bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urate-induced epigenetic modifications in myeloid cells
Authors: Badii M. , Gaal O. I. , Cleophas M. C. , Klück V. , Davar R. , Habibi E. , Keating S. T. , Novakovic B. , Helsen M. M. , Dalbeth N. , Stamp L. K. , Macartney-Coxson D. , Phipps-Green A. J. , Stunnenberg H. G. , Dinarello C. A. , Merriman T. R. , Netea M. G. , Crişan T. O. , Joosten L. A. B. 
Published: July 2021

Abstract
Objectives
Hyperuricemia is a metabolic condition central to gout pathogenesis. Urate exposure primes human monocytes towards a higher capacity to produce and release IL-1β. In this study, we assessed the epigenetic processes associated to urate-mediated hyper-responsiveness.

Methods
Freshly isolated human peripheral blood mononuclear cells or enriched monocytes were pre-treated with solubilized urate and stimulated with LPS with or without monosodium urate (MSU) crystals. Cytokine production was determined by ELISA. Histone epigenetic marks were assessed by sequencing immunoprecipitated chromatin. Mice were injected intraarticularly with MSU crystals and palmitate after inhibition of uricase and urate administration in the presence or absence of methylthioadenosine. DNA methylation was assessed by methylation array in whole blood of 76 participants with normouricemia or hyperuricemia.

Results
High concentrations of urate enhanced the inflammatory response in vitro in human cells and in vivo in mice, and broad-spectrum methylation inhibitors reversed this effect. Assessment of histone 3 lysine 4 trimethylation (H3K4me3) and histone 3 lysine 27 acetylation (H3K27ac) revealed differences in urate-primed monocytes compared to controls. Differentially methylated regions (e.g. HLA-G, IFITM3, PRKAB2) were found in people with hyperuricemia compared to normouricemia in genes relevant for inflammatory cytokine signaling.

Conclusion
Urate alters the epigenetic landscape in selected human monocytes or whole blood of people with hyperuricemia compared to normouricemia. Both histone modifications and DNA methylation show differences depending on urate exposure. Subject to replication and validation, epigenetic changes in myeloid cells may be a therapeutic target in gout.
Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy
Authors: Maredia Ashna , Guzzardi David , Aleinati Mohammad , Iqbal Fatima , Khaira Arshroop , Madhu Aiswarya , Wang Xuemei , Barker Alex J. , McCarthy Patrick M. , Fedak Paul W. M. , Greenway Steven C. 
Published: July 2021

Abstract
Background
The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy.

Methods
We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death.

Results
Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter.

Conclusions
In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.
Hepatic inflammatory pseudotumor-like follicular dendritic cell tumor: a case report
Authors: Pascariu Ana Daniela , Neagu Andreea Ioana , Neagu Andrei Valentin , Băjenaru Alexandru , Bețianu Cezar Iulian 
Published: July 2021

Abstract
Background
Inflammatory pseudotumor-like follicular dendritic cell sarcoma is a rare histological variant of follicular dendritic cell sarcoma involving typically the spleen and the liver, often linked to the presence of Epstein–Barr virus infection. Definite diagnosis of this type of sarcoma is difficult to make owing to nonspecific clinical and imaging findings and is based on histopathological features. Inflammatory pseudotumor-like follicular dendritic cell sarcoma is described as a low-aggressivity tumor with a favorable prognosis.

Case presentation
We report the case of a 34-year-old Caucasian woman, Epstein–Barr virus positive, diagnosed with hepatic inflammatory pseudotumor-like follicular dendritic cell sarcoma and surgically treated in November 2014, who developed 6 years later a recurrence for which she underwent once again surgical treatment. As far as we know, fewer than 30 reports of inflammatory pseudotumor-like follicular dendritic cell liver tumors have been reported in the English literature.

Conclusions
Although it is an uncommon tumor, inflammatory pseudotumor-like sarcoma is a diagnostic worth being taken in consideration, and surveillance is recommended owing to the possibility of recurrence.
Hypoglycemia as a cause of sudden cardiac arrest during cesarean delivery under spinal anesthesia: a case report and review of the literature
Authors: Tilahun Temesgen , Gudina Guteta 
Published: July 2021

Abstract
Background
Sudden cardiac arrest during spinal anesthesia is a rare event. However, its management by an unprepared team is difficult and carries poor outcomes. Hypoglycemia as the cause of sudden cardiac arrest is rarely reported. This case illustrates lifesaving procedures for sudden cardiac arrest secondary to hypoglycemia during cesarean delivery under spinal anesthesia.

