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  • 1
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    Online Resource
    Sex difference in the associations among obesity-related indices with incidence of diabetes mellitus in a large Taiwanese population follow-up study
    Frontiers Media SA ; 2023
    In:  Frontiers in Public Health Vol. 11 ( 2023-1-20)
    Details
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 11 ( 2023-1-20)
    Abstract: Obesity is a major risk factor for diabetes mellitus (DM), which is in turn a major risk factor for cardiovascular diseases such as coronary artery disease and stroke. As few studies have investigated sex differences in the association between obesity and incidence of DM, the aim of this longitudinal study was to explore this issue in a large group of Taiwanese participants. Methods A total of 24,346 participants were enrolled in this study, of whom 8,334 (mean age, 50.6 ± 11.0 years) were male and 16,012 (mean age, 50.5 ± 10.1 years) were female. The following obesity-related indices were studied: body mass index, waist-to-height ratio, waist-to-hip ratio (WHR), body roundness index, conicity index (CI), body adiposity index, abdominal volume index, lipid accumulation product (LAP), and visceral adiposity index (VAI). Results The analysis showed significant associations between all of these indices with incidence of DM (all p & lt; 0.001). In the male participants, the strongest predictors for incidence of DM were LAP (AUC = 0.692), WHtR (AUC = 0.684), and WHR (AUC = 0.683). In the female participants, the strongest predictors were LAP (AUC = 0.744), WHtR (AUC = 0.710) and VAI (AUC = 0.710), followed by BRI (AUC = 0.708). Conclusion Strong associations were found between the studied obesity-related indices and incidence of DM, and sex differences were found. Hence, to better control DM, reducing body weight may be beneficial in addition to lifestyle modifications, diet control, and pharmacological interventions.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    URL: Article
    DOI: 10.3389/fpubh.2023.1094471
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711781-9
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  • 2
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    DataSheet_4.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-21)
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    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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  • 3
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    presentation_1.pdf
    Frontiers Media SA ; 2018
    In:  Frontiers in Immunology Vol. 9 ( 2018-8-7)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 9 ( 2018-8-7)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2018.01828
    DOI: 10.3389/fimmu.2018.01828.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Assistive Navigation Using Deep Reinforcement Learning Guiding Robot With UWB/Voice Beacons and Semantic Feedbacks for Blind and Visually Impaired People
    Frontiers Media SA ; 2021
    In:  Frontiers in Robotics and AI Vol. 8 ( 2021-6-22)
    Details
    In: Frontiers in Robotics and AI, Frontiers Media SA, Vol. 8 ( 2021-6-22)
    Abstract: Facilitating navigation in pedestrian environments is critical for enabling people who are blind and visually impaired (BVI) to achieve independent mobility. A deep reinforcement learning (DRL)–based assistive guiding robot with ultrawide-bandwidth (UWB) beacons that can navigate through routes with designated waypoints was designed in this study. Typically, a simultaneous localization and mapping (SLAM) framework is used to estimate the robot pose and navigational goal; however, SLAM frameworks are vulnerable in certain dynamic environments. The proposed navigation method is a learning approach based on state-of-the-art DRL and can effectively avoid obstacles. When used with UWB beacons, the proposed strategy is suitable for environments with dynamic pedestrians. We also designed a handle device with an audio interface that enables BVI users to interact with the guiding robot through intuitive feedback. The UWB beacons were installed with an audio interface to obtain environmental information. The on-handle and on-beacon verbal feedback provides points of interests and turn-by-turn information to BVI users. BVI users were recruited in this study to conduct navigation tasks in different scenarios. A route was designed in a simulated ward to represent daily activities. In real-world situations, SLAM-based state estimation might be affected by dynamic obstacles, and the visual-based trail may suffer from occlusions from pedestrians or other obstacles. The proposed system successfully navigated through environments with dynamic pedestrians, in which systems based on existing SLAM algorithms have failed.
