bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key methylation differentially expressed genes in posterior fossa ependymoma based on epigenomic and transcriptome analysis
Authors: Wang Guanyi , Jia Yibin , Ye Yuqin , Kang Enming , Chen Huijun , Wang Jiayou , He Xiaosheng 
Published: April 2021

AbstractBackgroundPosterior fossa ependymoma (EPN-PF) can be classified into Group A posterior fossa ependymoma (EPN-PFA) and Group B posterior fossa ependymoma (EPN-PFB) according to DNA CpG island methylation profile status and gene expression. EPN-PFA usually occurs in children younger than 5 years and has a poor prognosis.MethodsUsing epigenome and transcriptome microarray data, a multi-component weighted gene co-expression network analysis (WGCNA) was used to systematically identify the hub genes of EPN-PF. We downloaded two microarray datasets (GSE66354 and GSE114523) from the Gene Expression Omnibus (GEO) database. The Limma R package was used to identify differentially expressed genes (DEGs), and ChAMP R was used to analyze the differential methylation genes (DMGs) between EPN-PFA and EPN-PFB. GO and KEGG enrichment analyses were performed using the Metascape database.ResultsGO analysis showed that enriched genes were significantly enriched in the extracellular matrix organization, adaptive immune response, membrane raft, focal adhesion, NF-kappa B pathway, and axon guidance, as suggested by KEGG analysis. Through WGCNA, we found that MEblue had a significant correlation with EPN-PF (R = 0.69, P = 1 × 10–08) and selected the 180 hub genes in the blue module. By comparing the DEGs, DMGs, and hub genes in the co-expression network, we identified five hypermethylated, lower expressed genes in EPN-PFA (ATP4B, CCDC151, DMKN, SCN4B, and TUBA4B), and three of them were confirmed by IHC.ConclusionssGSEA and GSVA analysis indicated that these five hub genes could lead to poor prognosis by inducing hypoxia, PI3K-Akt-mTOR, and TNFα-NFKB pathways. Further study of these dysmethylated hub genes in EPN-PF and the pathways they participate in may provides new ideas for EPN-PF treatment.
Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case–control study
Authors: Al-Daghri Nasser M. , Amer Osama E. , Alotaibi Naif H. , Aldisi Dara A. , Enani Mushira A. , Sheshah Eman , Aljohani Naji J. , Alshingetti Naemah , Alomar Suliman Y. , Alfawaz Hanan , Hussain Syed D. , Alnaami Abdullah M. , Sabico Shaun 
Published: April 2021

Abstract
Objectives
Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities.

Methods
In this multi-center, case–control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations.

Results
Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2–18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3–14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3–14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity.

Conclusions
Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.
Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept
Authors: Öman Anders , Dicksved Johan , Engstrand Lars , Berntson Lillemor 
Published: April 2021

AbstractBackgroundAlterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota.The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA.MethodsIn this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment.The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons.ResultsWe did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept.Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes.There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept.ConclusionsTreatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.
Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study
Authors: Marstein Henriette Schermacher , Godang Kristin , Flatø Berit , Sjaastad Ivar , Bollerslev Jens , Sanner Helga 
Published: April 2021

Abstract
Background
Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD.

Methods
JDM patients (n = 59) were examined median 16.8y (range 6.6–27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored.

Results
Reduced BMD Z-scores (<−1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively.

Conclusion
In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.
Is podocytopathy another image of renal affection in p-SLE?
Authors: Abdelnabi Hend H. 
Published: April 2021