Case summary
We report a case, from rural Ethiopia of sudden cardiac arrest secondary to hypoglycemia during cesarean delivery under spinal anesthesia. The case was successfully managed by a team of anesthetists and other operating teams. The mother and newborn were discharged from the hospital on the 7th postoperative day.

Conclusion
Hypoglycemia during cesarean delivery under spinal anesthesia can cause sudden cardiac arrest. Therefore, identifying patients at risk of developing hypoglycemia, monitoring the patient’s condition, and initiating prompt intervention at the first sign of cardiovascular instability is advisable. Determining serum blood glucose levels at admission to the labor ward and monitoring blood glucose levels during spinal anesthesia should be routine practices.
Mkx mediates tenogenic differentiation but incompletely inhibits the proliferation of hypoxic MSCs
Authors: Chen Guanyin , Fan Dong , Zhang Wangqian , Wang Shuning , Gu Jintao , Gao Yuan , He Lei , Li Weina , Zhang Cun , Li Meng , Zhang Yingqi , Liu Zhaohui , Hao Qiang 
Published: July 2021

Abstract
Background
Hypoxia has been shown to be able to induce tenogenic differentiation and proliferation of mesenchymal stem cells (MSCs) which lead hypoxia-induced MSCs to be a potential treatment for tendon injury. However, little is known about the mechanism underlying the tenogenic differentiation and proliferation process of hypoxic MSCs, which limited the application of differentiation-inducing therapies in tendon repair. This study was designed to investigate the role of Mohawk homeobox (Mkx) in tenogenic differentiation and proliferation of hypoxic MSCs.

Methods
qRT-PCR, western blot, and immunofluorescence staining were performed to evaluate the expression of Mkx and other tendon-associated markers in adipose-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) under hypoxia condition. Small interfering RNA technique was applied to observe the effect of Mkx levels on the expression of tendon-associated markers in normoxic and hypoxic BMSCs. Hypoxic BMSCs infected with Mkx-specific short hair RNA (shRNA) or scramble were implanted into the wound gaps of injured patellar tendons to assess the effect of Mkx levels on tendon repair. In addition, cell counting kit-8 assay, colony formation unit assay, cell cycle analysis, and EdU assay were adopted to determine the proliferation capacity of normoxic or hypoxic BMSCs infected with or without Mkx-specific shRNA.

Results
Our data showed that the expression of Mkx significantly increased in hypoxic AMSCs and increased much higher in hypoxic BMSCs. Our results also detected that the expression of tenogenic differentiation markers after downregulation of Mkx were significantly decreased not only in normoxic BMSCs, but also in hypoxic BMSCs which paralleled the inferior histological evidences, worse biomechanical properties, and smaller diameters of collagen fibrils in vivo. In addition, our in vitro data demonstrated that the optical density values, the clone numbers, the percentage of cells in S phage, and cell proliferation potential of both normoxic and hypoxic BMSCs were all significantly increased after knockdown of Mkx and were also significantly enhanced in both AMSCs and BMSCs in hypoxia condition under which the expression of Mkx was upregulated.

Conclusions
These findings strongly suggested that Mkx mediated hypoxia-induced tenogenic differentiation of MSCs but could not completely repress the proliferation of hypoxic MSCs.
Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model
Authors: Duan Ao , Shen Kai , Li Beichen , Li Cong , Zhou Hao , Kong Renyi , Shao Yuqi , Qin Jian , Yuan Tangbo , Ji Juan , Guo Wei , Wang Xipeng , Xue Tengfei , Li Lei , Huang Xinxin , Sun Yuqin , Cai Zhenyu , Liu Wei , Liu Feng 
Published: July 2021

Abstract
Background
Previous studies report that lipopolysaccharide (LPS)-preconditioned mesenchymal stem cells have enhanced trophic support and improved regenerative and repair properties. Extracellular vesicles secreted by synovial mesenchymal stem cells (EVs) can reduce cartilage damage caused by osteoarthritis (OA). Previous studies show that extracellular vesicles secreted by LPS-preconditioned synovial mesenchymal stem cells (LPS-pre EVs) can improve the response to treatment of osteoarthritis (OA). This study sought to explore effects of LPS-pre EVs on chondrocyte proliferation, migration, and chondrocyte apoptosis, as well as the protective effect of LPS-pre EVs on mouse articular cartilage.

