scholarly journals Development of an Early Prediction Model for Subarachnoid Hemorrhage With Genetic and Signaling Pathway Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Wanjing Lei ◽  
Han Zeng ◽  
Hua Feng ◽  
Xufang Ru ◽  
Qiang Li ◽  
...  
BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Leng ◽  
Dan Fan ◽  
Zhong Ren ◽  
Qiaoying Li

Abstract Background This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). Methods Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. Results Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. Conclusion LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.


2021 ◽  
Vol 1765 ◽  
pp. 147508
Author(s):  
İlker Güleç ◽  
Aslıhan Şengelen ◽  
Feyza Karagöz-Güzey ◽  
Evren Önay-Uçar ◽  
Burak Eren ◽  
...  

2018 ◽  
Vol 01 (01) ◽  
pp. 33-41
Author(s):  
Qin Bian ◽  
Shufen Liu ◽  
Yongjian Zhao ◽  
Jianhua Huang ◽  
Ziyin Shen

Objective: Icariin (ICA), an extract from epimedium, has been reported to be effective in promoting bone formation. The objective of the study is to search for the molecular targets of ICA in bone mesenchymal stem cells (bMSCs) from the mice with ovariectomy (OVX)-induced osteoporosis. Methods: Six-month-old Imprinting Control Region (ICR) mice that underwent OVX were treated with ICA. After three months, bone mass was evaluated by microcomputed tomography, morphometry and immunohistological detection. bMSCs were isolated from the femur and tibia to observe the self-renewal and differentiation capacities using colony-forming unit fibroblastic (CFU-F), colony-forming unit adipocyte (CFU-Adipo) and alkaline phosphatase (ALP) staining. In addition, microarray of bMSCs ex vivo was measured two weeks after ICA treatment and analyzed by heatmap and pathway analysis. The signaling pathway was further explored by western blot assay and inhibitors of p38 and ERK: SB203508 and PD98059. Results: [Formula: see text]CT displayed a decrease in bone mass for three months after OVX. ICA treatment increased the trabecular thickness (Tb.Th), osteoblast number while decreased osteoclast number, elevating osteocalcin (OC) protein levels in vivo and facilitating the self-renewal and osteoblastic differentiation of bMSCs ex vivo. Microarray data indicated ICA rescued several gene expressions that were dysregulated by OVX. Pathway analysis revealed that the core genes acted by ICA were highly involved in MAPK signaling pathway. Further study demonstrated ICA suppressed ERK while stimulated p38 phosphorylation to promote osteoblastic differentiation in vitro. Conclusion: ICA promotes osteoblastic differentiation of bMSCs in OVX mice. MAPK signaling pathway might be involved in the process.


Medicine ◽  
2021 ◽  
Vol 100 (8) ◽  
pp. e24901
Author(s):  
Li Liu ◽  
Lei Dong ◽  
Benping Zhang ◽  
Xi Chen ◽  
Xiaoqing Song ◽  
...  

2021 ◽  
Author(s):  
Celia ALVAREZ-ROMERO ◽  
Alicia MARTÍNEZ-GARCÍA ◽  
Jara Eloisa TERNERO-VEGA ◽  
Pablo DÍAZ-JIMÉNEZ ◽  
Carlos JIMÉNEZ-DE-JUAN ◽  
...  

BACKGROUND Due to the nature of health data, its sharing and reuse for research are limited by legal, technical and ethical implications. In this sense, to address that challenge, and facilitate and promote the discovery of scientific knowledge, the FAIR (Findable, Accessible, Interoperable, and Reusable) principles help organizations to share research data in a secure, appropriate and useful way for other researchers. OBJECTIVE The objective of this study was the FAIRification of health research existing datasets and applying a federated machine learning architecture on top of the FAIRified datasets of different health research performing organizations. The whole FAIR4Health solution was validated through the assessment of the generated model for real-time prediction of 30-days readmission risk in patients with Chronic Obstructive Pulmonary Disease (COPD). METHODS The application of the FAIR principles in health research datasets in three different health care settings enabled a retrospective multicenter study for the generation of federated machine learning models, aiming to develop the early prediction model for 30-days readmission risk in COPD patients. This prediction model was implemented upon the FAIR4Health platform and, finally, an observational prospective study with 30-days follow-up was carried out in two health care centers from different countries. The same inclusion and exclusion criteria were used in both retrospective and prospective parts of the study. RESULTS The prediction model for the 30-days hospital readmission risk was trained using the retrospective data of 4.944 COPD patients. The assessment of the prediction model was performed using the data of 100 recruited (22 from Spain and 78 from Serbia) out of 2070 observed (records viewed) patients in total for the observational prospective study from April 2021 to September 2021. The significant accuracy (0.98) and precision (0.25) of the prediction model generated upon the FAIR4Health platform was observed and, as a result, the generated prediction of 30-day readmission risk was confirmed in 87% of the cases. CONCLUSIONS A clinical validation was demonstrated through the implementation of federated machine learning models on top of the FAIRified datasets from different health research performing organizations, providing an assessment for predicting 30-days readmission risk in COPD patients. This demonstration allowed to state the relevance and need of implementing a FAIR data policy to facilitate data sharing and reuse in health research.


2020 ◽  
Vol 71 ◽  
pp. 144-149 ◽  
Author(s):  
Tokunori Kanazawa ◽  
Satoshi Takahashi ◽  
Yasuhiro Minami ◽  
Masahiro Jinzaki ◽  
Masahiro Toda ◽  
...  

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