease who receive haemodialysis experience a protracted treatment regimen that can result in an increased risk of depression and anxiety. Arts-based interventions could address this unique issue; however, no arts-based interventions have been developed for delivery within a haemodialysis unit and evaluation within a randomised controlled trials (RCTs).

Aim
To develop a complex arts-based intervention for patients with end-stage kidney disease whilst receiving haemodialysis.

Methods
The development process utilised the Arts in Health framework (Fancourt, 2017). The framework was addressed through the establishment of an interdisciplinary advisory group, collaboration and consultation with stakeholders, a scoping and realist review, shadowing of artists-in-residence, personal arts practice and logic modelling.

Results
The intervention involved six 1-h long, one-to-one facilitated sessions focused on creative writing and visual art. Patients could choose between art form and self-select a subject matter. The sessions had a primary focus on skill development and were delivered using principles derived from the psychological theory of flow.

Conclusion
The Arts in Health framework provided an appropriate and pragmatic approach to intervention development. Complex arts-based interventions can be developed for the purpose of evaluation within a trial framework. This intervention was designed to strike a balance between standardised components, and a person-centred approach necessary to address existential boredom.
Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment
Authors: Kim Seong-Jong , Han Hye Hyeon , Hahn Sei Kwang 
Published: June 2021

Abstract

Background
Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD.

Methods
We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD.

Results
HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes.

Conclusion
HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.
Maltese as a foreign language educators’ acquisition of intercultural capabilities
Authors: Żammit Jacqueline 
Published: June 2021

AbstractThis study sought to understand how teachers of Maltese as a foreign language (MFL) develop intercultural capabilities by exploring the importance of intercultural competence (IC) to MFL teachers, the characteristics of interculturally competent MFL educators, and the ways in which educators develop IC. The study adopted the interpretivist paradigm and a case study research design to collect qualitative data. Seventeen MFL teachers of adult learners were purposefully selected because they all taught MFL to non-native adults. These educators were interviewed, by answering the researcher’s ten unstructured questions. A smartphone was used to record the interviewees. Findings regarding the perceptions of the teachers who were interviewed are as follows. Firstly, the participants stated that IC is important for MFL teachers because it helps them to embrace diversity, to help adult learners to learn the target language (i.e. Maltese) better, and to be sensitive and accommodative to learners from different backgrounds. Secondly, according to the participants, an interculturally capable person is one who knows their own culture and others’ cultural aspects, respects and accepts other cultures. It was also found that teachers develop intercultural capabilities through learning at a school and by visiting other countries and being immersed in the cultures of those countries. The implications of the findings as supported by existing literature, are that IC is important for foreign language teachers and as a result, intercultural training, learning through interactions with others and visits to other countries are necessary to develop intercultural capabilities.
Etheno adducts: from tRNA modifications to DNA adducts and back to miscoding ribonucleotides
Authors: Guengerich F. Peter , Ghodke Pratibha P. 
Published: June 2021

AbstractEtheno (and ethano) derivatives of nucleic acid bases have an extra 5-membered ring attached. These were first noted as wyosine bases in tRNAs. Some were fluorescent, and the development of etheno derivatives of adenosine, cytosine, and guanosine led to the synthesis of fluorescent analogs of ATP, NAD+, and other cofactors for use in biochemical studies. Early studies with the carcinogen vinyl chloride revealed that these modified bases were being formed in DNA and RNA and might be responsible for mutations and cancer. The etheno bases are also derived from other carcinogenic vinyl monomers. Further work showed that endogenous etheno DNA adducts were present in animals and humans and are derived from lipid peroxidation. The chemical mechanisms of etheno adduct formation involve reactions with bis-electrophiles generated by cytochrome P450 enzymes or lipid peroxidation, which have been established in isotopic labeling studies. The mechanisms by which etheno DNA adducts miscode have been studied with several DNA polymerases, aided by the X-ray crystal structures of these polymerases in mispairing situations and in extension beyond mispairs. Repair of etheno DNA adduct damage is done primarily by glycosylases and also by the direct action of dioxygenases. Some human DNA polymerases (η, κ) can insert bases opposite etheno adducts in DNA and RNA, and the reverse transcriptase activity may be of relevance with the RNA etheno adducts. Further questions involve the extent that the etheno adducts contribute to human cancer.
An Axin2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a Chinese female monochorionic diamniotic twin family
Authors: Xu Jin , Yan Qing , Song Chengcheng , Liang Jingjia , Zhao Liang , Zhang Xin , Weng Zhenkun , Xu Cheng , Liu Qian , Xu Shuqin , Pang Lu , Zhang Liye , Sun Yuan , Wang Gang , Gu Aihua 
Published: June 2021

Abstract
Background
Craniosynostosis, defined as premature fusion of one or more cranial sutures, affects approximately 1 in every 2000–2500 live births. Sagittal craniosynostosis (CS), the most prevalent form of isolated craniosynostosis, is caused by interplay between genetic and perinatal environmental insults. However, the underlying details remain largely unknown.

