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  • Frontiers Media SA  (64)
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  • Frontiers Media SA  (64)
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  • 1
    Online Resource
    Online Resource
    Image1.jpg
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-6-29)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-6-29)
    Abstract: Background and aims: The outcomes of current treatment for non-small cell lung cancer (NSCLC) are unsatisfactory and development of new and more efficacious therapeutic strategies are required. The Notch pathway, which is necessary for cell survival to avert apoptosis, induces the resistance of cancer cells to antitumour drugs. Notch pathway activation is controlled by the cleavage of Notch proteins/receptors mediated by A disintegrin and metalloproteinase 17 (ADAM17); therefore, ADAM17 is a reliable intervention target for anti-tumour therapy to overcome the drug resistance of cancer cells. This work aims to develop and elucidate the activation of Compound 2b , a novel-structured small-molecule inhibitor of ADAM17, which was designed and developed and its therapeutic efficacy in NSCLC was assessed via multi-assays. Methods and results: A lead compound for a potential inhibitor of ADAM17 was explored via pharmacophore modelling, molecular docking, and biochemical screening. It was augmented by substituting two important chemical groups [R1 and R2 of the quinoxaline-2,3-diamine (its chemical skeleton)]; subsequently, serial homologs of the lead compound were used to obtain anoptimized compound ( 2b ) with high inhibitory activity compared with leading compound against ADAM17 to inhibit the cleavage of Notch proteins and the accumulation of the Notch intracellular domain in the nuclei of NSCLC cells. The inhibitory activity of compound 2b was demonstrated by quantitative polymerase chain reaction and Western blotting. The specificity of compound 2b on ADAM17 was confirmed via point-mutation. Compound 2b enhanced the activation of antitumor drugs on NSCLC cells, in cell lines and nude mice models, by targeting the ADAM17/Notch pathway. Conclusion: Compound 2b may be a promising strategy for NSCLC treatment.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1189245
    DOI: 10.3389/fphar.2023.1189245.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
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  • 2
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    Research Trends and Hotspots of Extracorporeal Membrane Oxygenation: A 10-Year Bibliometric Study and Visualization Analysis
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-10-26)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-10-26)
    Abstract: Objective: To determine the research hotspots and trends in the field of extracorporeal membrane oxygenation (ECMO), and to provide a reference for further and wider research in the future. Methods: The literatures on ECMO from January 2011 to July 2021 in the Web of Science Core Collection (WOSCC) database were searched, and Citespace5.8.R1 software was used to conduct bibliographic and visual analysis on the literature by country, institution, author and keywords. Results: A total of 5,986 articles were enrolled. According to an observation, the number of articles published in the past decade has increased, especially from 2019 to 2020. The USA had the largest number of publications, while less ECMO related studies were conducted among non-developed countries. The University of Michigan (Univ Michigan) was the institution that had the largest number of publications and the highest centrality, and Daniel B was the author who had the largest number of publications. However, more inter-institutional cooperation among author teams was needed. The focus of existing ECMO research has primarily been on the treatment of patients suffering from severe cardiopulmonary failure, and the prevention and management of complications during the application ECMO. Conclusion: Inter-regional and inter-institutional cooperation and exchanges should be carried out among ECMO research teams and institutions. The suggested research direction is to further broaden the application scope of ECMO, while determining the ways to reduce the incidence of complications and the cost, cultivate specialized team talents, and promote the application thereof.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2021.752956
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 3
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    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-28)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-28)
    Abstract: Recently, a phase III CROWN trial compared the efficacy of two anaplastic lymphoma kinase (ALK) inhibitors and demonstrated that lorlatinib displayed clinical improvement over crizotinib for advanced non-small cell lung cancer (NSCLC) patients. Therefore, the aim of this study was to estimate the cost-effectiveness of lorlatinib as a first-line therapy for patients with advanced ALK-positive (+) NSCLC. Materials and Methods A cost-effectiveness analysis was performed using a microsimulation model from the US payer perspective and a lifetime horizon (30 years) in patients with previous untreated advanced ALK+ NSCLC. Based on the CROWN trial, patient characteristics were obtained, and the transition probabilities were estimated. All direct costs were derived from official sources and published literature. The main outcomes of the model were total