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  • 1
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 10 ( 2019-10-31)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2021-9-2)
    Abstract: Background : Gallstone disease (GD) is associated with a high risk of cardiovascular disease. However, it is unknown whether GD contributes to atrial fibrillation (AF). We aimed to investigate the association between GD and AF. Methods : We performed a population-based cohort study using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. A GD cohort of 230,076 patients was compared with a control cohort consisting of an equal number of patients matched for age, sex, cardiovascular and gastrointestinal comorbidities. Results : In total, 5,992 (49.8/10,000 person-years) patients with GD and 5,804 (44.5/10,000 person-years) controls developed AF. GD increased AF risk with a hazard ratio (HR) of 1.20 [95% confidence interval (CI), 1.16–1.25]. In patients with GD but without cholecystectomy, the HR of AF reached 1.57 (95% CI = 1.50–1.63). After cholecystectomy, the HR of AF significantly decreased to 0.85 (95% CI = 0.81–0.90). Among the three age groups with GD ( & lt;45, 45–64, and ≥65 years), the adjusted HRs of AF were 1.59 (95% CI = 1.08–2.33), 1.31 (95% CI = 1.18–1.45), and 1.18 (95% CI = 1.13–1.22), respectively. Compared with patients with a CHA 2 DS 2 -VASc score equal to 0, the HRs of AF risk among total cohort patients and a score equal to 1, 2, 3, and ≥ 4 were 1.28 (95% CI = 1.15–1.43), 2.26 (95% CI = 2.00–2.56), 3.81 (95% CI = 3.35–4.34), and 5.09 (95% CI = 4.42–5.87), respectively. Conclusion : This population-based longitudinal follow-up study showed that patients with GD had an increased AF risk. Moreover, cholecystectomy was related to reduced AF risk. Cardiovascular checkups may be necessary for patients with GD, especially those who are young and have other typical risk factors.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2558898-9
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  • 3
    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
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Marine Science Vol. 9 ( 2022-5-18)
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 9 ( 2022-5-18)
    Abstract: The transient impact of flooding on the community composition of marine picoeukaryotes (PEs, cell size ≤5 μm) in the East China Sea (ECS) was revealed in this study. In a summer without flooding (i.e., July 2009), photosynthetic picoeukaryotes (PPEs) were more abundant in the area covered by the Changjiang River diluted water (CDW, salinity ≤31) than in the non-CDW affected area. According to the 18S ribosomal RNA phylogeny, Alveolata (all from the superclass Dinoflagellata) was the main community component accounting for 72 to 99% of the community at each sampling station during the nonflooded summer. In addition to Dinoflagellata, diatoms or Chlorophyta also contributed a considerable proportion to the PE assemblage at the stations close to the edge of CDW coverage. In July 2010, an extreme flooding event occurred in the Changjiang River basin and led to the CDW covering nearly half of the ECS. In the flooded summer, the abundance of PPEs in the CDW-covered area decreased significantly to less than 1 × 10 4 cells ml -1 . Compared to that during the nonflooded summer, the diversity of the PE composition was increased. While Dinophyceae still dominated the surface waters, Syndiniophyceae, which were represented by the uncultured Marine Alveolata Group (MALV)-I and MALV-II, accounted for a substantial amount in the Dinoflagellata superclass relative to this community composition in the nonflooded summer. Furthermore, a variety of plankton, including Cryptophyta, Haptophyta, Picobiliphyta, the uncultured Marine Stramenopiles (MASTs) and heterotrophic nanoflagellates, were observed. The nutrition modes of these PEs have been reported to be mixotrophic or heterotrophic. Therefore, it was inferred that the potentially mixotrophic and heterotrophic PE compositions might be favored in the marginal sea in the flooded summer.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2757748-X
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Pathology and Oncology Research Vol. 28 ( 2022-10-6)
    In: Pathology and Oncology Research, Frontiers Media SA, Vol. 28 ( 2022-10-6)
    Abstract: Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson’s chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.