AbstractBackgroundLupus podocytopathy (LP) is a renal affection described in systemic lupus erythematosus (SLE) patients with nephrotic range proteinuria, characterized by diffuse foot process effacement without immune deposits and glomerular proliferation. This study describes LP, its pathological features and outcomes of pediatric (p-SLE) patients in comparison to the usual lupus nephritis (LN) cases.MethodologyA retrospective cohort study conducted on a 10-year registration (2010–2019) of 140 p-SLE patients at the Pediatric Department, Tanta University. Histopathological analysis with light microscopy (LM) and immunofluorescence (IF) of all renal biopsies were evaluated according to the International Society of Nephrology Renal Pathology Society (ISN/RPS) grading system. In addition, some biopsies were examined with electron microscopy (EM).ResultsEighty-six p-SLE cases (61.4%) had renal involvement; seventy-nine biopsies (91.86%) of them met the classification criteria of LN as defined by ISN/RPS system. Five biopsies were normal (MCD) and two showed focal segmental sclerosis (FSGN) that did not meet any known classification of LN. Hence, they were reevaluated using EM that revealed diffuse effaced podocytes without glomerular sub-epithelial, endocapillary or basement membrane immune deposits, and were classified as having lupus podocytopathy, representing (8.14%) of all LN biopsies. Those seven cases showed good response to steroids with a complete remission duration of 3.40 ± 1.95 weeks. However, some case had 1–3 relapses during the duration of follow up.ConclusionsLP is a spectrum of p-SLE, not an association as it is related to disease activity and its initial presentation.
Suppression of neuroinflammation by an allosteric agonist and positive allosteric modulator of the α7 nicotinic acetylcholine receptor GAT107
Authors: Mizrachi Tehila , Marsha Oshrit , Brusin Karen , Ben-David Yael , Thakur Ganesh A. , Vaknin-Dembinsky Adi , Treinin Millet , Brenner Talma 
Published: April 2021

AbstractBackgroundThe α7 nicotinic acetylcholine receptor (α7 nAChR) negatively regulates the synthesis and release of pro-inflammatory cytokines by immune cells. Our previous studies showed that in encephalitogenic T cells, α7 nAChR expression is upregulated and that activation of the cholinergic system can attenuate experimental autoimmune encephalomyelitis (EAE). GAT107 is an allosteric agonist and positive allosteric modulator (ago-PAM) of α7 nAChR that can produce persistent activation of this receptor. Therefore, in the present study, we investigated the effect of GAT107 on neuroinflammation in EAE, the animal model used for the study of multiple sclerosis (MS) via α7 nAChR, and the inflammatory pathways involved.MethodsEAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35–55) in C57BL/6 mice. EAE mice were treated with the ago-PAM GAT107 or a placebo for 9 days, starting from the day of EAE induction. Clinical assessment and immunological evaluation of immune cells and cytokine production was performed.ResultsFollowing activation of the α7 nAChR by GAT107 during EAE, disease severity was significantly reduced by 70% and was correlated with a reduction in the extent of neuroinflammation in the CNS. The treatment reduced encephalitogenic T cell proliferation and the production of pro-inflammatory cytokines, as well as increased the production of the anti-inflammatory cytokine IL-10. Furthermore, the expression of immune cell markers was altered by GAT107 treatment, which induced a significant reduction in macrophages, dendritic cells, and B cells, as well as a reduction in anti-MOG35–55antibodies. Additionally, GAT107 was found to directly activate α7 nAChR in murine macrophage RAW264.7 cells and in human PBMCs derived from MS patients and healthy donors.ConclusionsOur results show that GAT107 can be a useful molecule for harnessing the cholinergic anti-inflammatory pathway for long-lasting and wide-ranging modulation and downregulation of neuroinflammation in EAE.
Design optimization of bidirectional arterial perfusion cannula
Authors: Abdel-Sayed Saad , Ferrari Enrico , Abdel-Sayed Philippe , Wilhelm Markus , von Segesser Ludwig-Karl , Berdajs Denis 
Published: April 2021

Abstract
Objectives
Determine if shortening the covered section of a self-expanding bidirectional arterial cannula, can enhance retrograde flow and thus reduce the risk of lower limb ischemia.

Methods
Outlet pressure vs flow rate was determined for three cannulas types: a 15F self-expanding bidirectional cannula having a covered section of 90 mm, the same cannula but with a shorter covered section of 60 mm, and a Biomedicus cannula as control. The performances of all the cannulas were compared using a computerized flow-bench with calibrated sensors and a centrifugal pump. Water retrograde flow was determined using a tank timer technique. Anterograde and retrograde flow rate versus outlet pressure were determined at six different pump speed.

