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  • Frontiers Media SA  (8)
  • 1
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-9-2)
    Abstract: Background: Linking genotypic changes to phenotypic traits based on machine learning methods has various challenges. In this study, we developed a workflow based on bioinformatics and machine learning methods using transcriptomic data for sepsis obtained at the first clinical presentation for predicting the risk of sepsis. By combining bioinformatics with machine learning methods, we have attempted to overcome current challenges in predicting disease risk using transcriptomic data. Methods: High-throughput sequencing transcriptomic data processing and gene annotation were performed using R software. Machine learning models were constructed, and model performance was evaluated by machine learning methods in Python. The models were visualized and interpreted using the Shapley Additive explanation (SHAP) method. Results: Based on the preset parameters and using recursive feature elimination implemented via machine learning, the top 10 optimal genes were screened for the establishment of the machine learning models. In a comparison of model performance, CatBoost was selected as the optimal model. We explored the significance of each gene in the model and the interaction between each gene through SHAP analysis. Conclusion: The combination of CatBoost and SHAP may serve as the best-performing machine learning model for predicting transcriptomic and sepsis risks. The workflow outlined may provide a new approach and direction in exploring the mechanisms associated with genes and sepsis risk.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2020-3-18)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2020-3-18)
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2737824-X
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-2-23)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-2-23)
    Abstract: Peritoneal dialysis (PD) is an effective replacement therapy for end-stage renal disease patients. However, long-term exposure to peritoneal dialysate will lead to the development of peritoneal fibrosis. Epigenetics has been shown to play an important role in peritoneal fibrosis, but the role of histone deacetylases 8 (HDAC8) in peritoneal fibrosis have not been elucidated. In this research, we focused on the role and mechanisms of HDAC8 in peritoneal fibrosis and discussed the mechanisms involved. Methods We examined the expression of HDAC8 in the peritoneum and dialysis effluent of continuous PD patients. Then we assessed the role and mechanism of HDAC8 in peritoneal fibrosis progression in mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis fluid by using PCI-34051. In vitro, TGF-β1 or IL-4 were used to stimulate human peritoneal mesothelial cells (HPMCs) or RAW264.7 cells to establish two cell injury models to further explore the role and mechanism of HDAC8 in epithelial-mesenchymal transition (EMT) and macrophage polarization. Results We found that HDAC8 expressed highly in the peritoneum from patients with PD-related peritonitis. We further revealed that the level of HDAC8 in the dialysate increased over time, and HDAC8 was positively correlated with TGF-β1 and vascular endothelial growth factor (VEGF), and negatively correlated with cancer antigen 125. In mouse model of peritoneal fibrosis induced by high glucose dialysate, administration of PCI-34051 (a selective HDAC8 inhibitor) significantly prevented the progression of peritoneal fibrosis. Treatment with PCI-34051 blocked the phosphorylation of epidermal growth factor receptor (EGFR) and the activation of its downstream signaling pathways ERK1/2 and STAT3/HIF-1α. Inhibition of HDAC8 also reduced apoptosis. In vitro, HDAC8 silencing with PCI-34051 or siRNA inhibited TGF-β1-induced EMT and apoptosis in HPMCs. In addition, continuous high glucose dialysate or IL-4 stimulation induced M2 macrophage polarization. Blockade of HDAC8 reduced M2 macrophage polarization by inhibiting the activation of STAT6 and PI3K/Akt signaling pathways. Conclusions We demonstrated that HDAC8 promoted the EMT of HPMCs via EGFR/ERK1/2/STAT3/HIF-1α, induced M2 macrophage polarization via STAT6 and PI3K/Akt signaling pathways, and ultimately accelerated the process of peritoneal fibrosis.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Genetics Vol. 14 ( 2023-5-5)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 14 ( 2023-5-5)
    Abstract: Endothelial cells (ECs) with senescence-associated secretory phenotypes (SASP) have been identified as a key mechanism of aging that contributes to various age-related kidney diseases. In this study, we used single-cell RNA sequencing (scRNA-seq) to create a transcriptome atlas of murine renal ECs and identify transcriptomic changes that occur during aging. We identified seven different subtypes of renal ECs, with glomerular ECs and angiogenic ECs being the most affected by senescence. We confirmed our scRNA-seq findings by using double immunostaining for an EC marker (CD31) and markers of specialized EC phenotypes. Our analysis of the dynamics of capillary lineage development revealed a chronic state of inflammation and compromised glomerular function as prominent aging features. Additionally, we observed an elevated pro-inflammatory and pro-coagulant microenvironment in aged glomerular ECs, which may contribute to age-related glomerulosclerosis and renal fibrosis. Through intercellular communication analysis, we also identified changes in signaling involved in immune regulation that may contribute to a hostile microenvironment for renal homeostasis and function. Overall, our findings provide new insights into the mechanisms of aging in the renal endothelium and may pave the way for the discovery of diagnostic biomarkers and therapeutic interventions against age-related kidney diseases.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606823-0
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychiatry Vol. 13 ( 2022-9-12)
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 13 ( 2022-9-12)