    Type of Medium: Online Resource
    ISSN: 1532-2807
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2002501-4
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  • 6
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 8 ( 2017-11-15)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2017
    detail.hit.zdb_id: 2587354-4
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  • 7
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-9-20)
    Abstract: This study aims to establish and validate a predictive model based on radiomics features, clinical features, and radiation therapy (RT) dosimetric parameters for overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with RT for portal vein tumor thrombosis (PVTT). Methods We retrospectively reviewed 131 patients. Patients were randomly divided into the training ( n = 105) and validation ( n = 26) cohorts. The clinical target volume was contoured on pre-RT computed tomography images and 48 textural features were extracted. The least absolute shrinkage and selection operator regression was used to determine the radiomics score (rad-score). A nomogram based on rad-score, clinical features, and dosimetric parameters was developed using the results of multivariate regression analysis. The predictive nomogram was evaluated using Harrell’s concordance index (C-index), area under the curve (AUC), and calibration curve. Results Two radiomics features were extracted to calculate the rad-score for the prediction of OS. The radiomics-based nomogram had better performance than the clinical nomogram for the prediction of OS, with a C-index of 0.73 (95% CI, 0.67–0.79) and an AUC of 0.71 (95% CI, 0.62–0.79). The predictive accuracy was assessed by a calibration curve. Conclusion The radiomics-based predictive model significantly improved OS prediction in HCC patients treated with RT for PVTT.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 8
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-9-13)
    Type of Medium: Online Resource
    ISSN: 1662-5102
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2452963-1
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Cellular and Infection Microbiology Vol. 14 ( 2024-3-26)
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 14 ( 2024-3-26)
    Abstract: The hemin acquisition system is composed of an outer membrane TonB-dependent transporter that internalizes hemin into the periplasm, periplasmic hemin-binding proteins to shuttle hemin, an inner membrane transporter that transports hemin into the cytoplasm, and cytoplasmic heme oxygenase to release iron. Fur and HemP are two known regulators involved in the regulation of hemin acquisition. The hemin acquisition system of Stenotrophomonas maltophilia is poorly understood, with the exception of HemA as a TonB-dependent transporter for hemin uptake. Methods Putative candidates responsible for hemin acquisition were selected via a homolog search and a whole-genome survey of S. maltophilia . Operon verification was performed by reverse transcription-polymerase chain reaction. The involvement of candidate genes in hemin acquisition was assessed using an in-frame deletion mutant construct and iron utilization assays. The transcript levels of candidate genes were determined using quantitative polymerase chain reaction. Results Smlt3896-hemU-exbB2-exbD2-tonB2 and tonB1-exbB1-exbD1a-exbD1b operons were selected as candidates for hemin acquisition. Compared with the parental strain, hemU and tonB1 mutants displayed a defect in their ability to use hemin as the sole iron source for growth. However, hemin utilization by the Smlt3896 and tonB2 mutants was comparable to that of the parental strain. HemA expression was repressed by Fur in iron-replete conditions and derepressed in iron-depleted conditions. HemP negatively regulated hemA expression. Like hemA , hemU was repressed by Fur in iron-replete conditions; however, hemU was moderately derepressed in response to iron-depleted stress and fully derepressed when hemin was present. Unlike hemA and hemU , the TonB1-exbB1-exbD1a-exbD1b operon was constitutively expressed, regardless of the iron level or the presence of hemin, and Fur and HemP had no influence on its expression. Conclusion HemA, HemU, and TonB1 contribute to hemin acquisition in S. maltophilia . Fur represses the expression of hemA and hemU in iron-replete conditions. HemA expression is regulated by low iron levels, and HemP acts as a negative regulator of this regulatory circuit. HemU expression is regulated by low iron and hemin levels in a hemP -dependent manner.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2619676-1
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  • 10
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-8-10)
    Abstract: To describe the time-dependent impact of granulomatosis with polyangiitis (GPA) on the risk of mortality and end-stage kidney disease (ESKD). The results would provide valuable insight regarding the most vulnerable period for patients with GPA. Methods We conducted a retrospective cohort study using a nationally representative database in Taiwan. Patients with incident GPA without prior ESKD were identified, and non-GPA control cohorts were selected and matched to GPA cohorts based on sex, age, entry time and comorbidities in a 1:4 ratio. Cox regression model was used to estimate hazard ratios (HR) for mortality and ESKD stratified by the follow-up period. Results We identified a total of 142 GPA patients and 568 matched controls. Of those, 52 GPA patients died during follow-up, 48.1% of whom did so within the first 6 months after diagnosis. The 1-, 3-, 5-, and 10-year survival rates of GPA were 78.2, 71.2, 62.6, and 54.7%, respectively. Patients with GPA exhibited the greatest risk of mortality within the first 6 months after follow-up compared with non-GPA cohorts (HR: 21.9, 95% CI: 8.41–57.5). The mortality risk diminished after 1 year and to a marginally significant level during the follow-up period of 5–10 years (HR: 2.71, 95% CI: 0.97–7.62). Ten (7.1%) of the GPA patients experienced ESKD, and these cases occurred exclusively in the first 3 years following diagnosis. Conclusion Our findings suggest that physicians should closely monitor the treatment response and complications of patients with GPA in the first critical 6-month period after diagnosis to improve long-term survival outcome.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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