Methods
The proband (a female monochorionic twin diagnosed with CS), her healthy co-twin sister and parents were enrolled. Obstetric history was extracted from medical records. Genetic screening was performed by whole exome sequencing (WES) and confirmed by Sanger sequencing. Functional annotation, conservation and structural analysis were predicted in public database. Phenotype data of Axin2 knockout mice was downloaded from The International Mouse Phenotyping Consortium (IMPC, http://www.mousephenotype.org).

Results
Obstetric medical records showed that, except for the shared perinatal risk factors by the twins, the proband suffered additional persistent breech presentation and intrauterine growth restriction. We identified a heterozygous mutation of Axin2 (c.1181G > A, p.R394H, rs200899695) in monochorionic twins and their father, but not in the mother. This mutation is not reported in Asian population and results in replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of Axin2 protein, which is highly conserved across species. The mutation was predicted to be potentially deleterious by in silico analysis. Incomplete penetrance of Axin2 haploinsufficiency was found in female mice.

Conclusions
Axin2 (c.1181G > A, p.R394H, rs200899695) mutation confers susceptibility and perinatal risk factors trigger the occurrence of sagittal craniosynostosis. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis in Chinese population.
Six-minute walk distance predicts hospitalization in elderly peritoneal dialysis patients: a single-center prospective cohort study
Authors: Yabe Hiroki , Imoto Yuto , Onoyama Ayaka , Ito Sayaka , Kono Kenichi , Moriyama Yoshifumi , Okada Keiko , Kasuga Hirotake , Ito Yasuhiko 
Published: June 2021

Abstract
Background
The risk of adverse events associated with peritoneal dialysis (PD) in elderly patients has not been thoroughly investigated. The purpose of this study was to assess the association between physical function and hospitalization in elderly PD patients.

Methods
This is a single-center prospective observational cohort study. Thirty-three aged patients (74.8 ± 5.9 years) participated in a 6-min walk distance, short physical performance battery (SPPB), lower extremity muscle strength, and 10-m walk speed. All subjects were followed until hospitalization to the end of the follow-up period.

Results
The 6-min walk distance was 332 ± 112.5 m; SPPB was 11 (8.3–12) points; the lower extremity muscle strength was 36.6 ± 9.6%; 10-m walk speed was 1.1± 0.2 m/s. During the follow-up, 19 patients (57.5%) were hospitalized. In the Kaplan-Meier survival analysis and log-rank test, a lower 6-min walk distance and PD vintage were significantly associated with hospitalization (p<0.05). After adjustment for PD vintage in Cox proportional analysis, the 6-min walk distance remained associated with hospitalization (95% confidence interval, 0.98–0.99).

Conclusion
Lower exercise tolerance assessed by the 6-min walk distance was significantly associated with hospitalization in elderly PD patients. Our findings indicate that measurement and intervention of exercise intolerance are essential to predict the clinical outcomes of elderly PD patients.

Trial registration
This study was prospectively registered at inception in the UMIN Clinical Trials Registry under identification number UMIN000038405.
Metamaterials subwavelength terahertz resonant cavities
Authors: Al-Rubaiee M. , Al-Janabi A. H. , Fleming S. C. , Argyros A. 
Published: June 2021

AbstractOne of the unique properties of metamaterials is the ability to manipulate electromagnetic waves at subwavelength scales, made possible by their structure on these scales. Here, rather than consider effective bulk properties, we consider the properties of microscopic features based on considering resonant unit cells. We used wire array metamaterials to form localized resonant cavities by changing the resonance frequency of one or more unit cells, surrounded by unchanged unit cells that do not support resonance for the propagating mode (i.e. forming a band gap). We validate our approach experimentally with electromagnetic waves in the terahertz range, demonstrating and characterizing subwavelength resonant cavities in this range. These resonant cavities can pave the way for ultra-compact subwavelength waveguides and other optical components.