costs, incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and life years (LYs). One-way and probabilistic sensitivity analyses and multiple scenario analyses were conducted to test the robustness of the model outcomes. Results In the base case analysis, in which 1 million patients were simulated, treatment with lorlatinib or crizotinib as the first-line treatment was related to a mean cost of $909,758 and $616,230 (incremental cost: $293,528) and a mean survival of 4.81 QALYs and 4.09 QALYs (incremental QALY: 0.72) per patient, respectively. The main drivers of cost effectiveness were drug price and subsequent cost. PAS indicated that lorlatinib has 90% cost-effectiveness when compared to crizotinib when the willingness-to-pay (WTP) threshold in increased to $448,000/QALY. Scenario analysis demonstrated that lorlatinib has 100% cost-effectiveness at a WTP threshold of 200,000/QALY compared to crizotinib treatment when the price of lorlatinib is decreased to 75% ($424.5) of its original price. Conclusions In this study, lorlatinib was unlikely to be cost effective compared with crizotinib for patients with previously untreated advanced ALK+ NSCLC at a WTP threshold of 200,000/QALY.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.684073
    DOI: 10.3389/fonc.2021.684073.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 4
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    Effects of Stress in Adaptation to Undergraduate Life on Psychiatric Morbidity: Mediating Effects of Early Trauma and Adverse Family Factors
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychiatry Vol. 13 ( 2022-4-8)
    Details
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 13 ( 2022-4-8)
    Abstract: University students experience high levels of stress, and the prevalence of depression is higher than in the general population. The reason is not clear. More effective interventions and better prevention are needed. Methods We did annual cross-sectional surveys of Chinese undergraduates 2014–2018 (mean age 18.7 [SD 2.1], N = 39,573). We measured adaptation to university life using the Adolescent Self-rating Life Events Checklist (ASLEC) and common mental disorders using standardized self-report instruments. Regression analyses identified associations between childhood maltreatment, current family problems, stress in adaptation to undergraduate life, and psychiatric morbidity. Mediation analyses further tested relationships between these factors. Results Childhood maltreatment, current family problems, stress in adaptation, and psychiatric morbidity were all significantly associated with each other. The strongest association between childhood experiences and psychiatric morbidity was for sexual abuse and depression (OR = 3.39, 95%CI: 2.38–4.83, p & lt; 0.001) and between stress from adaptation and somatic disorder (OR = 4.54, 95%CI: 3.62–5.68, p & lt; 0.001). Associations between childhood maltreatment and stress from university life were partly mediated by psychiatric morbidity. Associations between family problems and psychiatric morbidity were mediated by stress from university life. Conclusions Stress from adaptation to university life and pressures from academic study exert stronger effects on psychiatric morbidity among students than childhood traumatic experiences and current family problems, although these factors are closely interrelated. Mental health services for students should focus on adaptation to university life and pressures from academic study as well as external factors of childhood trauma and family problems.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    URL: Article
    DOI: 10.3389/fpsyt.2022.538200
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564218-2
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  • 5
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    Image_1.pdf
    Frontiers Media SA ; 2024
    In:  Frontiers in Nutrition Vol. 11 ( 2024-4-18)
    Details
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 11 ( 2024-4-18)
    Abstract: This study aimed to establish an accurate and efficient scientific calculation model for the nutritional composition of catering food to estimate energy and nutrient content of catering food. Methods We constructed a scientific raw material classification database based on the Chinese food composition table by calculating the representative values of each food raw material type. Using China’s common cooking methods, we cooked 150 dishes including grains, meat, poultry, fish, eggs, and vegetables and established a database showing the raw and cooked ratios of various food materials by calculating the ratio of raw to cooked and the China Total Diet Research database. The effects of various cooking methods on the nutritional composition of catering food were analyzed to determine correction factors for such methods on the nutritional components. Finally, we linked the raw material classification, raw and cooked ratio, and nutritional component correction factor databases to establish a model for calculating the nutritional components of catering food. The model was verified with nine representative Chinese dishes. Results We have completed the construction of an accurate and efficient scientific calculation model for the nutritional composition of catering food, which improves the accuracy of nutrition composition calculation. Conclusion The model constructed in this study was scientific, accurate, and efficient, thereby promising in facilitating the accurate calculation and correct labeling of nutritional components in catering food.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
