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  • Frontiers Media SA  (544)
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  • Frontiers Media SA  (544)
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  • 1
    Online Resource
    Online Resource
    DataSheet_4.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-21)
    Abstract: Drug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease. Methods Here, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC 50 = 0.4 μM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms. Results Our in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals. Conclusions We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1080897
    DOI: 10.3389/fimmu.2022.1080897.s001
    DOI: 10.3389/fimmu.2022.1080897.s002
    DOI: 10.3389/fimmu.2022.1080897.s003
    DOI: 10.3389/fimmu.2022.1080897.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
    Online Resource
    Online Resource
    Data_Sheet_1.PDF
    Frontiers Media SA ; 2018
    In:  Frontiers in Pharmacology Vol. 9 ( 2018-7-3)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2018-7-3)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2018.00708
    DOI: 10.3389/fphar.2018.00708.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 3
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    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-2-24)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-2-24)
    Abstract: To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC). Patients and methods This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage. Results 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p & lt;0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p & lt; 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p & lt;0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95–4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23–4.34). Conclusion Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.944321
    DOI: 10.3389/fonc.2023.944321.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 4
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    Online Resource
    Table_1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-5-16)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-5-16)
    Abstract: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort. Methods From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5). Results In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively. Conclusion We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.856654
    DOI: 10.3389/fmed.2022.856654.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 5
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    Online Resource
    Image_1.tif
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-3-10)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-3-10)
    Abstract: Hyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population. Methods A total of 120,267 adults aged 30–70 years were enrolled from the Taiwan Biobank data-base in this retrospective case–control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored. Results The frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09–1.28) and 1.12 (1.06–1.18) for TT and GT genotypes, respectively, compared with the GG genotype ( p & lt;0.001), specifically in the male population with hyperuricemia. Higher age, male sex, hyperlipidemia, hypertension, diabetes mellitus, hyperuricemia, smoking and overweight were independent risk factors for nephrolithiasis. In contrast, regular physical exercise is a protective factor against nephrolithiasis. Conclusions ABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2023.1074012
    DOI: 10.3389/fendo.2023.1074012.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 6
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    Online Resource
    Image_1.pdf
    Frontiers Media SA ; 2024
    In:  Frontiers in Neuroscience Vol. 18 ( 2024-4-23)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 18 ( 2024-4-23)
    Abstract: Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2024.1368552
    DOI: 10.3389/fnins.2024.1368552.s001
    DOI: 10.3389/fnins.2024.1368552.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2411902-7
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  • 7
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    Online Resource
    Deep learning to infer visual acuity from optical coherence tomography in diabetic macular edema
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-10-6)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-10-6)
    Abstract: Diabetic macular edema (DME) is one of the leading causes of visual impairment in diabetic retinopathy (DR). Physicians rely on optical coherence tomography (OCT) and baseline visual acuity (VA) to tailor therapeutic regimen. However, best-corrected visual acuity (BCVA) from chart-based examinations may not wholly reflect DME status. Chart-based examinations are subjected findings dependent on the patient’s recognition functions and are often confounded by concurrent corneal, lens, retinal, optic nerve, or extraocular disorders. The ability to infer VA from objective optical coherence tomography (OCT) images provides the predicted VA from objective macular structures directly and a better understanding of diabetic macular health. Deviations from chart-based and artificial intelligence (AI) image-based VA will prompt physicians to assess other ocular abnormalities affecting the patients VA and whether pursuing anti-VEGF treatment will likely yield increment in VA. Materials and methods We enrolled a retrospective cohort of 251 DME patients from Big Data Center (BDC) of Taipei Veteran General Hospital (TVGH) from February 2011 and August 2019. A total of 3,920 OCT images, labeled as “visually impaired” or “adequate” according to baseline VA, were grouped into training (2,826), validation (779), and testing cohort (315). We applied confusion matrix and receiver operating characteristic (ROC) curve to evaluate the performance. Results We developed an OCT-based convolutional neuronal network (CNN) model that could classify two VA classes by the threshold of 0.50 (decimal notation) with an accuracy of 75.9%, a sensitivity of 78.9%, and an area under the ROC curve of 80.1% on the testing cohort. Conclusion This study demonstrated the feasibility of inferring VA from routine objective retinal images. Translational relevance Serves as a pilot study to encourage further use of deep learning in deriving functional outcomes and secondary surrogate endpoints for retinal diseases.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.1008950
