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  • Frontiers Media SA  (34)
  • 1
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    Table_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-6-2)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-2)
    Kurzfassung: We aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC). Methods This retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models. Results The median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis ( p & lt; 0.001), more dialysis status ( p = 0.027), renal pelvic tumors ( p & lt; 0.001), and early pathological tumor stage ( p = 0.001). Symptomatic hydronephrosis was associated with female patients ( p & lt; 0.001), less dialysis status ( p = 0.001), less bladder cancer history ( p & lt; 0.001), ureteral tumors ( p & lt; 0.001), open surgery ( p = 0.006), advanced pathological tumor stage ( p & lt; 0.001), and postoperative chemotherapy ( p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p & lt; 0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661–0.942) and CSS (HR 0.772, 95% CI 0.607–0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142–1.683), CSS (HR 1.587, 95% CI 1.229–2.050), and DFS (HR 1.378, 95% CI 1.122–1.693). Conclusions Preoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.
    Materialart: Online-Ressource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.872849
    DOI: 10.3389/fonc.2022.872849.s001
    DOI: 10.3389/fonc.2022.872849.s002
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2649216-7
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  • 2
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    Association of Physical Fitness Performance Tests and Anthropometric Indices in Taiwanese Adults
    Frontiers Media SA ; 2020
    In:  Frontiers in Physiology Vol. 11 ( 2020-11-20)
    Details
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 11 ( 2020-11-20)
    Kurzfassung: The association between physical fitness performance tests and anthropometric indices is not clear. The study aims to explore the association between physical fitness performance and anthropometric indices in Taiwanese community-dwelling adults. This may help in monitoring anthropometric indices to improve physical fitness. Methods We recruited 2216 participants aged 23–64 years between 2014 and 2017. Physical fitness performance, including abdominal muscular endurance (60-s sit-up test), flexibility (sit-and-reach test), and cardiorespiratory endurance (3-min step test), was evaluated in all participants. The association of the physical fitness performance and anthropometric indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), was analyzed using linear regression, with adjustments for age and gender. Results Body mass index was negatively associated with abdominal muscular endurance ( p & lt; 0.001) and cardiorespiratory endurance ( p & lt; 0.001). Neither BMI, WC, WHR, nor WHtR were significantly associated with flexibility. Abdominal muscle endurance, flexibility, and cardiorespiratory endurance were significantly lower in obese participants when obesity was defined using a BMI of ≥27, 30, and 35 kg/m 2 . Participants with central obesity that was defined as WC ≥ 90 cm in men and 80 cm in women and WHtR ≥ 0.6 had lower abdominal muscular endurance than those without central obesity. Conclusion Body mass index is associated with abdominal muscular endurance and cardiorespiratory endurance in a reverse J-shaped manner. None of the anthropometric indices are significantly associated with flexibility. Obesity defined by BMI is linked to worse physical fitness performance and obesity defined using WHtR is linked to lower abdominal muscular endurance in Taiwanese community-dwelling adults.
    Materialart: Online-Ressource
    ISSN: 1664-042X
    URL: Article
    DOI: 10.3389/fphys.2020.583692
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2020
    ZDB Id: 2564217-0
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  • 3
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    Risk of Autoimmune Diseases Following Optic Neuritis: A Nationwide Population-Based Cohort Study
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-6-13)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-6-13)
    Kurzfassung: Optic neuritis is (ON) is believed to be an immune-mediated disease; however, the association between optic neuritis and autoimmune diseases remains unclear. This study aimed to identify the incidence rate and adjusted hazard ratio (aHR) of autoimmune diseases in patients with optic neuritis. Methods This nationwide, population-based, retrospective cohort study collected patients’ data between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 9,235 patients were included. Using 1:4 propensity scoring, 1,847 patients were enrolled in the optic neuritis group and 7,388 in the non-optic neuritis group according to age, sex, comorbidities, and corticosteroid use. Follow-up was started from the index date and the endpoint was a diagnosis of new-onset autoimmune diseases including, myasthenia gravis (MG), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Results The Kaplan-Meier curves depicted that patients with optic neuritis had a higher cumulative incidence of autoimmune diseases than patients without optic neuritis. Cox proportional hazard regression showed that patients with optic neuritis were at a high risk of autoimmune diseases (aHR: 1.40; 95% C.I., 1.05–1.87), including MG (aHR: 4.16, 95% C.I.: 1.33–12.94), SLE (aHR: 3.33, 95% C.I.: 1.24–8.97), and AS (aHR: 2.86, 95% C.I.: 1.54–5.31). Subgroup analysis provided that patients with optic neuritis aged below 65 years (aHR: 1.42, 95% C.I.: 1.03–1.96) or who were females (aHR: 1.59, 95% C.I.: 1.11–2.27) had a significantly increased risk of autoimmune diseases compared to respective controls. The use of corticosteroids reduced the risk of autoimmune diseases in patients with optic neuritis (aHR for corticosteroids non-users: 1.46, 95% C.I.: 1.03–2.07). Conclusion Patients with optic neuritis presented with a high risk of autoimmune diseases such as MG, SLE, and AS, especially patients with optic neuritis who were young or females. Corticosteroids attenuated the link between optic neuritis and subsequent autoimmune diseases.