Methods
Chondrocytes were extracted to explore the effect of LPS-pre EVs on proliferation, migration, and apoptosis of chondrocytes. In addition, the effect of LPS-pre EVs on expression level of important proteins of chondrocytes was explored suing in vitro experiments. Further, intraarticular injection of LPS-pre EVs was performed on the destabilization of the medial meniscus (DMM)-induced mouse models of OA to explore the therapeutic effect of LPS-pre EVs on osteoarthritis in vivo.

Results
Analysis showed that LPS-pre EVs significantly promoted proliferation and migration of chondrocytes and inhibited the apoptosis of chondrocytes compared with PBS and EVs. Moreover, LPS-pre EVs inhibited decrease of aggrecan and COL2A1 and increase of ADAMTS5 caused by IL-1β through let-7b. Furthermore, LPS-pre EVs significantly prevented development of OA in DMM-induced mouse models of OA.

Conclusions
LPS pretreatment is an effective and promising method to improve therapeutic effect of extracellular vesicles secreted from SMSCs on OA.
Sexual dimorphism of monocyte transcriptome in individuals with chronic low-grade inflammation
Authors: So Jisun , Tai Albert K. , Lichtenstein Alice H. , Wu Dayong , Lamon-Fava Stefania 
Published: July 2021

AbstractSexual dimorphism in the immune system is evidenced by a higher prevalence of autoimmune diseases in women and higher susceptibility to infectious diseases in men. However, the molecular basis of these sex-based differences is not fully understood. We have characterized the transcriptome profiles of peripheral blood monocytes from males and postmenopausal females with chronic low-grade inflammation. We identified 41 sexually differentially expressed genes [adjustedpvalue (FDR) < 0.1], including genes involved in immune cell activation (e.g.,CEACAM1,FCGR2B, andSLAMF7) and antigen presentation (e.g.,AIM2,CD1E, andUBA1) with a higher expression in females than males. Moreover, signaling pathways of immune or inflammatory responses, including interferon (IFN) signaling [z-score = 2.45, -log(p) = 3.88], were found to be more upregulated in female versus male monocytes, based on a set of genes exhibiting sex-biased expression (p< 0.03). The contribution of IFN signaling to the sexual transcriptional differences was further confirmed by direct comparisons of the monocyte sex-biased genes with IFN signature genes (ISGs) that were previously curated in mouse macrophages. ISGs showed a greater overlap with female-biased genes than male-biased genes and a higher overall expression in female than male monocytes, particularly for the genes of antiviral and inflammatory responses to IFN. Given the role of IFN in immune defense and autoimmunity, our results suggest that sexual dimorphism in immune functions may be associated with more priming of innate immune pathways in female than male monocytes. These findings highlight the role of sex on the human immune transcriptome.
Persistent deficiency of mucosa-associated invariant T (MAIT) cells during alcohol-related liver disease
Authors: Zhang Yujue , Fan Yuanyuan , He Wei , Han Yi , Bao Huarui , Yang Renjun , Wang Bingbing , Kong Derun , Wang Hua 
Published: July 2021

Abstract
Background
Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear.

Results
In this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8.

Conclusions
Our findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.
Results on fixed circles and discs for $L_{ (\omega,C ) }$-contractions and related applications
Authors: Ameer Eskandar , Aydi Hassen , Nazam Muhammad , De la Sen Manuel 
Published: July 2021

AbstractIn this paper, we study the behavior of $L_{ ( \omega,C ) }$

L

(
ω
,
C
)

-contraction mappings and establish some results on common fixed circles and discs. We explain the significance of our main theorems through examples and applications.
Effectiveness of mycofiltration for removal of contaminants from water: a systematic review protocol
Authors: Mnkandla Sanele Michelle , Otomo Patricks Voua 
Published: July 2021