Results
For each of the six pump speed, both bidirectional cannulas, 60-mm covered and 90-mm covered respectively, showed higher performance than Biomedicus cannula control, as demonstrated by higher flow rate and lower pressure. We also observed that for the bidirectional cannula with shorter covered section, i.e. 60 mm coverage, provides enhanced performance as compared to a 90-mm coverage. Finally, the flow rate and the corresponding pressure can be consistently measured by our experimental set-up with low variability.

Conclusions
The new configuration of a shorter covered section in a bidirectional self-expanding cannula design, may present an opportunity to overcome lower leg ischemia during extra-corporal life support with long term peripheral cannulation.
Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation
Authors: Zhao Juan , Li Hui , Chen Guangxin , Du Lijun , Xu Peiyan , Zhang Xiaoli , Xie Min , Cao Tiansheng , Li Haibo 
Published: April 2021

Abstract
Background
Aneuploidy is the most frequent cause of early-embryo abortion. Any defect in chromosome segregation would fail to satisfy the spindle assembly checkpoint (SAC) during mitosis, halting metaphase and causing aneuploidy. The mitotic checkpoint complex (MCC), comprising MAD1, MAD2, Cdc20, BUBR1 and BUB3, plays a vital role in SAC activation. Studies have confirmed that overexpression of MAD2 and BUBR1 can facilitate correct chromosome segregation and embryo stability. Research also proves that miR-125b negatively regulates MAD1 expression by binding to its 3′UTR. However, miR-125b, Mad1 and Bub3 gene expression in aneuploid embryos of spontaneous abortion has not been reported to date.

Methods
In this study, embryonic villi from miscarried pregnancies were collected and divided into two groups (aneuploidy and euploidy) based on High-throughput ligation-dependent probe amplification (HLPA) and Fluorescence in situ hybridization (FISH) analyses. RNA levels of miR-125b, MAD1 and BUB3 were detected by Quantitative real-time PCR (qRT-PCR); protein levels of MAD1 and BUB3 were analysed by Western blotting.

Results
statistical analysis (p < 0.05) showed that miR-125b and BUB3 were significantly down-regulated in the aneuploidy group compared to the control group and that MAD1 was significantly up-regulated. Additionally, the MAD1 protein level was significantly higher in aneuploidy abortion villus, but BUB3 protein was only mildly increased. Correlation analysis revealed that expression of MAD1 correlated negatively with miR-125b.

Conclusion
These results suggest that aneuploid abortion correlates positively with MAD1 overexpression, which might be caused by insufficient levels of miR-125b. Taken together, our findings first confirmed the negative regulatory mode between MAD1 and miR-125b, providing a basis for further mechanism researches in aneuploid abortion.
Mass transfer and flow characterization of novel algae-based nutrient removal system
Authors: Heyland Andreas , Roszell Jordan , Chau Jeremy , Chai Kevin , Eaton Andrew , Nolan Kathleen , Madden Kyle , Ahmed Wael H. 
Published: April 2021

Abstract
Background
Recirculating aquaculture systems (RAS) are an essential component of sustainable inland seafood production. Still, nutrient removal from these systems can result in substantial environmental problems, or present a major cost factor with few added value options. In this study, an innovative and energy-efficient algae based nutrient removal system (NRS) was developed that has the potential to generate revenue through algal commercialization. We optimized mass transfer in our NRS design using novel aeration and mixing technology, using air lift pumps and developed an original membrane cartridge for the continuous operation of nutrient removal and algae production. Specifically, we designed, manufactured and tested a 60-L NRS prototype. Based on specific airlift mixing conditions as well as concentration gradients, we assessed NRS nutrient removal capacity. We then examined the effects of different internal bioreactor geometries and radial orientations on the mixing efficiency.

Results
Using the start-up dynamic method, the overall mass transfer coefficient was found to be in the range of 0.00164–0.0074 $${\mathrm{s}}^{-1}$$

s

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1

, depending on flow parameters and we confirmed a scaling relationship of mass transfer across concentration gradients. We found the optimal Reynolds number to be 500 for optimal mass transfer, as higher Reynolds numbers resulted in a relatively reduced increase of mass transfer. This relationship between mass transfer and Reynolds number is critical to assess scalability of our system. Our results demonstrate an even distribution of dissolved oxygen levels across the reactor core, demonstrating adequate mixing by the airlift pump, a critical consideration for optimal algal growth. Distribution of dissolved gases in the reactor was further assessed using flow visualization in order to relate the bubble distribution to the mass transfer capabilities of the reactor. We run a successful proof of principle trial using the green alga Dunaliella tertiolecta to assess mass transfer of nutrients across the membrane and biomass production.