    Materialart: Online-Ressource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.903608
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2775999-4
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  • 4
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    Increased Interleukin-17 and Glucocorticoid Receptor-β Expression in Interstitial Lung Diseases and Corticosteroid Insensitivity
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-7-5)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-5)
    Kurzfassung: Treatment responsiveness to corticosteroids is excellent for cryptogenic organizing pneumonia (COP) and sarcoidosis, but suboptimal for idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). We hypothesise that the differential expression of IL-17 contributes to variable corticosteroid sensitivity in different interstitial lung diseases. Objective To determine the associations among expression of IL-17, glucocorticoid receptor-β and responsiveness to corticosteroid treatment in interstitial lung diseases. Methods Immunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded (FFPE) lung tissues obtained by bronchoscopic, CT-guided or surgical biopsies, and quantified by both cell counting (% positive cells) by individuals and by software IHC Profiler plugin of ImageJ (opacity density score). We studied the effect of IL-17 on corticosteroid sensitivity in human fibroblast MRC5 cell line. Results Compared with specimens from patients with COP (n =13) and sarcoidosis (n =13), those from IPF patients (n = 21) had greater GR-β and IL-17 expression and neutrophil infiltration. Radiographic progression after oral corticosteroid treatment was positively correlated with the expression in IL-17 and GR-β/GR-α ratio in all patients (COP, sarcoidosis and IPF) and also within the IPF subgroup only. IL-17 expression level was positively associated with GR-β and GR-β/GR-α ratio. In MRC5 cells, exogenous IL-17 increased the production of collagen I and up-regulated GR-β expression and dexamethasone’s suppressive effect on collagen I production was impaired by IL-17, and silencing IL-17 receptor A gene attenuated the effect of IL-17. Conclusion Up-regulation of GR-β/GR-α ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.905727
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606827-8
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  • 5
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    Data_Sheet_1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-1-31)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-1-31)
    Kurzfassung: Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are of significant clinical concern worldwide. Fosfomycin is one of the limited treatment options for CRKP. However, resistance to fosfomycin in CRKP has been observed. In this study, we aimed to investigate the fosfomycin resistance mechanism of CRKP. Fosfomycin-resistant Klebsiella pneumoniae isolates were collected from four medical centers in Taiwan from 2010 to 2018. The genes that contributed to fosfomycin resistance were amplified and sequenced. Carbohydrate utilization assays and mutagenesis studies were performed to determine the mechanisms underlying fosfomycin resistance. Forty fosfomycin-resistant CRKP strains were collected and used for further analysis. Fourteen strains exhibited low-level resistance (MIC = 256–512 mg/dl), while 26 strains showed high-level resistance (MIC ≥ 1,024 mg/dl). Chromosomal fosA KP I91V was detected in 39/40 fosfomycin-resistant CRKP strains. We observed that amino acid substitution of chromosomal fosA KP I91V increased the MIC of fosfomycin by approximately eight folds, and this was the only mechanism elucidated for low-level fosfomycin resistance. Among the 26 high-level resistance strains, fosA KP I91V combined with transporter deficiencies (18/26, 69.2%) was the most common resistant mechanism, and one strain showed transporter deficiency only. Plasmid-borne fosA3 accounted for 27.0% (7/26) of high-level resistance. Various G3P and G6P transporter gene mutations, including three novel single amino acid mutations (glpT E299D, glpT D274V, and uhpC A393V) were detected in 19 strains. No murA mutation was found in this study. Our study highlights the need for new therapeutic agents for CRKP infections in Taiwan.
    Materialart: Online-Ressource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.816806
    DOI: 10.3389/fmicb.2022.816806.s001
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2587354-4
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  • 6
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Psychiatry Vol. 14 ( 2023-6-19)
    Details
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 14 ( 2023-6-19)
    Kurzfassung: Post-stroke depression (PSD) is a serious mental disorder after ischemic stroke. Early detection is important for clinical practice. This research aims to develop machine learning models to predict new-onset PSD using real-world data. Methods We collected data for ischemic stroke patients from multiple medical institutions in Taiwan between 2001 and 2019. We developed models from 61,460 patients and used 15,366 independent patients to test the models’ performance by evaluating their specificities and sensitivities. The predicted targets were whether PSD occurred at 30, 90, 180, and 365 days post-stroke. We ranked the important clinical features in these models. Results In the study’s database sample, 1.3% of patients were diagnosed with PSD. The average specificity and sensitivity of these four models were 0.83–0.91 and 0.30–0.48, respectively. Ten features were listed as important features related to PSD at different time points, namely old age, high height, low weight post-stroke, higher diastolic blood pressure after stroke, no pre-stroke hypertension but post-stroke hypertension (new-onset hypertension), post-stroke sleep-wake disorders, post-stroke anxiety disorders, post-stroke hemiplegia, and lower blood urea nitrogen during stroke. Discussion Machine learning models can provide as potential predictive tools for PSD and important factors are identified to alert clinicians for early detection of depression in high-risk stroke patients.