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 8
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    Online Resource
    Table_2.docx
    Frontiers Media SA ; 2024
    In:  Frontiers in Cellular and Infection Microbiology Vol. 14 ( 2024-7-25)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 14 ( 2024-7-25)
    Abstract: Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSV A ) and B (HRSV B ) of HRSV. Next, the Pyrococcus furiosus Argonaute ( PfAgo ) protein utilizes small 5’-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/μL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSV A and HRSV B infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2024.1419949
    DOI: 10.3389/fcimb.2024.1419949.s001
    DOI: 10.3389/fcimb.2024.1419949.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2619676-1
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  • 9
    Online Resource
    Online Resource
    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Psychiatry Vol. 12 ( 2021-12-7)
    Details
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 12 ( 2021-12-7)
    Abstract: Background: The COVID-19 pandemic is our generation's greatest global challenge to our public health system. Vaccines are considered one of the most effective tools available for preventing COVID-19 infection and its complications and sequelae. Understanding and addressing the psychological stress related to COVID-19 vaccination may promote acceptance of these vaccines. Methods: We conducted an online survey from January 29 to April 26, 2021 to explore stress levels related to COVID-19 vaccination among the general public in China. Participants were asked to evaluate their psychological stress of considering whether or not to get vaccinated at the beginning period of the COVID-19 mass vaccination, after getting access to the information about the vaccine, as well as after getting vaccinated, using visual analog stress scale. Multiple linear regression analysis was performed to explore factors potentially associated with COVID-19-related psychological stress levels before and after getting vaccinated. Results: A total of 34,041 participants were included in the final analysis. The mean stress score concerning COVID-19 vaccination was 3.90 ± 2.60 among all participants, and significantly decreased over time. In addition, the vaccine-related stress level significantly decreased after accessing information about the COVID-19 vaccine ( N = 29,396), as well as after getting vaccinated ( N = 5,103). Multivariable regression analysis showed higher stress levels related to COVID-19 vaccination in participants who were younger, having lower education level, having history of chronic diseases, mistrusting vaccine's efficacy, experience of vaccine allergy events, being affected by the COVID-19 epidemic, and having mental illness symptoms. Moreover, mistrust in vaccine efficacy and experience of vaccine allergy events had a long-term impact on psychological stress levels about COVID-19 vaccination even after getting vaccinated. Conclusions: The current findings profiled the COVID-19 vaccine-related psychological stress among the general public in China. Population-specific management and interventions targeting the stress related to COVID-19 vaccination are needed to help governments and policy makers promote individual's willingness to get vaccinations for public well-being during the COVID-19 pandemic.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyt.2021.774504
    DOI: 10.3389/fpsyt.2021.774504.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564218-2
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  • 10
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    Online Resource
    Mitochondrial Function and Parkinson’s Disease: From the Perspective of the Electron Transport Chain
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Neuroscience Vol. 14 ( 2021-12-9)
    Details
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 14 ( 2021-12-9)
    Abstract: Parkinson’s disease (PD) is known as a mitochondrial disease. Some even regarded it specifically as a disorder of the complex I of the electron transport chain (ETC). The ETC is fundamental for mitochondrial energy production which is essential for neuronal health. In the past two decades, more than 20 PD-associated genes have been identified. Some are directly involved in mitochondrial functions, such as PRKN, PINK1 , and DJ-1 . While other PD-associate genes, such as LRRK2 , SNCA , and GBA1 , regulate lysosomal functions, lipid metabolism, or protein aggregation, some have been shown to indirectly affect the electron transport chain. The recent identification of CHCHD2 and UQCRC1 that are critical for functions of complex IV and complex III, respectively, provide direct evidence that PD is more than just a complex I disorder. Like UQCRC1 in preventing cytochrome c from release, functions of ETC proteins beyond oxidative phosphorylation might also contribute to the pathogenesis of PD.
    Type of Medium: Online Resource
    ISSN: 1662-5099
    URL: Article
    DOI: 10.3389/fnmol.2021.797833
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2452967-9
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