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  • Frontiers Media SA  (54)
  • 1
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 10 ( 2019-8-27)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2587354-4
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  • 2
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 11 ( 2020-12-23)
    Abstract: Magnetic resonance imaging (MRI) has a wide range of applications in medical imaging. Recently, studies based on deep learning algorithms have demonstrated powerful processing capabilities for medical imaging data. Previous studies have mostly focused on common diseases that usually have large scales of datasets and centralized the lesions in the brain. In this paper, we used deep learning models to process MRI images to differentiate the rare neuromyelitis optical spectrum disorder (NMOSD) from multiple sclerosis (MS) automatically, which are characterized by scattered and overlapping lesions. Methods We proposed a novel model structure to capture 3D MRI images’ essential information and converted them into lower dimensions. To empirically prove the efficiency of our model, firstly, we used a conventional 3-dimensional (3D) model to classify the T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) images and proved that the traditional 3D convolutional neural network (CNN) models lack the learning capacity to distinguish between NMOSD and MS. Then, we compressed the 3D T2-FLAIR images by a two-view compression block to apply two different depths (18 and 34 layers) of 2D models for disease diagnosis and also applied transfer learning by pre-training our model on ImageNet dataset. Results We found that our models possess superior performance when our models were pre-trained on ImageNet dataset, in which the models’ average accuracies of 34 layers model and 18 layers model were 0.75 and 0.725, sensitivities were 0.707 and 0.708, and specificities were 0.759 and 0.719, respectively. Meanwhile, the traditional 3D CNN models lacked the learning capacity to distinguish between NMOSD and MS. Conclusion The novel CNN model we proposed could automatically differentiate the rare NMOSD from MS, especially, our model showed better performance than traditional3D CNN models. It indicated that our 3D compressed CNN models are applicable in handling diseases with small-scale datasets and possess overlapping and scattered lesions.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2564217-0
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 10 ( 2023-3-23)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-3-23)
    Abstract: Among patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients. Methods Between January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression. Results Overall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden & gt;70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92–6.44], a low-density non-calcified plaque (LDNCP) volume & gt;30 mm 3 (HR: 3.40, 95% CI: 2.07–5.56), a minimal luminal area (MLA) & lt;4 mm 2 (HR: 2.30, 95% CI: 1.57–3.36), or a combination of three APCs (HR: 13.69, 95% CI: 9.34–20.12, p   & lt; 0.0001) than those not associated with recurrent MACEs. Sensitivity analysis regarding all indeterminate MACEs as NCL-related ones demonstrated similar results. Conclusions In DM patients who presented with CCS and underwent PCI, half of the MACEs occurring during the follow-up were attributable to recurrence at the site of NCLs. NCLs responsible for unanticipated MACEs were frequently characterized by a large plaque burden and LDNCP volume, a small MLA, or a combination of these APCs, as determined by CCTA.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 4
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-8-17)
    Abstract: Introduction: Temozolomide (TMZ) is the first-line drug for glioblastoma (GBM), but it is limited in clinical use due to the drug resistance, poor brain targeting, and side effects. Temozolomide hexadecyl ester (TMZ16e), a TMZ derivative with high lipophilicity, membrane permeability, and high anti-glioma properties, has the potential to reverse drug resistance. In this study, anti-ephrin type-A receptor 3 (EphA3) modified TMZ16e loaded nanoparticles (NPs) were prepared for targeted GBM therapy via intranasal administration to deliver TMZ16e to the brain, treat drug-resistant glioma effectively, and reduce peripheral toxicity. Methods: TMZ16e loaded NPs were prepared by emulsion solvent evaporation method followed by modified with anti-EphA3 (anti-EphA3-TMZ16e-NPs). In vitro evaluations were performed by an MTT assay and flow cytometry analysis. The orthotopic nude mice models were used to evaluate the anti-glioma effect in vivo . Additionally, we investigated the anti-drug resistant mechanism by western blot analysis. Results: The particle size of the prepared NPs was less than 200 nm, and the zeta potential of TMZ16e-NPs and anti-EphA3-TMZ16e-NPs were -23.05 ± 1.48 mV and -28.65 ± 1.20mV, respectively, which is suitable for nasal delivery. In vitro studies have shown that anti-EphA3 modification increased the cellular uptake of nanoparticles in T98G cells. The cytotoxicity in the anti-EphA3-TMZ16e-NPs treated group was significantly higher than that of the TMZ16e-NPs, TMZ16e, and TMZ groups ( p & lt; 0.01), and the cell cycle was blocked. Western blotting analysis showed that the TMZ16e-loaded NPs were able to effectively downregulate the expression level of O6-methylguanine-deoxyribonucleic acid-methyltransferase (MGMT) protein in T98G cells and reverse drug resistance. In vivo studies showed that the median survival time of tumor-bearing nude mice in the anti-EphA3-TMZ16e-NPs group was extended to 41 days, which was 1.71-fold higher than that of the saline group and the TUNEL staining results of the brain tissue section indicated that the TMZ16e-loaded NPs could elevate apoptosis in T98G cells. Conclusion: In conclusion, the TMZ16e-loaded NPs can be effectively delivered to the brain and targeted to gliomas, exhibiting better anti-glioma activity, indicating they possess great potential in the treatment of drug-resistant glioma.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2020-11-4)
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  • 6
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-7-10)
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2411902-7
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  • 7
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-9-14)
