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  • 1
    Online Resource
    Online Resource
    Optical Coherence Tomography Angiography in Diabetes and Diabetic Retinopathy
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 6 ( 2020-06-03), p. 1723-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 6 ( 2020-06-03), p. 1723-
    Abstract: Diabetic retinopathy (DR) is a common complication of diabetes mellitus that disrupts the retinal microvasculature and is a leading cause of vision loss globally. Recently, optical coherence tomography angiography (OCTA) has been developed to image the retinal microvasculature, by generating 3-dimensional images based on the motion contrast of circulating blood cells. OCTA offers numerous benefits over traditional fluorescein angiography in visualizing the retinal vasculature in that it is non-invasive and safer; while its depth-resolved ability makes it possible to visualize the finer capillaries of the retinal capillary plexuses and choriocapillaris. High-quality OCTA images have also enabled the visualization of features associated with DR, including microaneurysms and neovascularization and the quantification of alterations in retinal capillary and choriocapillaris, thereby suggesting a promising role for OCTA as an objective technology for accurate DR classification. Of interest is the potential of OCTA to examine the effect of DR on individual retinal layers, and to detect DR even before it is clinically detectable on fundus examination. We will focus the review on the clinical applicability of OCTA derived quantitative metrics that appear to be clinically relevant to the diagnosis, classification, and management of patients with diabetes or DR. Future studies with longitudinal design of multiethnic multicenter populations, as well as the inclusion of pertinent systemic information that may affect vascular changes, will improve our understanding on the benefit of OCTA biomarkers in the detection and progression of DR.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9061723
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 2
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    Co-Clinical Imaging Resource Program (CIRP): Bridging the Translational Divide to Advance Precision Medicine
    MDPI AG ; 2020
    In:  Tomography Vol. 6, No. 3 ( 2020-09-01), p. 273-287
    Details
    In: Tomography, MDPI AG, Vol. 6, No. 3 ( 2020-09-01), p. 273-287
    Abstract: The National Institutes of Health’s (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its overarching mission is to advance the practice of precision medicine by establishing consensus-based best practices for co-clinical imaging research by developing optimized state-of-the-art translational quantitative imaging methodologies to enable disease detection, risk stratification, and assessment/prediction of response to therapy. In this communication, we discuss our involvement in the CIRP, detailing key considerations including animal model selection, co-clinical study design, need for standardization of co-clinical instruments, and harmonization of preclinical and clinical quantitative imaging pipelines. An underlying emphasis in the program is to develop best practices toward reproducible, repeatable, and precise quantitative imaging biomarkers for use in translational cancer imaging and therapy. We will conclude with our thoughts on informatics needs to enable collaborative and open science research to advance precision medicine.
    Type of Medium: Online Resource
    ISSN: 2379-139X
    URL: Article
    DOI: 10.18383/j.tom.2020.00023
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2857000-5
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  • 3
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    Online Resource
    Environmental Assessment and Evaluation of Oxidative Stress and Genotoxicity Biomarkers Related to Chronic Occupational Exposure to Benzene
    MDPI AG ; 2019
    In:  International Journal of Environmental Research and Public Health Vol. 16, No. 12 ( 2019-06-25), p. 2240-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 16, No. 12 ( 2019-06-25), p. 2240-
    Abstract: Environmental and occupational exposure to benzene from fuels is a major cause for concern for national and international authorities, as benzene is a known carcinogen in humans and there is no safe limit for exposure to carcinogens. The objective of this study was to evaluate the genotoxic effects of chronic occupational exposure to benzene among two groups of workers: filling station workers (Group I) and security guards working at vehicles entrances (Group II), both on the same busy highway in Rio de Janeiro, Brazil. Sociodemographic data on the workers were evaluated; the concentration of benzene/toluene (B/T) in atmospheric air and individual trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (S-PMA) were measured; oxidative stress was analyzed by catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), thiol groups (THIOL) and malondialdehyde (MDA); genotoxicity was measured by metaphases with chromosomal abnormalities (MCA) and nuclear abnormalities, comet assay using the enzyme formamidopyrimidine DNA glycosylase (C-FPG), and methylation of repetitive element LINE-1, CDKN2B and KLF6 genes. Eighty-six workers participated: 51 from Group I and 35 from Group II. The B/T ratio was similar for both groups, but Group I had greater oscillation of benzene concentrations because of their work activities. No differences in ttMA and S-PMA, and no clinical changes were found between both groups, but linearity was observed between leukocyte count and ttMA; and 15% of workers had leukocyte counts less than 4.5 × 109 cells L−1, demanding close worker’s attention. No differences were observed between the two groups for THIOL, MDA, MCA, or nuclear abnormalities. A multiple linear relationship was obtained for the biomarkers MCA and C-FPG. A significant correlation was found between length of time in current job and the biomarkers C-FPG, MCA, GST, and MDA. Although both populations had chronic exposure to benzene, the filling station workers were exposed to higher concentrations of benzene during their work activities, indicating an increased risk of DNA damage.