Conclusions
Manipulation of the concentration gradient across the membrane demonstrates a more prominent role of airlift mixing at higher concentration gradients. Specifically, the mass transfer rate increased threefold when the concentration gradient was increased 2.5-fold. We found that we can grow algae in the reactor chamber at rates comparable to those of other production systems and that the membrane scaffolds effectively remove nutrients form the wastewater. Our findings provide support for scalability of the design and support the use of this novel NRS for nutrient removal in aquaculture and potentially other applications.
Cold-inducible RNA-binding protein (CIRP) potentiates uric acid-induced IL-1β production
Authors: Fujita Yuya , Yago Toru , Matsumoto Haruki , Asano Tomoyuki , Matsuoka Naoki , Temmoku Jumpei , Sato Shuzo , Yashiro-Furuya Makiko , Suzuki Eiji , Watanabe Hiroshi , Kawakami Atsushi , Migita Kiyoshi 
Published: April 2021

Abstract
Background
Gout is an autoinflammatory disease driven by interleukin-1 (IL-1) induction in response to uric acid crystals. IL-1β production is dependent on inflammasome activation, which requires a priming signal, followed by an activating signal. The cold-inducible RNA-binding protein (CIRP) has been recently identified as a damage-associated molecular pattern (DAMP). In this study, we evaluated the roles of CIRP in monosodium urate (MSU)-mediated IL-1β secretion using human neutrophils.

Methods
Human neutrophils were stimulated by MSU in the presence or absence of CIRP priming to determine NLRP3 inflammasome activation and subsequent caspase-1 activation and IL-1β production. Cellular supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) to determine the presence of IL-1β or caspase-1 (p20). The cellular supernatants and lysates were also analyzed by immunoblotting using anti-cleaved IL-1β or anti-cleaved caspase-1 antibodies.

Results
Neither CIRP nor MSU stimulation alone induced sufficient IL-1β secretion from neutrophils. However, MSU stimulation induced IL-1β secretion from CIRP-primed neutrophils in a dose-dependent manner. This MSU-induced IL-1β secretion from CIRP-primed neutrophils was accompanied by the induction of cleaved IL-1β (p17), which was inhibited by the pretreatment of MCC950, a specific inhibitor for NLRP3. Furthermore, cleaved caspase-1 was induced in the cellular lysates of CIRP/MSU-treated neutrophils. Additionally, CIRP stimulation induced the protein expression of pro-IL-1β in neutrophils.

Conclusions
Our data indicate that CIRP, an endogenous stress molecule, triggers uric acid-induced mature IL-1β induction as a priming stimulus for NLRP3 inflammasome in human neutrophils. We propose that CIRP acts as an important proinflammatory stimulant that primes and activates inflammasome and pro-IL-1β processing in response to uric acid in innate immune cells.
An access control model for the Internet of Things based on zero-knowledge token and blockchain
Authors: Song Lihua , Ju Xinran , Zhu Zongke , Li Mengchen 
Published: April 2021

AbstractInformation security has become a hot topic in Internet of Things (IoT), and traditional centralized access control models are faced with threats such as single point failure, internal attack, and central leak. In this paper, we propose a model to improve the access control security of the IoT, which is based on zero-knowledge proof and smart contract technology in the blockchain. Firstly, we deploy attribute information of access control in the blockchain, which relieves the pressure and credibility problem brought by the third-party information concentration. Secondly, encrypted access control token is used to gain the access permission of the resources, which makes the user's identity invisible and effectively avoids attribute ownership exposure problem. Besides, the use of smart contracts solves the problem of low computing efficiency of IoT devices and the waste of blockchain computing power resources. Finally, a prototype of IoT access control system based on blockchain and zero-knowledge proof technology is implemented. The test analysis results show that the model achieves effective attribute privacy protection, compared with the Attribute-Based Access Control model of the same security level, the access efficiency increases linearly with the increase of access scale.