    Abstract: Toludesvenlafaxine hydrochloride dihydrate is a novel chemical entity and a potential triple monoamine reuptake inhibitor. This study characterized the in vitro triple reuptake inhibition activity, antidepressant-like activity in animals, and pharmacokinetic profiles in rats of toludesvenlafaxine. Binding affinity was determined using human serotonin transporter (SERT) protein, norepinephrine transporter (NET) protein and dopamine transporter (DAT) protein, and the reuptake inhibition was determined using Chinese hamster ovary cells expressing human SERT, NET and DAT. The antidepressant-like activity was examined in rat chronic unpredictable mild stress model and olfactory bulbectomized model. In rats, the tissue distribution and pharmacokinetic parameters were determined. Toludesvenlafaxine had high binding affinity on SERT, NET and DAT, and significantly inhibited the reuptake of serotonin (IC 50 = 31.4 ± 0.4 nM), norepinephrine (IC 50 = 586.7 ± 83.6 nM) and dopamine (IC 50 = 733.2 ± 10.3 nM) in vitro . Toludesvenlafaxine demonstrated significant antidepressant-like effects in rat models at 8–16 mg/kg. In addition, toludesvenlafaxine significantly reduced serum corticosterone and significantly increased testosterone levels in rats. Toludesvenlafaxine was quickly absorbed and converted to O -desvenlafaxine (ODV) after oral administration, both of which were selectively distributed into the hypothalamus with high concentration. Plasma ODV exposure was proportionally related to the doses after oral dosing. These results suggest that toludesvenlafaxine is a triple reuptake inhibitor with relatively fast-acting antidepressant-like activity and good therapeutic profile including improvement of anhedonia and sexual function.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Microbiology Vol. 11 ( 2020-12-9)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 11 ( 2020-12-9)
    Abstract: NprR is a protein of Bacillus anthracis that exhibits moonlighting functions as either a phosphatase or a neutral protease regulator that belongs to the RNPP family. We previously observed that the extracellular protease activity of an nprR deletion mutant significantly decreased within in vitro cultures. To identify the genes within the regulatory network of nprR that contribute to its protease activity, integrated transcriptomic and proteomic analyses were conducted here by comparing the nprR deletion mutant and parent strains. A total of 366 differentially expressed genes (DEGs) between the strains were observed via RNA-seq analysis. In addition, label-free LC-MS/MS analysis revealed 503 differentially expressed proteins (DEPs) within the intracellular protein fraction and 213 extracellular DEPs with significant expressional differences between the strains. The majority of DEGs and DEPs were involved in environmental information processing and metabolism. Integrated transcriptomic and proteomic analyses indicated that oxidation-reduction-related GO terms for intracellular DEPs and endopeptidase-related GO terms for extracellular DEPs were significantly enriched in the mutant strain. Notably, many genes involved in protease activity were largely downregulated in the nprR deletion mutant cultures. Moreover, western blot analysis revealed that the major extracellular neutral protease Npr599 was barely expressed in the nprR deletion mutant strain. The mutant also exhibited impaired degradation of protective antigen, which is a major B. anthracis toxin component, thereby resulting in higher protein yields. Concomitantly, another global transcriptional regulator, SpxA1, was also dramatically downregulated in the nprR deletion mutant, resulting in higher sensitivity to oxidative and disulfide stress. These data consequently indicate that NprR is a transcriptional regulator that controls genes whose products function as extracellular proteases and also is involved in oxidative stress responses. This study thus contributes to a more comprehensive understanding of the biological function of NprR, and especially in the middle growth stages of B. anthracis .
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587354-4
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-4-25)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-4-25)
    Abstract: Recently developed base editors provide a powerful tool for plant research and crop improvement. Although a number of different deaminases and Cas proteins have been used to improve base editors the editing efficiency, and editing window are still not optimal. Fusion of a non-sequence-specific single-stranded DNA-binding domain (DBD) from the human Rad51 protein between Cas9 nickase and the deaminase has been reported to dramatically increase the editing efficiency and expand the editing window of base editors in the mammalian cell lines and mouse embryos. We report the use of this strategy in rice, by fusing a rice codon-optimized human Rad51 DBD to the cytidine base editors AncBE4max, AncBE4max-NG, and evoFERNY. Our results show that the addition of Rad51 DBD did not increase editing efficiency in the major editing window but the editing range was expanded in all the three systems. Replacing the human Rad51 DBD with the rice Rad51 DBD homolog also expanded the editing window effectively.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 10
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-8)
    Abstract: Tumor mutation burden (TMB) is an important biomarker for tumor immunotherapy. It plays an important role in the clinical treatment process, but the gold standard measurement of TMB is based on whole exome sequencing (WES). WES cannot be done in most hospitals due to its high cost, long turnaround times and operational complexity. To seek out a better method to evaluate TMB, we divided the patients with lung adenocarcinoma (LUAD) in TCGA into two groups according to the TMB value, then analyzed the differences of clinical characteristics and gene expression between the two groups. We further explored the possibility of using histopathological images to predict TMB status, and developed a deep learning model to predict TMB based on histopathological images of LUAD. In the 5-fold cross-validation, the area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.64. This study showed that it is possible to use deep learning to predict genomic features from histopathological images, though the prediction accuracy was relatively low. The study opens up a new way to explore the relationship between genes and phenotypes.
    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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