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph16122240
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2175195-X
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  • 4
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    Short-Time Recurrences of Plasmodium vivax Malaria as a Public Health Proxy for Chloroquine-Resistance Surveillance: A Spatio-Temporal Study in the Brazilian Amazon
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 10 ( 2021-05-11), p. 5061-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 10 ( 2021-05-11), p. 5061-
    Abstract: In Brazil, malaria caused by Plasmodium vivax presents control challenges due to several reasons, among them the increasing possibility of failure of P. vivax treatment due to chloroquine-resistance (CQR). Despite limited reports of CQR, more extensive studies on the actual magnitude of resistance are still needed. Short-time recurrences of malaria cases were analyzed in different transmission scenarios over three years (2005, 2010, and 2015), selected according to malaria incidence. Multilevel models (binomial) were used to evaluate association of short-time recurrences with variables such as age. The zero-inflated Poisson scan model (scanZIP) was used to detect spatial clusters of recurrences up to 28 days. Recurrences compose less than 5% of overall infection, being more frequent in the age group under four years. Recurrences slightly increased incidence. No fixed clusters were detected throughout the period, although there are clustering sites, spatially varying over the years. This is the most extensive analysis of short-time recurrences worldwide which addresses the occurrence of P. vivax CQR. As an important step forward in malaria elimination, policymakers should focus their efforts on young children, with an eventual shift in the first line of malaria treatment to P. vivax.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph18105061
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 5
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    Online Resource
    Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 23 ( 2020-11-27), p. 9015-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 23 ( 2020-11-27), p. 9015-
    Abstract: Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21239015
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    The Influence of Acitretin on Brain Lipidomics in Adolescent Mice—Implications for Pediatric and Adolescent Dermatological Therapy
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-08), p. 15535-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-08), p. 15535-
    Abstract: Administration of systemic retinoids such as acitretin has not been approved yet for pediatric patients. An adverse event of retinoid-therapy that occurs with lower prevalence in children than in adults is hyperlipidemia. This might be based on the lack of comorbidities in young patients, but must not be neglected. Especially for the development of the human brain up to young adulthood, dysbalance of lipids might be deleterious. Here, we provide for the first time an in-depth analysis of the influence of subchronic acitretin-administration on lipid composition of brain parenchyma of young wild type mice. For comparison and to evaluate the systemic effect of the treatment, liver lipids were analogously investigated. As expected, triglycerides increased in liver as well as in brain and a non-significant increase in cholesterol was observed. However, specifically brain showed an increase in lyso-phosphatidylcholine and carnitine as well as in sphingomyelin. Group analysis of lipid classes revealed no statistical effects, while single species were tissue-dependently changed: effects in brain were in general more subtly as compared to those in liver regarding the mere number of changed lipid species. Thus, while the overall impact of acitretin seems comparably small regarding brain, the change in individual species and their role in brain development and maturation has to be considered.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415535
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Online Resource
    Development and Evaluation of MR-Based Radiogenomic Models to Differentiate Atypical Lipomatous Tumors from Lipomas
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 7 ( 2023-04-05), p. 2150-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 7 ( 2023-04-05), p. 2150-