AbstractBackgroundMycofiltration is an environment friendly technology which involves the treatment of contaminated water by passing it through a network of fungal mycelium. This technology has gained momentum over the years, and the systematic review chartered in this protocol will compile and synthesise literature on mycofiltration studies, paying special attention to the types and levels of contaminants removed. The systematic review should provide insight into the removal efficiency of mycofiltration by synthesising the mycofiltration knowledge base. Moreover, the proposed contribution will inform further research and provide comprehensive information to relevant stakeholders, such as municipalities, which might be in need of interventions for alleviating wastewater-related pollution in surrounding water bodies.MethodsThis systematic review protocol is based on the question, “What is the effectiveness of mycofiltration for removal of contaminants from water?” A thorough search of peer reviewed journal articles and grey literature sources will be conducted on academic journal databases, websites, specialist sources such as environmental organisations as well social and networking sources. A supplemental search will also be performed by forward and backward citation tracing. A two-stage screening process at title, abstract and full text level, will be conducted, against predefined inclusion criteria. Studies that meet inclusion criteria will be subjected to quality assessment. Data will be extracted and compiled into a narrative synthesis and summarised into tables and figures. Meta-analysis will be performed where sufficient evidence-base allows.
Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson’s disease
Authors: He Shulei , Huang Lu , Shao Ci , Nie Tiejian , Xia Li , Cui Bozhou , Lu Fangfang , Zhu Lin , Chen Bolin , Yang Qian 
Published: July 2021

Abstract
Background
Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD.

Methods
A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants.

Results
WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD.

Conclusions
The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.
Risk assessment of soil erosion by using CORINE model in the western part of Syrian Arab Republic
Authors: Khallouf Alaa , Talukdar Swapan , Harsányi Endre , Abdo Hazem Ghassan , Mohammed Safwan 
Published: July 2021

AbstractBackgroundSoil erosion is a major threat to the natural ecosystem and agricultural sector in the western part of Lattakia Governorate, Syrian Arab Republic. The main goals of this research are to investigate erosion risk by using the Coordination of Information on the Environment (CORINE) Model and to prioritize areas for conservation practices. To achieve these goals, soil samples were collected from the field, the climatic data (i.e., rainfall) and Digital Elevation Model (DEM) were obtained and utilized to perform CORINE model in Geographic Information System (GIS) environment.ResultsThe results showed that only 13.2% of the study area was classified as high erodible. In addition, 45.24%, 49.15% and 5.29% of the study area were under low, moderate and high actual erosion risk, respectively. This research identified slope and land use/land cover as key factors responsible for soil erosion in the study area.ConclusionsThe CORINE model acknowledged as a good tool for predicting soil erosion and highlighting the areas affected by soil erosion in the study area with high precision.
A comprehensive analysis of copy number variation in a Turkish dementia cohort
Authors: Dehghani Nadia , Guven Gamze , Kun-Rodrigues Celia , Gouveia Catarina , Foster Kalina , Hanagasi Hasmet , Lohmann Ebba , Samanci Bedia , Gurvit Hakan , Bilgic Basar , Bras Jose , Guerreiro Rita 
Published: July 2021

AbstractBackgroundCopy number variants (CNVs) include deletions or multiplications spanning genomic regions. These regions vary in size and may span genes known to play a role in human diseases. As examples, duplications and triplications ofSNCAhave been shown to cause forms of Parkinson’s disease, while duplications ofAPPcause early onset Alzheimer’s disease (AD).ResultsHere, we performed a systematic analysis of CNVs in a Turkish dementia cohort in order to further characterize the genetic causes of dementia in this population. One hundred twenty-four Turkish individuals, either at risk of dementia due to family history, diagnosed with mild cognitive impairment, AD, or frontotemporal dementia, were whole-genome genotyped and CNVs were detected. We integrated family analysis with a comprehensive assessment of potentially disease-associated CNVs in this Turkish dementia cohort. We also utilized both dementia and non-dementia individuals from the UK Biobank in order to further elucidate the potential role of the identified CNVs in neurodegenerative diseases.We report CNVs overlapping the previously implicated genesZNF804A, SNORA70B, USP34, XPO1, and a locus on chromosome 9 which includes a cluster of olfactory receptors andABCA1. Additionally, we also describe novel CNVs potentially associated with dementia, overlapping the genesAFG1L, SNX3, VWDE, andBC039545.ConclusionsGenotyping data from understudied populations can be utilized to identify copy number variation which may contribute to dementia.