    URL: Article
    DOI: 10.3389/fnut.2024.1388645
    DOI: 10.3389/fnut.2024.1388645.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2776676-7
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  • 6
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    DataSheet1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-9-5)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-9-5)
    Abstract: Emerging evidence has demonstrated overlapping biological abnormalities underlying schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD); these overlapping abnormalities help explain the high heterogeneity and the similarity of patients within and among diagnostic categories. This study aimed to identify transdiagnostic subtypes of these psychiatric disorders based on lipidomics abnormalities. We performed discriminant analysis to identify lipids that classified patients (N = 349, 112 with SCZ, 132 with BP, and 105 with MDD) and healthy controls (N = 198). Ten lipids that mainly regulate energy metabolism, inflammation, oxidative stress, and fatty acylation of proteins were identified. We found two subtypes (named Cluster 1 and Cluster 2 subtypes) across patients with SCZ, BP, and MDD by consensus clustering analysis based on the above 10 lipids. The distribution of clinical diagnosis, functional impairment measured by Global Assessment of Functioning (GAF) scales, and brain white matter abnormalities measured by fractional anisotropy (FA) and radial diffusivity (RD) differed in the two subtypes. Patients within the Cluster 2 subtype were mainly SCZ and BP patients and featured significantly elevated RD along the genu of corpus callosum (GCC) region and lower GAF scores than patients within the Cluster 1 subtype. The SCZ and BP patients within the Cluster 2 subtype shared similar biological patterns; that is, these patients had comparable brain white matter abnormalities and functional impairment, which is consistent with previous studies. Our findings indicate that peripheral lipid abnormalities might help identify homogeneous transdiagnostic subtypes across psychiatric disorders.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2022.969575
    DOI: 10.3389/fcell.2022.969575.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 7
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Psychiatry Vol. 14 ( 2023-8-1)
    Details
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 14 ( 2023-8-1)
    Abstract: Negative attitudes of nurses toward mental disorders have been reported in various countries. Nurses’ stigmatizing attitudes can harm patients with mental disorders (PWMD), thereby delaying the provision of help to patients and leading to decreased quality of care. In this study, we aimed to assess Chinese nurses’ stigmatizing attitudes toward patients with mental illness and provide a basis for future development and testing of appropriate and culturally adapted interventions to reduce it. Objective This study aimed to assess the attitudes of Non-mental Health Nurses (NMHNs) in general hospitals in China toward the stigma of PWMD and determine the factors influencing them. Methods A cross-sectional survey of NMHNs in general hospitals were conducted. A self-designed WeChat-based questionnaire was used that included demographic information about the need for training on mental health issues. Participants were provided with a vignette of a depression case with suicidal thoughts. The Depression Stigma Scale (DSS) and Social Distance Scale (SDS) were used to assess attitudes toward mental disorders. Nine questions on the adequacy of knowledge about anxiety and depression and the current status of scale use were used to assess the current status of training needs for mental disorders. Descriptive analysis, chi-square test, and multivariate logistic regression were used for the table. Results A total of 8,254 nurses in non-mental health professions participated in this study. The mean DSS score of NMHNs was (17.24 ± 6.700), and the SDS score was (10.34 ± 3.154). The total detection rate of stigma among the survey respondents was 13.40% (1,107/8254). Multivariate logistic regression showed that age between 30 and 39 years [ p = 0.001, OR = 1.427 (1.154–1.764)], 4 years of work experience and above [ p = 0.018, OR = 1.377 (1.056–1.796)], having a bachelor’s degree [ p & lt; 0.001, OR = 0.742 (0.647–0.851)], adequate psychological knowledge [ p & lt; 0.001, OR = 1.567 (1.364–1.799)], full knowledge of communication with patients with anxiety and depression [ p & lt; 0.001, OR = 1.848 (1.389–2.459)], and the need to acquire skills to identify anxiety and depression were the influencing factors associated with stigma [ p & lt; 0.001, OR = 0.343 (0.236–0.499)]. Conclusion Stigmatizing attitudes toward PWMD exist among NMHNs in general hospitals in China. Thus, more mental health education programs for NMHNs are needed. Factors associated with higher morbidity stigma can be used to develop appropriate interventions to improve NMHNs’ stigmatizing attitudes and provide better quality care to PWMD.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyt.2023.1180034
    DOI: 10.3389/fpsyt.2023.1180034.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564218-2
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  • 8
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    DataSheet1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-12-13)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-12-13)