    Abstract: Background: The aim of this study was to develop and validate radiogenomic models to predict the MDM2 gene amplification status and differentiate between ALTs and lipomas on preoperative MR images. Methods: MR images were obtained in 257 patients diagnosed with ALTs (n = 65) or lipomas (n = 192) using histology and the MDM2 gene analysis as a reference standard. The protocols included T2-, T1-, and fat-suppressed contrast-enhanced T1-weighted sequences. Additionally, 50 patients were obtained from a different hospital for external testing. Radiomic features were selected using mRMR. Using repeated nested cross-validation, the machine-learning models were trained on radiomic features and demographic information. For comparison, the external test set was evaluated by three radiology residents and one attending radiologist. Results: A LASSO classifier trained on radiomic features from all sequences performed best, with an AUC of 0.88, 70% sensitivity, 81% specificity, and 76% accuracy. In comparison, the radiology residents achieved 60–70% accuracy, 55–80% sensitivity, and 63–77% specificity, while the attending radiologist achieved 90% accuracy, 96% sensitivity, and 87% specificity. Conclusion: A radiogenomic model combining features from multiple MR sequences showed the best performance in predicting the MDM2 gene amplification status. The model showed a higher accuracy compared to the radiology residents, though lower compared to the attending radiologist.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15072150
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Metabolic Biomarkers Assessed with PET/CT Predict Sex-Specific Longitudinal Outcomes in Patients with Diffuse Large B-Cell Lymphoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 12 ( 2022-06-14), p. 2932-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 12 ( 2022-06-14), p. 2932-
    Abstract: In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14122932
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) for the Resection of Sarcomas May Reduce the Positive Margin Rate: An Extended Case Series
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 24 ( 2021-12-14), p. 6284-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 24 ( 2021-12-14), p. 6284-
    Abstract: Background: Sarcomas are rare, aggressive cancers which can occur in any region of the body. Surgery is usually the cornerstone of curative treatment, with negative surgical margins associated with decreased local recurrence and improved overall survival. Indocyanine green (ICG) is a fluorescent dye which accumulates in sarcoma tissue and can be imaged intraoperatively using handheld near-infrared (NIR) cameras, theoretically helping guide the surgeon’s resection margins. Methods: Patients operated on between 20 February 2019 and 20 October 2021 for intermediate to high grade sarcomas at our centres received either conventional surgery, or were administered ICG pre-operatively followed by intra-operative NIR fluorescence guidance during the procedure. Differences between the unexpected positive margin rates were compared. Results: 115 suitable patients were identified, of which 39 received ICG + NIR fluorescence guided surgery, and 76 received conventional surgery. Of the patients given ICG, 37/39 tumours fluoresced, and surgeons felt the procedure was guided by the intra-operative images in 11 cases. Patients receiving ICG had a lower unexpected positive margin rate (5.1% vs. 25.0%, p = 0.01). Conclusions: The use of NIR fluorescence cameras in combination with ICG may reduce the unexpected positive margin rate for high grade sarcomas. A prospective, multi-centre randomised control trial is now needed to validate these results.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13246284
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 10
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    A Qualitative Strategy for Fusion of Physics into Empirical Models for Process Anomaly Detection
    MDPI AG ; 2022
    In:  Energies Vol. 15, No. 15 ( 2022-08-03), p. 5640-
    Details
    In: Energies, MDPI AG, Vol. 15, No. 15 ( 2022-08-03), p. 5640-
    Abstract: To facilitate the automated online monitoring of power plants, a systematic and qualitative strategy for anomaly detection is presented. This strategy is essential to provide credible reasoning on why and when an empirical versus hybrid (i.e., physics-supported) approach should be used and to determine the ideal mix of these two approaches for a defined anomaly detection scope. Empirical methods are usually based on pattern, statistical, and causal inference. Hybrid methods include the use of physics models to train and test data methods, reduce data dimensionality, reduce data-model complexity, augment data, and reduce empirical uncertainty; hybrid methods also include the use of data to tune physics models. The presented strategy is driven by key decision points related to data relevance, simple modeling feasibility, data inference, physics-modeling value, data dimensionality, physics knowledge, method of validation, performance, data availability, and suitability for training and testing, cause-effect, entropy inference, and model fitting. The strategy is demonstrated through a pilot use case for the application of anomaly detection to capture a valve packing leak at the high-pressure coolant injection system of a nuclear power plant.
    Type of Medium: Online Resource
    ISSN: 1996-1073
    URL: Article
    DOI: 10.3390/en15155640
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2437446-5
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