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  • Frontiers Media SA  (289)
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  • Frontiers Media SA  (289)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Pharmacology Vol. 10 ( 2019-5-28)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 10 ( 2019-5-28)
    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
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-10-28)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-10-28)
    Abstract: Background: In recent years, the rise of antibody–drug conjugates (ADCs) has changed the treatment paradigm for patients with HER2-low advanced breast cancer (ABC). DESTINY-Breast04 (NCT03734029) has demonstrated the antitumor activity of trastuzumab deruxtecan (T-DXd). However, the balance between the efficacy and cost of T-DXd remains undefined. Consequently, there is a great need to assess the cost-effectiveness of T-DXd for patients with HER2-low ABC when compared with chemotherapy. Methods: A Markov decision-analytic model with a time horizon of 15 years was employed to estimate the costs and clinical efficacy of trials with the administration of T-DXd in contrast to chemotherapy alone as a later-line therapy in a group of patients with hormone receptor-positive (HR+) or negative (HR-) HER2-low ABC. The US payer perspective was taken into account when factors such as medical lifetime expenditure, incremental cost-effectiveness ratios (ICERs), and quality-adjusted life years (QALYs) were calculated. Sensitivity analyses were used to determine the model’s stability. A subgroup analysis was also conducted on the HR+/HER2-low cohort. Results: T-DXd was associated with an improvement of 0.543, 0.558, and 0.789 QALYs when compared with treatment with chemotherapy for overall, HR+, and HR- HER2-low patients, respectively. However, incorporating T-DXd into later-line therapy led to increased costs ($161,406, $177,907, and $155,757), which causes the ICER for T-DXd to be $296,873, $318,944, and $197,355 per QALY. The cost of T-DXd and the patient’s weight were the most influential factors for ICER. T-DXd being the dominant strategy is about 1.5%, 0.5%, and 28.0% in overall, HR+, and HR- HER2-low ABC patients, respectively. In addition, the T-DXd regimen was not cost-effective in all subgroups. Conclusion: Compared with chemotherapy, T-DXd was not cost-effective for patients with HER2-low ABC in the United States. However, it can provide more health benefits to patients with HR+/HER2-low ABC.
    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
    Location Call Number Limitation Availability
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  • 3
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-8-15)
    Abstract: Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.
    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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  • 4
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-11-22)
    Abstract: The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW ( f T MSW ) and above the MPC ( f T & gt;MPC ) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-5-30)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-5-30)
    Abstract: Chronic pain is defined as pain that persists typically for a period of over six months. Chronic pain is often accompanied by an anxiety disorder, and these two tend to exacerbate each other. This can make the treatment of these conditions more difficult. Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family and plays a critical role in glucose metabolism. Previous research has demonstrated the multiple roles of GIP in both physiological and pathological processes. In the central nervous system (CNS), studies of GIP are mainly focused on neurodegenerative diseases; hence, little is known about the functions of GIP in chronic pain and pain-related anxiety disorders. Methods The chronic inflammatory pain model was established by hind paw injection with complete Freund’s adjuvant (CFA) in C57BL/6 mice. GIP receptor (GIPR) agonist (D-Ala 2 -GIP) and antagonist (Pro 3 -GIP) were given by intraperitoneal injection or anterior cingulate cortex (ACC) local microinjection. Von Frey filaments and radiant heat were employed to assess the mechanical and thermal hypersensitivity. Anxiety-like behaviors were detected by open field and elevated plus maze tests. The underlying mechanisms in the peripheral nervous system and CNS were explored by GIPR shRNA knockdown in the ACC, enzyme-linked immunosorbent assay, western blot analysis, whole-cell patch-clamp recording, immunofluorescence staining and quantitative real-time PCR. Results In the present study, we found that hind paw injection with CFA induced pain sensitization and anxiety-like behaviors in mice. The expression of GIPR in the ACC was significantly higher in CFA-injected mice. D-Ala 2 -GIP administration by intraperitoneal or ACC local microinjection produced analgesic and anxiolytic effects; these were blocked by Pro 3 -GIP and GIPR shRNA knockdown in the ACC. Activation of GIPR inhibited neuroinflammation and activation of microglia, reversed the upregulation of NMDA and AMPA receptors, and suppressed the enhancement of excitatory neurotransmission in the ACC of model mice. Conclusions GIPR activation was found to produce analgesic and anxiolytic effects, which were partially due to attenuation of neuroinflammation and inhibition of excitatory transmission in the ACC. GIPR may be a suitable target for treatment of chronic inflammatory pain and pain-related anxiety.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-4-16)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-4-16)