    Abstract: Stroke is a major cause of mortality and long-term physical and cognitive impairment. This study aims to: (1) examine the prevalence of depressive symptoms, disability and pain among Chinese adults with stroke; (2) test the associations of functional limitations and body pain with occurrence of depressive symptoms; (3) investigate gender and urban-rural disparities in these associations. Methods This study utilized the data from the China Health and Retirement Longitudinal Study in 2018, involving 969 patients with stroke among 17,970 participants aged ≥ 45 years. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CES-D) Scale. We performed multivariable logistic regression models to estimate the associations between activities of daily life (ADL), instrumental activities of daily life (IADL) and pain with depressive symptoms. Results Depressive symptoms were found among 40.2% of stroke patients, with a higher prevalence in females (48.2%) than males (32.7%). Prevalence of ADL limitations, IADL limitations and pain among stroke patients were 39.2, 49.8 and 14.0%, respectively. ADL and IADL limitations and pain were more prevalent among females and residents in rural areas. Multivariable regression analyses showed a significant association between ADL limitation (OR = 1.535, 95% CI = 1.168, 2.018), IADL limitation (OR = 1.666, 95% CI = 1.260, 2.203) and pain (OR = 2.122, 95% CI = 1.466, 3.073) with depressive symptoms. Stratified analyses revealed stronger associations among urban residents. Females had a higher association of ADL and IADL with depressive symptoms but similar in that of pain to the males. The impact of ADL and IADL in male patients is higher than in females, but the impact of pain on depressive symptoms is higher in female patients. Conclusion Depressive symptoms are common amongst post-stroke patients in China and are significantly associated with functional disability and physical pain. Our findings have implications for practitioners on the early assessment of pain and depression after stroke. Future research should explore effective intervention measures for physical-mental stroke complications.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564218-2
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  • 6
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-3)
    Abstract: To develop an artificial intelligence (AI) system that can predict optical coherence tomography (OCT)-derived high myopia grades based on fundus photographs. Methods In this retrospective study, 1,853 qualified fundus photographs obtained from the Zhongshan Ophthalmic Center (ZOC) were selected to develop an AI system. Three retinal specialists assessed corresponding OCT images to label the fundus photographs. We developed a novel deep learning model to detect and predict myopic maculopathy according to the atrophy (A), traction (T), and neovascularisation (N) classification and grading system. Furthermore, we compared the performance of our model with that of ophthalmologists. Results When evaluated on the test set, the deep learning model showed an area under the receiver operating characteristic curve (AUC) of 0.969 for category A, 0.895 for category T, and 0.936 for category N. The average accuracy of each category was 92.38% (A), 85.34% (T), and 94.21% (N). Moreover, the performance of our AI system was superior to that of attending ophthalmologists and comparable to that of retinal specialists. Conclusion Our AI system achieved performance comparable to that of retinal specialists in predicting vision-threatening conditions in high myopia via simple fundus photographs instead of fundus and OCT images. The application of this system can save the cost of patients' follow-up, and is more suitable for applications in less developed areas that only have fundus photography.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 7
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 10 ( 2023-8-24)
    Abstract: The study aimed to assess the accuracy of the FY-L formula in calculating intraocular lens (IOL) power after small-incision lenticule extraction (SMILE). Methods For the post-SMILE IOL calculation of the same eye, the IOL power targeting the pre-SMILE eyes' lowest myopic refractive error was used. The FY-L formula, the Emmetropia Verifying Optical Formula (EVO-L), the Barrett True-K no history, and the Shammas-L, respectively, were used to calculate the predicted refractive error of target IOL power. A comparison was made between the change in spherical equivalent induced by SMILE (SMILE-Dif) and the variance between IOL-Dif (IOL-Induced Refractive Error) before and after SMILE. The prediction error (PE) was defined as SMILE-Dif minus IOL-Dif. The proportion of eyes with PEs within ±0.25 D, ±0.50 D, ±0.75 D, and ±1.00 D, the numerical and absolute prediction errors (PEs and AEs), and the median absolute error (MedAE) were compared. Results In total, 80 eyes from 42 patients who underwent SMILE were included in the study. The FY-L formula generated the sample's lowest mean PE (0.06 ± 0.76 D), MAE (0.58 ± 0.50 D), and MedAE (0.47 D), respectively. The PEs in ±0.25 D, ±0.50 D, ±0.75 D, and ±1.00 D comprised 28.8%, 46.3%, 70.0%, and 87.5%, respectively, for the FY-L formula. Compared to other formulas, the FY-L formula produced the highest value with PEs for the percentage of eyes in ±0.50 D, ±0.75 D, and ±1.00 D. Conclusion This study demonstrates that the FY-L formula provides satisfactory outcomes in estimating the IOL power in the eyes after SMILE.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2775999-4
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  • 8
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-2-25)
    Abstract: RNA methylation has recently emerged as an important category of epigenetic modifications, which plays diverse physiopathological roles in various cancers. Recent studies have confirmed the presence of 5-methylcytosine (m 5 C) modification on mammalian mRNAs, mainly modified by NOP2/Sun RNA methyltransferase family member 2 (NSUN2), but little is known about the underlying functions of m 5 C. Gynecologic cancers are malignancies starting from women’s reproductive organs. The prevalence of gynecologic cancers leads to a massive economic burden and public health concern. In this study, we investigated the potential biological functions of NSUN2 in common gynecologic cancers including cervical cancer, ovarian cancer, and endometrial cancer. Remarkably, distinct scenarios were found. The levels of NSUN2 did not show alteration in endometrial cancer, and in ovarian cancer, depletion of upregulated NSUN2 did not reduce carcinogenesis in cancer cells, suggesting that the upregulated NSUN2 might be an incidental effect. On the contrary, NSUN2 played a role in tumorigenesis of cervical cancer; depletion of upregulated NSUN2 notably inhibited migration and invasion of cancer cells, and only wild-type but not catalytically inactive NSUN2 rescued these malignant phenotypes of cancer cells. Mechanistically, NSUN2 promoted migration and invasion by leading to m 5 C methylation on keratin 13 ( KRT13 ) transcripts, and methylated KRT13 transcripts would be recognized and stabilized by an m 5 C reader, Y-box binding protein 1 (YBX1). Collectively, these results not only displayed the nature of diversity among human malignancies, but also demonstrated a novel NSUN2-dependent m 5 C-YBX1-KRT13 oncogenic regulatory pathway.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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