    Abstract: Background: In a recent randomized, phase 3 trial (CheckMate 9ER), nivolumab combined with cabozantinib significantly improved patient outcomes compared with sunitinib. However, the cost-effectiveness of these novel agents for untreated advanced renal cell carcinoma (aRCC) remains unknown. Materials and Methods: We constructed a microsimulation decision-analytic model to measure the healthcare costs and outcomes of nivolumab plus cabozantinib compared with those of sunitinib for patients with aRCC. The transition probability of patients was calculated from CheckMate 9ER using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated for nivolumab-plus-cabozantinib treatment compared with sunitinib from a US payer perspective. We conducted one-way and probabilistic sensitivity analyses and a series of scenario analyses to evaluate model uncertainty. Results: Nivolumab plus cabozantinib was associated with an improvement of 0.59 LYs and 0.56 QALYs compared with sunitinib. However, incorporating nivolumab plus cabozantinib into first-line treatment was associated with significantly higher lifetime costs ($483,352.70 vs. $198,320.10), causing the incremental cost-effectiveness ratio for nivolumab plus cabozantinib to be $508,987/QALY. The patients’ age of treatment, first-line utility, and cost of nivolumab had the greatest influence on the model. The outcomes were robust when tested in sensitivity and scenario analyses. Conclusion: For aRCC, substituting nivolumab plus cabozantinib in the first-line setting is unlikely to be cost-effective under the current willingness-to-pay threshold ($150,000/QALY). Significant price decreases for nivolumab used in first-line therapy would be needed to drop ICERs to a more diffusely acceptable value.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.736860
    DOI: 10.3389/fphar.2021.736860.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
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    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-8-12)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-8-12)
    Abstract: In spite of impressive success in treating hematologic malignancies, adoptive therapy with chimeric antigen receptor modified T cells (CAR T) has not yet been effective in solid tumors, where identification of suitable tumor-specific antigens remains a major obstacle for CAR T-cell therapy due to the “on target off tumor” toxicity. Protein tyrosine kinase 7 (PTK7) is a member of the Wnt-related pseudokinases and identified as a highly expressed antigen enriched in cancer stem cells (CSCs) from multiple solid tumors, including but not limited to triple-negative breast cancer, non-small-cell lung cancer, and ovarian cancer, suggesting it may serve as a promising tumor-specific target for CAR T-cell therapy. In this study, we constructed three different PTK7-specific CAR (PTK7-CAR1/2/3), each comprising a humanized PTK7-specific single-chain variable fragment (scFv), hinge and transmembrane (TM) regions of the human CD8α molecule, 4-1BB intracellular co-stimulatory domain (BB-ICD), and CD3ζ intracellular domain (CD3ζ-ICD) sequence, and then prepared the CAR T cells by lentivirus-mediated transduction of human activated T cells accordingly, and we sequentially evaluated their antigen-specific recognition and killing activity in vitro and in vivo . T cells transduced with all three PTK7-CAR candidates exhibited antigen-specific cytokine production and potent cytotoxicity against naturally expressing PTK7-positive tumor cells of multiple cancer types without mediating cytotoxicity of a panel of normal primary human cells; meanwhile, in vitro recursive cytotoxicity assays demonstrated that only PTK7-CAR2 modified T cells retained effective through multiple rounds of tumor challenge. Using in vivo xenograft models of lung cancers with different expression levels of PTK7, systemic delivery of PTK7-CAR2 modified T cells significantly prevented tumor growth and prolonged overall survival of mice. Altogether, our results support PTK7 as a therapeutic target suitable for CAR T-cell therapy that could be applied for lung cancers and many other solid cancers with PTK7 overexpression.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
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    DOI: 10.3389/fimmu.2021.665970
    DOI: 10.3389/fimmu.2021.665970.s001
    DOI: 10.3389/fimmu.2021.665970.s002
    DOI: 10.3389/fimmu.2021.665970.s003
    DOI: 10.3389/fimmu.2021.665970.s004
    DOI: 10.3389/fimmu.2021.665970.s005
    DOI: 10.3389/fimmu.2021.665970.s006
    DOI: 10.3389/fimmu.2021.665970.s007
    DOI: 10.3389/fimmu.2021.665970.s008
    DOI: 10.3389/fimmu.2021.665970.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 10
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    Video_8.MP4
    Frontiers Media SA ; 2020
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2020-2-20)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2020-2-20)
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
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    DOI: 10.3389/fcell.2020.00018
    DOI: 10.3389/fcell.2020.00018.s001
    DOI: 10.3389/fcell.2020.00018.s002
    DOI: 10.3389/fcell.2020.00018.s003
    DOI: 10.3389/fcell.2020.00018.s004
    DOI: 10.3389/fcell.2020.00018.s005
    DOI: 10.3389/fcell.2020.00018.s006
    DOI: 10.3389/fcell.2020.00018.s007
    DOI: 10.3389/fcell.2020.00018.s008
    DOI: 10.3389/fcell.2020.00018.s009
    DOI: 10.3389/fcell.2020.00018.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2737824-X
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