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  • 1
    Online Resource
    Online Resource
    Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival
    MDPI AG ; 2021
    In:  Vaccines Vol. 9, No. 4 ( 2021-04-01), p. 334-
    Details
    In: Vaccines, MDPI AG, Vol. 9, No. 4 ( 2021-04-01), p. 334-
    Abstract: Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines9040334
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2703319-3
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  • 2
    Online Resource
    Online Resource
    Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients
    MDPI AG ; 2020
    In:  Vaccines Vol. 8, No. 1 ( 2020-02-06), p. 71-
    Details
    In: Vaccines, MDPI AG, Vol. 8, No. 1 ( 2020-02-06), p. 71-
    Abstract: T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4− (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines8010071
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2703319-3
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  • 3
    Online Resource
    Online Resource
    Time-Lapse In Situ 3D Imaging Analysis of Human Enamel Demineralisation Using X-ray Synchrotron Tomography
    MDPI AG ; 2023
    In:  Dentistry Journal Vol. 11, No. 5 ( 2023-05-09), p. 130-
    Details
    In: Dentistry Journal, MDPI AG, Vol. 11, No. 5 ( 2023-05-09), p. 130-
    Abstract: Caries is a chronic disease that causes the alteration of the structure of dental tissues by acid dissolution (in enamel, dentine and cementum) and proteolytic degradation (dentine and cementum) and generates an important cost of care. There is a need to visualise and characterise the acid dissolution process on enamel due to its hierarchical structure leading to complex structural modifications. The process starts at the enamel surface and progresses into depth, which necessitates the study of the internal enamel structure. Artificial demineralisation is usually employed to simulate the process experimentally. In the present study, the demineralisation of human enamel was studied using surface analysis carried out with atomic force microscopy as well as 3D internal analysis using synchrotron X-ray tomography during acid exposure with repeated scans to generate a time-lapse visualisation sequence. Two-dimensional analysis from projections and virtual slices and 3D analysis of the enamel mass provided details of tissue changes at the level of the rods and inter-rod substance. In addition to the visualisation of structural modifications, the rate of dissolution was determined, which demonstrated the feasibility and usefulness of these techniques. The temporal analysis of enamel demineralisation is not limited to dissolution and can be applied to other experimental conditions for the analysis of treated enamel or remineralisation.
    Type of Medium: Online Resource
    ISSN: 2304-6767
    URL: Article
    DOI: 10.3390/dj11050130
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2681351-8
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  • 4
    Online Resource
    Online Resource
    Hybrid EMD-RF Model for Predicting Annual Rainfall in Kerala, India
    MDPI AG ; 2023
    In:  Applied Sciences Vol. 13, No. 7 ( 2023-04-04), p. 4572-
    Details
    In: Applied Sciences, MDPI AG, Vol. 13, No. 7 ( 2023-04-04), p. 4572-
    Abstract: Rainfall forecasting is critical for the economy, but it has proven difficult due to the uncertainties, complexities, and interdependencies that exist in climatic systems. An efficient rainfall forecasting model will be beneficial in implementing suitable measures against natural disasters such as floods and landslides. In this paper, a novel hybrid model of empirical mode decomposition (EMD) and random forest (RF) was developed to enhance the accuracy of annual rainfall prediction. The EMD technique was utilized to decompose the rainfall signal into six intrinsic mode functions (IMFs) to extract underlying patterns, while the RF algorithm was employed to make predictions based on the IMFs. The hybrid RF–IMF model was trained and tested using a dataset of annual rainfall in Kerala from 1871 to 2020, and its performance was compared to traditional models such as RF regression and the autoregressive moving average (ARMA) model. Mean absolute error (MAE), mean absolute percentage error (MAPE), mean squared error (MSE), root mean squared error (RMSE), and coefficient of determination or R-squared (R2) were used to compare the performances of these three models. Model evaluation metrics show that the RF–IMF model outperformed both the RF model and ARMA model.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app13074572
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704225-X
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  • 5
    Online Resource
    Online Resource
    Synchrotron X-ray Studies of the Structural and Functional Hierarchies in Mineralised Human Dental Enamel: A State-of-the-Art Review
    MDPI AG ; 2023
    In:  Dentistry Journal Vol. 11, No. 4 ( 2023-04-07), p. 98-
    Details
    In: Dentistry Journal, MDPI AG, Vol. 11, No. 4 ( 2023-04-07), p. 98-
    Abstract: Hard dental tissues possess a complex hierarchical structure that is particularly evident in enamel, the most mineralised substance in the human body. Its complex and interlinked organisation at the Ångstrom (crystal lattice), nano-, micro-, and macro-scales is the result of evolutionary optimisation for mechanical and functional performance: hardness and stiffness, fracture toughness, thermal, and chemical resistance. Understanding the physical–chemical–structural relationships at each scale requires the application of appropriately sensitive and resolving probes. Synchrotron X-ray techniques offer the possibility to progress significantly beyond the capabilities of conventional laboratory instruments, i.e., X-ray diffractometers, and electron and atomic force microscopes. The last few decades have witnessed the accumulation of results obtained from X-ray scattering (diffraction), spectroscopy (including polarisation analysis), and imaging (including ptychography and tomography). The current article presents a multi-disciplinary review of nearly 40 years of discoveries and advancements, primarily pertaining to the study of enamel and its demineralisation (caries), but also linked to the investigations of other mineralised tissues such as dentine, bone, etc. The modelling approaches informed by these observations are also overviewed. The strategic aim of the present review was to identify and evaluate prospective avenues for analysing dental tissues and developing treatments and prophylaxis for improved dental health.
    Type of Medium: Online Resource
    ISSN: 2304-6767
    URL: Article
    DOI: 10.3390/dj11040098
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2681351-8
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