    Type of Medium: Online Resource
    ISSN: 2296-9144
    URL: Article
    DOI: 10.3389/frobt.2021.654132
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2781824-X
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  • 5
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    Table_2.DOCX
    Frontiers Media SA ; 2019
    In:  Frontiers in Cellular Neuroscience Vol. 13 ( 2019-9-13)
    Details
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-9-13)
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fncel.2019.00399
    DOI: 10.3389/fncel.2019.00399.s001
    DOI: 10.3389/fncel.2019.00399.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2452963-1
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  • 6
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    Oncologic impact of delay between diagnosis and radical nephroureterectomy
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-12-14)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-14)
    Abstract: This study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU). Methods In this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late ( & gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression. Results Of the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival. Conclusions For patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.1025668
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-3-29)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-3-29)
    Abstract: Activation of the Nod-like receptor 3 (NLRP3) inflammasome is important for activation of innate immune responses, but improper and excessive activation can cause inflammatory disease. We previously showed that glycolysis, a metabolic pathway that converts glucose into pyruvate, is essential for NLRP3 inflammasome activation in macrophages. Here, we investigated the role of metabolic pathways downstream glycolysis – lactic acid fermentation and pyruvate oxidation—in activation of the NLRP3 inflammasome. Using pharmacological or genetic approaches, we show that decreasing lactic acid fermentation by inhibiting lactate dehydrogenase reduced caspase-1 activation and IL-1β maturation in response to various NLRP3 inflammasome agonists such as nigericin, ATP, monosodium urate (MSU) crystals, or alum, indicating that lactic acid fermentation is required for NLRP3 inflammasome activation. Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production. By contrast, decreasing the activity of pyruvate oxidation by depletion of either mitochondrial pyruvate carrier 2 (MPC2) or pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) enhanced NLRP3 inflammasome activation, suggesting that inhibition of mitochondrial pyruvate transport enhanced lactic acid fermentation. Moreover, treatment with GSK2837808A reduced MSU-mediated peritonitis in mice, a disease model used for studying the consequences of NLRP3 inflammasome activation. Our results suggest that lactic acid fermentation is important for NLRP3 inflammasome activation, while pyruvate oxidation is not. Thus, reprograming pyruvate metabolism in mitochondria and in the cytoplasm should be considered as a novel strategy for the treatment of NLRP3 inflammasome-associated diseases.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.630380
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 8
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    Video_1.MP4
    Frontiers Media SA ; 2018
    In:  Frontiers in Molecular Neuroscience Vol. 11 ( 2018-11-26)
    Details
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 11 ( 2018-11-26)
    Type of Medium: Online Resource
    ISSN: 1662-5099
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fnmol.2018.00428
    DOI: 10.3389/fnmol.2018.00428.s001
    DOI: 10.3389/fnmol.2018.00428.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2452967-9
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  • 9
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-10-3)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-10-3)
    Abstract: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a valuable marker for identifying individuals at increased risk of metabolic dysfunction, liver-related complications, and cardiovascular disease. However, the association between MAFLD and testosterone deficiency (TD) in aging men remains poorly understood. This study aimed to investigate the association between MAFLD and the risk of TD in aging Taiwanese men, with a specific focus on those without metabolic syndrome (MetS). Methods A free health screening program was conducted for Taiwanese men aged over 40 years in Kaohsiung, Taiwan. Participants underwent physical examinations, completed questionnaires regarding demographics, medical history, and clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. Fatty liver index was used to evaluate the risk of fatty liver. Diagnostic criteria for MAFLD included fatty liver along with overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation. Results A total of 631 men (mean age: 54.4 ± 8.4 years) were enrolled. The prevalence rates of TD and MetS were significantly higher in men with MAFLD compared to those without (both p & lt; 0.001). Additionally, the presence of MAFLD showed a significant correlation with adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol-binding protein-4 (RBP-4) levels (all p & lt; 0.001). Among men without MetS, those with MAFLD had a 3.89- and 4.74-fold higher risk of total testosterone & lt; 300 ng/dL and TD, respectively, after adjusting for potential covariates. Conclusion MAFLD is associated with an elevated risk of TD in aging Taiwanese men, particularly in the absence of MetS. This finding suggests that MAFLD could serve as an early predictor of TD, facilitating the identification of high-risk individuals and enabling timely interventions. Further research is needed to validate these findings and explore the underlying mechanisms linking MAFLD, TD, and MetS in diverse populations.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2023.1252774
    DOI: 10.3389/fendo.2023.1252774.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 10
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    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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