    Abstract: Background: Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce. Objectives: This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients. Methods: Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding). Results: Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task. Conclusions: The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 7
    In: Frontiers in Ecology and Evolution, Frontiers Media SA, Vol. 5 ( 2017-06-23)
    Type of Medium: Online Resource
    ISSN: 2296-701X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2017
    detail.hit.zdb_id: 2745634-1
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Plant Science Vol. 10 ( 2019-7-16)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 10 ( 2019-7-16)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-4-28)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-4-28)
    Abstract: Verticillium wilt, caused by the soil-borne fungus Verticillium dahliae , is one of the most devastating diseases in cotton ( Gossypium spp.). Lignin in the cell wall forms a physical barrier to inhibit pathogen invasion, and defense-induced lignification reinforces secondary cell wall to prevent pathogens from further spreading. Cinnamyl alcohol dehydrogenases (CADs) catalyze the production of three main monolignols, p -coumaryl- (H), coniferyl- (G), and sinapyl-alcohols (S), which are the fundamental blocks of lignin. Here, we identified CAD genes in G. hirsutum , analyzed their expression profiles in cotton leaf, stem, and root from different developmental stages, and selected GhCAD35 , GhCAD45 , and GhCAD43 , which were consistently induced by V. dahliae inoculation in G. hirsutum cultivars resistant or susceptible to V. dahliae . On the basis of confirmation of the in vitro enzymatic activity of the three proteins in generation of the three monolignols, we used virus-induced gene silencing (VIGS) to investigate the effects of silencing of GhCAD35 , GhCAD45 , or GhCAD43 on resistance to V. dahliae as well as on deposition and the composition of lignin. Silencing each of the three CAD s impaired the defense-induced lignification and salicylic acid biosynthesis in stem, and compromised resistance to V. dahliae . Moreover, our study showed that silencing the three GhCAD s severely affected the biosynthesis of S-lignin, leading to a decrease of the syringyl/guaiacyl (S/G) ratio. Heterogeneous overexpression of GhCAD35 , GhCAD45 , or GhCAD43 in Arabidopsis enhanced disease resistance. Taken together, our study demonstrates a role of the three GhCAD s in defense-induced lignin biosynthesis and resistance to V. dahliae in G. hirsutum .
    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
    Location Call Number Limitation Availability
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  • 10
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 17 ( 2023-2-2)
    Abstract: Cervical spondylotic myelopathy (CSM) is a common form of non-traumatic spinal cord injury (SCI) and usually leads to remodeling of the brain and spinal cord. In CSM with gait instability, the remodeling of the brain and cervical spinal cord is unclear. We attempted to explore the remodeling of these patients’ brains and spinal cords, as well as the relationship between the remodeling of the brain and spinal cord and gait instability. Methods According to the CSM patients’ gait, we divided patients into two groups: normal gait patients (nPT) and abnormal gait patients (aPT). Voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (rs-FC) were performed for estimating brain changes. Cross-sectional area (CSA) and fractional anisotropy (FA) of the spinal cord were computed by Spinal cord toolbox. Correlations of these measures and the modified Japanese Orthopedic Association (mJOA) score were analyzed. Results We found that the zALFF of caudate nucleus in aPT was higher than that in healthy controls (HC) and lower than that in nPT. The zALFF of the right postcentral gyrus and paracentral lobule in HC was higher than those of aPT and nPT. Compared with the nPT, the aPT showed increased functional connectivity between the caudate nucleus and left angular gyrus, bilateral precuneus and bilateral posterior cingulate cortex (PCC), which constitute a vital section of the default mode network (DMN). No significantly different FA values or CSA of spinal tracts at the C2 level were observed between the HC, nPT and aPT groups. In CSM, the right paracentral lobule’s zALFF was negatively correlated with the FA value of fasciculus gracilis (FCG), and the right caudate zALFF was positively correlated with the FA value of the fasciculus cuneatus (FCC). The results showed that the functional connectivity between the right caudate nucleus and DMN was negatively correlated with the CSA of the lateral corticospinal tract (CST). Discussion The activation of the caudate nucleus and the strengthening functional connectivity between the caudate nucleus and DMN were associated with gait instability in CSM patients. Correlations between spinal cord and brain function might be related to the clinical symptoms in CSM.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2411902-7
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