    Materialart: Online-Ressource
    ISSN: 1664-0640
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyt.2023.1195586
    DOI: 10.3389/fpsyt.2023.1195586.s001
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2564218-2
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  • 7
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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)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    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
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606827-8
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  • 8
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-16)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-16)
    Kurzfassung: The endoplasmic reticulum (ER) stress of cancer cells not only determined cancer cell fate but also indirectly triggered proinflammatory or immunosuppressive responses of macrophages. In addition, ER stressed neutrophils were known to acquire immunosuppressive activity with surface expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Since the importance of tumor ER stress and immunosuppressive neutrophils has been emphasized in head and neck cancers, we hypothesized that the ER stress of oral squamous cell carcinoma (OSCC) could transform neutrophils into LOX-1 expressing immunosuppressive phenotype. Two human OSCC cell lines, SCC25 and OML1, were treated with either vehicle or thapsigargin (THG), an ER stress inducer. These tumor conditioned media (TCM) were collected accordingly. Then human peripheral blood neutrophils from healthy donors were cultured in these TCM. The results showed that neutrophils cultured in THG-treated TCM had higher expression of LOX-1 compared with those cultured in vehicle-treated TCM. Moreover, by interleukin-2/anti-CD3/anti-CD28 activated autologous T cell proliferation assay, neutrophils conditioned by THG-treated TCM were shown to inhibit T cell proliferation more significantly than those conditioned by vehicle-treated TCM. These novel findings indicated that the ER stress of OSCC could be transmitted to neutrophils which in turn expressed LOX-1 and obtained immunosuppressive ability. Our findings further supported the existence of “transmissible” ER stress between tumor cells and neutrophils.
    Materialart: Online-Ressource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.818192
    DOI: 10.3389/fonc.2022.818192.s001
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2649216-7
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  • 9
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    DataSheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-10-26)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-10-26)
    Kurzfassung: Heatstroke (HS) can cause acute lung injury (ALI). Heat stress induces inflammation and apoptosis via reactive oxygen species (ROS) and endogenous reactive aldehydes. Endothelial dysfunction also plays a crucial role in HS-induced ALI. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that detoxifies aldehydes such as 4-hydroxy-2-nonenal (4-HNE) protein adducts. A single point mutation in ALDH2 at E487K (ALDH2*2) intrinsically lowers the activity of ALDH2. Alda-1, an ALDH2 activator, attenuates the formation of 4-HNE protein adducts and ROS in several disease models. We hypothesized that ALDH2 can protect against heat stress-induced vascular inflammation and the accumulation of ROS and toxic aldehydes. Homozygous ALDH2*2 knock-in (KI) mice on a C57BL/6J background and C57BL/6J mice were used for the animal experiments. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro experiment. The mice were directly subjected to whole-body heating (WBH, 42°C) for 1 h at 80% relative humidity. Alda-1 (16 mg/kg) was administered intraperitoneally prior to WBH. The severity of ALI was assessed by analyzing the protein levels and cell counts in the bronchoalveolar lavage fluid, the wet/dry ratio and histology. ALDH2*2 KI mice were susceptible to HS-induced ALI in vivo . Silencing ALDH2 induced 4-HNE and ROS accumulation in HUVECs subjected to heat stress. Alda-1 attenuated the heat stress-induced activation of inflammatory pathways, senescence and apoptosis in HUVECs. The lung homogenates of mice pretreated with Alda-1 exhibited significantly elevated ALDH2 activity and decreased ROS accumulation after WBH. Alda-1 significantly decreased the WBH-induced accumulation of 4-HNE and p65 and p38 activation. Here, we demonstrated the crucial roles of ALDH2 in protecting against heat stress-induced ROS production and vascular inflammation and preserving the viability of ECs. The activation of ALDH2 by Alda-1 attenuates WBH-induced ALI in vivo .
    Materialart: Online-Ressource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.740562
    DOI: 10.3389/fimmu.2021.740562.s001
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2606827-8
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  • 10
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    Evaluation of the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry Bruker Biotyper for identification of Penicillium marneffei, Paecilomyces species, Fusarium solani, Rhizopus species, and Pseudallescheria boydii
    Frontiers Media SA ; 2015
    In:  Frontiers in Microbiology Vol. 6 ( 2015-07-08)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 6 ( 2015-07-08)
    Materialart: Online-Ressource
    ISSN: 1664-302X
    URL: Article
    DOI: 10.3389/fmicb.2015.00679
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2015
    ZDB Id: 2587354-4
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